Review of Medication-Assisted Treatment Guidelines and Measures for Opioid and Alcohol Use. Appendix A. Medication-assisted Treatment for Opioid Use Clinical Guidelines: Excerpts From Relevant Sections

11/25/2015

LIST OF TABLES

  • TABLE A.1: Practice Guidance for Buprenorphine for the Treatment of Opioid Use Disorders: Results of an Expert Panel Process
  • TABLE A.2: Institute of Obstetricians and Gynecologists, Royal College of Physicians of Ireland and Directorate of Strategy and Clinical Care Health Service Executive: Methadone Prescribing and Administration in Pregnancy
  • TABLE A.3: SAMHSA: Clinical Use of Extended-Release Injectable Naltrexone in the Treatment of Opioid Use
  • TABLE A.4: SAMHSA: Federal Guidelines for Opioid Treatment Programs
  • TABLE A.5: ASAM: National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use
  • TABLE A.6: WHO: Guidelines for the Identification and Management of Substance Use and SUD in Pregnancy
  • TABLE A.7: WHO: Consolidated Guidelines on HIV Prevention, Diagnosis, Treatment and Care for Key Populations
  • TABLE A.8: Washington State Department of Labor and Industries: Guideline for Prescribing Opioids to Treat Pain in Injured Workers
  • TABLE A.9: VA/DoD: Clinical Practice Guideline for Assessment and Management of Patients At-Risk for Suicide
  • TABLE A.10: Institute for Research, Evaluation and Training in Addictions: Management of Benzodiazepines in MAT
  • TABLE A.11: BAP Recommendations: Updated Evidence-Based Guidelines for the Pharmacological Management of Substance Abuse, Harmful Use, Addiction and Co-morbidity
  • TABLE A.12: Substance Misuse and Alcohol Use Disorders: Evidence-Based Geriatric Nursing Protocols for Best Practice
  • TABLE A.13: Guidelines for Improving Entry Into and Retention in Care and Antiretroviral Adherence for Persons with HIV: Evidence-Based Recommendations from an International Association of Physicians in AIDS Care Panel
  • TABLE A.14: Centre for Addiction and Mental Health: Buprenorphine-Naloxone for Opioid Dependence, Clinical Practice Guideline
  • TABLE A.15: Substance Use in Pregnancy
  • TABLE A.16: Colorado Division of Workers' Compensation: Chronic Pain Disorder Medical Treatment Guidelines
  • TABLE A.17: WFSBP: Guidelines for the Biological Treatment of Substance Use and Related Disorders, Part 2: Opioid Dependence
  • TABLE A.18: NOUGG: Canadian Guideline for Safe and Effective Use of Opioids for CNCP
  • TABLE A.19: New York State Department of Health: Preconception Care for HIV-Infected Women
  • TABLE A.20: VDH/ADAP OVHA: Vermont Buprenorphine Practice Guidelines
  • TABLE A.21: Commonwealth of Australia: National Guidelines for MAT for Opioid
TABLE A.1. Practice Guidance for Buprenorphine for the Treatment of Opioid Use Disorders: Results of an Expert Panel Process
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2015 Ambulatory care (deliberately broad to apply to a variety of provider settings) Literature Review "Panelists were instructed that a guideline statement should be considered valid if:

(a) Adequate scientific evidence or professional consensus exists to support a link between that practice and a health benefit to the patient with opiate dependence;

(b) A provider with high rates of adherence to that practice would be considered a higher quality provider;

(c) A majority of factors that determine adherence to the practice are under the influence of the provider."

9="definitely valid"

Authors noted that the level of evidence to support many of the guidelines was weak.

Yes. Yes--Generic recommendation for evidence-based psychosocial treatment; specific therapies specified for patients with co-occurring psychiatric disorders Domain Median Rating
(range)
1. Conduct assessments to determine candidacy for treatment:
1.1. Determine opioid use disorder by DSM-V standards. 9.0 (8-9)
1.2. Assess psychiatric history with attention to current compliance with medication. 8.0 (3-9)
1.3. Assess medical history with attention paid to liver and cardiac status, medications, and seizures. 8.0 (7-9)
1.4. Assess pregnancy status. 9.0 (3-9)
1.5. Assess psychosocial supports--employment, family, housing, 12-step involvement. 8.0 (5-9)
1.6. Assess substance use history and current substance use. 9.0 (8-9)
1.7. Assess treatment history--previous treatment episodes with buprenorphine, methadone. 8.5 (5-9)
1.8. Assess for current opioid agonist treatment by conducting a witnessed urine screen (methadone, buprenorphine, benzodiazepines). 9.0 (5-9)
1.9. Assess withdrawal status. 9.0 (6-9)
1.10. Assess addiction severity. 8.0 (7-9)
1.11. Assess potential treatment needs in relation to the physician's ability to accommodate them (intensive monitoring, interactions with legal system, employers, others). 8.0 (4-9)
1.12. Assess pain. 8.0 (6-9)
            Domain Median Rating
(range)
2. Patients who meet the following criteria are considered to be good candidates for treatment:
2.1. Have current opioid dependence. 9.0 (3-9)
2.2. If currently on methadone, are unable/unwilling to receive treatment from a methadone clinic. 8.0 (7-9)
2.3. Have adequate psychosocial support. 8.0 (1-9)
2.4. Do not have co-occurring mental disorder or COD is stable. 8.0 (1-9)
2.5. Are not suicidal. 8.5 (4-9)
2.6. May be pregnant. 8.0 (8-9)
2.7. Are expected to be reasonably compliant with treatment. 8.0 (5-9)
            Domain Median Rating
(range)
3. Prior to initiation of treatment, patients should complete and sign a treatment contract containing, at a minimum, the following components:
3.1. Discussion of voluntary participation in treatment. 9.0 (7-9)
3.2. Agreement to notify prescribing physician if they are or plan to become pregnant. 9.0 (8-9)
3.3. Discussion of the use of other medications. 9.0 (7-9)
3.4. Discussion of the use of alcohol and illicit drugs. 8.5 (4-9)
3.5. Agreement to use medications only as prescribed. 9.0 (7-9)
3.6. Agreement to attend scheduled appointments. 8.0 (6-9)
3.7. Compliance with required pill counts and drug tests. 9.0 (7-9)
3.8. Attendance at counseling and other referrals. 9.0 (7-9)
3.9. Consequences for attending appointments under the influence. 8.0 (3-9)
3.10. Policies for recovery and relapse. 7.5 (3-9)
3.11. Consequences for diversion. 9.0 (8-9)
3.12. Instructions on safe storage of medication. 9.0 (8-9)
            Domain Median Rating
(range)
4. Administer appropriate dosing of buprenorphine during induction, stabilization, and maintenance phases:
4.1. Induction: Ensure that patient is experiencing objective signs of withdrawal. 8.5 (7-9)
4.2. Induction: Day 2 maximum dose 8-16mg. 8.0 (1-9)
4.3. Induction after methadone: Induction for patients coming off methadone should be managed by experienced physicians only. 8.0 (7-9)
4.4. Induction after methadone: Monitor for withdrawal symptoms. If not observed within 24+ hours after last methadone treatment, wait prior to initiation. 8-0 (4-9)
4.5. Stabilization: Adjust dose (as needed) in no more than 2-4mg increments/week. 8.0 (2-9)
4.6. Stabilization: Daily dose has been established when patient is not using illicit opioids, withdrawal symptoms are not present, and the patient is not experiencing cravings. 8.0 (7-9)
4.7. Maintenance: After a period of time that varies with each patient but should reflect compliance with treatment, a prescription for 30 days may be written. 8.0 (7-9)
            Domain Median Rating
(range)
5. Provide or refer to concurrent psychosocial treatment:
5.1. Patients receiving buprenorphine should receive simultaneous psychosocial counseling. 9.0 (3-9)
5.2. Physicians should establish linkages with a variety of psychosocial supports and be able to refer to qualified providers. 9.0 (7-9)
5.3. Patients starting buprenorphine should receive an evidence-based psychosocial treatment. 8.0 (7-9)
5.4. Patients should receive weekly psychosocial therapy appointments during the stabilization phase. 8.0 (1-9)
5.5. Early in treatment, patients should be contacted if the physician is aware they are non-compliant with psychosocial therapy. 8.0 (7-9)
5.6. During the maintenance phase, psychosocial therapy can be less frequent than during stabilization. 8.0 (5-9)
            Domain Median Rating
(range)
6. Monitor treatment adherence and effectiveness:
6.1. During induction and stabilization phases, conduct weekly urine screens to detect alcohol and other drugs of abuse and the presence of the buprenorphine metabolite. 8.0 (1-9)
6.2. During the maintenance phase, conduct biweekly or monthly urine screens to detect alcohol and other drugs of abuse and the presence of the buprenorphine metabolite. 8.0 (1-9)
            Domain Median Rating
(range)
7. Discontinue treatment only when the following conditions are met:
7.1. Before discontinuing buprenorphine, patients must express a desire to discontinue. 9.0 (7-9)
7.2. Before discontinuing buprenorphine, patients must have stable housing and income. 7.5 (1-9)
7.3. Before discontinuing buprenorphine, patients must have adequate psychosocial support. 8.0 (4-9)
7.4. Conditions for termination and contingencies for treatment should be outlined in the treatment agreement. 9.0 (8-9)
            Domain Median Rating
(range)
8. Provide adequate assessment and treatment for patients with co-occurring depression and/or anxiety:
8.1. Screen for depression and anxiety. 8.5 (7-9)
8.2. Assess previous history of mental disorders and treatment, focusing on temporal relationship of symptoms to substance use and response to previous treatment. 8.5 (7-9)
8.3. Assess source of information, quantity, frequency, and time of last use of illicit substances or prescribed psychotropic drugs. 9.0 (7-9)
8.4. Assess family history of mental disorders. 8.0 (6-9)
8.5. Assess severity of depression/anxiety. 9.0 (7-9)
8.6. Reassess symptoms of depression and anxiety with regularity. 9.0 (7-9)
8.7. Refer to specialized behavioral health care if patient fails to respond to treatment provided by prescribing physician. 9.0 (8-9)
8.8. Refer to concurrent evidence-based psychosocial treatment, such as CBT, motivational interviewing, relapse prevention, CM, or supportive therapy. 8.5 (3-9)
8.9. Refer to 12-step facilitation, such as Dual Recovery Anonymous. 8.5 (2-9)
8.10. Once stabilized, if a patient continues to present symptoms of depression and anxiety, consider prescribing medications with low potential for abuse, such as SSRIs or tricyclic antidepressants. 8.0 (5-9)
8.11. Consider alternatives to benzodiazepines. 9.0 (8-9)
8.11a. Patients should be strongly advised against self-medicating with benzodiazepines. 9.0 (8-9)
8.11b. If a patient has a prescription for benzodiazepines at the outset of treatment, use caution taking him or her off of the benzodiazepines and do not discontinue abruptly. 9.0 (7-9)
8.12. Integrate treatment for opiate dependence and depression/anxiety to the greatest degree possible, as on-site integrated care is associated with better outcomes than referrals off-site. 9.0 (1-9)
  1. The full guideline can be found at http://www.ncbi.nlm.nih.gov/pubmed/25844527. See http://www.ccbh.com/providers/phealthchoices/articles/current/buprenorphine.php for earlier report. Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.2. Institute of Obstetricians and Gynecologists, Royal College of Physicians of Ireland and Directorate of Strategy and Clinical Care Health Service Executive: Methadone Prescribing and Administration in Pregnancy
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2013 (revised 2015) Inpatient Literature Review Not rated. Yes. No. TREATMENT FOR OPIOID DEPENDENCE
Key Recommendations:

1. MMT is the treatment of choice for opioid-dependent pregnant women. In adequate doses, methadone provides stability for the woman during pregnancy, avoiding repeated cycles of intoxication and withdrawal that may adversely affect the fetus.

2. Withdrawal from opioids can cause fetal death and preterm delivery. It is important that women who report illicit opiate use are assessed and treated in a timely manner.

3. Clear communication between maternity hospitals and local addiction services is required, particularly in relation to methadone doses and admission/discharge of methadone-maintained women.

4. Initiation of methadone may be required in a maternity hospital to avoid obstetric complications of opioid withdrawal. Careful initiation is required, as the highest risk of overdose mortality is in the first 2 weeks on methadone treatment.

5. A validated scoring tool should be used to assess signs of opioid withdrawal in opioid-dependent pregnant women.

6. Opioid-dependent pregnant women are at risk of under-treatment of peripartum pain.

7. Breastfeeding should be encouraged in women who are stable on MMT unless there are other medical contraindications.

8. The maternal methadone dose should be individually adjusted to control maternal craving or withdrawal symptoms.

Only summary guidelines are presented here. Please see original document for guidance organized based upon clinical scenarios.

  1. The full guideline can be found at http://www.emcdda.europa.eu/attachements.cfm/att_231326_EN_IE10_Opiate%20treatment%20in%20Pregnancy.pdf. Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.3. SAMHSA: Clinical Use of Extended-Release Injectable Naltrexone in the Treatment of Opioid Use
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
Revised 2015 Several- ambulatory care Consensus Not rated. Yes. Yes--Recommendation for CM, relapse prevention counseling, and motivational interviewing as strategies to improve adherence and reduce risk of relapse. Participation in mutual-help groups also suggested. TREATMENT FOR OPIOID DEPENDENCE
Clinical Recommendations. Although no definitive research supports which patients benefit most from extended-release injectable naltrexone, patients in the following categories may be good candidates for such treatment.[1]

Patients who have not had treatment success with methadone or buprenorphine: Depending on the reasons for treatment failure, individuals with an opioid use disorder who have not been successfully treated with methadone or buprenorphine may benefit from medically supervised withdrawal followed by a trial of extended-release injectable naltrexone.[51]

Patients who have a high degree of motivation for abstinence: Individuals who are highly motivated to achieve and maintain abstinence from opioids may be good candidates for treatment with extended-release injectable naltrexone.[50] This category includes people who are required to demonstrate abstinence on urine drug screens, such as individuals in programs for impaired health care professionals, parolees, probationers, and airline pilots.[52]

Patients who have been successful on opioid agonists who wish to discontinue agonist therapy or patients who are not interested in agonist therapy to treat their opioid use disorder: Some patients may be successful on agonist treatment and want continued pharmacologic help to prevent relapse but prefer another type of treatment.[51] Other patients may not be interested in agonist therapy.[1] The latter group typically includes individuals who: (1) feel they are discriminated against (or are embarrassed or ashamed) because they are on agonist therapy;[53] or (2) would like to reduce the time devoted to daily or multiple OTP visits per week, as is frequently required for methadone treatment.[1]

Patients may be suitable candidates for treatment with extended-release injectable naltrexone even if past episodes of MAT were not successful.[54] However, experts agree that the following patients are unlikely to do well on extended-release injectable naltrexone:[1]

Patients who do not tolerate extended opioid-free periods. For example, a patient who is not tolerating withdrawal is better managed with a partial agonist (buprenorphine) or an agonist (methadone) than with an antagonist medication.

Patients who are unable to complete withdrawal.

Patients who experience protracted abstinence symptoms following withdrawal.

Patients whose psychiatric symptoms worsen during withdrawal.

Patients whose chronic pain requires treatment with opioid analgesics. Treatment with extended-release naltrexone is not a viable option if pain requires chronic opioid therapy.

Patients who have advanced liver disease, impending liver failure, or acute hepatitis. Use of extended-release injectable naltrexone probably is safe in patients with chronic hepatitis B or C provided that the patient is not at the end stage and starting to go into liver failure. Patients with routine elevated liver enzymes usually tolerate naltrexone.

Integrating Pharmacologic and Non-pharmacologic Therapies

Some patients respond to psychosocial interventions or medication therapy alone, but most patients need both. The different approaches (MAT, professional counseling, and mutual-help groups) are complementary. They support the same goals while addressing different aspects of opioid use disorder: neurobiological, psychological, and social.

Offering the full range of effective treatments maximizes patient choice and outcomes, because no single approach is universally successful. Many studies show that the combination of pharmacologic and non-pharmacologic interventions may be more effective than either approach used alone.[55]

Sources of information on psychosocial therapies suitable for patients being treated in medical office settings are shown in Appendix B.

Encouraging Participation in Mutual-Help Programs. The support of a mutual-help group can be critical to long-term recovery. The oldest, best-known, and most accessible mutual-help program for people with an opioid use disorder is offered by NA. Patients may resist attending NA meetings and may fear that disclosure of medication use will make them unwelcome.[26] Although some NA members may have negative attitudes toward medication, the organization itself supports appropriate medication use. Providers should encourage patients to try meetings of different groups until they find 1 that is a good fit. Lists of local meetings to give to patients can be obtained from the NA World Services Web site (http://www.na.org).

Other mutual-help groups, although not as universally available as NA, have a strong presence in many communities. Contact information for several groups that may be helpful to patients and their families is provided in Appendix B.

Adolescents. The lack of treatment resources geared specifically to young people, coupled with the epidemic of prescription opioid and heroin abuse in this population, has left many young people with few effective treatment options.[67]

Ample evidence demonstrates the failure of detoxification-only treatments and the high rates of dropout from psychosocial-only treatments on the part of adolescents and young adults. Yet, despite an increasing body of evidence that medications such as buprenorphine, methadone, and naltrexone are effective and easily combined with psychosocial treatments, only buprenorphine is approved by the FDA for the treatment of patients younger than 18, and the safety and effectiveness of buprenorphine hydrochloride sublingual tablets in patients younger than 16 have not been established. Therefore, the best course of action is to refer young patients to an addiction specialist or program with experience in treating adolescents.[5]

Induction Onto Extended-Release Injectable Naltrexone Treatment

The clinician should consider how best to induct a patient into treatment with extended-release injectable naltrexone. Product labeling and standard practice call for 7-10 days of abstinence from short-acting opioids before starting naltrexone.[91] A urine drug screen should be conducted to verify abstinence before beginning induction.[51]

Dosing and Administration. For patients who are appropriate candidates, the recommended dose of extended-release injectable naltrexone is 380mg, delivered intramuscularly approximately every 30 days, alternating buttocks for each subsequent injection. The following cautions should be observed:[1,83,92]

See original guidelines for detailed information on treatment phases, special populations and much more.

Responding to Changes in Treatment Progress. Individuals receiving MAT often demonstrate dramatic improvement in addiction-related behaviors and psychosocial functioning. Such positive changes should be acknowledged and reinforced by the prescribing physician whenever possible.

However, lack of adherence to pharmacologic regimens occurs in a substantial proportion of patients, with some studies reporting that as many as 7 out of 10 patients fail to follow the treatment plan.[5] If a patient experiences problems with adherence, the clinician should revisit the treatment plan to determine whether different strategies or treatment modalities (pharmacologic or non-pharmacologic) might be useful. Other strategies to improve adherence and reduce the risk of relapse during treatment include providing incentives to take the monthly injections (i.e., CM); involving significant others in monitoring the patient to ensure adherence to the medication plan, in a manner consistent with patient privacy requirements; offering relapse prevention counseling; and using motivational interviewing techniques.

Behaviors that violate the treatment agreement or that indicate limited progress in treatment may not constitute grounds for automatic termination of MAT. Such behaviors should trigger a reassessment of the patient's needs and goals and a corresponding revision of the treatment plan. Aberrant or dysfunctional behaviors may indicate the need for more vigorous engagement in peer support, counseling, or psychotherapies or possibly referral to a more structured treatment setting.

Alternative pharmacologic therapies such as methadone or BMT also should be considered for these patients. Such changes should be documented in the patient's medical record.

  1. The full guideline can be found at http://store.samhsa.gov/shin/content/SMA14-4892/SMA14-4892.pdf. Text footnotes are from original guideline.

 

TABLE A.4. SAMHSA: Federal Guidelines for Opioid Treatment Programs
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2015 OTP Consensus Not graded. Yes. Yes--Generic recommendation. Diversion Control (Summary):

Diversion control section recommends regularly monitoring program environment; observing a patient take their dose, including taking a drink and speaking after; random call backs to inventory a patient's take-home doses; opening OTPs on Sundays for a short period to administer medications to patients not ready for an unsupervised dose; contacting other OTPs in geographical area to confirm patient is not enrolled in multiple OTPs; and checking for patient misuse of prescriptions by consulting the PDMP.

Drug Selection Excerpt:

If a patient has a mild or moderate opioid use disorder without meeting criteria for tolerance/withdrawal, opioid agonist medications that will themselves produce physical dependence must be carefully considered due to the difficulty experienced by many of the discontinuation of opioids on which an individual has become physically dependent. Other options such as psychotherapy or antagonist pharmacotherapy such as oral/injectable naltrexone treatment should be considered.

Informed Consent Excerpt:

Inform each patient about all treatment procedures, services, and other policies and regulations throughout the course of treatment. It should also ensure that each patient voluntarily chooses maintenance treatment and that all relevant facts concerning the use of the opioid drug are clearly and adequately explained to the patient.

  • Ensure that before medicating the patient the physician receives voluntary, written, program-specific informed consent to treatment with the specific pharmacotherapy ordered by the physician. Within 30 days post-admission, an appropriate program staff member should review informed consent with the patient.
  • Inform each patient at admission and upon a 30-day review that the goal of MAT is stabilization of functioning.
  • Inform each patient at admission of state-specific requirements and program policies regarding the report of suspected child abuse and neglect, as well as other forms of abuse (e.g., violence against women).
  • Include a written description of patients' rights and responsibilities that is reviewed with the patient. An example can be found at http://www.nlm.nih.gov/medlineplus/ency/article/001947.htm.

Detoxification Excerpt:

Detoxification can be considered the medically supported transition to a medication-free state or to antagonist therapy. Many OTPs do not provide a specific pathway for patients to go directly to a medication-free state because of the notoriously poor outcomes and high incidence of relapse to drug use. Please refer to TIP 43 (http://www.ncbi.nlm.nih.gov/books/NBK64164/pdf/TOC.pdf). With the decreased availability and insurance reimbursement for inpatient detoxification services and the advent of long-acting antagonist therapy, each program should evaluate the need to develop policies and procedures to provide this service so that treatment can be matched to the individual needs and preferences of the patient. Very careful review of the risks and benefits of detoxification must be provided and thorough informed consent obtained from patients choosing this treatment option. Because of the risk of fatal overdose if relapse occurs, detoxification services should be accompanied by relapse prevention counseling, overdose prevention education as well as a naloxone kit (naloxone dose and syringes) or an FDA-approved naloxone auto injector. The treatment and aftercare plans should always include a strategy to transition to MAT if needed.

Psychosocial Excerpts:

Both psychosocial and medical treatment should be of sufficient intensity and duration so as to be effective for each treatment stage. In general, a greater intensity of services is desirable at the beginning of treatment, or when staff members identify a patient's relapse or relapse "trigger" conditions exist. Many patients often need psychosocial services for an extended period of time because of the multiplicity of their problems.

Unless clinically indicated, there should be no limits on patients' duration of treatment or dosage level of medication. Likewise, there should be no limitations on the psychosocial services offered to patients, even when they no longer take medication.

Appropriately trained, experienced, and certified or licensed substance abuse counselors should provide services at the intensity and for the duration required to meet each patient's needs as referenced in the individualized treatment plan.

ROSC Excerpt:

OTPs should include recovery support services in their patient's treatment plan. Recovery support services may involve follow-up phone calls; face-to-face meetings; e-mails; and connecting patients to peer-to-peer services, 12-step, faith-based, and community groups.

Furthermore, under the ROSC framework, OTPs provide patients with continuing care. This includes a discharge plan, referrals to continuing outpatient care, procedures that address patients' physical and mental health problems following medically supervised withdrawal, plans for reentry to maintenance treatment if relapse occurs, and ongoing recovery management. OTPs also are encouraged to offer supportive counseling as a transitional service.

Standing Order/Caps Excerpts:

Standing orders regarding the dose, schedule, or re-administration of methadone are not appropriate because of the unique pharmacologic properties, the well-established potential for fatalities in the induction period, and the risk of relapse during medically supervised withdrawal. In an OTP, an unacceptable standing order is any formulaic policy generically applied to all patients meeting specific criteria or in specific situations without evaluation by a physician or other qualified health care provider. Common examples are dose adjustments made solely on the basis of a COWS score and remedicating a patient who vomits after dosing based on the time between dose administration and vomiting using a fixed percentage of the dose.

Program-wide dosage caps or ceilings are contrary to the current state of the medical literature and the principle of individualized treatment. Programs should eliminate their use. In addition, OTPs should avoid establishing procedures or policies that hinder the ability of physicians or authorized health care professionals, as appropriate, to adjust patient dosages whenever the need is indicated.

Aftercare Planning Excerpt:

Aftercare planning should begin upon admission. Taking a recovery oriented approach to care facilitates this process. Aftercare planning should include the need for ongoing management of medical and psychiatric problems. Untreated, these problems are associated with relapse to drug use. Antagonist medications (e.g., extended-release injectable naltrexone) should also be considered for inclusion in aftercare plans.

Adolescent Excerpt:

For the purpose of this document, adolescents are defined as youth ranging in age 13-18.

Programs develop and implement policies to ensure that adolescents are provided with developmentally appropriate treatment and evidence-based psychosocial support, such as family involvement, for that treatment. Screenings and assessments tailored to adolescents ensure that MAT is the most appropriate treatment for these patients.

  1. The full guideline can be found at http://store.samhsa.gov/shin/content//PEP15-FEDGUIDEOTP/PEP15-FEDGUIDEOTP.pdf .

 

TABLE A.5. ASAM: National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2015 OTP, OBOT, outpatient, inpatient Literature Review Not rated.

(RAND/UCLA Appropriateness Method used but individual ratings of specific guidelines not provided.)

Yes. Also includes clonidine, which is not FDA-approved. Yes--Generic recommendation. SUMMARY OF RECOMMENDATIONS
Part 1: Assessment and Diagnosis of Opioid Use Disorder

Assessment Recommendations

  • First clinical priority should be given to identifying and making appropriate referral for any urgent or emergent medical or psychiatric problem(s), including drug-related impairment or overdose.
  • Completion of the patient's medical history should include screening for concomitant medical conditions, including infectious diseases (hepatitis, HIV, and TB), acute trauma, and pregnancy.
  • A physical examination should be completed as a component of the comprehensive assessment process. The prescriber (the clinician authorizing the use of a medication for the treatment of opioid use disorder) may conduct this physical examination him/herself, or, in accordance with the ASAM standards, ensure that a current physical examination is contained within the patient medical record before a patient is started on a new medication for the treatment of his/her addiction.
  • Initial laboratory testing should include a complete blood count, liver function tests, and tests for hepatitis C and HIV. Testing for TB and sexually transmitted infections should also be considered. Hepatitis B vaccination should be offered, if appropriate.
  • The assessment of females presents special considerations regarding their reproductive health. Women of childbearing age should be tested for pregnancy, and all women of childbearing potential and age should be queried regarding methods of contraception given the increase in fertility that results from effective opioid use disorder treatment.
  • Patients being evaluated for addiction involving opioid use, and/or for possible medication use in the treatment of opioid use disorder, should undergo (or have completed) an assessment of mental health status and possible psychiatric disorders (as outlined in the ASAM standards).
  • Opioid use is often co-occurring with other substance-related disorders. An evaluation of past and current substance use as well as a determination of the totality of substances that surround the addiction should be conducted.
  • The use of marijuana, stimulants, or other addictive drugs should not be a reason to suspend opioid use disorder treatment. However, evidence demonstrates that patients who are actively using substances during opioid use disorder treatment have a poorer prognosis. The use of benzodiazepines and other sedative-hypnotics may be a reason to suspend agonist treatment because of safety concerns related to respiratory depression.
  • A tobacco use query and counseling on cessation of tobacco products and electronic nicotine delivery devices should be completed routinely for all patients, including those who present for evaluation and treatment of opioid use disorder.
  • An assessment of social and environmental factors should be conducted (as outlined in the ASAM Standards) to identify facilitators and barriers to addiction treatment, and specifically to pharmacotherapy. Before a decision is made to initiate a course of pharmacotherapy for the patient with opioid use disorder, the patient should receive a multidimensional assessment in fidelity with The ASAM Criteria: Treatment Criteria for Addictive, Substance-Related, and Co-Occurring Conditions (the "ASAM Criteria"). Addiction should be considered a bio-psychosocial-spiritual illness, for which the use of medication(s) is but only 1 component of overall treatment.

Diagnosis Recommendations

  • Other clinicians may diagnose opioid use disorder, but confirmation of the diagnosis by the provider with prescribing authority, and who recommends medication use, must be obtained before pharmacotherapy for opioid use disorder commences.
  • Opioid use disorder is primarily diagnosed on the basis of the history provided by the patient and a comprehensive assessment that includes a physical examination.
  • Validated clinical scales that measure withdrawal symptoms (e.g., the OOWS, the SOWS, and the COWS may be used to assist in the evaluation of patients with opioid use disorder).
  • Urine drug testing during the comprehensive assessment process, and frequently during treatment, is recommended. The frequency of drug testing is determined by a number of factors including: the stability of the patient, the type of treatment, and the treatment setting.
            TREATMENT FOR OPIOID DEPENDENCE
Part 2: Treatment Options
  • The choice of available treatment options for addiction involving opioid use should be a shared decision between clinician and patient.
  • Clinicians should consider the patient's preferences, past treatment history, and treatment setting when deciding between the use of methadone, buprenorphine, and naltrexone in the treatment of addiction involving opioid use. The treatment setting described as Level 1 treatment in the ASAM Criteria may be a general outpatient location such as a clinician's practice site. The setting as described as Level 2 in the ASAM Criteria may be an intensive outpatient treatment or partial hospitalization program housed in a specialty addiction treatment facility, a community mental health center, or another setting. The ASAM Criteria describes Level 3 or Level 4 treatment respectively as a residential addiction treatment facility or hospital.
  • The venue in which treatment is provided is as important as the specific medication selected. OTPs offer daily supervised dosing of methadone, and increasingly of buprenorphine. In accordance with federal law (21 CFR ASAM National Practice Guideline | May 27, 2015 15 §1306.07), OBOT, which provides medication on a prescribed weekly or monthly basis, is limited to buprenorphine. Naltrexone can be prescribed in any setting by any clinician with the authority to prescribe any medication. Clinicians should consider a patient's psychosocial situation, CODs, and risk of diversion when determining whether OTP or OBOT is most appropriate.
  • OBOT may not be suitable for patients with active alcohol use disorder or sedative, hypnotic, or anxiolytic use disorder (or who are in the treatment of addiction involving the use of alcohol or other sedative drugs, including benzodiazepines or benzodiazepine receptor agonists). It may also be unsuitable for persons who are regularly using alcohol or other sedatives but do not have addiction or a specific SUD related to that class of drugs. The prescribing of benzodiazepines or other sedative-hypnotics should be used with extreme caution in patients who are prescribed methadone or buprenorphine for the treatment of an opioid use disorder.
  • Methadone is recommended for patients who may benefit from daily dosing and supervision in an OTP, or for patients for whom buprenorphine for the treatment of opioid use disorder has been used unsuccessfully in an OTP or OBOT setting.
  • Oral naltrexone for the treatment of opioid use disorder is often adversely affected by poor medication adherence. Clinicians should reserve its use for patients who would be able to comply with special techniques to enhance their adherence (e.g., observed dosing). Extended-release injectable naltrexone reduces, but does not eliminate, issues with medication adherence.
            DETOXIFICATION
Part 3: Treating Opioid Withdrawal
  • Using medications for opioid withdrawal management is recommended over abrupt cessation of opioids. Abrupt cessation of opioids may lead to strong cravings, which can lead to continued use.
  • Patients should be advised about risk of relapse and other safety concerns from using opioid withdrawal management as standalone treatment for opioid use disorder. Opioid withdrawal management on its own is not a treatment method.
  • Assessment of a patient undergoing opioid withdrawal management should include a thorough medical history and physical examination focusing on signs and symptoms associated with opioid withdrawal.
  • Opioid withdrawal management in cases in which methadone is used to manage withdrawal symptoms must be done in an inpatient setting or in an OTP. For short-acting opioids, tapering schedules that decrease in daily doses of prescribed methadone should begin with doses 20-30mg/day and should be completed in 6-10 days.
  • Opioid withdrawal management in cases in which buprenorphine is used to manage withdrawal symptoms should not be initiated until 12-18 hours after the last dose of a short-acting agonist such as heroin or oxycodone, and 24-48 hours after the last dose of a long-acting agonist such as methadone. A dose of buprenorphine sufficient to suppress withdrawal symptoms is given (this can be 4-16mg/day) and then the dose is tapered. The duration of the tapering schedule can be as brief as 3-5 days or as long as 30 days or more.
  • The use of combinations of buprenorphine and low doses of oral naltrexone to manage withdrawal and facilitate the accelerated introduction of extended-release injectable naltrexone has shown promise. More research will be needed before this can be accepted as standard practice.
  • The Guideline Committee recommends, based on consensus opinion, the inclusion of clonidine as a practice to support opioid withdrawal. Clonidine is not FDA-approved for the treatment of opioid withdrawal but it has been extensively used off-label for this purpose. Clonidine may be used orally or trans-dermally at doses of 0.1-0.3mg every 6-8 hours with a maximum dose of 1.2mg daily to assist in the management of opioid withdrawal symptoms. Its hypotensive effects often limit the amount that can be used. Clonidine can be combined with other non-narcotic medications targeting specific opioid withdrawal symptoms such as benzodiazepines for anxiety, loperamide for diarrhea, acetaminophen or NSAIDs for pain, and ondansetron or other agents for nausea.
  • Opioid withdrawal management using anesthesia UROD is not recommended due to high risk for adverse events or death. Naltrexone-facilitated opioid withdrawal management can be a safe and effective approach but should be used only by clinicians experienced with this clinical method, and in cases in which anesthesia or conscious sedation are not being employed.
            TREATMENT FOR OPIOID DEPENDENCE
Part 4: Methadone
  • Methadone is a treatment option recommended for patients who are physiologically dependent on opioids, able to give informed consent, and who have no specific contraindications for agonist treatment when it is prescribed in the context of an appropriate plan that includes psychosocial intervention.
  • The recommended initial dose ranges for methadone are from 10-30mg with reassessment in 3-4 hours, and a second dose not to exceed 10mg on the first day if withdrawal symptoms are persisting.
  • The usual daily dosage of methadone ranges 60-120mg. Some patients may respond to lower doses and some patients may need higher doses. Dosage increases in 5-10mg increments applied no more frequently than every 7 days (depending on clinical response) are necessary to avoid over-sedation, toxicity, or even iatrogenic overdose deaths.
  • The administration of methadone should be monitored because unsupervised administration can lead to misuse and diversion. OTP regulations require monitored medication administration until the patient's clinical response and behavior demonstrates that the prescribing of non-monitored doses is appropriate.
  • Psychosocial treatment, though sometimes minimally needed, should be implemented in conjunction with the use of methadone in the treatment of opioid use disorder.
  • Methadone should be reinstituted immediately if relapse occurs, or when an assessment determines that the risk of relapse is high for patients who previously received methadone in the treatment of opioid use disorder but who are no longer prescribed such treatment.
  • Strategies directed at relapse prevention are an important part of comprehensive addiction treatment and should be included in any plan of care for a patient receiving active opioid treatment or ongoing monitoring of the status of their addictive disease.
  • Switching from methadone to another medication for the treatment of opioid use disorder may be appropriate if the patient experiences intolerable side effects or is not successful in attaining or maintaining treatment goals through the use of methadone.
  • Patients switching from methadone to buprenorphine in the treatment of opioid use disorder should be on low doses of methadone prior to switching medications.
  • Patients on low doses of methadone (30-40mg/day or less) generally tolerate transition to buprenorphine with minimal discomfort, whereas patients on higher doses of methadone may experience significant discomfort in switching medications.
  • Patients switching from methadone to oral naltrexone or extended-release injectable naltrexone must be completely withdrawn from methadone and other opioids, before they can receive naltrexone. The only exception would apply when an experienced clinician receives consent from the patient to embark on a plan of naltrexone-facilitated opioid withdrawal management.
  • Patients who discontinue agonist therapy with methadone or buprenorphine and then resume opioid use should be made aware of the risks associated with opioid overdose, and especially the increased risk of death.

Part 5: Buprenorphine

  • Opioid-dependent patients should wait until they are experiencing mild to moderate opioid withdrawal before taking the first dose of buprenorphine to reduce the risk of precipitated withdrawal. Generally, buprenorphine initiation should occur at least 6-12 hours after the last use of heroin or other short-acting opioids, or 24-72 hours after their last use of long-acting opioids such as methadone.
  • Induction of buprenorphine should start with a dose of 2-4mg. Dosages may be increased in increments of 2-4mg.
  • Clinicians should observe patients in their offices during induction. Emerging research suggests, however, that many patients need not be observed and that home buprenorphine induction may be considered. Home-based induction is recommended only if the patient or prescribing physician is experienced with the use of buprenorphine. This is based on the consensus opinion of the Guideline Committee.
  • Buprenorphine doses after induction and titration should be, on average, at least 8mg/day. However, if patients are continuing to use opioids, consideration should be given to increasing the dose by 4-8mg (daily doses of 12-16mg or higher). The FDA approves dosing to a limit of 24mg/day, and there is limited evidence regarding the relative efficacy of higher doses. In addition, the use of higher doses may increase the risk of diversion.
  • Psychosocial treatment should be implemented in conjunction with the use of buprenorphine in the treatment of opioid use disorder.
  • Clinicians should take steps to reduce the chance of buprenorphine diversion. Recommended strategies include frequent office visits (weekly in early treatment), urine drug testing, including testing for buprenorphine and metabolites, and recall visits for pill counts.
  • Patients should be tested frequently for buprenorphine, other substances, and prescription medications. Accessing PDMP data may be useful for monitoring.
  • Patients should be seen frequently at the beginning of their treatment. Weekly visits (at least) are recommended until patients are determined to be stable. There is no recommended time limit for treatment.
  • Buprenorphine taper and discontinuation is a slow process and close monitoring is recommended. Buprenorphine tapering is generally accomplished over several months. Patients should be encouraged to remain in treatment for ongoing monitoring past the point of discontinuation.
  • When considering a switch from buprenorphine to naltrexone, 7-14 days should elapse between the last dose of buprenorphine and the start of naltrexone to ensure that the patient is not physically dependent on opioids prior to starting naltrexone.
  • When considering a switch from buprenorphine to methadone, there is no required time delay since the addition of a full mu-opioid agonist to a partial agonist does not typically result in any type of adverse reaction.
  • Patients who discontinue agonist therapy and resume opioid use should be made aware of the risks associated with an opioid overdose, and especially the increased risk of death.

Part 6: Naltrexone

  • Naltrexone is a recommended treatment in preventing relapse in opioid use disorder. Oral formula naltrexone may be considered for patients where adherence can be supervised or enforced. Extended-release injectable naltrexone may be more suitable for patients who have issues with adherence.
  • Oral naltrexone should be taken daily in 50mg doses, or 3 times weekly in 2 100mg doses followed by 1 150mg dose.
  • Extended-release injectable naltrexone should be administered every 4 weeks by deep intramuscular injection in the gluteal muscle at a set dosage of 380mg/injection.
  • Psychosocial treatment is recommended in conjunction with treatment with naltrexone. The efficacy of naltrexone use in conjunction with psychosocial treatment has been established, whereas the efficacy of extended-release injectable naltrexone without psychosocial treatment has not been established.
  • There is no recommended length of treatment with oral naltrexone or extended-release injectable naltrexone. Duration depends on clinical judgment and the patient's individual circumstances. Because there is no physical dependence associated with naltrexone, it can be stopped abruptly without withdrawal symptoms.
  • Switching from naltrexone to methadone or buprenorphine should be planned, considered, and monitored. Switching from an antagonist such as naltrexone to a full agonist (methadone) or a partial agonist (buprenorphine) is generally less complicated than switching from a full or partial agonist to an antagonist because there is no physical dependence associated with antagonist treatment and thus no possibility of precipitated withdrawal. Patients being switched from naltrexone to buprenorphine or methadone will not have physical dependence on opioids and thus the initial doses of methadone or buprenorphine used should be low. Patients should not be switched until a significant amount of the naltrexone is no longer in their system, about 1 day for oral naltrexone or 30 days for extended-release injectable naltrexone.
  • Patients who discontinue antagonist therapy and resume opioid use should be made aware of the increased risks associated with an opioid overdose, and especially the increased risk of death.

Part 7: Psychosocial Treatment in Conjunction with Medications for the Treatment of Opioid Use Disorder

  • Psychosocial treatment is recommended in conjunction with any pharmacological treatment of opioid use disorder. At a minimum, psychosocial treatment should include the following: psychosocial needs assessment, supportive counseling, links to existing family supports, and referrals to community services.
  • Treatment planning should include collaboration with qualified behavioral health care providers to determine the optimal type and intensity of psychosocial treatment and for renegotiation of the treatment plan for circumstances in which patients do not adhere to recommended plans for, or referrals to, psychosocial treatment.
  • Psychosocial treatment is generally recommended for patients who are receiving opioid agonist treatment (methadone or buprenorphine).
  • Psychosocial treatment should be offered with oral and extended-release injectable naltrexone. The efficacy of extended-release injectable naltrexone to treat opioid use disorder has not been confirmed when it has been used as pharmacotherapy without accompanying psychosocial treatment.

Part 10: Special Populations: Adolescents

  • Clinicians should consider treating adolescents who have opioid use disorder using the full range of treatment options, including pharmacotherapy.
  • Opioid agonists (methadone and buprenorphine) and antagonists (naltrexone) may be considered for treatment of opioid use disorder in adolescents. Age is a consideration in treatment, and federal laws and FDA approvals need to be considered for patients under age 18.
  • Psychosocial treatment is recommended in the treatment of adolescents with opioid use disorder.
  • Concurrent practices to reduce infection (e.g., sexual risk reduction interventions), are recommended as components of comprehensive treatment for the prevention of sexually transmitted infections and blood-borne viruses.
  • Adolescents may benefit from treatment in specialized treatment facilities that provide multidimensional services.

See original guidelines for guidelines on other special populations including pregnant women, individuals with pain, and the incarcerated population. Also see original guidelines for more information.

  1. Full guideline can be found at http://www.asam.org/docs/default-source/practice-support/guidelines-and-consensus-docs/national-practice-guideline.pdf?sfvrsn=22. Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.6. WHO: Guidelines for the Identification and Management of Substance Use and SUD in Pregnancy
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2014 Primary care, other outpatient settings inferred, inpatient Literature Review GRADE Working Group Grades of Evidence

High quality: Further research is very unlikely to change confidence in the estimate of effect.

Moderate quality: Further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate.

Low quality: Further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate.

Very low quality: The GDG is very uncertain about the estimate.

Strength of Recommendation

Strong: The GDG was confident that the quality of the evidence of effect, combined with certainty about the values, preferences, benefits and feasibility, made this a recommendation that should be done in most circumstances and settings.

Conditional: There was less certainty about the quality of the evidence and values, preferences, benefits and feasibility of this recommendation. Thus, there may be circumstances or settings in which it should not apply.

Yes. Yes--Recommend CBT, CM and motivational interviewing/enhancement. SCREENING
Recommendation 1

Health care providers should ask all pregnant women about their use of alcohol and other substances (past and present) as early as possible in the pregnancy and at every antenatal visit. (Strength of recommendation: Strong; Quality of evidence: Low)

See original guidelines for remarks.

Recommendation 2

Health care providers should offer a brief intervention to all pregnant women using alcohol or drugs. (Strength of recommendation: Strong; Quality of evidence: Low)

See original guidelines for remarks.

Recommendation 3

Health care providers managing pregnant or post-partum women with alcohol or other SUDs should offer comprehensive assessment and individualized care. (Strength of recommendation: Conditional; Quality of evidence: Very low)

Remarks

A comprehensive assessment of women using alcohol or drugs in pregnancy and the post-partum period includes an assessment of patterns of substance use, medical or psychiatric co-morbidity, family context, as well as social problems.

Individualized care involves selecting appropriate psychosocial interventions of different intensity based on the particular needs of the pregnant women and the resources available. Psychosocial interventions include a number of psychological treatments and social supports, ranging from lesser to higher intensity. The psychosocial treatment and support referred to in this section is a more intensive set of interventions typically delivered by people with specific training in the management of SUDs, and usually includes repeated contact with the patient. The kinds of specific psychological techniques considered in this category include CBT, CM and motivational interviewing/enhancement. The kinds of social support referred to in this section include assistance with accommodation, vocational training, parenting training, life-skills training, legal advice, home-visiting and outreach.

Despite the benefits of psychosocial treatment outweighing the harms, this recommendation was considered to be conditional given the absence of strong evidence and the potential resource implications.

          DETOXIFICATION AND TREATMENT FOR OPIOID DEPENDENCE
            Recommendation 5

Pregnant women dependent on opioids should be encouraged to use opioid maintenance treatment whenever available rather than to attempt opioid detoxification. (Strength of recommendation: Strong; Quality of evidence: Very low)

Remarks

Opioid maintenance treatment in this context refers to either MMT or BMT.

Pregnant patients with opioid dependence who wish to undergo detoxification should be advised that relapse to opioid use is more likely following medication-assisted withdrawal than while undertaking opioid maintenance treatment.

Such medication-assisted withdrawal from opioids should be attempted only in an inpatient unit, using a gradual reduction in methadone or buprenorphine doses. Inpatient care should also be considered for the initiation and optimization of maintenance treatment.

Psychosocial treatment should be an integral component of such treatment.

Pregnant women who fail to complete medication-assisted withdrawal should be offered opioid agonist pharmacotherapy.

It was decided that this recommendation should be strong despite the low quality of evidence of effectiveness from RCTs, as the rate of relapse to opioid use following detoxification has been shown to be high and the risks of harm to both mother and fetus from failed detoxification are catastrophic compared to the very low risks of harm from opioid maintenance treatment.

            TREATMENT FOR OPIOID DEPENDENCE
Recommendation 11

Pregnant patients with opioid dependence should be advised to continue or commence opioid maintenance therapy with either methadone or buprenorphine. (Strength of recommendation: Strong; Quality of evidence: Very low)

Remarks

Pregnant patients with opioid dependence should be encouraged to commence opioid agonist pharmacotherapy, which should be combined with psychosocial interventions.

Opioid-dependent pregnant women who are already taking opioid maintenance therapy with methadone should not be advised to switch to buprenorphine due to the risk of opioid withdrawal. Pregnant opioid-dependent women taking buprenorphine should not be advised to switch to methadone unless they are not responding well to their current treatment.

In opioid-dependent pregnant women, the buprenorphine mono formulation should be used in preference to the buprenorphine-naloxone formulation.

Regardless of the choice of medication, psychosocial interventions should be an integral component of treatment.

Opioid-dependent pregnant patients who wish to receive opioid antagonist pharmacotherapy should be discouraged from such a choice.

It was decided that this recommendation should be strong despite the low quality of evidence as the rate of relapse to opioid use following detoxification is high and the risks of harm from failed detoxification are catastrophic compared to the small risks of harm from opioid maintenance treatment.

See original guidelines for full guidelines, particularly sections on infants and breastfeeding.

  1. Full guideline can be found at http://www.guideline.gov/content.aspx?id=48894&search=(%22naltrexone%22+OR+%22buprenorphine%22+OR+%22methadone%22). Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.7. WHO: Consolidated Guidelines on HIV Prevention, Diagnosis, Treatment and Care for Key Populations
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2014 Not specified Literature Review Significance of the 4 GRADE Levels of Evidence

High: Further research is very unlikely to change confidence in the estimate of effect.

Moderate: Further research is likely to have an important impact on confidence in the effect.

Low: Further research is very likely to have an important impact on the estimate of effect and is likely to change the estimate.

Very Low: Any estimate of effect is very uncertain.

Strength of Recommendations

A strong recommendation (for or against) is 1 for which there is confidence that the desirable effects of adherence to the recommendation clearly outweigh the undesirable effects.

A conditional recommendation (for or against) is 1 for which the quality of evidence may be low or may apply only to specific groups or settings; or the panel concludes that the desirable effects of adherence to the recommendation probably outweigh the undesirable effects or are closely balanced, but the panel is not confident about these trade-offs in all situations.

If implemented, a conditional recommendation should be monitored closely and evaluated rigorously. Further research will be required to address the uncertainties and is likely to provide new evidence that may change the calculation of the balance of trade-offs.

The values and preferences of the end users (key populations), feasibility and cost as well as consideration of potential benefits and harms contribute to determining the strength of a recommendation.

Yes. Yes--Generic recommendation. TREATMENT FOR OPIOID DEPENDENCE
Opioid Substitution Therapy

Recommendations and Guidance

All Key Population Groups

  • All people from key populations who are dependent on opioids should be offered OST in keeping with WHO guidance (Strong recommendation, Low quality of evidence) ("WHO, UNDOC, UNAIDS technical guide," 2012; "Tool," Forthcoming; "Guidelines for the psychosocially," 2009), including those in prison and other closed settings ("Interventions to address HIV," 2007).

Additional remarks

  • To maximize the safety and effectiveness of OST programmes, policies and regulations should encourage flexible dosing structures, without restricting dose levels or duration of treatment ("Guidelines for the psychosocially," 2009). Usual methadone maintenance doses should be in the range of a minimum of 60-120mg/day, and average buprenorphine maintenance doses should be at least 8mg/day ("Guidelines for the psychosocially," 2009). Take-home doses can be offered when the dose and social situation are stable and when there is little risk of diversion for illegitimate purposes ("Guidelines for the psychosocially," 2009). OST is most effective as a maintenance treatment for longer periods of time (treatment for years may be necessary). Detoxification or opioid withdrawal (rather than maintenance treatment) results in poor outcomes in the long term. However, patients should be helped to withdraw from opioids if it is their informed choice to do so ("Guidelines for the psychosocially," 2009).
  • OST should be used for the treatment of opioid dependence in pregnancy rather than attempt opioid detoxification ("Guidelines for the psychosocially," 2009; "Guidelines for identification," 2014).
  • Psychosocial support should be available to all opioid-dependent people, in association with pharmacological treatments of opioid dependence. At a minimum this support should include assessment of psychosocial needs, supportive counselling and links to family and community services ("Guidelines for the psychosocially," 2009).
  • For opioid-dependent people with TB, viral hepatitis B or C or HIV, opioid agonists should be administered in conjunction with medical treatment. There is no need to wait for abstinence from opioids to start treatment for these conditions ("Guidelines for the psychosocially," 2009).
  • Treatment services should offer hepatitis B vaccination to all opioid-dependent patients (whether or not they are participating in OST programmes) ("Guidelines for the psychosocially," 2009).
  • Care settings that provide OST should initiate and maintain ART for eligible people living with HIV ("Consolidated guidelines," 2013).

Related Recommendations and Contextual Issues for Specific Key Population Groups

People in Prisons and Other Closed Settings

  • Prison authorities in countries where OST is available in the community should urgently introduce OST programmes and expand them to scale as soon as possible ("Interventions to address HIV," 2007).
  • Countries should affirm and strengthen the principle of providing treatment, education and rehabilitation as an alternative to conviction and punishment for drug-related offences ("WHO, UNODC, UNAIDS technical guide," 2012).
  • Care should be taken to see that people on OST before entering prisons or other closed settings can continue OST without interruption while imprisoned and when transferred between settings ("Interventions to address HIV," 2007; "Guidelines for the psychosocially," 2009) and can be linked to community-based OST upon release ("Rolling out," 2013).
  • Provision of OST before release can help reduce overdose-related mortality (Degenhardt et al., 2014).

Transgender People

There is no evidence of drug interactions between OST and medications used for gender affirmation; however, research is very limited.

Adolescents from Key Populations

WHO guidance does not specify age restrictions for OST.

See original guidelines for full guidelines.

  1. Full guideline can be found at http://www.guideline.gov/content.aspx?id=48766&search=(%22naltrexone%22+OR+%22buprenorphine%22+OR+%22methadone%22). Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.8. Washington State Department of Labor and Industries: Guideline for Prescribing Opioids  to Treat Pain in Injured Workers
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2013 Community-based settings, inpatient, residential Literature Review Not graded. Yes. Also includes clonidine which is not FDA-approved. Yes--Suggested CBT for detoxification. DETOXIFICATION
STEP 1: Discontinuing Opioids in a Community Care Setting

In most cases, workers who are not on chronic high dose opioids or who do not have co-morbid SUD or a significant mental health disorder may be tapered in a straightforward manner. A gradual taper of approximately 10%/week (see AMDG Guideline, Tapering or Discontinuing Opioids and Appendix H at http://www.agencymeddirectors.wa.gov/Files/OpioidGdline.pdf External Web site Policy) can be carried out by the AP. Adjuvant agents like clonidine and psychological support such as CBT can be provided to assist with the taper process. The department or insurer may also authorize temporary coverage of buprenorphine or buprenorphine-naloxone to assist with the tapering process (see L&I coverage policy). The AP may also seek consultative assistance from a pain management specialist.

STEP 2: Discontinuing Opioids in an Intensive Setting

For those workers who have failed step 1 or who are at high risk for failure due to high dose, concurrent benzodiazepine use, or co-morbid substance use or mental health disorder, the prescriber should consider seeking consultative assistance from a pain management specialist, a SIMP provider or addiction medicine specialist. Adjuvant agents and psychological support can be provided to assist with the taper process. The department or insurer may also authorize temporary coverage of buprenorphine or buprenorphine-naloxone to assist with the tapering process (see L&I coverage policy). In these situations, formal inpatient detoxification and/or a 4-week SIMP treatment program may be required.

Due to the lack of high quality evidence of safety and comparative efficacy, UROD (e.g., within 3 days), using antagonist drugs with or without sedation, will not be covered.

            TREATMENT FOR OPIOID DEPENDENCE
Additional Services

If a worker has failed Steps 1 and 2, AND meets the DSM-V criteria for opioid use disorder, the department or insurer may cover up to 6 months of addiction treatment through a licensed chemical dependency treatment center as an aid to recovery. A list of treatment centers certified by the Division of Behavior Health and Recovery is available at http://www.dshs.wa.gov/dbhr/dadirectory.shtml External Web site Policy.

Refer to the original guideline document for more information about additional services.

Treatment Options for Opioid Use Disorder

MAT
Buprenorphine (Subutex®, Suboxone®)
Methadone
Naltrexone (Depade®, Revia®, Vivitrol®)
Drug-free outpatient treatment
Residential treatment

  1. Full guideline can be found at http://www.guideline.gov/content.aspx?id=43745&search=(%22naltrexone%22+OR+%22buprenorphine%22+OR+%22methadone%22). Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.9. VA/DoD: Clinical Practice Guideline for Assessment and Management of Patients At-Risk for Suicide
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2013 Not specified Literature Review Ratings not associated with opioid section (but used for other sections). Yes. No. TREATMENT FOR OPIOID DEPENDENCE
M8. Use of Methadone and Naloxone to Reduce Death from Opioid Overdose

1. Methadone substitution therapy should be considered in opiate dependent patients to reduce the risk of death by overdose (see VA/DoD clinical practice guideline for management of SUD External Web site Policy).

  1. Full guideline can be found at http://www.guideline.gov/content.aspx?id=47023&search=(%22naltrexone%22+OR+%22buprenorphine%22+OR+%22methadone%22). Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.10. Institute for Research, Evaluation and Training in Addictions: Management of Benzodiazepines in MAT
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2013 Not specified Literature Review Not rated. Yes. Yes. Generic statement that CM can be incorporated and in case of non-compliance, consider providing increased intensity of psychosocial treatment. General Guidelines
  • CNS depressant use is not an absolute contraindication for either methadone or buprenorphine, but is a reason for caution because of potential respiratory depression. Serious overdose and death may occur if MAT is administered in conjunction with benzodiazepines, sedatives, tranquilizers, antidepressants, or alcohol.
  • People who use benzodiazepines, even if used as a part of long-term therapy, should be considered at-risk for adverse drug reactions including overdose and death.
  • Many people presenting to services have an extensive history of multiple substance dependence and all substance abuse, including benzodiazepines, should be actively addressed in treatment. MAT should not generally be discontinued for persistent benzodiazepine abuse, but requires the implementation of risk-management strategies.
  • Clinicians should ensure that every step of decision making is clearly documented.
  • Clinicians would benefit from the development of a toolkit about the management of benzodiazepines in methadone treatment that includes videos and written materials for individuals in MAT.
  • In case of non-compliance, consider providing increased intensity of psychosocial treatment.

See original guidelines for more specific guidelines covering:

Assessment for MAT
Addressing benzodiazepine use
MAT for patients with concurrent benzodiazepine use
Non-compliance with treatment agreement
Risk-management/Impairment assessment
Special circumstances

  1. Full guideline found at http://www.ccbh.com/pdfs/providers/healthchoices/bestpractice/bp_guidelines_for_benzodiazepines.pdf. Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.11. BAP Recommendations: Updated Evidence-Based Guidelines for the Pharmacological Management  of Substance Abuse, Harmful Use, Addiction and Co-morbidity
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2012 Not specified, but inferred as several Literature Review Categories of evidence for causal relationships and treatment:

Ia: Evidence from meta-analysis of randomised controlled trials.

Ib: Evidence from at least 1 randomised controlled trial.

IIa: Evidence from at least 1 controlled study without randomization.

IIb: Evidence from at least 1 other type of quasi-experimental study.

III: Evidence from non-experimental descriptive studies, such as comparative studies, correlation studies and case-control studies.

IV: Evidence from expert committee reports or opinions and/or clinical experience of respected authorities.

Proposed categories of evidence for observational relationships:

I: Evidence from large representative population samples.

II: Evidence from small, well-designed, but not necessarily representative samples.

III: Evidence from non-representative surveys, case reports.

IV: Evidence from expert committee reports or opinions and/or clinical experience of respected authorities.

Strength of recommendation:

A: Directly based on category I evidence.

B: Directly based on category II evidence or extrapolated recommendation from category I evidence.

C: Directly based on category III evidence or extrapolated recommendation from category I or II evidence.

D: Directly based on category IV evidence or extrapolated recommendation from category I, II or III evidence.

S: Standard of care.

Yes. Also includes diamorphine and lofexide, which are not FDA-approved. Yes--Generic recommendation. TREATMENT FOR OPIOID DEPENDENCE
Recommendations: opioid maintenance treatment for opioid dependence

Methadone maintenance treatment

MMT is an appropriate treatment option for opioid-dependent patients. It is effective in reducing heroin use, injecting, and sharing of injecting equipment (A).

MMT is more effective at doses in the range 60-120mg than at lower doses. Following safe induction of methadone treatment (see Department of Health Guidelines), consideration should be given to higher maintenance doses (A).

Buprenorphine maintenance treatment

BMT is an appropriate treatment option for opioid-dependent patients. It is effective in reducing heroin use (A).

Buprenorphine should be prescribed at doses of 8mg or higher when used for maintenance treatment (B), and preferably at doses over 12mg (D).

Where concerns over diversion are paramount, buprenorphine-naloxone combinations may be preferred (B).

Choice of methadone or BMT

Both methadone and buprenorphine are effective treatments. Opioid-dependent patients should be offered either medication, guided by patient choice and safety considerations. (A).

Additional therapies

MMT or BMT should be provided in conjunction with psychosocial interventions such as regular counselling (B).

Injectable opioid maintenance treatments

Highly supervised injectable diamorphine maintenance treatment should be considered for patients who have failed to respond to optimised MMT or BMT (B).

We do not recommend injectable methadone treatment at present, although further studies are warranted (C).

          DETOXIFICATION
Recommendations: management of withdrawal from opioid drugs

There is a robust evidence base for 3 approaches to opioid detoxification: methadone at tapered doses, buprenorphine, or an α2 adrenergic agonist (usually lofexidine) (A).

The choice of agent will depend on what treatment patients are already receiving, for example methadone or buprenorphine and individual preference. However, if short duration of treatment is desirable, or in patients with mild or uncertain dependence, α2 adrenergic agonists may be preferable (A).

SROM is not recommended for opioid detoxification (B).

UROD is not recommended (A).

Pharmacological management of withdrawal should be supported by psychosocial treatment (A).

Recommendations: naltrexone for treatment of opioid dependence

Oral naltrexone treatment should be considered for formerly opioid-dependent people who are highly motivated to remain abstinent (D).

Recommendations: younger people

There is limited evidence on treatment of SUDs in younger people on which to base recommendations to guide specific pharmacological approaches. However, it is important that pharmacotherapy be considered, particularly in alcohol, opioid or nicotine dependence, and ideally by a specialist multidisciplinary service.

Pharmacological treatment should follow the evidence base for the general adult population with appropriate dose adjustments for age-related pharmacokinetic and pharmacodynamic changes (C).

Younger people with harmful substance use, abuse or dependence should have full routine health screens with identification and treatment of psychiatric or physical health problems (S).

There should be a lower threshold for admission for inpatient assessment and treatment, for example for assisted alcohol withdrawal, opioid stabilisation in younger people (D).

Recommendations: opioids and pregnancy

Methadone and buprenorphine (not buprenorphine-naloxone) maintenance treatment improves maternal and foetal outcomes, and substitution treatment should be offered to pregnant opioid-dependent women (B).

The choice of medication should be based on individual need and preference following full assessment, and the dose of methadone prescribed should be that which maintains clinical stability (C).

Buprenorphine may be associated with less NAS (B).

Detoxification should be avoided in the first trimester, is preferred in the second and only with caution in third trimester (S).

See original guidelines for guidelines on opioid treatment for patients with CODs, and opioid treatment for older people.

  1. Full guideline found at http://www.ncbi.nlm.nih.gov/pubmed/22628390. Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.12. Substance Misuse and Alcohol Use Disorders: Evidence-Based Geriatric Nursing Protocols for Best Practice
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2008, revised 2012 Office-based practice, state licensed clinics Literature Review Level I: Systematic reviews (integrative/meta-analyses/clinical practice guidelines based on systematic reviews).

Level II: Single experimental study (RCTs).

Level III: Quasi-experimental studies.

Level IV: Non-experimental studies.

Level V: Care report/program evaluation/narrative literature reviews.

Level VI: Opinions of respected authorities/ consensus panels.

Yes. Yes--Generic recommendation; relapse prevention section for all types of substance abuse recommends group psychotherapy using CBT. See broad screening guidelines for substance abuse in alcohol table.
TREATMENT FOR OPIOID DEPENDENCE
Heroin or opioid dependence
  • Older long-term opioid users may continue use, relapse, and seek treatment. Methadone or buprenorphine are current pharmacological treatment options, effective in conjunction with self-help programs and/or psychosocial interventions.
  • Treatment with methadone, a synthetic narcotic agonist, suppresses withdrawal symptoms and drug cravings associated with opioid dependence but requires daily dosing of 60mg, minimum. It is dispensed only in state licensed clinics.
  • Buprenorphine (Subutex or Suboxone), recently approved for use in office practice by trained physicians, is an opioid partial agonist-antagonist. Alone and in combination with naloxone (Suboxone), it can prevent withdrawal when someone ceases use of an opioid drug and then be used for long-term treatment. Naloxone is an opioid antagonist used to reverse depressant symptoms in opiate overdose and at different dosages to treat dependence (CSAT, 2004 [Level VI]).

Close collaboration with the prescriber is required because these drugs should not be abruptly terminated or used with antidepressants and interact negatively with many prescription medications.

Naltrexone, a long-acting opioid antagonist, blocks opioid effects and is most effective with those who are no longer opioid dependent but are at high risk for relapse (Srisurapanont & Jarusuraisin, 2005 [Level III]).

Treatment and relapse prevention

  • Monitor pharmacologic treatment such as naltrexone as short-term treatment for alcohol dependence. The benefits of this treatment are dependent on adherence and psychosocial treatment should accompany its use (WHO, 2000 [Level I]). Methadone or buprenorphine should be used for long-term treatment of opioid dependence.
  • Group psychotherapy in limited studies using a cognitive behavioral approach has produced good outcomes with older adults (Payne & Marcus, 2008 [Level III]).
  • Refer to community-based groups such as AA, NA, Al-Anon groups, and encourage attendance.
  • Educate family and patient regarding signs of risky use or relapse to heavy or alcohol-dependent behavior.
  • Counsel patient to reduce drug use (harm reduction) and engage in relationship healing or building, community or intellectually rewarding activities, spiritual growth, and so on that increase valued non-drinking rewards.
  • Counsel in the development of coping skills:
  • Anticipate and avoid temptation.
  • Learn cognitive strategies to avoid negative moods.
  • Make lifestyle changes to reduce stress, improve the quality of life, and increase pleasure.
  • Learn cognitive and behavioral activities to cope with cravings and urges to use.
  • Encourage development or expansion of patient's social support system.

See original guidelines for full guidelines.

  1. Full guideline found at http://www.guideline.gov/content.aspx?id=43939&search=(%22naltrexone%22+OR+%22buprenorphine%22+OR+%22methadone%22). Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.13. Guidelines for Improving Entry Into and Retention in Care and Antiretroviral Adherence for Persons with HIV: Evidence-Based Recommendations from an International Association of Physicians in AIDS Care Panel
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2012 Not specified Literature Review Quality of the Body of Evidence

Excellent (I): RCT evidence without important limitations. Overwhelming evidence from observational studies.

High (II): RCT evidence with important limitations. Strong evidence from observational studies.

Medium (III): RCT evidence with critical limitations. Observational study evidence without important limitations.

Low (IV): Observational study evidence with important or critical limitations.

Strength of Recommendations

Strong (A): Almost all patients should receive the recommended course of action.

Moderate (B): Most patients should receive the recommended course of action. However, other choices may be appropriate for some patients.

Optional (C): There may be consideration for this recommendation on the basis of individual patient circumstances. Not recommended routinely.

Yes. No. TREATMENT FOR OPIOID DEPENDENCE
Substance Use Disorders

Individuals with alcohol and other SUDs are at increased risk for poor retention in care, poor adherence, and virologic failure. Several adherence strategies not recommended for general clinic populations are effective among those with SUDs.

Recommendation 27: Offering buprenorphine or methadone to opioid-dependent patients is recommended (II A).

Recommendation 29: Integration of DAART into MMT for opioid-dependent patients is recommended (II B).

  1. Full guideline found at http://www.guideline.gov/content.aspx?id=36947&search=(%22naltrexone%22+OR+%22buprenorphine%22+OR+%22methadone%22). Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.14. Centre for Addiction and Mental Health: Buprenorphine-Naloxone for Opioid Dependence, Clinical Practice Guideline
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2011 Ambulatory-primary care setting, specialized addiction treatment setting Literature Review Levels of Evidence

I: Evidence from randomized, controlled trial(s).

II-1: Evidence from controlled trial(s) without randomization.

II-2: Evidence from cohort or case-control analytic studies, preferably from more than 1 centre or research group.

II-3: Evidence from comparisons between times or places with or without the intervention; dramatic results in uncontrolled experiments could be included here.

III: Opinions of respected authorities, based on clinical experience; descriptive studies or reports of expert committees.

Grades of Recommendation

A: There is good evidence to recommend the action.

B: There is fair evidence to recommend the action.

C: The existing evidence is conflicting and does not allow making a recommendation for or against the use of the action; however, other factors may influence decision making.

D: There is fair evidence to recommend against the action.

E: There is good evidence to recommend against the action.

I: There is insufficient evidence (in quantity and/or quality) to make a recommendation; however, other factors may influence decision making.

Adapted from Definitions of Levels of Evidence and Grades of Recommendations of the Canadian Task Force on Preventive Health Care. Available from the CMAJ Web site External Web site Policy.

Yes. No. TREATMENT FOR OPIOID DEPENDENCE
Selecting Buprenorphine-Naloxone Maintenance Therapy

1. Once a patient is diagnosed with opioid dependence and is deemed appropriate for opioid agonist treatment, prescribers are encouraged to consider prescribing either buprenorphine-naloxone or methadone in order to increase retention in treatment and decrease opioid misuse. (Level I, Grade A)

Clinical Assessment

2. Buprenorphine-naloxone maintenance treatment can be prescribed to patients in either a primary care setting or in a specialized addiction treatment setting. (Level I, Grade A)

3. Prior to initiating maintenance opioid agonist treatment the patient should meet the diagnostic criteria for opioid dependence. (Level III, Grade A)

4. The decision to initiate opioid agonist therapy with either buprenorphine-naloxone or methadone maintenance should be guided by the individual clinical circumstances and the patient's preferences. (Level III, Grade I)

Initiation, Maintenance, and Discontinuation of Buprenorphine-Naloxone Maintenance Treatment

5. A physician should have a structured approach, to initiating buprenorphine-naloxone maintenance treatment in order to stabilize a patient at their maintenance dose as rapidly as possible while at the same time avoiding over-sedation or precipitated withdrawal. (Level III, Grade A)

6. Prior to initiation of buprenorphine-naloxone treatment, the patient must provide informed consent and there must be physician documentation that the patient has been informed of the physical dependence on the medication and possible long-term nature of the maintenance treatment. (Level III, Grade A)

7. Once a stable maintenance dose is achieved, physicians can consider non-daily dosing of buprenorphine-naloxone as effective as daily dosing of buprenorphine-naloxone with respect to retention in treatment and reduction in illicit drug use. (Level I, Grade A)

8. When monitoring a patient on buprenorphine-naloxone maintenance, the physician should adopt a patient-centered urine drug testing strategy that maximizes clinical utility while avoiding testing without indication. (Level III, Grade I)

9. In making decisions regarding the provision of take-home doses of buprenorphine-naloxone, providers should use a clinical risk stratification strategy that aims to support patient autonomy while at the same time respecting patient and public safety. (Level III, Grade A)

Overdose, Mortality, and Other Adverse Effects

10. Policymakers should be aware that in countries where buprenorphine is equally available as methadone, buprenorphine has a lower attributable death rate than methadone. (Level II-3, Grade A)

11. Limited public funding is currently the major barrier to accessibility of buprenorphine-naloxone maintenance treatment in Ontario. The guideline authors recommend that policymakers remedy this barrier. (Level III, Grade B)

Clinicians should be aware that there is little in the medical literature to guide them in terms of which opioid maintenance agent to prescribe an individual opioid-dependent patient. In making this decision, the prescriber and patient should consider the following, which is based on clinical experience.

12. Buprenorphine-naloxone may be preferred over methadone to treat opioid dependence in the following patient populations:

a. When methadone is absolutely or relatively contraindicated, such as:

i. Presence of, history of or increased risk of prolonged QT interval. (Level I, Grade A)
ii. History of methadone allergy. (Level III, Grade A)

b. History of significant side effects on methadone such as:

i. Sexual side effects on methadone. (Level II-2, Grade B)
ii. Severe sedation or constipation with methadone. (Level III, Grade C)

c. Increased risk of toxicity from a full mu-opioid agonist:

i. If suspect a lower tolerance to opioids. (Level III, Grade B)
ii. If concurrent heavy or unstable use of sedating drugs/medication. (Level II-3, Grade B)
iii. If elderly. (Level III, Grade B)
iv. If significant respiratory illness. (Level III, Grade B)

d. Good prognostic factors:

i. Briefer history (i.e., less than 1 year) of opioid misuse. (Level III, Grade C)
ii. Social supports. (Level III, Grade C)
iii. Adolescents and young adults. (Level III, Grade B)

e. Past history of successful stabilization with buprenorphine-naloxone. (Level III, Grade I)

f. Patient choice and access. In particular patients residing in geographic areas where methadone is not available in a timely manner, or when challenging pharmacy access makes the possibility of alternate-day dosing of buprenorphine-naloxone desirable. (Level III, Grade B)

13. Methadone may be preferred over buprenorphine-naloxone in the following patient populations:

a. Pregnancy (specifically avoiding the naloxone component in the buprenorphine-naloxone combination product). (Level III, Grade A)

b. Clinical situations where opioid withdrawal during induction is particularly hazardous (i.e., cardiovascular instability). (Level III, Grade B)

c. Prior inability to stabilize on buprenorphine-naloxone maintenance treatment. (Level III, Grade B)

d. History of abusing buprenorphine-naloxone via injection. (Level III, Grade A)

e. Patient side effects with or allergy to buprenorphine-naloxone or to excipients including acesulfame. (Level III, Grade A)

f. Patients experiencing dry mouth of severity that would interfere with dissolution and absorption of sublingual buprenorphine-naloxone tablets (dry mouth may be due to side effects of concurrent medications, chemotherapy, or conditions causing dry mouth, e.g., Sjogren's syndrome). (Level III, Grade A)

g. Past history of successful stabilization with methadone. (Level III, Grade I)

h. Patient choice and access, in particular patients with limited financial resources that make reliable long-term use of buprenorphine-naloxone uncertain. (Level III, Grade B)

  1. Full guideline found at http://www.guideline.gov/content.aspx?id=39351&search=(%22naltrexone%22+OR+%22buprenorphine%22+OR+%22methadone%22). Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.15. Substance Use in Pregnancy
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2011 Not specified, but likely outpatient Literature Review I: Evidence obtained from at least 1 properly RCT.

II-1: Evidence from well-designed controlled trials without randomization.

II-2: Evidence from well-designed cohort (prospective or retrospective) or case-control studies, preferably from more than 1 centre or research group.

II-3: Evidence obtained from comparisons between times or places with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of treatment with penicillin in the 1940s) could also be included in this category.

III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

*Adapted from the Evaluation of Evidence criteria described in the Canadian Task Force on Preventive Health Care.

Classification of Recommendations†

A. There is good evidence to recommend the clinical preventive action.

B. There is fair evidence to recommend the clinical preventive action.

C. The existing evidence is conflicting and does not allow to make a recommendation for or against use of the clinical preventive action; however, other factors may influence decision making.

D. There is fair evidence to recommend against the clinical preventive action.

E. There is good evidence to recommend against the clinical preventive action.

L. There is insufficient evidence (in quantity or quality) to make a recommendation; however, other factors may influence decision making.

Yes. No. SCREENING
Identification of Substance-related Disorders in Pregnancy

Screening and Assessment/Role of Toxicology Testing

1. All pregnant women and women of childbearing age should be screened periodically for alcohol, tobacco, and prescription and illicit drug use. (III-A)

2. When testing for substance use is clinically indicated, urine drug screening is the preferred method. (II-2A) Informed consent should be obtained from the woman before maternal drug toxicology testing is ordered. (III-B)

3. Policies and legal requirements with respect to drug testing of newborns may vary by jurisdiction, and caregivers should be familiar with the regulations in their region. (III-A)

Components of Office Management

4. Health care providers should employ a flexible approach to the care of women who have substance use problems, and they should encourage the use of all available community resources. (II-2B)

5. Women should be counselled about the risks of periconception, antepartum, and post-partum drug use. (III-B)

          TREATMENT FOR OPIOID DEPENDENCE
Opioid Dependence/Opioids for CNCP

7. MMT should be standard of care for opioid-dependent women during pregnancy. (II-IA) Other slow-release opioid preparations may be considered if methadone is not available. (II-2B)

8. Opioid detoxification should be reserved for selected women because of the high risk of relapse to opioids. (II-2B)

See original guidelines for full guidelines including effects of dependence on neonates and breastfeeding considerations.

  1. Full guideline found at http://www.guideline.gov/content.aspx?id=33136&search=(%22naltrexone%22+OR+%22buprenorphine%22+OR+%22methadone%22)#Section420. Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.16. Colorado Division of Workers' Compensation: Chronic Pain Disorder Medical Treatment Guidelines
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2011 Outpatient, licensed methadone and buprenorphine clinics, inpatient Literature Review Not rated. Yes--For those medications that were FDA-approved at the time of the guideline's publication. Yes--Generic recommendation. OPIOID/CHEMICAL TREATMENT PROGRAMS
Chemical dependency, which for worker compensation issues will usually be related to opioids, anxiolytics, or hypnotics as prescribed for the original workers compensation injury, should be treated with specific programs providing medical and psychological assessment, treatment planning and individual as well group counseling and education.

They may be inpatient or outpatient programs, depending upon the level of intensity of services required. Formal treatment programs are appropriate for patients who have more intense (e.g., use extraordinarily excessive doses of prescription drugs to which they have developed tolerance) or multiple drug abuse issues (e.g., benzodiazepines and/or alcohol) and those with complex medical conditions or psychiatric issues drug misuse. A medical physician with appropriate training preferably board certified in addiction medicine, should provide the initial evaluation and oversee the program. Full primary assessment should include behavioral health assessment; medical history; physical examination; mental status; current level of functioning; employment history; legal history; history of abuse, violence, and risk taking behavior; education level; use of alcohol, tobacco and other drugs; and social support system.

Addiction counselors, and other trained health care providers as needed, are involved in the program. Peer and group support is an integral part of the program and families are encouraged to attend. There should be good communication between the program and other external services, external health care providers, Al-Anon, AA and pain medicine providers. Drug screening is performed as appropriate for the individual, minimally initially and at least weekly during the initial detoxification and intensive initial treatment.

            DETOXIFICATION
Clear withdrawal procedures are delineated for voluntary, against medical advice, and involuntary withdrawal. Withdrawal programs must have a clear treatment plan and include description of symptoms of medical and emotional distress, significant signs of opioid withdrawal, and actions taken. All programs should have clear direction on how to deal with violence in order to assure safety for all participants. Transition and discharge should be carefully planned with full communication to outside resources. Duration of inpatient programs is usually 4 weeks while outpatient programs may take 12 weeks.

Drug detoxification may be performed on an outpatient or inpatient basis. Detoxification is unlikely to succeed in isolation when not followed by prolonged chemical dependency treatment. Isolated detoxification is usually doomed to failure with very high recidivism rates.

Neither UROD nor rapid-detoxification are recommended due to possible respiratory depression and death and the lack of evidence for long range treatment success.

            TREATMENT FOR OPIOID DEPENDENCE
Abstinence models are preferred by most chemical dependency treatment programs but are problematic for those chronic pain patients who may require the continued use of opioid analgesics. Methadone, buprenorphine, or buprenorphine-naloxone are usually the first-line agents for treating such patients; however, continued use in an outpatient setting of methadone for opioid dependency requires dispensing by a licensed methadone clinic and buprenorphine, for the same purpose, by a physician possessing a special DEA license. As of the time of this guideline writing, some formulations of buprenorphine-naloxone have been FDA-approved for the treatment of opioid dependence. It is strongly recommended that the use of either drug for the purpose of treating chronic pain be limited to physicians with additional training. In the case of methadone, there are increasing numbers of inadvertent deaths due to misuse, including prescribing errors. In the case of buprenorphine, its use as an analgesic is not currently FDA-approved and conversion to this drug from other opioids is difficult. It should never be a first-line analgesic for chronic pain due to high cost and the presence of other opioids that may be more effective for moderate-to-severe chronic pain.
            DETOXIFICATION
Tapering opioids on an outpatient basis requires a highly motivated patient and diligent treatment team and may be accomplished by decreasing the current dose 10%/day or week. Tapering should be accompanied by addiction counseling. Failing a trial of tapering a patient should be sent to a formal addiction program. When the dose has reached one-third of the original dose, the taper should proceed at half or less of the initial rate. Doses should be held or possibly increased if severe withdrawal symptoms, pain, or reduced treatment failure otherwise occurs. This method is tedious, time consuming and more likely to fail than more rapid and formalized treatment programs.

Refer to the original guideline document for time to produce effect, frequency, and optimum/maximum duration of programs.

  1. Full guideline can be found at http://www.guideline.gov/content.aspx?id=38441&search=(%22naltrexone%22+OR+%22buprenorphine%22+OR+%22methadone%22). Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.17. WFSBP: Guidelines for the Biological Treatment of Substance Use and Related Disorders, Part 2: Opioid Dependence
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2011 Outpatient, inpatient Literature Review A. Full Evidence From Controlled Studies is based on:

2 or more double-blind, parallel-group, RCTs showing superiority to placebo (or in the case of psychotherapy studies, superiority to a "psychological placebo" in a study with adequate blinding).
AND
1 or more positive RCT showing superiority to or equivalent efficacy to established comparator treatment in a 3-arm study with a placebo control or in a well-powered non-inferiority trial (only required if such a standard treatment exists).

In the case of existing negative studies (studies showing non-superiority to placebo or inferiority to comparator treatment), these must be outweighed by at least 2 additional positive studies or a meta-analysis of all available studies showing superiority to placebo and non-inferiority to an established comparator treatment.

Studies must fulfil established methodological standards. The decision is based on the primary efficacy measure.

B. Limited Positive Evidence From Controlled Studies is based on:

1 or more RCTs showing superiority to placebo (or in the case of psychotherapy studies, superiority to a "psychological placebo").
OR
A randomized controlled comparison with a standard treatment without placebo control with a sample size sufficient for a non-inferiority trial.
AND
In the case of existing negative studies (studies showing non-superiority to placebo or inferiority to comparator treatment), these must be outweighed by at least 1 additional positive study or a meta-analysis of all available studies showing superiority to placebo or at least 1 more randomized controlled comparison showing non-inferiority to an established comparator treatment.

C. Evidence from Uncontrolled Studies or Case Reports/Expert Opinion

C1. Uncontrolled studies is based on:

1 or more positive naturalistic open studies (with a minimum of 5 evaluable patients).
OR
A comparison with a reference drug with a sample size insufficient for a non-inferiority trial.
AND
No existing negative controlled studies.

C2. Case reports is based on:

1 or more positive case reports
AND
No existing negative controlled studies.

C3. Based on the opinion of experts in the field or clinical experience.

D. Inconsistent results:

Positive RCTs are outweighed by an approximately equal number of negative studies.

E. Negative evidence:
The majority of RCTs or exploratory studies show non-superiority to placebo (or in the case of psychotherapy studies, non-superiority to a "psychological placebo") or inferiority to comparator treatment.

F. Lack of evidence

Adequate studies proving efficacy or non-efficacy are lacking.

Recommendation Grade (RG)

Based on:

1. Category A evidence and good risk-benefit ratio.

2. Category A evidence and moderate risk-benefit ratio.

3. Category B evidence.

4. Category C evidence.

5. Category D evidence.

Yes. Also includes heroin-assisted treatment, lofexide and clonidine, which are not FDA-approved. The following options are mentioned, with a stated variation in the strength of the evidence in support of the options: CM, CBT, family therapy, relapse prevention, self-help groups. MMT can be enhanced when combined with CM, whereas there is no indication that CM increases the efficacy of BMT. TREATMENT FOR OPIOID DEPENDENCE
Recommendation: Methadone is the standard medication for the treatment of opioid dependence (RG1). Its efficacy can be enhanced when combined with CM (RG1).

Injectable methadone has occasionally been used in the treatment of opioid dependence (Hartnoll et al. 1980; Strang et al. 2010), but the results are disappointing (Strang et al. 2000, 2010). This form will, therefore, not be discussed further in these practice guidelines.

Recommendation: There is compelling evidence for the efficacy of heroin-assisted treatment in treatment refractory, opioid-dependent patients (3). Based on data from Switzerland (Uchternhagen 2010) and the Netherlands (Blanken et al. 2010), it appears that heroin-assisted treatment can be implemented routinely in medical settings. Further study of this treatment is needed. Despite ethical concerns among both scientists and the lay public over heroin substitution, such treatment is routine in some countries.

Recommendation: Buprenorphine and buprenorphine-naloxone are standard medications for the treatment of opioid dependence (1). Whether the combination of buprenorphine and naloxone has advantages over buprenorphine alone requires empirical validation. There are no indications that adding CM to BMT enhances its effectiveness (1).

Recommendation: Oral naltrexone is not a first-line treatment for opioid dependence (1). However, oral naltrexone might be effective in a small subgroup of highly motivated and well-integrated patients (3). Retention in naltrexone treatment is usually poor.

          DETOXIFICATION
Recommendation: Methadone is a standard and safe medication for opioid detoxification (1).

Recommendation: Buprenorphine is a standard and safe medication for opioid detoxification (Kleber et al. 2007; NICE 2007) (RG1).

Recommendation: Clonidine (3) and lofexidine (3) are less effective than methadone and buprenorphine in reducing the symptoms of opioid withdrawal. Rapid-detoxification using naltrexone in combination with clonidine

Recommendation: There is no convincing evidence for the use of the combination of opioid antagonists plus clonidine under heavy sedation. Given the lack of evidence for a substantial advantage of this approach, the associated risks and costs do not appear to be justified.

Pregnancy:

Recommendation: During pregnancy, detoxification should be avoided, especially in the first trimester (RG4). Methadone and buprenorphine are effective and safe in the treatment of opioid-dependent pregnant women.

Use of multiple substances by opioid-dependent individuals

Recommendation: Increasing the dosage of methadone or buprenorphine, particularly in conjunction with CM, are generally effective in the treatment of cocaine use by opioid dependent individuals (RG4).

Excerpted table:

Table II. Categories of evidence (CE) and grade of recommendation (RG) for pharmacological treatments in opioid dependence.

Medication and CE RG Typical recommended daily dose for adults

Abuse and dependence
Methadone A 1 40-100mg
Buprenorphine A 1 4-16mg
Buprenorphine-naloxone A 1 4-16mg
Naltrexone B 3 50mg
Heroin B 3 200-600mg

Withdrawal
Methadone A 1 40-100mg initial
Buprenorphine A 1 4-16mg initial
Buprenorphine-naloxone A + 4-16mg initial
Clonidine B 3 0.3mg
Lofexide/clonidine C 4 1.6-3.2mg
Naltrexone under general anesthesia D 5

1. Full guideline can be found at http://www.ncbi.nlm.nih.gov/pubmed/21486104 . Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.18. NOUGG: Canadian Guideline for Safe and Effective Use of Opioids for CNCP
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2010 Not specified Literature Review Canadian Guideline Recommendation Grading

Grade A: Recommendations are supported by evidence from RCTs.

Grade B: Recommendations are supported by:

Evidence from controlled trial(s) without randomization.
OR
Evidence from cohort or case-control analytic studies, preferably from more than 1 centre or research group.
OR
Evidence from comparisons between times or places with or without the intervention; dramatic results in uncontrolled experiments could be included here.

Grade C: Recommendations are supported by consensus opinion of the National Advisory Panel.

Yes. No. TREATMENT FOR OPIOID DEPENDENCE
Cluster 5: Managing Opioid Misuse and Addiction in CNCP Patients

For patients with CNCP who are addicted to opioids, 3 treatment options should be considered: methadone or buprenorphine treatment (Grade A), structured opioid therapy (Grade B), or abstinence-based treatment (Grade C). Consultation or shared care, where available, can assist in selecting and implementing the best treatment option (Grade C).

Relevant section excerpted above. See original guidelines for full guidelines.

  1. Full guideline can be found at http://www.guideline.gov/content.aspx?id=35111&search=(%22naltrexone%22+OR+%22buprenorphine%22+OR+%22methadone%22). Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.19. New York State Department of Health: Preconception Care for HIV-Infected Women
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2010 Not specified; several settings inferred Literature Review Rating information provided, but not connected to footnote. Yes. No. b. For opioid-dependent pregnant women, MMT is effective therapy, does not adversely affect fetal or post-natal development, and is preferred to detoxification.

(Above is a footnote of a table).

  1. Full guideline can be found at http://www.guideline.gov/content.aspx?id=24033&search=(%22naltrexone%22+OR+%22buprenorphine%22+OR+%22methadone%22). Many of these guidelines were based upon a consensus process informed by the literature reviews.

 

TABLE A.20. VDH/ADAP OVHA: Vermont Buprenorphine Practice Guidelines
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2010 Office-based Other (collaborative effort of VDH, ADAP, OVHA and local treatment providers) Not rated. Yes. Yes--Suggested: CBT, Motivation Enhancement Therapy, Dialectical Behavioral Therapy. Excerpts:

Psychosocial Treatment-Related:

To qualify for a [DATA 2000] waiver, the physician must have the capacity to refer patients for appropriate counseling and other services that might be needed in conjunction with buprenorphine treatment. These services include the following:

Different levels of chemical dependency treatment services
Psychiatric consultation
Consultation for medical co-morbidities
12 Step program

Physicians should expect that clinicians to whom they refer their buprenorphine treated patients will have been trained in evidence-based therapies such as CBT, Motivation Enhancement Therapy, Dialectical Behavioral Therapy, etc.

Buprenorphine:

The following 2 available buprenorphine medications are both dissolved sublingually: Subutex is a mono-therapy containing only buprenorphine. It is available from a pharmaceutical house in small supply to be kept in physicians' offices. It may be used for induction but is not necessary for this.

2. Suboxone is a combination therapy, containing both buprenorphine and naloxone. Naloxone has been added to avoid diversion and IV abuse. Suboxone is the recommended preparation for induction, maintenance, and, if necessary, supervised withdrawal (detoxification).

To minimize diversion of buprenorphine, especially the mono-therapy product, it is recommended that Subutex only be used during the management of pregnant, opioid dependent women or in the extremely rare occurrence of allergy or intolerance to Suboxone (not just because the patient does not like the taste of Suboxone).

Treatment Settings:

Office-Based Practice Care may be provided by a solo practitioner or a group practice with the required training and ability to provide clinical evaluation, buprenorphine induction, maintenance and follow-up. The practitioner or group also must be able to provide consultation and referrals as needed with Primary Care Providers and medical specialists. Some practitioners may be able to provide all services on their own (e.g., an addictions psychiatrist with buprenorphine training).

OTPs may provide Subutex or Suboxone following the same regulations that exist for methadone treatment (42 CFR Part 8: Code of Federal Regulations, Title 42: Public Health, Part 8--Certification of OTPs,http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr;sid= d5f2d13f11085410f289dd08209805f4;rgn=div5;view=text;node= 42% 3A1.0.1.1.9;idno=42;cc=ecfr), including a take-home schedule in which buprenorphine is dispensed from the window without giving a prescription. Due to the long-acting nature of buprenorphine, multiple day dosing can occur 2-3 times per week. Buprenorphine is part of the OTP's DEA registration, not an individual physician's; consequently, physicians working in OTPs do not have to seek a waiver or complete the 8 hour training. In addition, these programs are exempt from the 30 patient limit.

Screening/Intake:

Initial screening for opioid addiction should consist of a combination of interviews, objective screening instruments and laboratory evaluations (see Appendices B-I and B-II for examples of screening and assessment tools that may help determine how appropriate a patient is for office-based treatment), and include the following:

Medical history with attention paid to liver and cardiac status and medications.
Psychiatric history with attention to current compliance with medications.

Substance abuse history and treatment history to identify whether patient was ever on buprenorphine and to insure patient is not currently on methadone but meets criteria for Opiate Dependence (see Appendix A, DSM-IV Diagnosis of Opiate Dependence). If a patient reports they have been using buprenorphine obtained on the street, and even provides the dose they have been taking, they still should go through the induction process to determine the appropriate clinical dose.

Social, work, and family circumstances history.

Physical exam, mental status exam.

Lab screening for ALT, AST, hepatitis B and C, HIV, gonorrhea, chlamydia, syphilis, TB test.
Urine screen (witnessed) with attention to opiates, including methadone and buprenorphine, and benzodiazepines.

If urine is negative for opiates (which may occur with synthetic opiates), evidence of IV puncture marks on the skin and evidence of withdrawal symptoms, such as runny eyes, sniffling, yawning, tremor, sweating, gooseflesh, vomiting, abdominal cramps, muscle aches, pupil dilation. The CINA Scale for withdrawal symptoms can be very useful (see Appendix D).

In some cases, dependence may be diagnosed through the use of 1cc of naloxone (Narcan) (0.4mg/ml) injected subcutaneously followed by observing the patient for up to 30 minutes for evidence of precipitated withdrawal. Naltrexone (ReVia) would not be used due to the protracted withdrawal syndrome it causes.

Sometimes a patient previously detoxed from opiates will present for treatment due to high risk of returning to opiate use. Examples include individuals recently released from prison. Physicians are encouraged to consult with a substance abuse counselor or addiction specialist in these cases.

11. Women using illicit opioids may experience menstrual cycle irregularity and infertility. Unplanned pregnancy can occur as women recover and improve their health status. As opioid agonist therapy is initiated, the potential for pregnancy should be addressed and a plan for contraception developed. If pregnancy is desired, women should receive a prescription for prenatal vitamins (for additional folic acid).

Possible Indications of Less Appropriate Candidacy. Certain factors may suggest a patient is LESS likely to be an appropriate candidate for office-based buprenorphine treatment (see Appendices B-I and B-II for criteria and guidelines for assessing candidacy). Some factors to consider include the following:

Dependence on high doses of benzodiazepines, alcohol, or other CNS depressants

Significant psychiatric co-morbidity
Active or chronic suicidal or homicidal ideation or attempts
Multiple previous treatments and relapses
Non-response to buprenorphine in the past
High level of physical dependence (risk for severe withdrawal)
High relapse risk
Pregnancy
Current medical conditions that could complicate treatment
Poor support systems
Patient needs cannot be addressed with existing office-based resources

            TREATMENT FOR OPIOID DEPENDENCE
II. Induction

Induction onto buprenorphine is considered to be an ambulatory procedure not requiring an inpatient admission unless there are medical complications or other extenuating circumstances. The induction steps listed below are guidelines intended to ensure close monitoring during the initial phases of treatment. Dosing guidelines based on reported drug use can be helpful in targeting eventual final buprenorphine doses. (See Guide for Dose Targets, end of this section.)

General Guidelines for patients physically dependent on opioids:

Begin induction early in the week.

Plan on 3-5 days for stable dosing.

Patient's last reported use should have been at least 6 hours prior to induction.

MAKE SURE THE PATIENT IS NOT ON METHADONE as buprenorphine may cause an acute withdrawal syndrome; if patient is on methadone, see below protocol for long-acting opiates.

Day 1: Give the patient a prescription for #2 2mg Suboxone tablets.

Patient takes the prescription to the pharmacy and returns to the office with the medication.

Patient takes the tablet and lets it dissolve under the tongue for 5 minutes with no talking, drinking, or swallowing.

Target buprenorphine dose range should be 12-16mg/day, with a recommended maximum of 16mg daily.

If more than 8mg are needed, gradually increase the dose in 2mg increments over the next several days.

The patient's condition before dosing time is 1 of the best ways to assess adequacy of the dose. (Refer to Appendix E: COWS, for assessing withdrawal symptoms before the first dose is given and throughout the Induction period.

Guidelines for patients NOT physically dependent on opioids (e.g., coming out of incarceration or otherwise high risk for relapse):

First dose: 2mg sublingual buprenorphine.
Monitor for 2+ hours and consider 2mg incremental dosage increases over the next several days.

Note: See original guidelines for specific guidelines for treating patients dependent on short-acting opioids and long-acting opioids.

III. Stabilization

Patient should receive daily dose until stabilized.

An option is to shift to alternate-day dosing, by increasing the amount on the dosing day by the amount not received on the intervening days (see #5 below).

Urine screens should be done once a week.

Non-attendance for counseling for more than 2 consecutive sessions should trigger an automatic call from the counselor. The physician should schedule an office visit with the patient to make sure the patient understands that failure to follow through with counseling jeopardizes treatment and puts them outside of "good standing."

Write 7 days' worth of medication at a time for 2 months.

IV. Maintenance and Follow-Up

Once patient has remained compliant with counseling and physician visits, has not had any mishaps with the Suboxone, and feels ready to do so, extend the prescriptions to 14 days for the next 2 months.

A patient may choose to take Suboxone every 2-3 days. The dose is doubled or tripled, depending on the time frame, and taken all at once. This is very effective in controlled settings, such as dispensing by a family member or clinic, but may be done for patient preference only.

After a period of time that varies with each patient but should reflect compliance with treatment, a prescription for 30 days may be written. Pill counts may be a useful monitoring tool at this point.

Urine drug testing is now available for determining the presence of the buprenorphine metabolite and this may be used as a clinical tool to encourage success in treatment, as well as a precautionary measure for avoiding diversion.

Note: See original guidelines for guidelines on tapering patients off of buprenorphine.

            DETOXIFICATION
VI. Detoxification

Rapid-detox: 3 days or less.
Low doses of buprenorphine given 2-3 times daily.
More effective in suppressing withdrawal than clonidine.
Long-term efficacy not well documented.
Not recommended due to poor outcomes and should only be done when there is a compelling reason for patient to be detoxed quickly (e.g., out of country travel, imminent incarceration).

Moderate detox: 30 days or less.
Raise dose daily over 4 days to equal opiates taken, then decrease by 2mg every 1-2 days until weaned.
Better tolerated than clonidine.
Few studies of buprenorphine for this time period.

Long detox: more than 30 days.
Raise dose daily over 4 days to equal opiates taken, then reduce by 2mg weekly until weaned.
Not well studied but some evidence suggests this approach is more efficacious than briefer ones, especially if naltrexone is started after an appropriate wash out period.

  1. Full guideline can be found at http://www.healthvermont.gov/adap/treatment/documents/BuprenorphinePracticeGuidelinesFINAL_01-15-2010.pdf.

 

TABLE A.21. Commonwealth of Australia: National Guidelines for MAT for Opioid
Year Care Setting Guideline Source
of Information1
Statement Grade and
Rating Scale Definition
FDA-Approved
Medications
Psychosocial Treatment Guideline Statement
2014 Generalist settings (general practice and hospital, clinic or community settings not specialized in treatment of alcohol and other drug problems) Literature Review **** Body of evidence can be trusted to guide practice

*** Body of evidence can be trusted to guide practice in most situations

** Body of evidence provides some support for recommendation(s) but care should be taken in its application

* Body of evidence is weak and recommendations must be applied with caution

(C)
Recommendations based on a consensus of clinical experience.

(S)
Recommendations reflecting a standard of care that should be routine in competent clinical practice.

(R)
Recommendations established by regulatory requirements.

♦ is used to indicate areas where caution is required and specialist advice or referral is recommended.

Note: symbols used are different from original guideline's symbols (e.g., asterisks instead of stars).

Yes. Also clonidine, which is not FDA-approved. Yes--Cognitive and behavioral approaches and CM can increase effectiveness of MAT. Financial management/advice and participation in self-help groups also encouraged. ASSESSMENT EXCERPT
Co-existing health and psychosocial conditions are likely to influence the preferred treatment approach, setting and broad (holistic) treatment plan, including the need for specialist advice or referral (S).

The clinician should assess general health and well-being, targeted within the context of the patient's substance use. Opioid and other substance use is commonly associated with a range of:

  • Physical conditions (e.g., chronic non-malignant pain, liver, cardiovascular, injecting related infections, endocrine).
  • Psychiatric conditions (e.g., anxiety, depression, cognition).
  • Social problems (e.g., unemployment, housing, financial, relationships).
  • High-risk behaviours (e.g., overdose, self-harm, child protection and domestic violence).

Treatment Planning Excerpt:

As in other areas of chronic disease management, addiction treatment planning should:

  • Be a continuous process.
  • Involve the patient and reflect the patient's circumstances and case complexity.
  • Be based on coordinated care across service providers to address multiple domains.
  • Be documented so as to be meaningful to the patient, their carers and other service providers (S).

All types of available treatment for opioid dependence should be considered in consultation with the patient, taking into account the patient's circumstances and treatment preferences, and be based upon the evidence of effectiveness and safety of available options (S).

The principles of informed consent should be observed in selecting and referring patients to treatment services (S).

A stepped care approach to treatment delivery suggests using less restrictive treatment approaches for those with low severity dependence (e.g., detoxification, counselling), increasing to more intensive treatment options (substitution treatment, residential) for those with more severe and entrenched problems (C).

Factors that indicate particular treatment directions (C):

  • Certain medical and psychiatric conditions (e.g., chronic pain, psychotic disorders, acute medical conditions such as infective endocarditis, HIV) can be destabilized during detoxification and attempts at sustaining an opioid-free lifestyle; such patients are often better directed to opioid substitution treatment.
  • Women who are opioid-dependent and pregnant should usually be directed to opioid substitution treatment due to the risk of antenatal complications associated with detoxification, and high rates of relapse to heroin or other opioid use with other treatment approaches.
  • People with a preference for abstinence-based interventions who are well supported and well motivated are more likely to respond to counselling with or without naltrexone.
  • People with poor living skills.
            DETOXIFICATION EXCERPTS
Detoxification in opioid dependence should always be considered as part of a structured treatment approach (C).

Settings for Withdrawal Excerpt:

Management of withdrawal may occur in a range of settings:

  • Hospitals, particularly when drug users have been admitted for other reasons.
  • Residential services, which provide a safe, supportive environment for withdrawal management, but a lower level of medical care than hospitals.
  • Ambulatory (outpatient and/or home-based services) for those individuals with stable social settings and without significant medical or psychiatric complications or dependence on other drugs.

Selection of setting and approach to detoxification should take into account the goal of the care episode, the purpose of detoxification and timescale (S).

Intensive inpatient care is appropriate with:

  • Unstable medical or psychiatric condition.
  • Polydrug dependence.
  • History of medical or psychiatric conditions, or uncertain past drug use indicate a need for close monitoring.

Supported residential care, such as a community withdrawal unit, is appropriate with:

  • Unsupportive home environment, such as with other drug users, or without anyone reliable to supervise and support the patient.
  • Repeated failure at outpatient withdrawal.

Psychosocial Support Excerpt:

Psychosocial support during the withdrawal episode should be aimed specifically at helping the patient through problems associated with withdrawal and in facilitating post-withdrawal links.

Patient Information Excerpt:

Patients need information regarding:

  • The risk of overdose should they relapse after withdrawal as well as approaches to prevent and manage overdose.
  • The nature and duration of withdrawal symptoms.
  • Strategies for coping with symptoms and cravings.
  • Strategies to manage high-risk situations.
  • The role of medication.

Medication Approaches for Withdrawal Excerpt:

Two distinct medication approaches are recommended for the management of opioid withdrawal:

  • Abrupt cessation of opioid use and symptom amelioration using non-opioid drugs (usually benzodiazepines, NSAIDs, antiemetics, clonidine, antispasmodic drugs (such as hyoscinebutylbromide) for relief of symptoms.
  • Short-course (usually less than 1 month) of reducing doses of buprenorphine.

Both of these approaches are well supported by evidence, but the use of buprenorphine to manage withdrawal is associated with significantly better amelioration of withdrawal than clonidine and supplementary medications (****). It is the most flexible approach in that it supports cessation of medication with minimal rebound withdrawal symptoms while also enabling transfer to naltrexone for relapse prevention treatment, or to substitution treatment if the detoxification attempt is not successful.

The appropriate starting dose of buprenorphine and duration of withdrawal treatment will vary according to the clinical presentation of each individual. In general, higher doses and longer duration of treatment would be preferred in outpatient settings where the risk of unsanctioned opioid use is greater.

The first dose of buprenorphine should be administered once mild withdrawal is apparent to avoid the risk of precipitated withdrawal.

There is research evidence for the use of reducing doses of methadone for the management of opioid withdrawal, but the duration of tapered methadone withdrawal interventions tend to be greater than a month, blurring the line between withdrawal management and substitution treatment. While research evidence directly comparing methadone and buprenorphine for the management of opioid withdrawal remains limited, the flexibility of buprenorphine provides advantages in a withdrawal context.

Detoxification can also be achieved using opioid antagonists (naltrexone and/or naloxone), also known as antagonist-induced withdrawal or rapid-detoxification. This approach should only be considered as a means of facilitating induction of naltrexone to support relapse prevention treatment. Antagonist-induced withdrawal with minimal sedation is feasible, but the evidence base is weak (**). Specialist referral is recommended. Antagonist-induced withdrawal should only be provided in facilities that have the capacity to retain people as inpatients in the event of severe withdrawal, and only following approval by that facility's drug review committee or other formal approval mechanism. Patients should be properly informed, and consent obtained, which includes information that the use of naltrexone is an off-label indication.

            TREATMENT FOR OPIOID DEPENDENCE EXCERPTS
Choice of Medication Excerpt:

A substantial body of research evidence supports a conclusion that both methadone and buprenorphine are safe and effective in the treatment of opioid dependence (****). The choice between methadone or buprenorphine for opioid substitution treatment should be made in consultation with the patient, and informed by the patient's preference and goals. However, there are factors that indicate particular directions, as summarized below.

  • It is easier to transition in and out of treatment with buprenorphine compared to methadone. This is both an advantage in terms of greater patient flexibility, and a disadvantage with lower rates of retention in treatment with buprenorphine (***).
  • Whilst both buprenorphine and methadone typically have a range of opioid-like side effects, there is considerable individual variation in the experience of side effects with different opioids. If side effects are experienced with 1 medication, it is worth trying the other. Some longer-term side effects (e.g., impact on sex hormones (**), sleep apnoea (*), prolonged corrected QT (QTc) interval (**)) are more common with methadone.
  • Drug interactions are more likely to be clinically relevant with methadone (***). In particular, interactions with medications metabolised by the CYP450 hepatic system are clinically more relevant with methadone, with either induction of methadone metabolism (reduced methadone effects), or inhibition (increased methadone effects) that require monitoring of symptoms and may require dose adjustment. This can be particularly relevant for patients taking medications for HIV or TB.
  • Some patients report that methadone has greater impact upon cognition than buprenorphine, with stronger sedation and opioid-like subjective effects (*). This can be a therapeutic advantage for some patients with concurrent psychological distress. In contrast, many patients describe greater "clarity of thought"' with buprenorphine--an advantage for patients requiring good cognitive function (e.g., those employed, caring for children, studying, driving, elderly patients with other conditions affecting cognition, and patients taking other sedative medications).
  • Methadone has greater sedating effects and is more commonly associated with overdose than buprenorphine, particularly in the context of: (a) The first 2 weeks of treatment as tolerance increases (***). (b) In combination with other sedatives (alcohol, benzodiazepines) (*). (c) Use by individuals for whom the medication was not prescribed--in particular children and other opioid-naïve individuals (***). Consequently buprenorphine should be the preferred medication where there is limited opportunity for monitoring or supervision of dosing.
  • Induction of substitution treatment with buprenorphine is usually safer and easier with maintenance doses reached more quickly than is the case with methadone (***). However, precipitated withdrawal can be an issue if buprenorphine is commenced too soon after the last use of a full opioid agonist, and this can be a barrier for some patients commencing and engaging in treatment (**).

Induction Excerpt:

The goal of the first month of treatment is to safely achieve an adequate dose of medication, stabilise the patient's opioid use, and to address co-existing conditions (C).

Key objectives of the induction dose regimen are:

  • Reduction of withdrawal symptoms.
  • Reduction of cravings.
  • Reduced unsanctioned opioid and other drug use.
  • Patient satisfaction and engagement in treatment.

The differing pharmacological properties of methadone and buprenorphine mean that induction strategies are different. The greater risk of opioid toxicity and overdose during induction with methadone necessitates commencing at a low dose and a slow rate of dose increase (usually over weeks in outpatient settings). The partial agonist properties of buprenorphine result in less effect on respiratory function allowing for more rapid induction to a higher dose. Achieving an adequate dose of buprenorphine as quickly as possible (usually within 3 days) is associated with an improved rate of retention in treatment.

Methadone

Key principles:

1. Methadone is sedating and can cause overdose in too high doses, particularly in those with low opioid tolerance, and in combination with other sedatives, or in those with altered pharmacokinetics (e.g., due to hepatic failure, drug interactions).

2. The elimination half-life of methadone is typically in the range 24-48 hours, but extremes either side of this range have been recorded. Methadone accumulates in the plasma during induction, with achievement of steady state equilibrium on a dose after approximately 3-5 half-lives (4-7 days). Patients should be told to expect increasing opioid effects after each dose during this time.

3. Methadone has a delayed onset of action--with peak effects achieved 2-4 hours after dosing. Patients should be cautious in using other drugs (e.g., benzodiazepines, alcohol) during initiation of methadone treatment. Patients should be assessed 2-3 hours after a dose to observe the peak effects of methadone (assessing for intoxication), and 24 hours after a dose to assess the extent to which methadone dose is preventing withdrawal.

(a) Recommended regimen for outpatients with unsanctioned use of opioids (excerpt):

  • The opioids involved are likely to include heroin, and injected morphine, and codeine.
  • All doses of methadone should be supervised, where possible, and a clinician (doctor, nurse, pharmacist) should review the patient daily during the first week of treatment, corresponding to the greatest risk period for methadone-related overdose. The review provides an opportunity to assess intoxication (e.g., sedation, constricted pupils) or withdrawal symptoms, side effects, other substance use and the patient's general well-being.
  • Commence with 20-30mg daily. Lower doses (e.g., 20mg or less) are suited to those with low or uncertain levels of opioid dependence, with high-risk polydrug use (alcohol, benzodiazepines) or with severe other medical complications. Higher doses (30-40mg) should be considered with caution if clinically indicated, at the discretion of the prescriber. Consultation with a specialist is recommended before commencing patients at doses greater than 40mg because of the risk of overdose.
  • Dose increases should be made following review of the patient and should reflect side effects, features of withdrawal (suggesting not enough methadone) or intoxication (suggesting too much methadone or other drug use), ongoing cravings and substance use.
  • Dose increments of 5-10mg every 3-5 days will result in most patients being on doses of 30-50mg by the end of the first week, and 40-60mg by the end of the second week.
  • Supplementary doses can be considered for patients returning in severe withdrawal 4-6 hours after dosing, but only after review by the prescriber. This requires coordination between the prescriber and dispenser.
  • The dose should be gradually increased in order to achieve cessation (or marked reduction) in unsanctioned opioid use, and alleviation of cravings and opioid withdrawal features between doses, whilst minimising methadone side effects. Daily methadone doses above 80mg will also markedly reduce the effects of any ongoing heroin or other opioid use.

Consider specialist advice or referral in the following circumstances ♦:

  • Patients with an unclear level of opioid tolerance, high-risk polydrug use, concomitant physical conditions or use of other medications that may affect the metabolism of methadone.
  • Patients seeking higher and more rapid dose increases (inpatient settings with close monitoring may also be helpful).
  • Patients who have difficulty stabilising on a dose of methadone due to continued substance use, side effects or other complications.

When deciding on induction of methadone, take account of pharmacy availability for supervision of dosing and monitoring of response. If 7-day pharmacy services are not available, the commencement of treatment should be timed so that induction is well underway before the first day of unsupervised dosing.

Buprenorphine Excerpt:

Key principles:

1. Patients choosing buprenorphine should be commenced on the combination preparation (buprenorphine-naloxone) unless pregnant or breastfeeding or with a proven allergy to naloxone. This is an abuse deterrent strategy as buprenorphine-naloxone combination preparations are less likely to be injected than mono preparations containing only buprenorphine (**). Furthermore, it is easier to supervise the dosing of the film preparation, compared to tablets, of buprenorphine-naloxone.

2. As a partial agonist, buprenorphine is a safer opioid than methadone with regard to the potential for over-sedation, respiratory depression and overdose. Hence, dose increases can be more rapid and, in general, most patients can achieve their target dose within 2-3 days (***).

3. Buprenorphine has higher mu-opioid receptor affinity and lower intrinsic activity than most other opioids (including heroin, morphine, methadone, oxycodone). As such, it can cause precipitated opioid withdrawal symptoms if given too soon after a recent dose of a full agonist. This is because buprenorphine displaces the agonist but has lower activity as a partial agonist, which can be experienced as precipitated withdrawal (***).

4. The general principle for safe induction is that the first dose of buprenorphine should be delayed until there is incipient withdrawal (***) as assessed by a suitably trained clinician or measured by a validated scale or scales that assess both objective signs and subjective symptoms (e.g., the COWS).

(a) Recommended induction regimen for outpatients using heroin and/or short-acting pharmaceutical opioids.

  • Initial doses should be supervised, and a clinician (doctor, nurse, pharmacist) should review the patient daily during the first few days of treatment while the dose is stabilised. The review provides an opportunity to assess intoxication (e.g., sedation, constricted pupils) or withdrawal symptoms, side effects, other substance use and the patient's general well-being.
  • Defer the first dose of buprenorphine until the patient is experiencing mild to moderate withdrawal (anxiety, abdominal or joint pain, dilated pupils, sweating). The use of a validated rating scale such as COWS can be helpful:
    -- For the patient with mild withdrawal (subjective symptoms but no signs of opioid withdrawal that would produce a score less than 8 with the COWS), provide an initial dose of 4mg, with the possibility of a subsequent dose of 4mg after 1-2 hours ('split dosing' reduces the risk of precipitated withdrawal).
    -- For the patient with moderate or severe withdrawal at the time of the first dose, an initial dose of 8mg is appropriate.
    -- Lower doses (e.g., 2-4mg total on day 1) are suited to those with low or uncertain levels of opioid dependence, with high-risk polydrug use (alcohol, benzodiazepines) or with other severe medical complications. Seek specialist advice if concerned (C). ♦

Delivering Safe and Effective Agonist Maintenance Treatment Excerpt:

Patient input to treatment decisions, including determination of dosing levels, promotes a good therapeutic relationship by enhancing patient trust and self-responsibility. Doses should be tailored to each patient, adjusting the dose in response to:

  • Medication effects (intoxication or sedation from too high a dose, withdrawal from an inadequate dose).
  • Side effects--many opioid side effects subside in the first 2-4 weeks of treatment, but some are persistent and may require dose adjustment (seek specialist advice if uncertain).
  • Continued drug use--increasing doses of methadone or buprenorphine is often an effective response to unsanctioned opioid use, but has a limited role in addressing use of other drugs (e.g., alcohol, cannabis, benzodiazepines, stimulants).
  • Patient report of dose adequacy and treatment goals.

Methadone Excerpt:

Adjust doses by 5-10mg at a time, as needed, with at least 3 days between each dose adjustment.

Methadone in doses of 60mg/day or greater is more effective than lower doses in terms of retention in treatment, reduction in unsanctioned opioid use and associated high-risk behaviours (****).

Most patients require methadone doses in the range 60-120mg/day to achieve stabilisation and this should be regarded as an appropriate range for maintenance doses. A small proportion of patients may require higher (e.g., up to 150mg/day) or lower (e.g., 30-40mg/day) doses to achieve their treatment goals. Doses above 150mg/day are generally associated with little additional benefit and increase the risk of dose-related adverse events (C). Specialist referral is recommended for patients seeking methadone doses greater than 150mg/day (C) for an investigation of the reasons for the high dose requirement. ♦ There may also be jurisdictional requirements for approval of doses greater than 120mg/day.

Buprenorphine Excerpt:

Adjust doses by 2-8mg at a time as needed. Evidence indicates that buprenorphine doses of 8-16mg are superior to lower doses in terms of retention in treatment, reduction in unsanctioned opioid use, and associated high-risk behaviours (****).

Most patients require daily buprenorphine doses in the range 12 -24mg to achieve stabilisation, although some patients require higher (e.g., up to 32mg/day) or lower (4-8mg/day) doses to achieve their treatment goals. Doses greater than 16mg are associated with increased duration of action, with little or no increase in the degree of opioid effect. The maximum possible dose of 32mg is a regulatory and manufacturer's limit (R). Higher doses may be associated with dose-related adverse events; specialist consultation is recommended for patients seeking doses greater than 32mg. ♦

The characteristics of buprenorphine allow a wide range of dosing regimens, from several times daily to once every 2-3 days. The main reasons for considering reduced frequency dosing are convenience for patients, and reduced staffing requirements for supervised dose administration.

Patients interested in less than daily dosing should first be stabilised on daily dosing before trying alternate-day dosing for 2 weeks. If this is successful, the patient can then be tried on a 3-times-a-week regimen. If a patient cannot be stabilised on such dosing regimens due to the onset of withdrawal, cravings, side effects or features of intoxication, they should be returned to a more frequent dosing regimen.

            RELAPSE PREVENTION
Naltrexone Excerpt:

The evidence on the effectiveness of naltrexone maintenance treatment is limited by low rates of retention in studies, and the small number of comparable studies. Current evidence indicates no significant difference in treatment retention or abstinence for people treated with naltrexone, with or without adjunctive psychosocial therapy, compared to placebo or psychosocial therapy alone (**).

The best approach to initiation of naltrexone maintenance treatment is to manage withdrawal from opioids with small doses of buprenorphine before commencing naltrexone.

Introduce naltrexone with caution if there is any uncertainty about time of last opioid use (C). An interval of 5 days between last buprenorphine and first naltrexone is recommended for generalist settings. If heroin was the last opioid used, an interval of 7 days is recommended, and 10-14 days if methadone was the last opioid used. If a faster transition is desired, seek specialist advice or referral. ♦

Urine drug screening is of little use during naltrexone induction. The best approach is to advise the patient that the first dose of naltrexone may precipitate withdrawal if opioids have been used recently. If there is a risk of precipitated withdrawal due to uncertain recent opioid use, seek specialist advice (C).

Commence naltrexone at 25mg/day for 3 days, then increase to 50mg/day if tolerated (C). Note that the onset of withdrawal triggered by naltrexone can be delayed following buprenorphine treatment.

Psychosocial Support:

Psychosocial support is an integral component of MAT.

People who are opioid dependent often have complex issues--social, housing, legal, employment, mental health, etc. The first aim of treatment is stabilization--it is best to delay interventions for relapse prevention and structural behavioural therapies until immediate needs have been addressed.

Psychosocial interventions delivered as one-on-one and group sessions--including cognitive and behavioural approaches and CM techniques--can add to the effectiveness of MAT. Psychosocial services should be made available to all patients, although those who do not take up the offer should not be denied effective pharmacological treatment.

Psychosocial support should be tailored to the individual and should include issues such as financial management and advice (C). Psychosocial support also encompasses the promotion of treatment compliance.

Participation in self-help groups (e.g., NA, SMART Recovery) should be recommended to patients, but attendance should not be mandatory (C). The effectiveness of self-help groups is related to participation, not just attendance, and mandatory attendance can be counterproductive.

Adolescents:

Treatment of adolescents (generally those aged less than 18), should take into account a broader health and welfare context. The emphasis should be on psychosocial responses, family intervention approaches, vocational issues, and harm reduction, particularly around prevention of sexually transmitted diseases and blood-borne viruses. Nonetheless pharmacotherapy may also be an important component of treatment for some young people (C).

Pharmacotherapy should only be used after careful assessment of risks and benefits, and in the context of a comprehensive treatment plan embracing various psychosocial approaches (C). The legal and regulatory requirements of the relevant jurisdiction should be checked before prescribing methadone or buprenorphine to a patient less than 18 years of age.

If pharmacotherapy is used, buprenorphine may be preferred over methadone because of easier cessation. Doses may need to be adjusted from those used for adults.

Depending on their drug use history and social circumstances, adolescents may stabilise quickly on substitution treatment enabling cessation of pharmacotherapy to be considered more quickly than would be the case with adult s (C). However, as with adults, adolescent patients should be monitored for signs of destabilisation and substitution treatment reinstated if necessary.

See original guidelines for much more information.

  1. Full guideline can be found at http://www.nationaldrugstrategy.gov.au/internet/drugstrategy/Publishing.nsf/content/AD14DA97D8EE00E8CA257CD1001E0E5D/$File/National_Guidelines_2014.pdf. Many of these guidelines were based upon a consensus process informed by the literature reviews.

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