Access and Utilization of New Antidepressant and Antipsychotic Medications. A. Treatment Guidelines and Preferred Medications

Guidelines for the treatment of schizophrenia, depression and other mental disorders have been produced by various sources. By and large, however, these have been the products of individual health plans, health service programs, or professional associations. Two sets of guidelines have come from national sources: The Agency for Health Care Policy and Research (AHCPR) has published guidelines for the treatment of depression in primary care³⁰ as well as the findings of the Patient Outcomes Research Team (PORT) study on the treatment of Schizophrenia.³¹ The American Psychiatric Association produces clinical practice guidelines for a variety of mental illnesses including Major Depressive Disorder³² and Schizophrenia.³³ In general, all guidelines list effectiveness, safety, patient history, and cost as important factors to consider in making treatment decisions.

• National Guidelines

  • The AHCPR depression guidelines, published in 1993, describe a range of issues to be considered in the selection of a pharmacological therapy for depression. These guidelines specify that one of the SSRIs available at the time of publication (fluoxetine, sertraline, and paroxetine), bupropion, trazadone, or a secondary amine TCA (e.g., notriptyline, desipramine) are appropriate first-line choices for the treatment of depression. The guidelines also make specific recommendations regarding dosing of each type of agent, recognizing that TCAs are frequently underdosed. These guidelines recognize that the case for superior efficacy of any one single agent is not clear and that patient preference and physician experience should factor into the decision.

    Similarly, the recommendations of the PORT focus on dosing and management of care.³¹ The guidelines recommend that an antipsychotic other than clozapine be used first line and that the dosing level be in the range of 300 -- 1,000 chlorpromazine equivalents per day for at least six weeks. Specifically the guidelines state

    Since studies have found no superior efficacy of any antipsychotic medication over another in the treatment of positive symptoms, except for clozapine in the treatment-refractory patients, choice of the antipsychotic medication should be made on the basis of patient acceptability, prior individual drug response, individual side-effect profile, and long-term treatment planning.

    Guidelines from The American Psychiatric Association for the treatment of both depression³² and schizophrenia³³ are similar to guidelines discussed above. They provide general guidance to the physician on approach to treatment, but fall short of endorsing any one particular agent or class thereof. The APA depression guideline recommends that any non-MAO antidepressant is an appropriate first-line therapy for a patient with depression unless the patient presents with atypical depression or has had a prior good response to a MAO inhibitor. For patients with atypical depression either an SSRI or a MAO inhibitor is an appropriate first choice. The schizophrenia guideline recommends conventional antipsychotics and risperidone are reasonable first-line medications for patients in acute phases of schizophrenia. Although not completely reviewed at the time of publication, these guidelines recognize that olanzapine and quetiapine may fall into this category as well. The APA schizophrenia guidelines reserve clozapine for treatment-refractory schizophrenia.

    Neither the NMHA nor NAMI endorse any particular treatment algorithm. The consumer associations generally believe that all drugs should be available on formulary and defer to the medical community for the choice of individual drugs for an individual patient.

• Public Program Guidelines

  • The Health Care Financing Administration(now known as Centers for Medicare and Medicaid Services(CMS)) does not in general instruct States on the choice of individual pharmaceutical agents for inclusion in formulary or treatment guidelines. However, HCFA(now known as CMS) has sent a letter to State Medicaid Directors urging the coverage of atypical antipsychotics as first line agents for the treatment of schizophrenia.²⁵

    In general, State Medicaid and State Mental Health programs have not adopted treatment guidelines for depression or schizophrenia. This situation has begun to change somewhat with the advent of Medicaid Managed Care. The outstanding example of treatment guidelines in development and implementation are those developed by the Texas Medication Algorithm Project (TMAP), which is being conducted in four phases.³⁴ In Phase I, algorithms for schizophrenia, depression, and bipolar disorder were developed.

    The algorithm for the treatment of nonpsychotic depression makes treatment recommendations for six stages of therapy. In Stage I, the algorithm recommends monotherapy with an SSRI, bupropion, nefazadone, venlafaxine or mirtazapine. In Stage II (after partial or nonresponse), the algorithm recommends trying either a different medication from the Stage I list or a TCA. Alternatively, augmentation is recommended after partial response at each stage. In Stage III, the algorithm recommends use of an antidepressant in a class other than one used in Stage I or II. The algorithm also states that the use of a MAOI may be appropriate in Stage III. Stages IV-VII recommend (in this order) lithium augmentation, combination therapy, electroconvulsive therapy (ECT), or any other antidepressant not listed in Stages I-III.³⁵

    The TMAP schizophrenia algorithm recommends use in any order of olanzapine, quetiapine or risperidone whether or not the patient has a history of failure on a typical antipsychotic. After non-response to the two remaining atypical agents or to a typical agent (in patients with no history of failure on a typical agent), clozapine is recommended. In the case of non-compliance with the second atypical antipsychotic, haloperidol decanoate or fluphenazine decanoate is recommended. With partial response to clozapine, an augmenting agent is recommended. With non-response or refusal on clozapine, the algorithm recommends either the use of combinations of atypical and/or typical antipsychotics or the combination of an antipsychotic with ECT.³⁵

    In Phase II of TMAP, a feasibility trial determined the suitability of the recommendations, as well as strategies and resources necessary for implementation into the public sector. Phase III, a clinical impact study, compares treatment as usual (TAU) to the algorithms. This study will determine whether the algorithms and associated efforts (e.g., patient/family education and increase in clinical staff to implement the algorithms) produce better clinical outcomes and whether they affect service utilization (and therefore cost). Phases II and III provided clinical staff and physicians with continuing education to ensure understanding and use of the algorithms and medications. Preliminary results indicate that the physicians largely followed the algorithms, requested ongoing continuing medical education/information for the new algorithms, and plan to continue use of the algorithms after completion of the study.³⁵ Respondents within the VA and the DoD reported that treatment guidelines have been found useful in the management of patients with mental illness within organizations.

    The VA's Medical Advisory Panel (MAP) for Pharmacy Benefits Management recently developed guidelines for the pharmacologic management of major depression as part of a greater effort to standardize and reduce treatment costs for common diseases within the VA. Currently there are no guidelines for the management of schizophrenia at the national level within the VA or the DoD.³⁶

    These guidelines for the treatment of depression rely primarily on APA, AHCPR and other evidence-based published guidelines. Guidelines are reviewed and updated routinely. The guidelines are intended to "assist practitioners in clinical decision-making, to standardize and improve the quality of patient care, and to promote cost-effective drug prescribing."

    The guidelines focus on pharmacotherapy from a primary care perspective, encouraging monitoring, appropriate dosage, and maintenance therapy, or referral to a psychiatrist if necessary. The guidelines also state that a psychiatrist should immediately evaluate patients who present with depression and suicidal thoughts and/or symptoms of psychosis. Though no one therapy for depression is recognized as clearly superior, SSRIs are recommended as first-line antidepressants due to the lower risk for suicide in overdose. In developing the guidelines, the MAP did not find sufficient evidence to recommend one SSRI over another.

• Private Sector Guidelines

  • Several health care payers and health maintenance organizations have produced more explicit guidelines for the choice of antidepressant and antipsychotic medications. These range in scope from designations of preferred medications to more comprehensive sets of guidelines for the management of these illnesses.

    Among the payers interviewed in this study, there was no consensus on the choice of recommended first line agents. In general, however, payers are more concerned about managing antidepressant utilization than they are about managing the utilization of antipsychotics. This is largely because the antidepressants (in particular the SSRIs) have a far greater potential for misuse, including their use in the promotion of weight loss, performance enhancement (the "better than well" effect), and the treatment of melancholy that does not constitute depression.

    In designing treatment guidelines/disease management, most MCOs try to integrate pharmaceuticals with non-pharmacotherapies. Plans may recommend choice of agents by brand, drug class, dose, duration of therapy, side effects, and required follow-up care. Although distribution of guidelines is not common, one of the five plans interviewed reported distributing these materials to the patient as well as making them available for sale to other health plans. The focus of the program at one large, group-model HMO was more one of physician monitoring and education. This MCO has implemented guidelines to insure better management of depressed patients.

    Another large, group-model HMO recommends that either a TCA or an SSRI is an appropriate first-line choice for an antidepressant, leaving the option to the physician. Another group-model HMO admitted to recommending the least expensive agent available, whether it was an SSRI or a TCA.

    First-line choices for antipsychotics likewise vary by payer, although few actively promote the use of atypical over typical antipsychotics. One HMO reported promoting the use of typical antipsychotics first-line even though prior authorization requests for atypicals are never denied.

    Several PBMs are in the process of developing diagnosis and treatment guidelines (e.g., disease management, preferred drug list). Several reported using the AHCPR guidelines for depression, while others reported following those of their MCO clients. One large PBM has organized an outcomes research division to inform its development of guidelines for the diagnosis and treatment of depression. On the other hand, another large PBM feels that its role in the treatment selection should be minimal and that guidelines should be as general as possible. PBMs reported marketing the guidelines and programs they develop to providers, consumers, and employer and MCO clients.

    Often, treatment guidelines published by PBMs have embraced the most up-to-date pharmacotherapies. For example, treatment guidelines published by the pharmaceutical benefits manager PCS state that SSRIs are the drugs of first choice for the treatment of depression, citing less risk of overdose, decreased side effects, increased patient compliance, and demonstrated cost effectiveness. At the time of publication, the national formulary of PCS included all five SSRIs currently available in the US. These guidelines also recommend atypical antipsychotics as first-line therapy for "patients experiencing psychotic episodes in which both positive and negative symptoms are apparent."³⁷ PCS has also implemented formal disease management programs for both depression and schizophrenia.

    Pharmaceutical manufacturers play a role in developing treatment guidelines, although these generally cannot focus on their product or pharmacotherapy alone. Rather, they aim for broad coverage of a class of drugs and integration of pharmaceuticals into overall treatment of the disease. One manufacturer stated that most schizophrenia guidelines have atypicals as first-line. Manufacturers may also assist academic institutions with the development of treatment guidelines. This was particularly true for schizophrenia guidelines, such as TMAP.

    Employers do not generally concern themselves with the selection of preferred or covered pharmaceutical agents. Likewise, they do not develop or adopt treatment guidelines or disease algorithms for depression, bipolar disorder or obsessive-compulsive disorder. However, health benefits consultants report that they generally encourage employers to cover the most up-to-date pharmacotherapies for mental illness. Only one employer interviewed reported implementing a disease management program for depression, although others expressed interest. This program was a PBM-sponsored program monitored through the PBM contract.

    Surprisingly, most BHMCOs are not involved in the writing of clinical practice guidelines for the treatment of mental illnesses. Magellan, the largest BMHCO, recently announced a program to produce general guidelines on the use of antidepressant medications as a component of comprehensive mental health care. However, these guidelines will focus on prescribing practices and appropriate use. They will not endorse specific pharmaceutical agents. The guidelines are being developed within a 3-year program designed to identify prescribing patterns for antidepressants. These guidelines will develop an independent Expert Consensus Panel Guidelines that specify a standard of care. The program will also analyze prescribing data to identify the appropriateness of prescribing in current practice. Finally, the program will develop an educational program to instruct physicians on appropriate prescribing protocols. These guidelines are being developed in collaboration with Eli Lilly.³⁸

• Special Population Guidelines

  • The New York State department of Corrections currently administers treatment algorithms and guidelines for the treatment of mental illness. The primary goals of these programs are to provide the highest level of care combined with some level choice to individuals with mental illness.

    The Navaho region of the IHS reports no formal guidelines for the treatment of depression or schizophrenia. The principal goal of the treatment strategy within the IHS is symptomatic relief. The Service believes that its primary obstacle to providing effective treatment of mental illnesses within Native American populations is a resistance to "Anglo" medicine a priori. Therefore, the IHS often partners with traditional Medicine Men or seeks to portray itself as an alternative to these.