The antidepressants and antipsychotics of interest to this study are shown Exhibits I-1 and I-2, respectively, by generic and brand names. The principal antidepressants considered in this study include the Selective Serotonin Reupatke Inhibitors (SSRIs) and other newer antidepressants including venlafaxine, bupropion, nefazadone, and mirtazapine. These agents contrast with older classes of antidepressants, namely the Tricylcic Antidepressants (TCAs) and Monoamine Oxidase Inhibitors (MAOIs).
Pharmacotherapy is an important component of effective treatment of mental illness. Effective treatments for mental disorders date to the 1950s. For example, older antidepressants (e.g., TCAs) have proven to be effective; however, difficulties in dosing often lead to less than satisfactory results in common use (i.e., the "real world"). Furthermore, the lethal dose of TCAs is relatively low compared to the standard therapeutic dose. This danger is especially high for patients in crisis who may be suicide-prone. Newer agents such as SSRIs have generally proven as efficacious as the TCAs, and often have simpler (i.e. once a day) dosing and are far less lethal in overdose. They have also proven helpful in treating an array of other illnesses including obsessive-compulsive disorder, panic disorder, and social phobia.
Nonetheless, the side effect profiles of both TCAs and newer agents can be unpleasant. TCAs are associated with side effects such as constipation, dry mouth, urinary retention, and sedation, while SSRIs, carry the risk of sexual dysfunction, sleep disruptions, and increased anxiety. Venlafaxine has an associated risk of hypertension, while bupropion has a risk of seizures. In general, however, simpler dosing regimens and more acceptable side effect profiles for the newer drugs are thought to improve compliance and success.5
Exhibit I-1. Representative Antidepressants Marketed the United States, 1999
The antipsychotic agents (Exhibit I-2) principally considered in this study include the archetype of the "atypical" antipsychotics, clozapine, together with three newer agents, risperidone, olanzapine, and quetiapine. These agents were designed to replace older generation pharmaceuticals including the phenothiazine class, haloperidol, and other miscellaneous antipsychotic agents.
Exhibit I-2. Representative Antipsychotics Marketed in the United States, 1999
Similarly, older antipsychotics (e.g., haloperidol, chlorpromazine) have proven effective for many patients. However, the duration of effect is often short-lived and these agents have no benefit for the so-called negative symptoms of schizophrenia, such as social withdrawal. The older agents are also associated with very high risks of extrapyramidal side effects (EPS) and tardive dyskinesia (TD) that often are associated with poor patient compliance and severe distress for both the patient and their families. The newer agents (e.g., risperidone, olanzapine, quetiapine) are generally as effective as the older agents and show promise in the treatment of negative symptoms. Clozapine has shown superior efficacy, especially in treatment-refractory patients. The newer agents typically have milder side effect profiles that may assist with compliance. Clozapine, however, is associated with a significant risk of agranulocytosis. Risperidone is not without some risk of EPS, while olanzapine is associated with weight gain, and quetiapine with somnolence.5