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In an era of constrained health care financing, clinicians are increasingly faced with considering the economic consequences in addition to the clinical outcomes associated with initiating a patient on antidepressant therapy. This has increased the demand for health economic studies comparing antidepressant use and associated health care expenditures in clinical practice. These health economics studies have used methods ranging from clinical trials to other types of analyses including prospective naturalistic trials or retrospective studies which may be less familiar to clinicians. Prospective and retrospective health economics studies performed in clinical practice complement the experience gained from clinical trials in assessing antidepressant use and economic outcomes in light of patient and provider behavior within the usual care environment of a complex health care system. Broadly considered, health economic studies of antidepressants have consistently found differences in clinical practice between the tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitors (SSRIs) as well as among the SSRIs. These differences relate to the pattern and duration of antidepressant use as well as total direct health care expenditures. Future health economic research studies in clinical practice should focus on the economic consequences of long-term antidepressant use as well as the impact of antidepressant use on indirect costs such as productivity and absenteeism.

Concomitant use of psychoactive medications is a common practice in most clinical trials of antidepressant medications. However, the relative therapeutic impact of such use on trial results has not been the subject of much attention. We conducted a meta-analysis to determine whether concomitant use of psychoactive medications confounded the efficacy or safety results of a series of fluoxetine trials. Data were evaluated from 25 randomized, double-blind clinical trials comparing fluoxetine with placebo or a tricyclic antidepressant (TCA) in 4,016 patients with major depression. We compared incidence rates of concomitant use of anxiolytics, sedatives, and antipsychotics between treatments. In addition, we compared the change in total score for the 21-Item Hamilton Depression Rating Scale (HAMD21): incidence rates of any worsening, emergence, or improvement in psychomotor agitation; and incidence of suicidal acts and any worsening, emergence, or improvement in suicidal ideation between treatment groups among patients taking/not taking a sedative. Anxiolytic and antipsychotic drug use was uncommon (8.3% and 0.9% overall use, respectively) and did not substantially increase over time. Sedative drugs were used most often (29.6% overall), but only 29.8% of the fluoxetine-treated patients took one or more doses. Regarding efficacy, fluoxetine was superior to placebo in decreasing HAMD21 total scores among patients taking/not taking sedatives. Effects on safety were assessed by examining agitation and suicidal ideation. Use of sedatives did not affect the change in the HAMD agitation score; scores were similar in patients receiving fluoxetine, placebo, and TCAs. In all treatment groups, anxiolytic use tended to increase as the HAMD anxiety score increased. Fluoxetine was superior to placebo in treating suicidal ideation, and the concomitant use of sedatives did not influence this effect. Overall, concomitant use of psychotropic medications in the fluoxetine depression clinical trials was uncommon. Our meta-analysis demonstrated that the clinical efficacy and safety of fluoxetine were not confounded by the concomitant use of medications. Depression and Anxiety 6:31–39, 1997. © 1997 Wiley-Liss, Inc.

Psychomotor agitation, a common clinical feature of major depression, may first emerge or intensify during pharmacotherapy. Whether agitation is part of the underlying course of depression or iatrogenic complicates treatment planning. We analyzed data from blinded clinical trials involving 4,737 patients with major depression assigned to a selective serotonin reuptake inhibitor (fluoxetine), a comparator antidepressant (usually a tricyclic antidepressant [TCA]), or placebo. Item 9 of the Hamilton Depression Rating Scale was used to assess the degree of psychomotor agitation. The vast majority of depressed patients exhibited baseline psychomotor agitation. The rate of increased agitation from baseline during acute pharmacotherapy was comparable between fluoxetine and either placebo or TCAs. Substantial emergence of psychomotor agitation also occurred at a similar incidence across the three treatment groups and typically appeared within the first 3 wk. Improvement in agitation was significantly more prominent (P < 0.001) among fluoxetine-treated than among placebo-treated patients. Fluoxetine-treated patients demonstrated numerically superior improvement rates compared with TCA-treated patients; however, this difference was not significant. Data derived from this large series of clinical trials suggested no evidence that either fluoxetine or TCAs induced psychomotor agitation at rates exceeding the natural course of the disorder over time (placebo cohort). On the contrary, pharmacotherapy with either fluoxetine or TCAs was typically associated with diminished agitation, probably as part of the response pattern of depression.