Antidepressants versus placebo effects

Antidepressant Medications Drug versus Placebo Effects... 

Imipramine treatment resulted in a higher rate of remission of anxiety symptoms than trazodone, diazepam, or placebo (e.g., 73% versus 69% versus 66% versus 47%) in an 8-week controlled trial of DSM-III-diagnosed GAD patients. Antidepressants were more effective than diazepam or placebo in reducing psychic symptoms of anxiety. The use of TCAs generally is limited by bothersome adverse effects (e.g., sedation, orthostatic hypotension, anticholinergic effects, and weight gain). 

This can be hard to explain. Potential causes include a worsening of the depression, the development of tolerance to the medication s effect, or the loss of placebo effect. Some believe that in our efforts to find safer and more tolerable medications, we have produced a new generation of antidepressants that are not as effective when used long-term. This harkens back to the rich pharmacology versus dirty drug debate. Could the older medications with their multiple receptor actions work better long-term We really don t know. 

Because many antidepressant compounds are also effective in panic disorder, we performed a trial of inositol in panic (Benjamin et al. 1995). Twenty-one patients with panic disorder with or without agoraphobia completed a double-blind, random assignment crossover treatment trial of inositol 12 g/ day versus placebo, with 4 weeks in each treatment phase. Frequency of panic attacks and severity of panic disorder and of agoraphobia declined significantly more on inositol than on placebo the effect was comparable to that of imipramine in previous studies. Side effects were minimal. 

A number of studies have been performed on the efficacy of St. John s Wort as an antidepressant. Several meta-analyses of these studies have also been published. The first such metaanalysis involved 23 randomized trials (15 placebo-controlled and eight active-controlled) involving 1,757 outpatients. It concluded that there was preliminary evidence supporting hypericum extracts as being superior to placebo in patients with mild to moderate clinical depression ( 233). Two more recent reviews of subsequent, placebo-controlled studies also concluded that hypericum is more effective than placebo but possibly less effective than TCAs ( 234, 235). At least two large-scale, multicenter, double-blind, placebo- and active-controlled studies are ongoing in the United States, testing the efficacy of hypericum versus an SSRI in patients with major depression. The results of these studies should further clarify the role of hypericum in the treatment of depressive disorders. 

ECT is superior in efficacy when compared with placebo, sham ECT, and active drug therapy. Upon the introduction of effective pharmacotherapy for severe depression, the relative efficacy of drug versus ECT was frequently studied. Our review of the relevant literature led to an extrapolation of the data from selected studies (primarily class I or II designs) for a quantitative analysis of the efficacy of ECT versus other treatments for an acute depressive episode ( 53). The comparisons with ECT included simulated (or sham) ECT, placebo, the standard tricyclic antidepressants, and the monoamine oxidase inhibitors [ Table 8-1 (54, 55, 56, 57, 58 and 59), Table 8 2 (0g 6i 62 and 63), Table 8-3 (56, 61, 62, 63, 64, 65 and 66), and Table 8-4 (55, 60, 61, 62 and 63)]. We also compared the relative efficacy of the bilateral versus the UNID forms of administration [Table 8-5 (42, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77 and 78)]. A meta-analysis was... 

Soloff et al. (225) carried out a particularly important comparison of phenelzine versus halopehdol in BPD with depression. Although this study had reasonable sample sizes (i.e., 38 on phenelzine, 36 on haloperidol, and 34 on placebo), it failed to find a clear advantage for phenelzine over placebo. It did, however, find that phenelzine produced a significantly better improvement in hostility than placebo and a greater antidepressant response than haloperidol. The authors then maintained their patients on these same regimens for an additional 4 months, with little evidence that phenelzine had a continued greater beneficial effect than placebo. 

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