Placebo versus antidepressants

S. Wessely and R. Hardy, Active Placebos Versus Antidepressants... 

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). 

Sneed, Joel R., Bret R. Rutherford, David Rindskopf, David T. Lane, Harold A. Sackeim and Steven P. Roose, Design Makes a Difference A Meta-Analysis of Antidepressant Response Rates in Placebo-Controlled Versus Comparator Trials in Late-Life Depression , American Journal of Geriatric Psychiatry 16, no. 1 (2008) 65-73... 

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. 

TABLE 20-1. Efficacy of antidepressant maintenance versus placebo in prevention of unipolar depression... 

There have been five double-blind studies comparing the antidepressant efficacy of different SSRIs versus different TCAs in patients with HDRS scores of 25 or more (122, 123,124, 125 and 126). Three of these studies permitted inclusion of both inpatients and outpatients ( 122, 123 and 124), whereas the other two were solely done in outpatients (125, 126). Three were placebo-controlled (1.23, 125,126). In these three studies, the SSRI (i.e., fluvoxamine, paroxetine, or sertraline) was either superior to both the f CA and placebo or was comparable with the TCA and superior to placebo. In the other two studies, the SSRI was not different from the TCA and there was no placebo control. There have also been four studies and one metaanalysis of European clinical trials which found no difference in antidepressant efficacy between several different SSRIs and several different tertiary amine TCAs in patients hospitalized for major depression ( 127,128, 129,130 and 131). Finally, there have been two relatively small studies showing that fluoxetine and fluvoxamine both had antidepressant efficacy superior to placebo in patients with melancholia ( 132, 133). Another larger study failed to find a difference between paroxetine and amitriptyline in treating such patients ( 134). 

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. 

TABLE 7-19. Tricyclic antidepressants versus placebo maintenance therapy... 

Kasper S, Moller H-J, Montgomery SA, et al. Antidepressant efficacy in relation to item analysis and severity of depression a placebo-controlled trial of fluvoxamine versus imipramine. Int Clin Psychopharmacol 1995 9 3-12. 

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... 

TABLE 13-5. Tricyclic antidepressant versus placebo treatment of panic disorder... 

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. 

Antidepressants versus placebo for short-term treatment... 

Fergusson et al. (2005) searched the literature and found 702 randomized clinical trials (87,650 patients) comparing SSRIs with either placebo or an active non-SSRI control medication. They found a statistically significant, more than two-fold increased risk of suicide attempts on SSRIs compared to placebo. The odds ratio of suicide attempts in SSRI-treated patients versus placebo patients was 2.28 (p = 0.02) and a 95% confidence interval (Cl) of 1.14-4.55. They also found an increased suicide risk between SSRIs and other medications, excluding tricyclic antidepressants. There was no difference between the SSRIs and tricyclics in suicide risk. Overall, their results documented an association between suicide attempts and the use of SSRIs. ... 

Antidepressant Medications Drug versus Placebo Effects... 

Bacaltchuk, J. and P. Hay (2003). Antidepressants versus placebo for people with bulimia nervosa. Cochrane Database Syst Rev (4) CD003391. 

---