Placebo responses antidepressants

Early landmark studies utilizing Hispanic subjects in the 1980s (Escobar Tuason, 1980 Marcos Cancro, 1982) compared the efficacy and response of several tricyclic antidepressants to placebo. They were the first to hint at a possible heightened placebo response in Hispanics and they suggested that certain Hispanic subjects... 

These continuation trials tell a very different story from that told by relapse-prevention trials. They show that there is little difference between antidepressant and placebo even when the clinical trial is extended over a longer period of time. Across the eight continuation trials that have been published, 79 per cent of patients on placebo and 93 per cent of patients on active medication remained well throughout the treatment period. In these long-term studies, placebo treatment was 95 per cent as effective as drug treatment. The authors of a meta-analysis of these trials concluded that the widely held - and probably erroneous - belief that the placebo response in depression is short-lived appears to be based largely on intuition and perhaps wishful thinking .17... 

Khan, Arif, Nick Redding and Walter A. Brown, The Persistence of the Placebo Response in Antidepressant Clinical Trials , Journal of Psychiatric Research 42, no. 10 (2008) 791-96 Kihlstrom, John F., Attributions, Awareness and Dissociation In Memoriam Kenneth S. Bowers, 1937-199 6 , AmericanJournal of Clinical Hypnosis 40, no. 3 (1998) 194-205... 

Another meta-analysis of placebo-controlled trials in depression published between 1980 and 2000 showed an increase in the response rates in the placebo arms of trials with a variety of antidepressants (Walsh et al.y 2002). Responses to placebo increased significantly in recent years, as shown by the high positive correlation with the year of publication. The association between response rate and year of publication was more statistically robust for placebo than for active medication. The change in placebo response rate did not appear to be explained directly by changes in study characteristics such as patient age, placebo lead-in or minimum required Hamilton Rating Scale for Depression score. A potential explanation could be the changing awareness of patients and the fact that many patients in recent clinical trials had been exposed to several previous treatments and thus expected to improve (see Box 5.4). 

The high placebo response rate found in children and adolescents with MDD may also be due to the heterogeneous nature of the disorder in this population. Hughes and colleagues (115) found that children and adolescents with major depression plus concomitant conduct or oppositional disorder had a higher response rate to placebo than to imipramine. Nevertheless, an empirical trial of an antidepressant, particularly the safer newer antidepressants, may still be warranted in such patients. 

Of the more recently introduced methods for smoking cessation, bupropion (an antidepressant with dopaminomimetic properties) has recently been introduced. Clinical trial data, in which the nicotine patch, bupropion at 300 mg, and a combination of the two drugs were compared with placebo treatment, have shown cessation of smoking rates of 36% for the patch, 49% for bupropion and 58% for the combined treatments following 7 weeks of treatment. The placebo response rate was 23%. All subjects received relapse prevention therapy. Thus bupropion appears to be a reasonably safe and effective treatment for nicotine dependence. It is however contraindicated in those subject to epilepsy its main side effects are dry mouth and insomnia. 

Current textbooks state that antidepressants are 20% to 40% more effective than placebo, achieving an average 60% response rate compared to placebo response rates of between 20% and 40% Dubovsky, Davies, Dubovsky 2001 Gelder, Mayou, Cowen 2001). The Royal College of Psychiatrists information leaflet states that antidepressants produce substantial improvement in 50-65% of people compared with 25-30% of people given placebo tablets (Royal College of Psychiatrists 2007). 

In a double-blind, placebo-controlled study in 90 patients with sexual dysfunction who were taking a variety of 5HT re-uptake inhibitor antidepressants, sildenafil (50-100 mg) produced improvement in all aspects of the sexual response in 54% of antidepressant-treated patients compared with a placebo response rate of 4.4% (NNT = 2) (6). This suggests that sildenafil is an effective treatment for antidepressant-induced sexual dysfunction. 

A major problem with antidepressants is that placebo response rates tend to be as high as 30-40% in subjects diagnosed with major depression thus, clinical distinctions between active drug and placebo are difficult to prove. 

Wagner etal. (1998) investigated the ethnic differences in antidepressant response to fluoxetine or placebo in 118 depressed, predominantly male, HIVpositive patients (White n = 79, Hispanic n = 17, African American n = 22). Nine Hispanic subjects (53%) dropped out of treatment making the results difficult to interpret. Among completers in the placebo arm, 80% (four out of five) of Hispanic subjects were responders as compared to 36% of African American subjects and 43% of White subjects. 

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