Is the antidepressive effect of second-generation antidepressants a myth?

Abstract

Two recent meta-analyses on second-generation antidepressants versus placebo in mild to moderate forms of major depression, based on data on all randomized clinical trials using the Hamilton Depression Scale (HAMD) submitted to FDA, have shown an effect size of y0.30 in favour of antidepressants in the acute therapy of major depression. The clinical significance of an effect size at this level was found to be so poor that these meta-analyses have subscribed to the myth of an exclusively placebo-like effect of second-generation antidepressants. A re-allocation of HAMD items focusing on those items measuring severity of clinical depression, the HAMD 6 , has identified effect sizes of o0.40 for second-generation antidepressants in placebo-controlled trials for which even a dose-response relationship can be demonstrated. In the relapse-prevention phase during continuation therapy of patients with major depression, the advantage of second-generation antidepressants over placebo was as significant as in the acute therapy phase. To explore a myth is not to deny the facts but rather to re-allocate them.

A Systematic Review of the Clinimetric Properties of the 6-Item Version of the Hamilton Depression Rating Scale (HAM-D₆)

“…Table 4). These findings are likely to reflect a combination of the following: (i) HAM-D 6 captures the core symptoms of depression more specifically and is unbiased than the HAM-D 17 (which also taps into the side effects of many psychopharmacological agents, that is, nausea, sexual dysfunction, unintended weight gain, and sexual dysfunction) [47], (ii) HAM-D 6 is likely to be associated with lower placebo response rates than HAM-D 17 [68], (iii) many antidepressant therapies are more clinically effective than previously thought (and indicated by the HAM-D 17 ) [69]. …”

Struggle for Subtypes in Primary and Secondary Depression and Their Mode-Specific Treatment or Healing

“…A review of the first controlled clinical trials in outpatients with major depression using zimeldine against amitriptyline demonstrated that amitriptyline was superior on non-core depressive symptoms, such as the sleep factor of the HAM-D, while no difference between the two drugs was seen concerning the HAM-D core symptoms of depression, such as depressed mood, guilt, work and interests, psychic anxiety, psychomotor retardation, and general somatic symptoms [42]. When evaluating the specific antidepressive effect, therefore, these core items (HAM-D 6 ) are to be used as the outcome measure and when using this scale the effect size is 0.40 or higher when SSRIs are compared to placebo [43]. …”

Placebo, Prozac and PLoS: significant lessons for psychopharmacology

“…A number of other commentators, e.g. (Bech, 2009;Broich, 2009;Hegerl and Mergl, 2010;Khan and Khan, 2008;Mathew and Charney, 2009;McAllisterWilliams, 2008a;Moller, 2008;Nutt and Malizia, 2008;Parker, 2009;Turner and Rosenthal, 2008) have also criticized the Kirsch et al (2008) paper. The main arguments advanced by one or more of these commentators include:…”