Comparative Benefits and Harms of Second-Generation Antidepressants for Treating Major Depressive Disorder

Abstract

Agency for Healthcare Research and Quality.

Randomized, Placebo-Controlled Trials of Antidepressants for Acute Major Depression: Thirty-Year Meta-Analytic Review

“…The present findings are congruent with reviews discussed above indicating that antidepressant drug-vs-placebo differences in published reports of controlled trials are generally moderate (Baldessarini, 2005;Gartlehner et al, 2008;Kirsch et al, 2008;Tsapakis et al, 2008;Bridge et al, 2009;Wooley et al, 2009;Masi et al, 2010;Pigott et al, 2010;Khin et al, 2011). This conclusion was reached in the previous literature despite typical reliance on initial improvement on scale ratings rather than less readily achieved clinical remission, and despite growing evidence of publication bias toward underreporting of studies without significant drugplacebo differences (Ioannidis, 2008;Turner et al, 2008).…”

“…It is evidently widely held that differences in efficacy among specific drugs or types of antidepressants in the treatment of acute episodes of major depressive disorder are generally minor (Healy, 1997;Baldessarini, 2005Baldessarini, , 2012Cipriani et al, 2007;Gartlehner et al, 2008;Ghaemi, 2008;Pigott et al, 2010;Khin et al, 2011). The present findings support the conclusion that pooling of data from placebocontrolled trials does not yield clear rankings of specific drugs or drug-types by apparent efficacy (Figure 1).…”

“…The superiority of most clinically employed antidepressants over placebos in controlled trials has been modest in adult patients diagnosed with major depression, even lower in juvenile depressed patients, and probably has declined in recent years (Walsh et al, 2002;Baldessarini, 2005;Cipriani et al, 2007;Papakostas et al, 2007;Gartlehner et al, 2008;Kirsch et al, 2008;Tsapakis et al, 2008;Bridge et al, 2009;Wooley et al, 2009;Masi et al, 2010;Pigott et al, 2010;Khin et al, 2011). Evident decline in superiority of drugs over placebos has occurred despite evidence of selective reporting of positive findings of potential commercial interest from therapeutic trials (Ioannidis, 2008;Turner et al, 2008).…”

“…Moreover, there is little evidence that one antidepressant or pharmacological class of antidepressants is clearly and convincingly more effective than others (Anderson, 2001;Baldessarini, 2005Baldessarini, , 2012Cipriani et al, 2007;Papakostas et al, 2007;Gartlehner et al, 2008;Kirsch et al, 2008;Khin et al, 2011). In part, this lack of clear differentiation may arise from the modest drug-placebo differences in many controlled trials of antidepressants, which, in turn, may reflect broad clinical heterogeneity arising from the current broad concept of 'major depression' (Healy, 1997;Ghaemi, 2008).…”

Molecular, Functional, and Structural Imaging of Major Depressive Disorder

“…MDD is associated with numerous negative consequences, including health and social issues, among which suicide is the most devastating consequence attempted by as many as 8% of severe MDD patients [4]. Strikingly, only *50% of MDD patients respond to standard-of-care antidepressants [5], with *70% failing to achieve complete remission [6]. Thus, it is necessary to understand the potential mechanisms in order to explore more effective diagnostic and therapeutic strategies for MDD.…”