“What is the success rate for antidepressants?” is a question that has been widely debated in recent years. The debate raged on across social media and in countless editorial columns when the results of a 6-years-in-the-making systematic review and meta-analysis assessing the success rate of antidepressants were published in 2018 in The Lancet (Cipriani, et al., 2018). In this Lancet meta-analysis, Cipriani and colleagues evaluated 21 antidepressants and placebo in 522 double-blind randomized controlled trials with 116,477 adults with moderate to severe depression. This exhaustively researched meta-analysis was hailed by some as the final word on the antidepressant controversy.
Psychiatric disorders account for 22·8% of the global burden of diseases. The leading cause of this disability is depression. With an estimated 350 million people affected globally, the economic burden of depressive disorders in the USA alone has been estimated to be more than $210 billion. Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence (Cipriani, et al., 2018).
The Lancet Study Results on the Success Rate of Antidepressants
The Lancet study found that all 21 antidepressants were more likely to produce a treatment response after eight weeks of treatment than a placebo. The most effective antidepressant compared to placebo was the tricyclic antidepressant amitriptyline, which increased the chances of treatment response more than two-fold. The least effective was the serotonin and noradrenaline reuptake inhibitor (SSRI) reboxetine, which increased treatment response by 37%. Drop-out rates by eight weeks of treatment were similar to placebo for the majority of antidepressants. People were 30% more likely to stop taking the tricyclic clomipramine than placebo and slightly less likely to stop taking agomelatine (an “atypical” antidepressant) or the SSRI fluoxetine (National Institute for Health Research, 2018).
More specifically, head-to-head efficacy comparisons of antidepressants disclosed these seven antidepressants as distinctly more effective:
These four antidepressants were found to be somewhat less effective than the other antidepressants:
Concluding Remarks on the Success Rate of Antidepressants
Although seven antidepressants had higher efficacy than the other antidepressants, after factoring in acceptability, three emerged as preferable: agomelatine, escitalopram, and vortioxetine. Three antidepressants had a poor profile of efficacy and acceptability: fluvoxamine, reboxetine, and trazodone. A direct clinical implication is that the three net efficacious antidepressants might be considered the first choice, whereas the three less efficacious antidepressants might be avoided initially. Depression severity or other patient characteristics might also argue for first-line consideration of the remaining so-called superior agents in terms of efficacy—namely, amitriptyline and venlafaxine (Parikh & Kennedy, 2018).
The findings from this network meta-analysis (Cipriani, et al., 2018) represent the most comprehensive currently available evidence base to guide the initial choice about pharmacological treatment for acute major depressive disorder in adults. These results of this Lancet study should serve evidence-based practice and inform patients, carers, physicians, guideline developers, and policymakers on the relative merits of the different antidepressants.
These results must be tempered by the potential limitations of the methodology, the complexity of specific patient populations, and the uncertainties that might result from the choice of dose or treatment setting. The meta-analysis was unable to look at the potentially different effects of treatment on subgroups based on age, sex, the severity of symptoms or duration of illness. The review did not consider combined drug and psychological treatments, as recommended by NICE for moderate to severe depression, or long-term effects which limit its applicability (National Institute for Health Research, 2018).
Cipriani, A. et al., 2018. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. The Lancet, 391(10128), pp. 1357-1366.
National Institute for Health Research, 2018. The most effective antidepressants for adults revealed in major review. [Online]
Available at: https://discover.dc.nihr.ac.uk/content/signal-00580/the-most-effective-antidepressants-for-adults-revealed-in-major-review
[Accessed 11 Sep 2019].
Parikh, S. V. & Kennedy, S. H., 2018. More data, more answers: picking the optimal antidepressant. The Lancet, 391(10128), pp. 1333-1334.