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Background The average treatment effect of antidepressants in major depression was found to be about 2 points on the 17-item Hamilton Depression Rating Scale, which lies below clinical relevance. Here, we searched for evidence of a relevant treatment effect heterogeneity that could justify the usage of antidepressants despite their low average treatment effect. Methods Bayesian meta-analysis of 169 randomized, controlled trials including 58,687 patients. We considered the effect sizes log variability ratio (lnVR) and log coefficient of variation ratio (lnCVR) to analyze the difference in variability of active and placebo response. We used Bayesian random-effects meta-analyses (REMA) for lnVR and lnCVR and fitted a random-effects meta-regression (REMR) model to estimate the treatment effect variability between antidepressants and placebo. Results The variability ratio was found to be very close to 1 in the best fitting models (REMR: 95% highest density interval (HDI) [0.98, 1.02], REMA: 95% HDI [1.00, 1.02]). The between-study standard deviation τ under the REMA with respect to lnVR was found to be low (95% HDI [0.00, 0.02]). Simulations showed that a large treatment effect heterogeneity is only compatible with the data if a strong correlation between placebo response and individual treatment effect is assumed. Conclusions The published data from RCTs on antidepressants for the treatment of major depression is compatible with a near-constant treatment effect. Although it is impossible to rule out a substantial treatment effect heterogeneity, its existence seems rather unlikely. Since the average treatment effect of antidepressants falls short of clinical relevance, the current prescribing practice should be re-evaluated.

Lithium has been the treatment of choice for patients with bipolar disorder (BD) for nearly 70 years. It is recommended by all relevant guidelines as a first-line treatment for maintenance therapy. In this review, we outline the current state of evidence for lithium in the treatment of BD over the lifespan. First, we summarize the evidence on efficacy in general, from relapse prevention to acute anti-manic treatment and its role in treating mood episodes with mixed features and bipolar depression. As patients are often treated for many years and different aspects have to be considered in different phases of life, we discuss the particularities of lithium in the treatment of paediatric BD, in older aged individuals and in pregnant women. Lastly, we discuss the evidence on lithium's proposed suicide-preventive effects, the dangers of rapid discontinuation and lithium's adverse effects, particularly with regard to long-term treatment.

Practitioners and researchers alike assume that there is individual variability in the effects of treatments for mental disorders. However, for psychotherapy, up to now this assumption has never been empirically tested. Using a large database of randomized-controlled trials on psychotherapy of depression in adults (306 trials including a total of 51,853 patients), we performed a Bayesian variance ratio metaregression. For the entire sample, we found a 9% higher variance in the intervention groups compared with the control groups. Depending on the depression scale used, this corresponds to a standard deviation of the individual treatment effect of 3 to 4 points. Subgroup analyses revealed that the effect variability of some types of therapy is larger than others. Our results are the first to indicate that patients do benefit differently from psychotherapy. We conclude that there is a sound basis for the paradigm of personalized psychotherapy, which brings about implications for both research and clinical practice. Public Health Significance StatementIn recent years, studies with high methodological quality have pointed out that the efficacy of psychotherapy in the treatment of depression is less satisfactory than previous research suggested. To optimize psychotherapy for non-responders, the paradigm of personalized therapy is coming into the research focus. In this study, we show for the first time that the effects of psychological interventions vary more than those of control conditions. This shows that differential response to treatments is inherent to intervention effects. Thus, it could indeed be beneficial to better tailor psychotherapy to individual patients. In practice, session-by-session outcome monitoring should be used to detect non-responding cases in ongoing treatments. Statistical methods guiding the selection of treatment components capitalize on the heterogeneity of treatment effects and are thus likely to improve outcomes. These findings pave the way for broad research and implementation of approaches that support personalization (e.g., monitoring and feedback systems) as well as a new shaping of training beyond the traditional schools of thought in psychotherapy.