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Therapy and prevention for mental health: What if mental diseases are mostly not brain disorders?
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In the target article Borsboom et al. argue convincingly that mental diseases are (mostly) not brain disorders, but represent highly complex network relations that depend on cultural, historical, and environmental mechanisms. They are highly variable across settings, across individuals, and even for the same individual in different settings, circumstances, and life periods. This narrative has major implications for the treatment and prevention of these conditions. The new narrative explains why focusing on neurobiology (e.g., neurochemistry) to explain mechanisms and to develop effective treatments for mental conditions has achieved limited progress. The failure is so prominent that big pharma has largely abandoned new drug development in this field, despite its huge burden of disease and potential market (Chandler 2013). The largest meta-analyses to date show that for most mental health diseases, available drug treatments result in modest average treatment effects (d = 0.2–0.4) (Cipriani et al. 2018; Huhn et al. 2014; Leucht et al. 2017), with small, incremental benefits over placebo. True treatment effects may be even smaller, if we consider biases (Ioannidis 2008). Some scientists even argue that extremely widely used drugs such as antidepressants are entirely ineffective and cause more harm than good (Gotzsche 2013), although this is probably an extreme position. For example, the recent largest meta-analysis on antidepressants found that almost all antidepressants were better than placebo for moderate/severe major depression, but the summary effect size for efficacy on a continuous scale was d = 0.30. There was also novelty bias: In head-to-head comparison trials, antidepressants seemed to work better when they were first marketed but then seemingly lost in efficacy as they became older (Cipriani et al. 2018). This further erodes the credibility of the estimated treatment effects in placebo-controlled trials, since these trials are mostly performed early in the licensing process when expectations are heightened. Responses to drug and psychological...