“In her book Chemically Imbalanced, Joanna Moncrieff, Professor of Critical and Social Psychiatry at University College London, synthesizes three key questions around the use of SSRIs [selective serotonin reuptake inhibitors]. First, on effectiveness, Moncrieff references a 2002 meta-analysis, which concluded that compared with placebo their effects were clinically negligible. However, other studies have shown effectiveness, including a 2018 meta-analysis in The Lancet, which concluded that all antidepressants are more efficacious than placebo in adults with a diagnosis of major depressive disorder, with odds ratios ranging between 2·23 and 1·37.
Second, Moncrieff reviews the so-called serotonin hypothesis of depression. In 1975, Wong and colleagues reported that fluoxetine increased levels of serotonin in rat brains by blocking reuptake in the synapse. However, Moncrieff argues, indubitable evidence for the idea that low concentrations or reduced activity of serotonin in the brain is the problem remains elusive. Some psychiatrists have argued that delineating a clear mechanism of action is unimportant as long as the treatment is effective. Exploration of the pathophysiology of depression, however, will continue to generate lively scientific exchanges.
Third, Moncrieff comments on the “creeping medicalisation of a widening array of life problems”. Certainly, there has been a growing tendency to medicalise misery or unhappiness, along with other aspects of the human condition, including worry, bad behaviour, and grief. A longitudinal study in New Zealand reported that 35% of people aged 11–15 years met the criteria for a mental disorder, rising to 44% at age 45 years; does this finding represent a true escalation in mental ill health, or is it a reflection of changing criteria of what qualifies as disease?
Additionally, the need for a quick fix is undoubtedly contributing to over-prescription and inappropriate use of medications. The latest NICE guidelines recommend that antidepressants should not be routinely offered as a first-line treatment for less severe depression, unless that is a person’s preference—guided self-help should be the first treatment option. First-line treatments for more severe depression should be individual cognitive therapy combined with an antidepressant. However, provision of and access to non-pharmaceutical psychiatric services is patchy for many people and non-existent for others, funding is lacking, and many general practitioners are pressed for time and short on options. A pill, the reasoning goes, might be better than nothing. But the result is that for too many patients antidepressants are used readily, while there is little attempt to examine and address underlying psychosocial stressors. An analysis in The Lancet Psychiatry estimates that just 9·1% of women and 7·2% of men worldwide with a diagnosis of major depressive disorder receive minimally adequate treatment (which they define as either pharmacotherapy or psychotherapy). The result is a huge unmet medical need.”
Full editorial, The Lancet, 2025.5.10