Is it time to scrap the serotonin hypothesis to explain depression?

In the midst of the current crisis in mental health, new evidence from UCL challenges the way we think about depression.

Photo Courtesy: Somnus Therapy

For over six decades the serotonin hypothesis has dominated both public and clinical understandings of major depressive disorder (MDD), pinning the cause of the disorder to a biochemical imbalance in the brain and making antidepressants the most common treatment for it across the Western world. New research published by University College London, however, could be challenging this hypothesis and changing the trajectory of mental health research going forwards. 

Popularised in the 1960s, the ‘serotonin hypothesis’ evolved off the back of research on hypertension, in which it was found that patients receiving the drug reserpine to help treat high blood pressure, also began to show depressive symptoms. It was later found that reserpine not only alleviated hypertension but depleted levels of the neurotransmitter serotonin (5HT), popularly referred to as the ‘happiness hormone’, in the brain. The research, though now disputed, provoked the advent of the biochemical explanation for depression and led to the development of the first biochemical treatment for the disorder. Indeed, by the 1990s, selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed class of antidepressant to this day, had been approved for public use, changing the worldview on depression entirely. 

Fast-forward to the present, the meta-analysis led by UCL professor of psychiatry Joanna Moncrieff, is one in a string of reports highlighting that the serotonin hypothesis may lack satisfactory evidence to explain the causes of the disorder and support the use of antidepressants in its treatment. The comprehensive review, the largest of its kind, assembled all relevant research on the link between serotonin and depression. Based on the available evidence, the analysis found no significant association between reduced serotonin activity in people with depression compared to people without. No significant gene variations were found between the two populations in relation to serotonin production or function. And no depressive symptoms were observed in participants whose levels of serotonin had been artificially reduced. 

For the NHS and healthcare providers globally, the research anticipates a need for alternative first-line approaches to treating MDD, potentially moving away from a biochemical approach. Up to 80% of the public and many GPs believe depression to be caused by a chemical imbalance in the brain. The paradigm has become a benchmark for mental health provision globally, leading to an overprescription of antidepressants worldwide and a negative understanding amongst patients that it’s not possible to treat depression with other psychiatric methods. Often more expensive and time-consuming therapies like psychotherapy, Cognitive Behavioural Therapy (CBT) and mindfulness have all shown promising results. Encouraging further research in these areas but pointing to an already growing need to reduce wait times and increase funding for mental health within the British healthcare system.

Importantly, whilst the landscape of mental health research may be changing, it remains crucial to those who are struggling with mental health to still seek professional help. This review may be among the first to challenge existing ideas around the causes of depression; ongoing research in this field is therefore key to aiding our understanding of the disorder and helping to develop new and improved methods of treatment.