Study Finds No Link between Clinical Depression and Low Serotonin Level

An umbrella review of seventeen studies published in Nature found no evidence that depression was associated with lower serotonin concentrations or activity.  The studies’ authors indicated that the serotonin theory of old may have led to an overdependence on anti-depressant drugs as well as years of research based on an outdated theory of depression.  

Results from the review indicated that low serotonin concentrations in individual participants did not cause or were not associated with depression, based on evidence included in the analyses, reviews, and studies explored in the paper. The research and analyses integrated into the umbrella review looked at areas including serotonin and serotonin metabolites, 5-HIAA concentration, serotonin receptor binding, and SERT gene associations. They excluded subtypes of depression like bipolar depression.  

The primary limitations of the overarching review were its inclusion of participants using anti-depressant drugs and the low quality of the component studies. Most of the studies involved were rated as low-quality according to the appraisal tool used for systematic reviews. 

Joanna Moncrieff, MD, is the Professor of Critical and Social Psychiatry at University College London and the review’s lead author. Moncrieff’s work has long focused on the use of antidepressants to treat depression, and her recent study was conceived with an expectation that it would produce results critical of the public understanding of depression. The review has been accessed almost half-a-million times since being published on July 20, 2022. 

Despite its constraints, the review exposes the underdeveloped understanding of the mechanisms of depression and the mechanisms by which antidepressants act to limit symptoms of depression.  

Unfortunately, the rate of depression has grown regardless of the limited understanding of its causes. During the first year of the pandemic, clinicians prescribed 23% of Americans a psychotherapeutic agent or mental health medication used to treat anxiety or depression. The rate of adults in the United States suffering from depression tripled that same year.  

Caring for this growing population of depressed adults is a public health challenge that corporations and the federal government are working on. Grants, including a recent National Institutes of Health study, provide patients with resources to track and understand their mental health conditions. Provider groups are also pushing their digital edge to connect with patients and address mental health gaps. Virtual care for depression, anxiety, and other mental health conditions may be the most accessible route as the population of depressed individuals grows faster than the number of clinicians able to care for them.