What New Study Findings Tell Us About Serotonin, Depression and SSRIs: A Chief Psychiatrist’s Take

by Vidya Krishnan, MD, Chief Psychiatrist and Medical Director, Catherine T. Harvey Center for Clinical Services, CHC

Approximately 280 million people around the globe have depression, according to a report from the World Health Organization. The personal, familial, and societal effects of this condition are profound. Especially considering that depression, at its worst, can lead to suicide. Suicide is the 2nd leading cause of death among 15-29-year-olds. The causes and treatment of depression have been the subject of serious scholarly work over many decades. Despite all the efforts of researchers, there is still much we need to learn.

Our current focus are the implications of a systematic umbrella review of the Serotonin Theory of Depression published in Molecular Psychiatry in July of this year. The study concluded that there is no convincing evidence that depression is caused by or associated with lower serotonin concentration or activity. This brings up two important questions for all of us:

1. If low serotonin levels do not cause depression, what does?
2. Why, then, do we use SSRIs (Selective Serotonin Reuptake Inhibitors) in the treatment of depression?

While it is simpler to refer to depression as a chemical imbalance, serotonin deficiency or low-serotonin state, it has long been acknowledged that depression is neither a single illness nor has just one chemical cause. Depression is, in fact, a short-hand term that refers to a heterogeneous group of conditions with a complex web of causes including genetics, biology (sleep, nutrition, hormones, immune, inflammatory), personal (trauma, loss, stress), social (poverty, racism), and environmental (school, work) with a wide variety of neurochemical and brain circuitry changes.

Therefore, while the recent study clarifies the long held misconception about the monoamine theory of depression, it does not offer any new explanations. Research into alternative theories of why depression happens and newer treatment options have been ongoing for some time now. And while we do not have all the answers yet, we are certainly moving towards greater understanding of this complex condition.

The role of serotonin in the causation of depression is separate from the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). The use of medication treatments that affect serotonin levels predates the hypothesis that depression was caused by a serotonin deficiency. While SSRIs in the short-term alter the balance of serotonin concentrations inside and outside the neuron, the antidepressant benefits are likely due to complex changes in brain cell functioning. The FDA’s approval of SSRIs to treat depression was due to their demonstrated clinical and functional benefit in improving symptoms and not the medications’ effect on serotonin levels.

In conclusion, depression is a complex and debilitating condition that has far reaching implications. Despite the fact that serotonin deficiency is not the sole cause of depression, it does not diminish the value of SSRI/antidepressant medication as one of many treatment options for managing depression. After all, we use anti-fever medication to help someone feel better even If we do not know the cause of the fever. It is important that we are careful not to have knee-jerk reactions to this study and abruptly discontinue ongoing and effective treatment without the consultation or supervision of a trained professional.

A combined treatment approach including talk therapy, nutritional support, sleep hygiene, regular physical activity, medical oversight, stress management, addressing trauma, and other social or environmental factors in addition to antidepressant medication is still the best evidence-based option.

Whether you know exactly what’s going on with your child and are ready to get help, or you just know something’s not right and are looking for answers, CHC’s Catherine T. Harvey Center for Clinical Services is here for you and your family. Care Coordinators can arrange a free 30-minute Care Consultation so you can explore options with an expert. Call or email us at 650.688.3625 or careteam@chconline.org to set up an initial Consultation appointment.