The Environment Matters When It Comes To Antidepressant Response



by David Mintz, MD

David Mintz, MD, Team Leader/Staff Psychiatrist at the Austen Riggs Center.Though the theory of “chemical imbalance” has long been discredited within psychiatry and among the educated public, it continues to be a story that is told over and over to explain to depressed patients why they should take an antidepressant. Part of the problem is that there is not really a better story to tell. Despite significant advances in the basic neurosciences over the last several decades, we still do not know how antidepressants actually work. New research presented at the European College of Neuropsychopharmacology offers some intriguing clues about how antidepressants might work, and also why they work for some people and not others.

Silvia Poggini, of the Istituto Superiore di Sanità in Rome, Italy, led a team of researchers who tested the effects of SSRIs in different environments. Their research revealed an interesting interaction between antidepressants and the environment. They stressed mice to induce a depression-like state. The mice were then administered antidepressant medications. Some of the mice remained in a stressful environment, while others were placed in an enriched environment. The mice who were placed in an enriched environment showed significant reductions on depressive symptoms and neurochemical markers of depression. The mice who remained in stressful environments not only did not improve, but showed increasing signs of depression. The research suggests that antidepressants may operate by increasing neural plasticity and increasing the possibility of learning. In other words, mice on antidepressants learned more quickly, but those in enriched environments learned to be less stressed, while those in stressful environments learned to be more stressed.

This finding is consistent with other studies suggesting that antidepressants may enhance neuroplasticity and learning, including the 2005 study by Castrén suggesting that antidepressants increase plasticity and connectivity of neural networks through increased neuronal turnover and increasing connections between neurons.

These findings, if borne out by future research, dovetail with and help explain a number of other interesting observations. For one, they may help explain why antidepressants work for some people and don’t work for others. It may be that people in stressful or unsupportive environments are less able to reap potential benefits from antidepressants because those medications only solidify depressive expectations. It may also help explain why depressed patients who receive concurrent medications and psychotherapy have better outcomes than patients with either treatment alone (2006, Mintz). Patients in psychotherapy may be considered to be in enriched environments that help patients develop less depressed expectations. Antidepressants may work, in part, by facilitating this new learning. 

While much is still not understood, one thing seems to be increasingly clear: a disservice is done to depressed patients when their illness and its treatment is seen purely through the lens of disordered biology. Aiming treatment only at a “chemical imbalance” not only ignores half of the patient and half of the potential tools for treating depression, but it also may help patients on antidepressants to learn a passive stance towards their illness while they wait for the doctor’s ministrations to cure them. The most effective treatments do not assign all of the healing potential to the doctor, but instead challenge the patient to learn and to effectively address problems in the patient’s environment.


Castrén, E. “Is Mood Chemistry?,” Nature Reviews: Neuroscience, 6, no. 3 (2005): 241-246. doi: 10.1038/nrn1629. 

Mintz, D. “Combining Drug Therapy and Psychotherapy for Depression.Psychiatric Times, 23, no. 11 (2006): 18-21. 


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