A new study, about to be published in the journal Brain, Behavior, and Immunity, investigates the role a stressful environment plays in antidepressant effectiveness. The results of this study, conducted on mice to examine brain inflammation, indicate that SSRIs such as fluoxetine (Prozac) may only be effective for those who live relatively unstressed lives. Indeed, those with stressful lives may actually find their symptoms worsened by the use of such antidepressant medications.
Since the simplistic serotonin imbalance theory of depression has fallen out of favor, other neurological theories have taken its place in the attempt to find a medical intervention for depression. One current theory involves an immune response in the brain. In previous studies, SSRIs were found to decrease inflammatory responses in the brain, which was theorized to be part of the mechanism of their antidepressant effect.
However, attempts to replicate these studies were inconsistent. Some researchers found pro-inflammatory responses in the brain, while others found anti-inflammatory responses. Because of this, it is unclear whether pro- or anti-inflammatory responses are associated with antidepressant effects.
Given these contradictory results, researchers have hypothesized that the degree of inflammatory response caused by SSRI use is dependent on another factor, the environment. “The increase in serotonin levels induced by SSRIs enhances neural plasticity, rendering individuals more susceptible to environmental conditions,” write the researchers, led by Silvia Alboni at the University of Modena and Reggio Emilia, Modena, Italy.
In this study, researchers attempted to discover whether antidepressant medications were more or less effective due to differences in environmental stress. Mice were exposed to stressful situations for 14 days to induce symptoms theorized to mimic human depressive symptoms. The mice were then separated into a stressful condition, an enriched condition, and a standard condition, and in each condition, half were given the SSRI fluoxetine (trade name Prozac).
The results were striking. The antidepressant appeared to increase susceptibility to environmental effects. The mice placed in enriched conditions experienced the pro-inflammatory effect theorized to be helpful, while the mice were continuing to experience stressful conditions experienced an anti-inflammatory effect, which the researchers hypothesized could be even more damaging than no treatment.
There are significant limitations to this study. For instance, it is unclear whether mice that were stressed using puffs of air, doors that were unpredictable, and being placed in a cage with other mice can be considered an appropriate parallel to human depressive symptoms or stressful human situations. It is also unclear whether this inflammatory effect on a microcellular level relates to any change in a person’s experience of depressive symptoms.
However, these results confirm the growing body of literature that indicates that antidepressant drugs may only be effective for individuals who are living relatively unstressed lives. This finding calls into question the effectiveness of these medications for those who need appropriate treatment most—those who have particularly taxing occupations, who live in poverty, who are homeless, who are facing an abusive partner, or who deal with racism on a daily basis, for instance. Indeed, if antidepressants increase susceptibility to stress, as this study indicates, then these drugs may even be less effective than no treatment for most people with depression.
Alboni, S., Poggini, S., Garofalo, S., Milior, G., El Hajj, H., Lecours, C., . . . Branchi, I. (2016). Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment. Brain Behav. Immun. http://dx.doi.org/10.1016/j.bbi.2016.07.155 (Abstract)