A new animal study from Wake Forest Baptist Medical Center suggests Zoloft, a commonly prescribed antidepressant, may alter the brains of depressed people and non-depressed people in different ways. Zoloft (sertraline) significantly increased the volume of one brain region in depressed study subjects but decreased the volume of two brain regions in non-depressed subjects, the results of this government-funded study indicated.

In 1991, the Food and Drug Administration approved Zoloft to treat major depression. In the 20-plus years since then, the drug has won additional FDA approvals for treatment of PTSD (post-traumatic stress disorder), panic, obsessive compulsive disorder, social anxiety, and premenstrual dysphoric disorder, according to a website sponsored by Pfizer, the drug-maker. In practice, doctors commonly prescribe Zoloft and similar drugs to treat bulimia, hot flashes, stroke recovery, and even sexual dysfunction, say the authors of the study. Meanwhile, a recent Columbia University study of prescription drug abuse finds "antidepressants are abused at high doses and via a variety of routes of administration (e.g., intranasal, intravenous)" mostly by people wanting to achieve a psychostimulant-like effect.

Primate Study

Zoloft is classified as a selective serotonin reuptake inhibitor (or SSRI). As described by the Mayo Clinic, most antidepressants work by disrupting the activity of neurotransmitters, natural chemicals found in the brain that are responsible for communication among neurons. SSRIs, unlike other forms of antidepressants, interfere with just one neurotransmitter, serotonin. The natural effects of serotonin include improving mood, creating a satisfied feeling after eating, and, possibly, promoting relaxation and sleep.

The Wake Forest study began with a pre-phase. Here, 42 middle-aged female monkeys were fed a diet formulated to replicate that consumed by many Americans for 18 months. Any show of depressive behavior was recorded during this time. Interestingly, brain scans revealed the depressed monkeys had smaller brain volumes in the dorsal anterior cingulate cortex compared to the non-depressed animals.

This mirrors results from human studies comparing brain scans of depressed and non-depressed people. In humans, the most commonly reported brain structure differences are smaller volumes of the cingulate cortex and hippocampus for depressed compared to non-depressed people, the researchers said.

After the pre-phase, the monkeys were divided into two groups equally balanced for weight, BMI, and depressive behavior. Then, one group received Zoloft in daily doses, while the second group received a placebo over 18 months. At the end of this period, the researchers observed reduced anxiety but not less depressive behavior in monkeys given Zoloft.

In the Zoloft group, brain scans revealed significantly increased volume in the anterior cingulate cortex for depressed monkeys. However, this same region plus the hippocampus, particularly the right anterior hippocampus, had decreased for non-depressed monkeys given Zoloft.

Importantly, both these brain regions are implicated in depression. Yet, Dr. Carol A. Shively, a professor of pathology-comparative medicine and lead author of the study, told Medical Daily that she and her co-authors did not observe depressed behavior among these monkeys.

In the placebo group, depressed monkeys had smaller right anterior hippocampus and left anterior cingulate cortex than nondepressed monkeys.

“Given the number of different disorders for which SSRIs are prescribed, the findings need to be investigated further in patient populations to see if these drugs produce similar effects in humans,” Shively said in a press release. One in every four women in their 40s and 50s takes an antidepressant. Overall, one in every 10 Americans takes these drugs.

Source: Willard SL, Uberseder B, Clark A, et al. Long term sertraline effects on neural structures in depressed and nondepressed adult female nonhuman primates. Neuropharmacology. 2015.