Common SSRI antidepressant may not be effective for depressive symptoms

One of the most commonly prescribed antidepressants of the selective serotonin reuptake inhibitor (SSRI) class, known generically as sertraline, may not be as clinically effective at reducing depressive symptoms as previously thought, a new study found.

The findings, researchers say, were accomplished without direct funding from pharmaceutical companies. The results were available in The Lancet Psychiatry.

Sertraline, often referred to by its trade name Zoloft, is used for alleviating symptoms associated with depressive and anxiety disorders. Theoretically, the drug’s mechanism of action involves the inhibition of the reuptake of the neurotransmitter serotonin at the pre-synaptic nerve ending, subsequently resulting in improved mood and sleep.

The study, carried out by researchers at the University College London, involved the testing of 653 adult participants. Ranging from 18 to 74 years of age, all the participants included reported persistent complaints of depression in different severity over a span of two years.

For treatment, nearly half of the participants received the SSRI sertraline and the other half placebo. As a dosage, researchers administered both sets of treatments via oral administration, once a day, for one week — then twice a day, for up to 11 weeks.

As the results indicate, sertraline was found not to be as clinically significant in reducing the severity of depressive symptoms as previously thought, including during its peak timespan for full therapeutic effect at 12 weeks. Moreover, a few instances of adverse reactions were referenced in the findings, however, one such instance may not have been linked to the study.

“We found no evidence that sertraline led to a clinically meaningful reduction in depressive symptoms at 6 weeks,” the study’s co-authors wrote, as attributed in the findings. “The mean 6-week PHQ-9 score was 7·98 (SD 5·63) in the sertraline group and 8·76 (5·86) in the placebo group (adjusted proportional difference 0·95, 95% CI 0·85–1·07; p=0·41).”

Upon assessing its clinical efficiency with anxiety, the findings recognized the drug’s purported effectiveness in alleviating such symptoms, supporting prior studies. “For secondary outcomes, we found evidence that sertraline led to reduced anxiety symptoms, better mental (but not physical) health-related quality of life, and self-reported improvements in mental health,” according to the findings.

With depression affecting over 300 million worldwide, according to a 2018 World Health Organization report, the study presents a different comprehensive standpoint of SSRI efficiency towards patients with depressive complaints, contradictory to existing studies on the subject.

Although our understanding of SSRIs is still obscure, future research may reduce clinical uncertainty as to how and why these set of pharmaceutical treatments reach their intended therapeutic effectiveness.

“SSRIs are among the most commonly prescribed medications in the world and yet we still have an imperfect knowledge of their clinical effectiveness and indications for their use. Investigation of pharmacological treatments after regulatory approval is needed.”