Efficacy of SSRIs for Depression

By Dr Ananya Mandal, MD

There is controversy regarding exactly how effective selective serotonin reuptake inhibitors (SSRIs) are in the treatment of clinical depression. Some reviews of clinical trial data have suggested that SSRIs do not show significant clinical effects.

In one analysis of data submitted to the US Food and Drug Administration covering the period 1987 to 1999, 80% of the treatment response to the six most common SSRIs was also seen in patients who were given placebo.4

A meta-analysis of studies into SSRIs in 2010 showed the therapy had small, nonsignificant benefits over placebo in mild and moderate depression but clinically significant benefits over placebo in severe clinical depression.

Currently, SSRIs are mainly used as first-line medications in the treatment of moderate-to-severe depression and the treatment has shown significant clinical benefits, especially if it is combined with a talking therapy such as cognitive behavioral therapy.

SSRIs are not commonly recommended for treating mild depression, with the exception of mild depression that has lasted for over two years or in cases where a patient has experienced episodes of moderate or severe depression in the past.

Other uses of SSRIs include the treatment of mental health conditions such as anxiety disorder, obsessive compulsive disorder, panic disorder, some phobias such as agoraphobia (fear of open spaces) and social phobia, eating disorders such as bulimia, and post traumatic stress disorder.

These agents have shown benefits in each of these mental health conditions, especially in severe cases. Treatment with SSRIs, however, is often supplemented with other treatment modalities such as psychotherapy and cognitive behavioral therapy.

Five of the main SSRIs used today (fluoxetine, sertraline, paroxetine, fluvoxamine and citalopram) are generally considered to be equally effective. Fifteen of 18 head-to-head studies showed equal effectiveness among the five agents.7 Of the other three studies, one that looked at 106 geriatric patients showed that paroxetine (20-40 mg/day) was superior to fluoxetine (20-60 mg/day), with more participants responding to paroxetine and showing improved scores on both depression and cognitive scales by week 3.

Of the other two studies, one showed in an intent-to-treat analysis that sertraline was superior to paroxetine but completer analysis showed no real difference between the two agents, possibly because so many participants (41%) from the paroxetine group dropped out of the study due to side effects.7 In the last study, paroxetine showed improved effects over fluoxetine in geriatric patients but the proportion of responders in both groups was low, at 38% and 17% , respectively7.

Further Reading

Last Updated: Jun 10, 2023

Dr. Ananya Mandal

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.


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