Common Antidepressants May Work in Unexpected Way

Many people who take the antidepressant Zoloft report feeling better. But new research suggests the drug may be treating their anxiety, rather than their depression, at least in the early weeks.

Zoloft (sertraline) -- and the family of similar drugs it belongs to -- may actually take months to ease classic symptoms of depression, U.K. researchers found.

That doesn't mean the drugs aren't making patients feel better relatively soon, however. That's because Zoloft appears to have a much speedier effect on anxiety. Within six weeks the drug notably cut down on feelings of nervousness, worry and tension, said study senior author Glyn Lewis, a professor of epidemiological psychiatry at University College London.

Zoloft is in a group of commonly prescribed antidepressants known as selective serotonin reuptake inhibitors, or SSRIs. Although the study focused only on Zoloft, Lewis and his team "think that results for other SSRI antidepressants, including Prozac, are likely to be very similar." Celexa, Paxil and Lexapro are other common SSRIs.

The study was conducted between 2015 and 2017. It involved 653 patients cared for at primary care facilities across four British cities. Half were assigned to receive Zoloft for 12 weeks and half got a placebo pill.

Patients completed depression symptom questionnaires at two weeks, six weeks and 12 weeks. General anxiety screenings were also conducted.

Symptoms of depression typically include poor concentration, low mood, difficulty sleeping, and an inability to enjoy life, Lewis explained.

"At six weeks there was only a 5% reduction in depressive symptoms," he said, "and this was not significant. In other words, this could have been just a chance result.

"In contrast, there was a 21% reduction in anxiety symptoms at six weeks, and a 24% reduction by 12 weeks," said Lewis.

By the end of the trial, there were indications that Zoloft had become more effective at cutting down symptoms of depression, but evidence of that impact was deemed "weak," according to the researchers.

However, Lewis and his associates made the point that most patients who struggle with depression also struggle with anxiety.

And the study found that patients on Zoloft did realize significant quality-of-life improvements.

Patients who took Zoloft "were twice as likely to report feeling better overall than those on placebo," said Lewis. Plus, they did not experience any serious side effects.

Study participants were between 18 and 74 years old. For varying periods of time, more than half had struggled with clinical depression, while just under half had been diagnosed with generalized anxiety. Nearly a third suffered from both, while 15% had a distinct disorder that involved elements of both, according to the study.

Zoloft "benefited a wider group of people than previously believed, including those with mild to moderate depressive symptoms," Lewis said. These were people who may not warrant a full-blown depression or anxiety diagnosis.

The study authors said physicians should not hesitate to prescribe Zoloft and other SSRIs for the treatment of depression, since so many report feeling better.

But how is it that researchers are only now coming to understand the true measure of a medication that's been prescribed to millions since its introduction in 1992?

The answer is that times have changed, and so have the types of patients who take antidepressants, investigators said. Most SSRI studies are decades old, they noted, and conducted when antidepressants were mostly prescribed by specialists for patients battling severe forms of depression.

By contrast, SSRIs today are typically prescribed by a much larger group of general practitioners addressing the needs of a far wider group of patients, many of whom struggle with relatively mild depression.

Turhan Canli is an associate professor psychology at State University of New York at Stony Brook. He suggested that Lewis' investigation offers an "impressive" corrective window into how SSRIs really work.

The upshot, he said, is that popular antidepressants may not be "all that effective in the treatment of depression."

"On the other hand," said Canli, "the finding that the drug reduced anxiety symptoms and improved quality-of-life measures suggests that patients -- particularly those who experience symptoms of worry or restlessness -- may still benefit, albeit in ways different than expected."

The study was published Sept. 19 online in The Lancet Psychiatry.

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