Sertraline, an antidepressant that doctors commonly prescribe, appears to work by reducing anxiety first and doesn’t start tackling depressive symptoms until weeks later.

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New research sheds fresh light on how antidepressants work.

This was the main finding of a study on the use of antidepressants in primary care settings in the United Kingdom.

The researchers suggest that sertraline is effective, although the method is unexpected, for those who are likely to receive a prescription for antidepressants in primary care.

Sertraline is a selective serotonin reuptake inhibitor (SSRI). It works by increasing brain levels of the “happy chemical” serotonin.

Symptoms of depression include the inability to feel pleasure, low mood, and poor concentration.

The study reveals that sertraline appears to have no effect on these symptoms within 6 weeks, but shows a weak effect by 12 weeks.

While impact on depressive symptoms appears to be absent, the researchers did observe reductions in anxiety together with improvements in quality of life and self-measured mental health within 6 weeks.

A recent paper on the study, which took the form of a placebo-controlled trial, features in The Lancet Psychiatry journal.

“It appears that people taking the drug are feeling less anxious, so they feel better overall, even if their depressive symptoms were less affected,” says lead study author Gemma Lewis Ph.D., who is a lecturer and researcher in psychiatry at University College London, in the U.K.

In the United States, as in the U.K., antidepressants are among the most common prescription drugs, and their use has risen substantially since the turn of the century.

Antidepressant use in the U.S. rose by nearly 65% in the 15 years leading up to 2014, according to the Centers for Disease Control and Prevention (CDC).

During 1999-2002, 7.7% of people over the age of 12 years had used an antidepressant in the past month. This figure rose to 12.7% during 2011-2014.

Doctors prescribe antidepressants not only for depression but also for other conditions, such as anxiety.

Altogether, the researchers enrolled 653 people aged 18-74 years who had experienced mild to severe depressive symptoms during the past 2 years.

The recruitment took place at 179 general practitioner (GP) centers in four cities in England, U.K.

The researchers point out that in all cases, neither the GPs nor their patients were sure whether antidepressants would be of benefit.

They saw no evidence that taking sertraline was more likely to cause side effects than taking a placebo.

Most previous trials of antidepressants have taken place in specialized mental health settings and have not included people with undiagnosed or mild symptoms of depression.

Many of these previous trials were completed decades ago when antidepressants use was more limited, and the purpose of the trials was to gain regulatory approval.

The team suggests that the participants of the new study better represent the people who are receiving antidepressant prescriptions today.

“Our findings,” write the authors, “support the prescription of SSRI antidepressants in a wider group of participants than previously thought, including those with mild to moderate symptoms who do not meet diagnostic criteria for depression or generalized anxiety disorder.”

Comments from experts who were not involved in the research have been generally supportive.

Guy Goodwin, a professor of psychiatry at the University of Oxford in the U.K., praises the researchers for “providing light rather than heat” to a controversial debate about “the increased use of antidepressants in general practice.”

Like the authors, Goodwin also recommends that further studies take place to examine the longer value of antidepressant treatment and the difficulties of withdrawal.

Dr. Paul Keedwell, a consultant psychiatrist at Cardiff University in the U.K., suggests that the lack of reduction in depressive symptoms could be due to insufficient numbers of severely depressed individuals in the sample.

“Further research is needed,” he adds, “in this important primary care population, with individuals grouped according to severity, and a more flexible dosing regimen.”

The researchers believe that the study is the largest antidepressant trial to date that has not received funding from the pharmaceutical industry.

We hope that we have cast new light on how antidepressants work, as they may be primarily affecting anxiety symptoms, such as nervousness, worry, and tension, and taking longer to affect depressive symptoms.”

Gemma Lewis Ph.D