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Weight gain was tied to use of antidepressants, a long-term study in Britain found.

Men and women prescribed antidepressants were more likely to experience a 5% or greater weight gain compared to people not taking antidepressants (adjusted rate ratio 1.21, 95% CI 1.19-1.22, P<0.001), reported Rafael Gafoor, PhD, of the School of Population Health and Environmental Sciences at King's College London, and colleagues.

This elevated risk for weight gain was maintained over six years of antidepressant prescribing, they wrote in .

Moreover, use of antidepressants was also tied to a graduation in weight class:

• Normal weight to overweight: adjusted RR 1.29 (95% CI 1.25-1.34)
• Overweight to obesity: adjusted RR 1.29 (95% CI 1.25-1.33)

"The risk of weight gain was substantially increased during the second and third years of treatment," Gafoor's group wrote, highlighting that the risk of 5% or greater weight gain was 46% higher during the second year of treatment compared to those not on antidepressants.

Less than one year of antidepressant use, however, was not tied to weight gain.

"This level of risk might look modest, but the effect at population level could be substantial," commented Alessandro Serretti, MD, PhD, and Stefano Porcelli, MD, of the University of Bologna in Italy, in an . "If roughly 13% of the U.K. population take an antidepressant, many thousands of people will gain weight each year because of their treatment."

In praising Gafoor's group for their study, the editorialists agreed with the recommendation that providers provide lifestyle and weight management advice to patients on these agents and to utilize these findings when selecting patients' antidepressant prescriptions.

"Currently, we are still unable to identify patients at higher risk of weight gain with antidepressants. Hopefully it will be possible in the not too distant future to identify a genetic predisposition and recognise those at higher risk before treatment is started," Serretti and Porcelli wrote.

The population-based study drew on the U.K. Clinical Practice Research Datalink, using a sample of 136,762 men and 157,957 women who had at least three recordings of body mass index in their primary care electronic health records. Of this group, 17,803 (13.0%) men and 35 307 (22.4%) women were prescribed antidepressants in 2004.

Use of antidepressants was more common among patients with comorbidities, including stroke and diabetes, as well as co-prescriptions, including antiepileptics and antipsychotics.

Antidepressant use was initially classified into type for the analysis, which included tricyclic and related antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin/noradrenaline reuptake inhibitors, and other antidepressant drugs. The authors further analyzed use according to specific drugs, including mirtazapine, duloxetine, sertraline, venlafaxine, citalopram, fluoxetine, escitalopram, trazodone, amitriptyline, paroxetine, nortriptyline, and dosulepin (also known as dothiepin).

Among the individual drugs assessed, mirtazapine was tied to the highest risk of weight gain (aRR 1.50, 95% CI 1.45-1.56). Other antidepressants that were tied to the highest associated risks for weight gain compared to other antidepressants included duloxetine (1.23, 95% CI 1.15-1.31), escitalopram (1.23, 95% CI 1.17-1.29), and citalopram (1.26, 95% CI 1.23-1.28).

In general, the researchers found that older generation drugs, such as monoamine oxidase inhibitors and tricyclic antidepressants, tended to be associated with a higher risk for weight gain versus newer drug classes, like SSRIs.