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Antidepressant use may contribute to long-term increased risk of weight gain

Stephen Padilla
01 Jun 2018

Long-term use of antidepressants, particularly during the second and third years of treatment, may lead to increases in body weight, a recent study has found.

“During the second year of treatment, the risk of ≥5-percent weight gain is 46.3 percent higher than in a general population comparison group,” the authors said. “The increasingly widespread use of antidepressants is of concern in the context of the increasing prevalence of obesity.

A total of 17,803 (13.0 percent) men and 35,307 (22.4 percent) women (mean age 51.5 years) received antidepressant prescriptions at baseline.

The incidence of new episodes of ≥5-percent weight gain during 1,836,452 person-years of follow-up was greater in participants prescribed antidepressants than in those not prescribed antidepressants (11.2 vs 8.1 per 100 person-years; adjusted rate ratio [ARR], 1.21; 95 percent CI, 1.19–1.22; p<0.001). This increased risk of weight gain persisted during at least 6 years of follow-up. [BMJ 2018;361:k1951]

In the second year of antidepressant use, there were 27 (25–29) participants who received treatment for 1 year with an additional episode of ≥5-percent weight gain. Individuals who initially had normal weight showed an ARR of 1.29 (1.25–1.34) for transition to overweight or obesity, while those who were initially overweight had an ARR of 1.29 (1.25–1.33) for transition to obesity.

The associations between antidepressant use and weight gain may not be causal, and an overestimation of these associations might have been driven by residual confounding.

In a previous systematic review of short-term studies, the investigators estimated weight increases over a follow-up period of 8 months. Another study that used electronic health records to evaluate weight gain up to 2 years estimated a 2.1-kg weight increase with fluoxetine treatment and about a 4.8-kg increase with sertraline.

“Our study adds to previous data by providing longer follow-up (up to 10 years) of antidepressant treatment, showing that the risk of weight gain is increased for at least the first 5 years of treatment,” the authors said. “Our study also adds a comparison with a general population sample that was not treated with antidepressant drugs, showing an association between antidepressant use and transitions to overweight and obesity.”

A well-known side effect of antipsychotic treatment is weight gain, but prescribing guidelines allot less attention to weight management in the context of antidepressant treatment. Obesity and depression are not only common but often coexist and correlate with physical comorbidity and worse health outcomes. [Taylor D, Barnes TRE, Young AH. The Maudsley Prescribing Guidelines. 13th ed. Infomra Health Care, 2018; National Institute for Health and Care Excellence. Depression in adults with a chronic physical health problem: recognition and management. CG91.NICE, 2009; Fam Pract 2014;31:38-43]

“Researchers have observed that the negative perceptions associated with either a depression diagnosis or an obesity diagnosis may be potentiated when the conditions overlap. This makes weight management and obesity prevention particularly important in this population. The relation between depression symptoms and health behaviours that might contribute to weight gain is also a relevant concern,” the authors said.

The present population-based cohort study evaluated long-term association between antidepressant prescribing and body weight in 136,762 men and 157,957 women with three or more records for body mass index. The main outcomes were antidepressant prescribing incidence of ≥5-percent increase in body weight, and transition to overweight or obesity. A Poisson model, adjusting for age, sex, depression recording, comorbidity, coprescribing of antiepileptics or antipsychotics, deprivation, smoking and advice on diet, was generated to estimate ARRs.

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