June 6, 2014
Using electronic health records, Sarah R. Blumenthal, from Massachusetts General Hospital in Boston, and colleagues identified 22,610 adult patients with available weight data who began receiving specific antidepressants. Additional index prescriptions, including the anti-asthma medication albuterol sulfate and the anti-obesity medications orlistat, phentermine hydrochloride, and sibutramine hydrochloride, were also evaluated.
After adjusting for sociodemographic and clinical features, the researchers observed a significantly decreased rate of weight gain among individuals treated with bupropion (P=0.02), amitriptyline(P=0.001), and nortriptyline (P<0.001), compared to citalopram. For individuals discontinuing treatment prior to 12 months, differences were less pronounced.
"Antidepressants differ modestly in their propensity to contribute to weight gain," the authors write. "Short-term investigations may be insufficient to characterize and differentiate this risk."
Several authors disclosed financial ties to the pharmaceutical industry.
To estimate weight gain associated with specific antidepressants over the 12 months following initial prescription in a large and diverse clinical population.
Conclusions and Relevance
Antidepressants differ modestly in their propensity to contribute to weight gain. Short-term investigations may be insufficient to characterize and differentiate this risk.
Multiple prior reports have suggested an association between antidepressant use and weight gain. Because more than 10% of Americans are prescribed antidepressants at any given time, the potential health consequences could be substantial. Obesity has been associated with higher incidence of cardiovascular disease, type 2 diabetes mellitus, hypertension, stroke, dyslipidemia, osteoarthritis, and some cancers, as well as significantly reduced life expectancy and increased all-cause mortality. The prevalence of antidepressant use increases to more than one-third for severely depressed individuals, a group that may be particularly at risk for obesity. In fact, up to a quarter of obesity may be attributable in part to an underlying mood disorder.
Differences between medication classes in their propensity to cause weight gain have been reported; 1 early review suggested older antidepressants, including the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors, were more likely to cause weight gain than the selective serotonin reuptake inhibitors or other new antidepressants. The atypical antidepressant mirtazapine and the TCAs amitriptyline hydrochloride and nortriptyline hydrochloride are still widely accepted as contributing to weight gain in patients based on randomized, controlled short-term trials.
Among studies examining acute treatment, generally defined as 4 to 12 weeks, the selective serotonin reuptake inhibitors all resulted in average weight loss, as did the serotonin and norepinephrine-reuptake inhibitors venlafaxine hydrochloride and duloxetine hydrochloride, while nortriptyline and mirtazapine resulted in significant weight gain. The only medications with evidence of long-term weight changes (ie, over 4 months or more) were amitriptyline, which caused weight gain, and bupropion hydrochloride, which caused weight loss. Data from long-term treatment with other drugs were either nonexistent or inconclusive and no 12-month data could be identified.
Thus, 2 major questions of clinical importance relating to antidepressants and weight gain remain unanswered. First, what magnitude of weight gain is associated with longer-term antidepressant use in general clinical populations rather than clinical trial populations? Second, are there clinically significant differences between these interventions in terms of weight gain because most studies lack direct head-to-head comparisons?
To address these topics, we examined electronic health records from a large New England health care system encompassing more than 4.2 million individuals. By extracting prescribing data and documented patient weights, we assessed the association between specific antidepressants and weight change over the 12 months following medication initiation in more than 22 000 individuals.