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Depression linked to obesity, drugs linked to weight gain

MDD with atypical features associated with a higher increase in adiposity in terms of BMI, incidence of obesity and waist circumference
Antidepressants differ modestly in their propensity to contribute to weight gain

Two studies have provided new insights into the issue surrounding depression, antidepressants and obesity. The first concludes that major depressive disorder (MDD) appears to be associated with obesity, whilst a second paper reports that some antidepressants can lead to weight gain among patients.

Writing in JAMA Psychiatry (‘Depression With Atypical Features and Increase in Obesity, Body Mass Index, Waist Circumference, and Fat Mass - A Prospective, Population-Based Study’), Dr Aurélie M Lasserre of Lausanne University Hospital, Switzerland, and colleagues, note that understanding the mechanisms underlying the association between MDD and obesity is important.

In order to determine whether the subtypes of major depressive disorder (MDD; melancholic, atypical, combined, or unspecified) are predictive of adiposity in terms of the incidence of obesity and changes in BMI, waist circumference and fat mass, they designed a  prospective population-based cohort study, CoLaus (Cohorte Lausannoise)/PsyCoLaus (Psychiatric arm of the CoLaus Study), that included 3,054 randomly selected residents (mean age 49.7; 53.1% were women) of the city of Lausanne, Switzerland.


At baseline, 7.6 percent of participants met the criteria for MDD. Among the participants with MDD, about 10 percent had atypical and melancholic episodes, 14 percent had atypical episodes, 29 percent had melancholic episodes and 48 percent had unspecified episodes.

They found that participants with the atypical subtype of MDD at baseline revealed a higher increase in adiposity during follow-up than participants without MDD. The associations between this MDD subtype and body mass index (β = 3.19; 95% CI, 1.50-4.88), incidence of obesity (odds ratio, 3.75; 95% CI, 1.24-11.35), waist circumference in both sexes (β = 2.44; 95% CI, 0.21-4.66), and fat mass in men (β = 16.36; 95% CI, 4.81-27.92) remained significant after adjustments for a wide range of possible cofounding.

The study suggests the higher BMI increase in participants with MDD with atypical features also was not temporary and persisted after remission of the depressive episode.

“The atypical subtype of MDD is a strong predictor of obesity,” they conclude. “This emphasises the need to identify individuals with this subtype of MDD in both clinical and research settings. Therapeutic measures to diminish the consequences of increased appetite during depressive episodes with atypical features are advocated.”


In the second study also published in JAMA Psychiatry (‘An Electronic Health Records Study of Long-Term Weight Gain Following Antidepressant Use’), Sarah R Blumenthal from the Massachusetts General Hospital, Boston, and colleagues sought to assess the weight gain associated with specific antidepressants over the 12 months following initial prescription in a large and diverse clinical population.

Using electronic health records from a large New England health care system, they identified 22, 610 adult patients who began receiving a medication of interest with available weight data. They extracted prescribing data and recorded weights for any patient with an index antidepressant prescription including amitriptyline hydrochloride, bupropion hydrochloride, citalopram hydrobromide, duloxetine hydrochloride, escitalopram oxalate, fluoxetine hydrochloride, mirtazapine, nortriptyline hydrochloride, paroxetine hydrochloride, venlafaxine hydrochloride, and sertraline hydrochloride.

As measures of assay sensitivity, additional index prescriptions examined included the antiasthma medication albuterol sulfate and the antiobesity medications orlistat, phentermine hydrochloride, and sibutramine hydrochloride. Mixed-effects models were used to estimate rate of weight change over 12 months in comparison with the reference antidepressant, citalopram.


A total of 19,244 adults were treated with an antidepressant for at least three months and 3,366 received a non-psychiatric intervention. Compared with citalopram, in models adjusted for sociodemographic and clinical features, significantly decreased rate of weight gain was observed among individuals treated with bupropion (−0.063 [0.027]; p=0.02), amitriptyline (−0.081 [0.025]; p=0.001), and nortriptyline (−0.147 [0.034]; p<0.001). Differences were less pronounced among individuals discontinuing treatment prior to 12 months.

They noted that although short-term studies suggest antidepressants are associated with modest weight gain little is known about longer-term effects and differences between individual medications in general clinical populations. The potential health consequences could be significant because more than 10 percent of Americans are prescribed an antidepressant at any given time.

"Taken together, our results clearly demonstrate significant differences between several individual antidepressant strategies in their propensity to contribute to weight gain,” the authors write. “While the absolute magnitude of such differences is relatively modest, these differences may lead clinicians to prefer certain treatments according to patient preference or in individuals for whom weight gain is a particular concern."

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