Patients starting bupropion gained less weight—both at six and 24 months—than those starting one of seven other first-line antidepressants, according to a two-year population study published in Annals of Internal Medicine. Meanwhile, escitalopram users averaged the highest six-month weight gain.
Notably, overall adherence among all these medications was low: Only about one in three patients were still taking their originally prescribed medication at six months.
“There are some patients that are very concerned about weight effects from any prescription medication,” lead author Jason P. Block, M.D., M.P.H., an internal medicine physician and associate professor of population medicine at Harvard Medical School, told Psychiatric News. “This study gives people information about what they can expect.”
The weight effects of various medications are not always top of mind for prescribers, but weight gain is a commonly reported side effect of antidepressant use that can affect patients’ long-term metabolic health. “Treatment-related weight gain is also a common reason for lack of adherence,” Block said, “leading to poor clinical outcomes, including increased risk for psychiatric relapse and hospitalization.”
Researchers analyzed weight outcomes for more than 183,000 adults being treated at medical centers across the country who were initiating one of eight common antidepressants—sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. The three most common diagnoses were anxiety (39% of the study population), depression (36%), and neuropathic pain (16%).
Researchers mined electronic health records, examining the weight impact six, 12, and 24 months after patients initiated the medication. They also reported “significant” weight gains—5% or more of baseline weight.
Researchers excluded adults with previous antidepressant use, those with recent weight-changing conditions such as cancer, pregnancy, or bariatric surgery, and those who were taking steroids, stimulants, or weight-loss drugs.
Short-Term Weight Impact
The subset of patients who continued to take their initially prescribed antidepressants averaged the following weight changes after six months:
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Escitalopram: 2.5 lb. gain
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Paroxetine: 1.75 lb. gain
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Duloxetine: 1.25 lb. gain
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Citalopram: 0.75 lb. gain
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Sertraline: 0.25 lb. gain
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Venlafaxine: 0.5 lb. loss
Patients taking escitalopram, paroxetine, and duloxetine also had the greatest risk of significant weight gain after six months.
The researchers noted that due to poor adherence, reliable weight trends at 12 and 24 months were difficult to establish, although bupropion continued to be associated with the least weight gain.
According to the National Institutes of Health, 31% of U.S. adults are overweight, and another 42% are obese or severely obese. However, people with major depressive disorder are more likely to be overweight than adults without depression, and the proportion rises along with the severity of depressive symptoms, according to Centers for Disease Control and Prevention data. Among individuals taking antidepressants and still experiencing symptoms, 55% are obese.
That bupropion was associated with the least weight gain and the least risk of significant weight gain across different time points should serve as no surprise, since bupropion is used as a weight-loss drug in combination with naltrexone, Block said. The favorable weight profile of bupropion may be due to its ability to activate the hypothalamic melanocortin system, which regulates feeding behaviors and energy balance.
Low Antidepressant Adherence
Researchers noted low patient adherence to their prescribed antidepressant regimen (28% to 36%) at six months, except for bupropion, which was slightly higher (41%). However, at 24 months, only 4% to 5% of participants continued to take their initial antidepressant as prescribed, across the board.
“Adherence is much lower than clinicians think it is,” Block added. “In general, patients take only about 50% of the medication they’re prescribed. Some patients never pick up their first prescription…. We need to do much more to provide people with information before we prescribe, so they know what to expect before starting medications.”
Block pointed out that many factors go into clinician selection of an antidepressant, including patient treatment history, what has worked well or not been helpful for that individual, and the subtle differences among these drugs.
The study was funded by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. ■