Research Reveals Which Antidepressants Lead to Less Weight Gain

Researchers compared eight common antidepressants and found that one led to significantly less weight gain than others.

Treatments for depression often include antidepressant medication and psychotherapy. While medications can help ease the symptoms, they also come with a range of side effects, such as digestive issues, dizziness, and weight increases.

These potential adverse effects — especially the risk of putting on a few pounds — can make a person hesitant to fill their antidepressant prescription or stop taking the medication before it has had a chance to work.

The concern is so prevalent that some mental health professionals are prescribing blockbuster weight loss drugs like Ozempic to treat antidepressant-related weight gain.

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However, new research findings published in the Annals of Internal Medicine may help clarify which antidepressants are linked to a lower risk of gaining weight.

To conduct the study, scientists from the Harvard Pilgrim Health Care Institute reviewed electronic health record prescription data from 183,118 adults ages 18 to 80 years who recently began taking antidepressants.

The data came from eight health systems in the United States actively involved in the National Patient-Centered Clinical Research Network (PCORnet).

The research team compared the participants' weight at six, 12, and 24 months after they began taking either sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), paroxetine (Paxil), bupropion (Wellbutrin), duloxetine (Cymbalta), and venlafaxine (Effexor). The data showed that sertraline was the most commonly prescribed antidepressant among the participants.

At each time point, the researchers tracked the participants' weight and noted when they experienced a gain of 5% or more.

After analyzing the data, the team found that six-months into treatment, participants taking paroxetine, duloxetine, or escitalopram had a 15% higher risk of gaining weight than those taking sertraline. In contrast, people taking bupropion gained the least amount of weight and were 15% less likely to experience weight increases.

While individuals taking venlafaxine or citalopram also experienced more weight gain than those taking sertraline, people prescribed fluoxetine did not experience notable weight changes at six months.

The researchers also discovered that a significant number of participants were taking an antidepressant linked to a higher risk of weight gain when they could be prescribed a drug in the same class with a lower risk.

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For example, paroxetine, escitalopram, and sertraline are all selective serotonin reuptake inhibitors (SSRIs). However, sertraline was associated with less weight gain.

In addition, the analysis showed that adherence to antidepressants waned over time. While 28% to 41% of participants continued to take their medication at six months, that percentage dropped to 16% to 21% at 12 months and fell to around 5% at 24 months.

"Keeping the limitations of low adherence in mind, 24-month weight gain was lower for duloxetine and venlafaxine than for sertraline, which was due to plateauing weight gain around 12 to 18 months for the SNRIs (vs. a continual increase in weight gain for the SSRIs). We also observed a narrowing of the initial differences in weight change between SSRIs after 24 months. Bupropion continued to be associated with the least weight gain at 12 and 24 months after initiation," the study's authors wrote.

The researchers suggest that since some antidepressants can lead to more weight gain than others, especially early on in treatment, patients concerned about this side effect and their healthcare providers could consider choosing a medication that best fits their needs.

"Patients and their clinicians often have several options when starting an antidepressant for the first time. This study provides important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants," said lead author Joshua Petimar, a Harvard Medical School assistant professor at the Harvard Pilgrim Health Care Institute, in a news release. "Clinicians and patients can use this information, among other factors, to help decide on the right choice for them."

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