Which antidepressants cause less weight gain?

3 minute read


A US study shows which drugs might be best avoided by patients who are concerned about weight gain as a side effect.


Sertraline is the antidepressant with the least effect on weight, escitalopram causes the greatest weight gain and bupropion is actually associated with weight loss.  

In a US study of patients starting their first antidepressant treatment, researchers identified the antidepressants associated with the greatest and lowest risk of weight gain after six months of treatment and show trends of continued weight changes at 12 and 24 months. 

Escitalopram (Lexapro), paroxetine (Apotex), and duloxetine (Cymbalta) were associated with 10%-15% higher risk of weight gain than sertraline, which was used as a reference point with a nil weight gain.  

Over 180,000 participants were included between 2010 and 2019, with weight measurements taken at baseline, six months, 12 months, and 24 months. The rates were determined by how many participants on each treatment gained at least 5% of their starting weight, but the amount of weight gained throughout treatment was also analysed. 

Sertraline was the most common antidepressant initiated, accounting for 20% of the participants, followed by citalopram (16%) and bupropion (Zyban SR, 15%). Paroxetine was the least common at 4%. The mean age of participants was 48, 65% were female, and the average BMI was 29.4 (overweight range). 

Adherence rates were initially higher for bupropion than all other medications in the study, at 41%, while all other medications were between 28% and 36% at six months. Adherence did drop for all treatments over time, including bupropion. At 12 months, adherence was between 16 and 21%, while at 24 months it had dropped to just 4-5%. 

Bupropion (NDRI) 

This was the only treatment that led to a weight reduction, with users showing an average 0.22kg weight loss from baseline.  

Bupropion continued to show an increased weight reduction at subsequent followups, with users showing a mean weight change from baseline of -0.71 kg at 12 months and -0.91 kg at 24 months compared to sertraline. 

SSRIs 

Escitalopram showed the highest average weight gain from baseline of any of the treatment. There was an average weight gain among users of 0.41kg at six months, which remained the same at 12 months. However, this had reduced to a gain of 0.16kg at 24 months. 

Paroxetine was associated with small weight gains of 0.37kg at six months and 0.15kg at 12 months, but a 0.14kg weight loss by 24 months. 

Fluoxetine (Prozac) showed insignificant weight reductions compared to sertraline. 

Citalopram produced a slight change in baseline weight at six months but this reduced at subsequent followups. 

SNRIs 

Duloxetine showed one of the highest average weight gains at six months (0.34kg), while venlafaxine (Efexor-XR) was associated with a 0.17kg weight gain from baseline compared to sertraline.  

There was a plateau in weight gain for both duloxetine and venlafaxine, leading to a reduction of -0.11kg and -0.12kg respectively. They both continued to reduce similarly at 24 months (-0.69kg and -0.59kg respectively). 

Annals of Internal Medicine 2024, online 2 July. 

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