Does duloxetine (Cymbalta) cause weight gain?

Duloxetine and Weight Gain

Duloxetine can cause weight gain in some patients, particularly with long-term use, though initial treatment may be associated with weight loss. 1, 2

Evidence on Duloxetine and Weight Changes

• In short-term treatment (8-9 weeks), duloxetine typically causes modest weight loss (average -0.5 kg) compared to placebo (+0.2 kg) 2
• With longer-term treatment (34-52 weeks), duloxetine can lead to modest weight gain (0.9-1.1 kg), which is statistically significant compared to placebo 2
• The FDA label for duloxetine notes that decreased weight is among the most common adverse reactions in pediatric populations, occurring in 14% of duloxetine-treated patients compared to 6% of placebo-treated patients 3
• In adults, weight gain has been observed as a nonserious adverse event with duloxetine, along with other anticonvulsants like pregabalin and gabapentin 1

Comparative Weight Effects Among Antidepressants

• A recent large-scale study (2024) comparing antidepressants found that duloxetine was associated with higher weight gain (0.34 kg more) at 6 months compared to sertraline 4
• Escitalopram, paroxetine, and duloxetine showed higher weight gain than citalopram, while bupropion was associated with weight loss 5, 4
• The risk of gaining at least 5% of baseline weight was 10-15% higher with duloxetine compared to sertraline 4
• When duloxetine is used in combination with pregabalin for neuropathic pain, the combination is associated with more weight gain (+5.5 lb) than duloxetine alone (-0.8 lb) 6

Weight Effects by Indication and Duration

• In chronic pain conditions, weight changes vary by condition:
  • Patients with fibromyalgia and chronic low back pain treated with duloxetine for up to 15 months experienced mean weight increases up to 1.1 kg 7
  • Patients with diabetic peripheral neuropathic pain showed overall mean weight loss (-0.33 to -1.7 kg) with long-term duloxetine treatment 7
• Dose may influence weight changes:
  • Higher duloxetine doses (60 mg twice daily) were associated with more weight gain (0.9 kg) than lower doses (40 mg twice daily, 0.7 kg) in 34-week studies 2
  • In veterans with neuropathy, duloxetine monotherapy was associated with minimal weight change or slight weight loss (-0.8 lb) after 12-18 months 6

Monitoring and Management

• Regular monitoring of weight is recommended during duloxetine treatment 3
• For patients experiencing significant weight gain on duloxetine, consider:
  • Evaluating for other contributing factors
  • Potentially switching to a more weight-neutral option if clinically appropriate 5
• In pediatric patients, weight and height should be monitored regularly, as duloxetine-treated pediatric patients experienced a 0.1 kg mean decrease in weight at 10 weeks in clinical trials 3
• The proportion of patients experiencing clinically significant weight gain (≥5% of baseline) ranges from 0.4-16%, while clinically significant weight loss occurs in 2.5-9.9% 7

Important Caveats

• Individual responses to duloxetine vary considerably 2, 7
• Weight changes with duloxetine appear to be modest for most patients, with initial weight loss often followed by gradual weight gain over time 2
• The clinical significance of these weight changes must be evaluated in the context of the patient's overall health status and treatment goals 7
• Duloxetine's weight effects may be less pronounced than those seen with certain antipsychotics, mood stabilizers, and tricyclic antidepressants 5