Do doxepin, Tofranil (imipramine), Fetzima (levomilnacipran), or Pamelor (nortriptyline) cause weight gain?

Weight Gain Associated with Doxepin, Imipramine (Tofranil), Levomilnacipran (Fetzima), and Nortriptyline (Pamelor)

Tricyclic antidepressants (TCAs) like doxepin, imipramine (Tofranil), and nortriptyline (Pamelor) are associated with significant weight gain, while levomilnacipran (Fetzima) has a more neutral weight profile. 1, 2

Medication-Specific Weight Effects

Tricyclic Antidepressants (TCAs)

• Doxepin: Associated with weight gain as a side effect, with the FDA label specifically listing "weight gain" among reported adverse effects 3
• Imipramine (Tofranil): Causes significant weight gain, with research showing an average weight increase of 1.3-2.9 lbs/month, leading to total weight gain of 3-16 lbs depending on dose and duration 4
• Nortriptyline (Pamelor): Similar to other TCAs, associated with weight gain during both acute and long-term treatment 4, 5

Newer Antidepressants

• Levomilnacipran (Fetzima): As an SNRI, it has a more favorable weight profile compared to TCAs, with lower risk of weight gain 2, 6

Mechanism of Weight Gain

TCAs like doxepin, imipramine, and nortriptyline may cause weight gain through:

• Histamine H1 receptor antagonism, increasing appetite 6
• Anticholinergic effects that slow metabolism 1
• Increased preference for sweets and carbohydrates 4

Clinical Significance

Weight gain with TCAs is not trivial:

• Can be substantial enough to interfere with treatment adherence
• Research shows excessive weight gain was the most common cause of discontinuation of TCA treatment, occurring in approximately 50% of patients 4
• Weight gain tends to be linear over time, suggesting cumulative effects with continued treatment 4

Monitoring and Management

For patients on these medications:

• Regular monitoring of weight is essential, with particular attention to unintentional weight gain >2 kg in a month or ≥7% increase from baseline 1
• Consider medication alternatives if weight gain becomes problematic:
  • For patients requiring TCAs, nortriptyline may have slightly less weight gain potential than doxepin or imipramine
  • Consider levomilnacipran or other SNRIs as alternatives with better weight profiles
  • Bupropion is associated with weight loss and may be an alternative if clinically appropriate 2, 6

Practical Considerations

• Weight gain risk must be balanced against therapeutic benefits
• Patients with a history of weight issues or metabolic disorders may be more vulnerable
• Medication-induced weight gain can worsen existing conditions like diabetes, hypertension, and dyslipidemia 7
• Significant weight gain can negatively impact quality of life and medication adherence

When prescribing these medications, discuss potential weight effects with patients beforehand and implement regular weight monitoring to detect and address changes early.