David Baxter PhD
Late Founder
How to control weight gain when prescribing antidepressants
Current Psychiatry Online, Vol. 6, No. 5 / May 2007
by Thomas L. Schwartz, MD, Zsuzsa S. Meszaros, MD, PhD, Rahat Khan, MD, and Nikhil Nihalani, MD
Weight gain occurs with most antidepressants but is frequently overlooked, perhaps because clinicians are focused instead on metabolic effects of antipsychotics and mood stabilizers. Patients taking antidepressants often complain of weight gain, however, and many of the drugs’ FDA-approved package inserts acknowledge this effect.
Two-thirds of patients with major depression present with weight loss, and gaining weight can be associated with successful treatment. Weight gain is of concern—and likely to be drug-induced—if it exceeds the disease-induced weight loss and continues after depressive symptoms improve.
Weight may change early or late during antidepressant treatment, and gaining in the first weeks usually predicts future gains.1 Patients who are overweight when treatment begins are especially at risk if given weight-promoting agents. This article:
Paroxetine seems to be the SSRI most likely to cause weight gain. A 26- to 32-week comparison trial by Fava et al showed that weight gain risk with SSRI therapy varies with the drug used. In this trial, 284 patients with major depressive disorder were randomly assigned to double-blind treatment with paroxetine, sertraline, or fluoxetine:
Citalopram may cause a 1- to 1.5-kg weight gain over 1 year,8 whereas fluvoxamine has been shown not to affect weight in obese patients.11 Citalopram (like TCAs) can cause carbohydrate craving and early weight gain.18 Escitalopram caused a modest (0.5 kg) weight gain in elderly patients during an 8-week trial.13
Initial weight loss followed by overall weight gain after 1 year of SSRI treatment is a common clinical finding that was not noted in initial acute SSRI drug trials. In a comparison of fluoxetine’s acute and long-term effects,19 839 patients experiencing a major depressive episode were first treated with open-label fluoxetine, 20 mg/d. After 12 weeks, 395 patients who met criteria for remission were randomly assigned to continue with placebo or fluoxetine, 20 mg/d, for 14, 38, or 50 weeks.
In the acute phase, a small but statistically significant weight loss (mean 0.35 kg, P<0.01) was noted. In the continuation phase, statistically significant weight gain occurred among all patients. Mean absolute weight changes were:
Antidepressants’ relative long-term effects on body weight Effect
Loss: Bupropion, fluoxetine
Gain: Modest: citalopram, duloxetine, escitalopram, sertraline, trazodone, venlafaxine
Relatively more: amitriptyline, imipramine, mirtazapine, paroxetine, phenelzine
Neutral: Fluvoxamine, nefazodone, nortriptyline
Current Psychiatry Online, Vol. 6, No. 5 / May 2007
by Thomas L. Schwartz, MD, Zsuzsa S. Meszaros, MD, PhD, Rahat Khan, MD, and Nikhil Nihalani, MD
Weight gain occurs with most antidepressants but is frequently overlooked, perhaps because clinicians are focused instead on metabolic effects of antipsychotics and mood stabilizers. Patients taking antidepressants often complain of weight gain, however, and many of the drugs’ FDA-approved package inserts acknowledge this effect.
Two-thirds of patients with major depression present with weight loss, and gaining weight can be associated with successful treatment. Weight gain is of concern—and likely to be drug-induced—if it exceeds the disease-induced weight loss and continues after depressive symptoms improve.
Weight may change early or late during antidepressant treatment, and gaining in the first weeks usually predicts future gains.1 Patients who are overweight when treatment begins are especially at risk if given weight-promoting agents. This article:
- compares antidepressant effects on patient weight
- discusses mechanisms by which antidepressants may cause weight gain
- outlines a plan to prevent excess weight gain when patients start antidepressant therapy
- recommends diet, exercise, cognitive-behavioral therapy (CBT), and medications for overweight patients on long-term antidepressant treatment.
Paroxetine seems to be the SSRI most likely to cause weight gain. A 26- to 32-week comparison trial by Fava et al showed that weight gain risk with SSRI therapy varies with the drug used. In this trial, 284 patients with major depressive disorder were randomly assigned to double-blind treatment with paroxetine, sertraline, or fluoxetine:
- More of those taking paroxetine gained >7% in weight from baseline, and their weight gain was statistically significant.
- Sertraline-treated patients had modest, nonsignificant weight gain.
- Fluoxetine-treated patients had modest, nonsignificant weight loss.
Citalopram may cause a 1- to 1.5-kg weight gain over 1 year,8 whereas fluvoxamine has been shown not to affect weight in obese patients.11 Citalopram (like TCAs) can cause carbohydrate craving and early weight gain.18 Escitalopram caused a modest (0.5 kg) weight gain in elderly patients during an 8-week trial.13
Initial weight loss followed by overall weight gain after 1 year of SSRI treatment is a common clinical finding that was not noted in initial acute SSRI drug trials. In a comparison of fluoxetine’s acute and long-term effects,19 839 patients experiencing a major depressive episode were first treated with open-label fluoxetine, 20 mg/d. After 12 weeks, 395 patients who met criteria for remission were randomly assigned to continue with placebo or fluoxetine, 20 mg/d, for 14, 38, or 50 weeks.
In the acute phase, a small but statistically significant weight loss (mean 0.35 kg, P<0.01) was noted. In the continuation phase, statistically significant weight gain occurred among all patients. Mean absolute weight changes were:
- 1.1 kg at 26 weeks (P <0.001)
- 2.2 kg at 38 weeks (P <0.001)
- 3.1 kg at 50 weeks (P <0.001).
Antidepressants’ relative long-term effects on body weight Effect
Loss: Bupropion, fluoxetine
Gain: Modest: citalopram, duloxetine, escitalopram, sertraline, trazodone, venlafaxine
Relatively more: amitriptyline, imipramine, mirtazapine, paroxetine, phenelzine
Neutral: Fluvoxamine, nefazodone, nortriptyline
