ADVANCES IN PHARMACOLOGY: ANTIDEPRESSANT-INDUCED WEIGHT GAIN

Medicine and Health Rhode Island, Oct 2005 by Kachur, Sarah Grace, Hannan, Christine L, Ward, Kristina E

The weight gain associated with mirtazapine may be due to its activity at histamine receptors.9 In a long-term continuation of a trial of acute treatment, patients continued treatment with mirtazapine, amitriptyline, or placebo for up to two years.10 Weight gain was more common with amitriptyline (22%) than mirtazapine (13%) patients, but significantly more mirtazapine than placebo patients experienced weight gain. In a four-week study of healthy subjects, those treated with mirtazapine experienced a significant increase in body weight from baseline (mean increase 3.64 lb.), suggesting that the weight gain caused by mirtazapine is independent of the weight changes associated with recovering depression.11 This trial also quantified the changes in total cholesterol, LDL and triglycerides associated with mirtazapine treatment.11 After four weeks of therapy, mirtazapine-treated subjects experienced a significant increase in total cholesterol (mean increase 7.6 mg/dL) and nonsignificant increases in LDL and triglyceride levels compared to baseline, while no significant changes were noted in placebo-treated patients. Among treated patients, weight increase was linearly associated with increasing total cholesterol. The results of this short-term trial suggest that weight and cholesterol changes associated with mirtazapine occur independent of depression recovery.

A small, open-label trial compared the effects of mirtazapine and venlafaxine on weight.12 During the four weeks of treatment, mirtazapine-treated patients experienced a mean weight gain of 2.4 kg while venlafaxine-treated patients had a mean loss of 0.4 kg. A twelve-week trial did not detect weight change with either venlafaxine- or fluoxerine-treated patients.13 In another trial, weight changes in elderly patients treated with venlafaxine or citalopram for six months were not clinically significant.14 More research is needed to clarify the effects of venlafaxine on weight, although the agent is most likely not associated with significant weight gain or loss.

Bupropion is generally associated with weight loss. In an eight-week trial comparing sustained release (SR) bupropion 150-400 mg/day to sertraline 50-200 mg/day, bupropion patients experienced a mean 1.06 kg decrease in weight from baseline to endpoint compared with 0.79 kg decrease for sertraline and a 0.21 kg increase for placebo; these differences were not statistically significant.15 During an eight-week placebo-controlled trial, bupropion SR 300 mg/day and 400 mg/day caused weight loss greater than 5 pounds in 14% and 19% of patients, respectively, compared with 6% of placebo patients. Weight loss of greater than 10 pounds occurred in 2%, 6% and 2% of bupropion 300 mg, 400 mg and placebo patients.2

DISCUSSION

Because of the difficulty separating the effects of antidepressant medications from the effects of depression, the true effects of SSRI and non-SSRI antidepressants on weight have yet to be completely understood. In general, SSRIs and other newer antidepressants have a more favorable metabolic profile than TCAs or MAOIs. Among SSRIs, paroxetine is associated with weight gain early in therapy but the long-term effects are undear. Fluoxetine may cause short-term weight loss that resolves with continued treatment. Other SSRIs are either weight-neutral or the effects have yet to be determined. Nefazodone appears less likely to cause weight gain dun SSRIs. Bupropion is often associated with weight loss while mirtazapine is associated with weight gain and the effects of venlafaxine remain unclear.