Antidepressants and Weight Gain

Weight gain is a reported side effect of nearly all antidepressants. Weight gain is a relatively common problem during both acute and long-term treatment with antidepressants, and it is an important contributing factor to noncompliance. However, it is not clearly known how antidepressant medications cause weight gain.

Tricyclic antidepressants (TCAs) appear to slow metabolism and may promote carbohydrate cravings. Because tertiary tricyclic antidepressants such as amitriptyline, imipramine, and doxepin are stronger histamine blockers than are secondary tricyclics such as desipramine and nortriptyline, the tertiary tricyclic drugs are more likely to cause weight gain.

Mirtazapine (Remeron) may be placed between the SSRIs and the TCAs in terms of relative risk for weight gain. Weight gain is the most commonly reported side-effect of this antidepressant. It is likely to be related to weight gain in both the short term and the long term through blockade of histamine H1 and serotonin 2C receptors. The weight gain may occur even during the first 4 weeks of treatment with mirtazapin.

Selective Serotonin Reuptake Inhibitors (SSRIs) cause less weight gain than tricyclic antidepressants. Weight gain is less likely with SSRIs when they are used for 6 months or less. SSRIs-induced weight change is probably related to alteration in serotonin 2C receptor activity, appetite increase, carbohydrate craving, or recovery from clinical depression. Paroxetine (Paxil) appears to cause the greatest incidence of weight gain than the other SSRIs.

Venlafaxine (Effexor) appears to be a weight-neutral antidepressant.

Bupropion (Wellbutrin) is unlikely to cause weight gain, and is commonly associated with weight loss. Its chemical structure is similar to that of diethylpropion (Tenuate), an appetite suppressant. A number of clinical studies have shown it’s weight loss potential. The results of the 48-week double-blind, placebo- controlled trial have shown, that bupropion SR is associated with a 24-week weight loss of 10.1% and sustained weight losses at 48 weeks.