Many individuals have the experience of weight gain while receiving treatment with an antidepressant, and often wonder if selective serotonin reuptake inhibitors (SSRIs) are associated with weight gain. This is an excellent, complex, and clinically important question.
Depression, anxiety, appetite, and weight: There is a relationship between appetite and depression, with changes in appetite representing a core symptom of major depressive disorder. Many individuals with anxiety disorders also note appetite changes when their anxiety symptoms are not well controlled. Some individuals lose weight when they are experiencing depression or anxiety, and some notice increased appetite and weight gain. Therefore, at the time of starting an antidepressant, some individuals may be at either a lower or higher weight than they would be at in the absence of a mood or anxiety disorder.
Drugs with known weight gain: Some medications used commonly in psychiatry have well established side effects of weight changes. For example, valproic acid, some of the atypical antipsychotic medications, lithium, the antidepressant mirtazapine (Remeron), and tricyclic antidepressants are associated with weight gain. There has been little systematic long-term data regarding weight effects of SSRI antidepressants (which include fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), paroxetine (Paxil), and fluvoxamine (Luvox), and the SNRIs venlafaxine (Effexor) and duloxetine (Cymbalta), although some studies suggest weight gain may occur and may vary by gender, specific medication, and other patient variables. Bupropion (Wellbutrin) is usually considered weight neutral.
Whether or not a study was short- or long-term – or clinically how long a patient has been on a medication – may influence the likelihood of weight changes. A recent meta-analysis assessed studies with available data (Serretti and Mandelli, 2010). In acute studies (4-12 weeks duration), most SSRIs, SNRIs, and bupropion have been associated with weight loss. In longer term studies (longer than four months), most antidepressant medications with available data did not have significantly associated weight gain, and the most was seen with paroxetine and the older antidepressant amitriptyline (mean weight gain about 5-6 lbs). Only bupropion was associated with significant weight loss (about 4 lbs).
SSRIs: Data that inform risk of weight gain and how specific medications compare to each other
There have been a few studies to provide head-to-head comparisons of weight gain amongst those treated with specific SSRIs. For example, Fava and colleages (2000) completed a study in which patients with major depression were randomly assigned to either fluoxetine, sertraline, or paroxetine. Only those that completed the 26-32 week trial were included in the final analysis of weight gain. Those who received paroxetine experienced a statistically significant weight gain from baseline to end point. Those who received fluoxetine had a trend for weight loss (not statistically significant), and those who received sertraline had a trend for moderate weight gain (not statistically significant).
Those that received paroxetine were also significantly more likely than those who received fluoxetine or sertraline to gain >7% of their original body weight, the threshold used in many studies to indicate clinically important weight gain. Mean percent changes in weight from the beginning of the study to the end were: 0.2% weight loss with fluoxetine, 1% weight gain with sertraline, and 3.6% weight increase with paroxetine. Therefore, if the typical participant weighted 150 lbs, the weight gain would be about 5.4 lbs with paroxetine and 1.5 lbs with sertraline, and the weight loss would be less than 1 pound with fluoxetine. While these are overall modest differences from the baseline weights, they are means, so some individual patients could certainly have had very different experiences than the mean.
In another study (Maina 2004), researchers assessed patients in an anxiety disorder clinic for weight changes with the tricyclic antidepressant clomipramine or SSRIs over a 2.5 year period. The group included 138 patients with obsessive compulsive disorder. They were not randomly assigned to medication. On average, the patients as a group gained 2.5% of their baseline weight (1.58 kg or 3.5 pounds over 2.5 years of treatment). 14.5% of the sample gained >7% of their initial body weight. For all medications except fluoxetine, which did not have significant weight gain, the others (clomipramine, citalopram, fluvoxamine, paroxetine, and sertraline) were associated with statistically significant weight gain over the 2.5 year duration of study. Clomipramine had the greatest percentile of patients who gained >7% of body weight, while fluoxetine and sertraline had the lowest. Women were more likely to gain weight than men.
Wisner and colleagues (2005) specifically looked at the weight impact of treatment with nortriptyline, sertraline, or placebo in women with histories of postpartum depression (PPD) who took medication after childbirth to prevent having PPD again. Mean weights after 17 weeks of treatment were not significantly different between the treatment groups. On average, women lost about 1.8 pounds over the course of the study. Because the study was a depression prevention study, women were not experiencing depression at the time of study entry, so the treatment of depressive symptoms would not be a driving factor for weight change.
The Bottom Line
Antidepressant medications can potentially contribute to weight gain, and certain antidepressants may carry a higher risk. Specifically among SSRIs, from these studies data suggest paroxetine carries the highest risk of weight gain and fluoxetine the lowest risk in the class. Additionally, recovery from depression and anxiety disorders may also contribute to increased appetite and weight. Not everyone will experience the same benefits or side effects to specific drugs. If over time, weight gain occurs and it appears that the antidepressant appear to be a major contributor to weight gain, one might consider switching to another medication or non-pharmacologic treatments.
Marlene Freeman, MD
Serretti A & Mandelli L. Antidepressants and Body Weight: A Comprehensive Review and Meta-Analysis. J Clin Psychiatry 2010;71(10):1259–1272.
Wisner et al. Weight changes in postpartum women with remitted depression. J Clin Psychiatry. 2005; 66(3):291-3.
Fava M, Judge R, Hoog SL, Nilsson ME, Koke SC. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. J Clin Psychiatry. 2000; 61(11):863-7.
Maina G, Albert U, Salvi V, Bogetto F. Weight gain during long-term treatment of obsessive-compulsive disorder: a prospective comparison between serotonin reuptake inhibitors. J Clin Psychiatry. 2004; 65(10):1365-71.