Weight Gain Associated with SSRIs
Abstract & Commentary
Synopsis: Long-term data suggest that SSRIs, particularly paroxetine (Paxil), may be associated with weight gain.
Source: Sussman N, Ginsberg D. Weight gain associated with SSRIs. Prim Care Psychiatry 1998;1:28-37.
The side effect profile of a medication is one of many important issues affecting the selection of an antidepressant medication. Patients are increasingly interested in medication side effects, particularly regarding weight gain and sexual dysfunction. This article discusses common perceptions regarding weight gain or loss associated with selective serotonin reuptake inhibitors (SSRIs), by reviewing short- and long-term clinical studies. According to short-term studies used to establish efficacy for depression, SSRIs were believed to reduce appetite and preoccupation with food, resulting in weight loss for some patients. However, observations by clinicians in-practice have raised questions about this assumption. Sussman and Ginsberg reviewed the literature regarding weight gain or loss with the SSRIs fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). Information about amitriptyline (Elavil) and venlafaxine (Effexor) was included from studies that directly compared these agents with SSRIs.
Three short-term studies (£ 6 weeks) have revealed the following: a greater frequency of weight gain with fluoxetine (1.1%) compared to sertraline (0.5%), with weight loss more common for both; a greater frequency of weight gain with paroxetine (8.1%) compared to fluoxetine (4%); and a mean weight loss in fluoxetine-treated patients and a slight weight gain in paroxetine-treated patients. Two long-term studies (6-52 weeks) have revealed the following: a mean weight gain with paroxetine and amitriptyline, and a mean weight loss for fluoxetine; and a greater frequency of weight gain with paroxetine compared with fluoxetine, sertraline, and venlafaxine. It appears that weight gain may occur early in treatment, but most patients experience the onset of weight after several weeks or months of treatment. The amount of weight gain reported varies according to the drug, length of time on that drug, and one’s weight on initiation of the drug. Generally, it is not uncommon to have a weight gain of up to 20 pounds or a 7% increase of overall body weight. Sussman and Ginsberg provide an excellent review of potential mechanisms for SSRI-induced weight gain. Animal studies suggest that acute SSRIs increase the metabolic rate. The acute effects of SSRIs may reduce appetite and weight by activation of 5-HT2C receptors in the hypothalamus. Weight gain may be explained by antagonism of these receptors (e.g., by metabolites of fluoxetine) and the fact that chronic SSRI administration decreases responsiveness of these receptors. SSRIs have also been shown to decrease dopamine turnover via serotonergic projections, which is relevant because dopamine agonists reduce body fat stores and improve carbohydrate and lipid metabolism without significantly altering food consumption. This is consistent with the trend that paroxetine causes more weight gain than other SSRIs, since it has been shown to have the most dopamine blockade. It is also possible that SSRIs modify appetite and weight by effects on other receptors (e.g., histamine1), neuropeptides (neuropeptide Y), or medication concurrently taken to alleviate side effects from SSRIs (e.g., benzodiazepines for insomnia). It is unlikely that weight gain is a normalization of events caused by depression since patients often exceed baseline weight and SSRIs also induce weight gain in patients with anxiety disorders. Sussman and Ginsberg correctly conclude that the data presented suggest that SSRI-induced weight gain is not an isolated occurrence. Weight gain has likely been underreported due to onset later in the treatment. There are, however, only a handful of reports that specifically mention the prevalence and degree of weight gain in SSRI-treated patients. The possibility that SSRIs promote weight gain needs to be explored in a more systematic way.
Comment by Donald M. Hilty, MD
A rational approach to selection of an antidepressant includes consideration of side effects (e.g., weight gain) and other factors such as comorbidity (e.g., anxiety), personal and family history of response, drug interactions, medical contraindications, cost, ease of adherence per the dosing regimen, and potential for overdose. An increasingly important part of the informed consent process is advising patients of common side effects and performing a rudimentary risk-benefit analysis in order to maximize adherence to medication for depression. Common side effects that are important to patients include weight gain, sexual dysfunction, anxiety or activation, sedation, and insomnia.
Given the increasing diversity of available antidepressant medications, it is possible to avoid many specific side effects that might compromise compliance. In order to avoid weight gain, the primary care physician could select bupropion (Wellbutrin), sertraline, nefazodone (Serzone), or fluoxetine. In order to avoid sexual dysfunction, bupropion, nefazodone, or mirtazepine (Remeron) could be initiated. Sertraline, nefazodone, venlafaxine, or fluoxetine may be used in a patient with depression and anxiety, obesity, or other medical conditions adversely affected by weight gain.
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