Neuropharmacology of Paradoxic Weight Gain with Selective Serotonin Reuptake Inhibitors

Abstract

It has been suggested that weight gain associated with tricyclic antidepressants (TCA) reflect actions on dopamine (DA) and histamine receptors. However, a definitive cause is purely assumptive given the nonselective pharmacology of these agents. The selective serotonin reuptake inhibitors (SSRIs), as well as agents like dexfenfluramine (DFF), have emphasized the pivotal role of serotonin (5HT) in reducing carbohydrate (CHO) intake, and have provided a more selective tool with which to study appetite regulation. It would be expected that all SSRIs should exert a similar anorectic action. However, recent reports provide evidence to the contrary. Despite their claimed selectivity, SSRIs still interact, either directly or indirectly, with various critical neurotransmitter systems. In addition, although the anorectic action of fluoxetine (FLX) is well recognized, long-term follow-up studies in depressed patients and in obese nondepressed patients reveal that its weight-reducing effects are transient, even leading to a gain in body weight. Similarly, paroxetine (PRX) and citalopram (CTP) have also been associated with weight gain. These latter observations are unexpected because PRX and CTP are highly potent and selective SSRIs. A neuropharmacologic rationale for the apparent paradoxic effects of SSRIs on appetite not a review of neuronal regulation of appetite is presented in this article. As with the regulation of feeding, paradoxic weight gain observed with SSRIs appears to rest on the interaction of 5HT with multiple mechanisms, with the extent of weight gain observed being dependent on subtle, yet important pharmacologic differences within the group. Finally, the neurobiology of depressive illness itself, and of recovery from it, is a major contributing factor to individual response to these drugs.

Changes in mood, cognitive performance and appetite in the late luteal and follicular phases of the menstrual cycle in women with and without PMDD (premenstrual dysphoric disorder)

“…In fact, several studies have shown that long-term treatment with SSRIs can result in significant weight gain (e.g. Fogelson, 1991;Harvey & Bouwer, 2000). Consequently, women with PMDD may need to be cautioned about the risks of increased food cravings and food intake, particularly in combination with specific drugs or medications (e.g.…”

Common Medications Which Lead to Unintended Alterations in Weight Gain or Organ Lipotoxicity

“…Paroxetine was responsible for weight gain of 3.6 % above baseline body weight. The mechanism underlying weight gain with these agents may involve several factors, primarily the remission of depression with improved appetite and carbohydrate craving due to a direct role of 5-HT on appetite regulation [71]. There is an increased risk of developing diabetes mellitus from the weight gain associated with long-term treatment with SSRIs.…”

Metabolic issues and cardiovascular disease in patients with psychiatric disorders

“…Antidepressants have been associated with weight gain to varying degrees. For the selective serotonin reuptake inhibitor (SSRI) class of antidepressants (fluoxetine, sertraline, paroxetine, and citalopram), this may reflect their multiple serotonergic activities, 31 one of which is an affinity for serotonin (5-hydroxytryptamine 2C [5-HT 2C ]) receptors. Recent research has implicated these receptors as having a role in the regulation of appetite.…”