Can paroxetine (selective serotonin reuptake inhibitor, SSRI) cause weight gain?

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From the Guidelines

Paroxetine is associated with a significant risk of weight gain, making it one of the SSRIs with the highest potential for this side effect. According to a study published in Gastroenterology in 2017 1, paroxetine and amitriptyline were found to have the greatest risk for weight gain among the SSRI and tricyclic antidepressant classes of drugs. This is in contrast to other SSRIs like fluoxetine and sertraline, which have been associated with weight loss with short-term use and weight neutrality with long-term use 1. The exact mechanism of paroxetine-induced weight gain is not fully understood, but it is thought to involve its effects on serotonin receptors, which can increase appetite and carbohydrate cravings, as well as potential changes in metabolism.

Some key points to consider when prescribing paroxetine include:

  • Monitoring weight changes in patients taking paroxetine
  • Discussing the potential for weight gain with patients before starting treatment
  • Considering alternative SSRIs with less impact on weight, such as fluoxetine or sertraline
  • Avoiding abrupt discontinuation of paroxetine due to weight concerns, as this can cause withdrawal symptoms

It is essential to weigh the potential benefits of paroxetine against the risk of weight gain, particularly in patients with a history of weight-related issues or other health concerns. By being aware of the potential for weight gain and taking steps to mitigate it, healthcare providers can help patients make informed decisions about their treatment and minimize the risk of adverse effects. As noted in the study, the choice of agent must still be guided by best practice for the individual patient’s circumstance 1.

From the FDA Drug Label

Decreased appetite and weight loss have been observed in association with the use of SSRIs Consequently, regular monitoring of weight and growth should be performed in children and adolescents treated with an SSRI such as PAXIL

The FDA drug label does not mention weight gain as a side effect of paroxetine. Instead, it mentions decreased appetite and weight loss as associated with the use of SSRIs, including paroxetine. Therefore, based on the available information, paroxetine is not likely to cause weight gain. 2

From the Research

Weight Gain and Paroxetine

  • Paroxetine, a selective serotonin reuptake inhibitor (SSRI), has been associated with weight gain in several studies 3, 4, 5, 6, 7.
  • A study comparing the effects of fluoxetine, sertraline, and paroxetine on weight found that paroxetine-treated patients experienced a significant weight increase, while fluoxetine-treated patients had a modest but nonsignificant weight decrease, and sertraline-treated patients had a modest but nonsignificant weight increase 3.
  • Another study reviewed the literature on weight gain and antidepressants, including SSRIs, and found that paroxetine may be more likely to cause weight gain than other SSRIs during long-term treatment 4.
  • The neuropharmacology of paradoxic weight gain with SSRIs, including paroxetine, has been studied, and it is suggested that the interaction of serotonin with multiple mechanisms may contribute to the apparent paradoxic effects of SSRIs on appetite 5.
  • A review of paroxetine's current status in psychiatry noted that the potential for discontinuation syndrome and weight gain appears to be slightly higher with paroxetine than with other SSRIs 6.
  • A comprehensive meta-analysis of antidepressants and body weight found that paroxetine was associated with a greater risk of weight gain, along with amitriptyline and mirtazapine 7.

Comparison with Other SSRIs

  • Paroxetine has been compared to other SSRIs, such as fluoxetine and sertraline, in terms of its effects on weight, and it appears to have a higher risk of weight gain 3, 4, 7.
  • Fluoxetine, in particular, has been found to have a weight-reducing effect, at least in the acute phase of treatment, whereas paroxetine has been associated with weight gain 4, 7.
  • The differences in weight effects between SSRIs may be due to subtle pharmacologic differences within the group, as well as individual patient characteristics 5, 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Weight gain and antidepressants.

The Journal of clinical psychiatry, 2000

Research

Paroxetine: current status in psychiatry.

Expert review of neurotherapeutics, 2007

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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