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

From the Guidelines

Yes, paroxetine can cause weight gain, as it is associated with a higher risk of weight gain compared to other medications in its class, with approximately 25% of patients experiencing weight gain, typically ranging from 5 to 15 pounds over several months of treatment, as reported in studies such as 1 and 1.

Key Points to Consider

• The weight gain associated with paroxetine tends to be more pronounced with long-term use and may be dose-dependent, as suggested by studies including 1.
• The mechanism behind this side effect involves paroxetine's effects on appetite regulation, metabolism, and carbohydrate cravings, as well as its stronger antihistamine properties compared to other SSRIs, which can contribute to increased appetite and weight gain, as noted in 1.
• If weight gain becomes problematic while taking paroxetine, patients should not stop the medication abruptly but should discuss their concerns with their healthcare provider, who may consider alternative antidepressants with lower weight gain potential, such as fluoxetine, sertraline, or bupropion, as mentioned in 1 and 1.
• Lifestyle modifications, including regular physical activity and dietary adjustments, may help mitigate weight gain while continuing necessary treatment, as a general principle of managing weight gain associated with medication use.

Relevant Evidence

• A study published in the journal Gastroenterology in 2017 1 noted that paroxetine and amitriptyline were associated with the greatest risk for weight gain among antidepressants.
• Another study published in the Annals of Internal Medicine in 2008 1 reported that mirtazapine and paroxetine resulted in higher weight gain than sertraline, trazodone, or venlafaxine.
• The same study 1 also mentioned that paroxetine had higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline.
• A clinical practice guideline from the American College of Physicians published in 2008 1 and 1 discussed the adverse effects of second-generation antidepressants, including weight gain, and noted that paroxetine was associated with an increased risk for sexual dysfunction.

From the FDA Drug Label

Weight and Vital Sign Changes Significant weight loss may be an undesirable result of treatment with PAXIL for some patients but, on average, patients in controlled trials had minimal (about 1 pound) weight loss versus smaller changes on placebo and active control

• Weight gain is not mentioned as a common side effect of paroxetine in the provided drug labels.
• The labels do mention that patients in controlled trials had minimal weight loss.
• Therefore, based on the provided information, it cannot be concluded that paroxetine causes weight gain, but rather that it may be associated with minimal weight loss in some patients 2.

From the Research

Paroxetine and Weight Gain

• Paroxetine has been associated with a significant weight increase in patients, as shown in a study published in The Journal of Clinical Psychiatry 3.
• The study found that paroxetine-treated patients experienced a significant weight increase, while fluoxetine-treated patients had a modest but nonsignificant weight decrease, and patients treated with sertraline had a modest but nonsignificant weight increase.
• Another study published in BMJ Open found that SSRI use, including paroxetine, was associated with weight gain, particularly in individuals with unhealthy lifestyles 4.
• A comprehensive review and meta-analysis published in The Journal of Clinical Psychiatry found that paroxetine was associated with a greater risk of weight gain, along with other antidepressants such as amitriptyline and mirtazapine 5.
• A target trial emulation study published in Annals of Internal Medicine found that paroxetine was associated with a higher estimated 6-month weight gain compared to sertraline, and a higher risk of gaining at least 5% of baseline weight 6.
• A systematic review published in Obesity Reviews found that most studies showed a 5% weight gain in individuals using antidepressant therapy, including paroxetine, and that weight loss was found in individuals treated with bupropion 7.