What is the role of Selective Serotonin Reuptake Inhibitors (SSRIs) in weight loss?

From the Guidelines

SSRIs are not recommended as primary medications for weight loss, and their use for this purpose should be approached with caution due to variable effects on weight and potential side effects. While some SSRIs like fluoxetine may cause temporary weight loss in some individuals, with a pooled weight loss of 4.74 kg at 6 months and 3.15 kg at 12 months 1, most SSRIs are actually associated with weight gain over time. The evidence for SSRIs in weight loss is limited, and the available data are often from studies with co-interventions such as diet and exercise, making it difficult to isolate the effect of the medication alone. For example, in studies of fluoxetine, diet was a co-intervention in 78% of the studies, and exercise was included in 12% of the studies 1.

Key Considerations

• The use of SSRIs for weight loss is not approved by the FDA, and these medications are primarily indicated for treating depression, anxiety disorders, and other mental health conditions.
• The effects of SSRIs on weight vary greatly between individuals and medications, with some causing weight loss and others leading to weight gain.
• For effective and safe weight management, a comprehensive approach including dietary changes, regular physical activity, and potentially weight-loss medications specifically designed for this purpose is recommended.
• FDA-approved weight loss medications like phentermine-topiramate (Qsymia), semaglutide (Wegovy), or orlistat (Xenical) would be more appropriate options under medical supervision.

Important Factors

• The optimal duration of treatment for weight loss has not been determined, with most data available for up to 12 months of therapy 1.
• The presence of comorbid conditions and potential side effects should be carefully considered when evaluating the use of any medication for weight loss.
• Always consult with a healthcare provider before starting any medication for weight loss to ensure it's appropriate for your specific health situation.

From the FDA Drug Label

Altered Appetite and Weight — Significant weight loss, especially in underweight depressed or bulimic patients may be an undesirable result of treatment with Prozac. In US placebo–controlled clinical trials for major depressive disorder, 11% of patients treated with Prozac and 2% of patients treated with placebo reported anorexia (decreased appetite). Weight loss was reported in 1. 4% of patients treated with Prozac and in 0. 5% of patients treated with placebo. However, only rarely have patients discontinued treatment with Prozac because of anorexia or weight loss (see also Pediatric Use under PRECAUTIONS). In US placebo–controlled clinical trials for OCD, 17% of patients treated with Prozac and 10% of patients treated with placebo reported anorexia (decreased appetite) One patient discontinued treatment with Prozac because of anorexia (see also Pediatric Use under PRECAUTIONS). In US placebo–controlled clinical trials for bulimia nervosa, 8% of patients treated with Prozac 60 mg and 4% of patients treated with placebo reported anorexia (decreased appetite). Patients treated with Prozac 60 mg on average lost 0.45 kg compared with a gain of 0. 16 kg by patients treated with placebo in the 16–week double–blind trial. Weight change should be monitored during therapy.

The role of Selective Serotonin Reuptake Inhibitors (SSRIs) in weight loss is that they may cause weight loss as a side effect, particularly in patients with major depressive disorder, OCD, or bulimia nervosa. Key points include:

• Anorexia (decreased appetite) was reported in 11% of patients treated with Prozac for major depressive disorder, 17% for OCD, and 8% for bulimia nervosa.
• Weight loss was reported in 1.4% of patients treated with Prozac for major depressive disorder.
• Patients treated with Prozac 60 mg for bulimia nervosa lost an average of 0.45 kg compared to a gain of 0.16 kg in the placebo group. It is essential to monitor weight change during therapy with SSRIs like Prozac 2.

From the Research

Role of SSRIs in Weight Loss

• SSRIs have been associated with weight loss during acute treatment, but the effects of long-term treatment on weight are not well characterized 3, 4.
• Studies have shown that fluoxetine, a type of SSRI, reduces food, energy, and carbohydrate intake and increases resting energy expenditure, which may account for the moderate and transient body weight loss observed with its use 5.
• A study found that patients who completed 50 weeks of therapy with fluoxetine had a mean absolute weight increase similar to that of patients taking placebo, and weight gain was related to improvement in appetite after recovery 4.
• Another 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 6.
• An animal study found that fluoxetine caused a decrease in body weight in albino rats, with higher doses leading to more significant weight loss and even death due to excessive body weight loss, loose stools, and muscle twitching 7.

Comparison of SSRIs

• Different SSRIs may have differential effects on weight, with paroxetine associated with significant weight gain and fluoxetine associated with modest weight loss 6.
• The risk of weight gain during extended SSRI treatment differs depending on which SSRI is used, with paroxetine having a higher risk of weight gain compared to fluoxetine and sertraline 6.

Clinical Implications

• SSRIs may be a useful treatment option for obese psychiatric patients, as they can cause weight loss without the need for withdrawal of the drug 7.
• Clinicians should consider the potential for weight changes when prescribing SSRIs, particularly paroxetine, and monitor patients' weight regularly 3, 6.