Do Selective Serotonin Reuptake Inhibitors (SSRIs) cause weight gain?

Do SSRIs Cause Weight Gain?

Yes, SSRIs can cause weight gain, but the effect varies significantly between different medications within this class, with paroxetine associated with the greatest risk for weight gain and bupropion (not an SSRI but often used as an antidepressant) associated with weight loss or weight neutrality. 1

Weight Effects of Different SSRIs

Different SSRIs have varying effects on weight:

• Paroxetine (Paxil): Associated with the greatest risk for weight gain within the SSRI class 1
• Escitalopram (Lexapro): Associated with higher weight gain (0.41 kg more than sertraline at 6 months) 2
• Sertraline (Zoloft): Associated with modest weight changes; used as a reference in comparative studies 2
• Fluoxetine (Prozac): Associated with weight loss during short-term use and weight neutrality with long-term use 1
• Bupropion (Wellbutrin): Not an SSRI but often used as an antidepressant; consistently associated with the least weight gain or even weight loss 1, 2

Magnitude of Weight Changes

• In a comprehensive study comparing antidepressants, the estimated 6-month weight differences compared to sertraline were:

  • Escitalopram: +0.41 kg
  • Paroxetine: +0.37 kg
  • Fluoxetine: -0.07 kg (slightly weight neutral)
  • Bupropion: -0.22 kg (weight loss) 2

• In pediatric trials with sertraline, there was a difference in weight change between sertraline and placebo of roughly 1 kilogram, representing a slight weight loss for sertraline compared to a slight gain for placebo 3

Timing of Weight Changes

• Weight changes with SSRIs often follow a temporal pattern:
  • Initial weight loss may occur in the first few weeks of treatment
  • Weight gain typically becomes more evident with long-term use 4
  • With sertraline specifically, patients began gaining weight compared to baseline by week 12 of treatment 3

Risk Factors for SSRI-Associated Weight Gain

The association between SSRI use and weight gain is stronger among individuals with:

• High intake of Western diet
• Greater sedentary activity
• Smoking habits 5

Clinical Implications

1. For patients with significant weight concerns:

   • Consider bupropion as a first choice due to its association with the least weight gain or even weight loss 1
   • Fluoxetine or sertraline are reasonable second choices due to their relatively weight-neutral effects with long-term use 1

2. Medications to avoid if weight gain is a significant concern:

   • Paroxetine
   • Escitalopram
   • Mirtazapine (not an SSRI but an antidepressant with high risk of weight gain) 1

3. Monitoring recommendations:

   • Regular monitoring of weight is recommended, especially with long-term SSRI treatment 3
   • Weight changes may be more pronounced in children and adolescents, with about 7% of children experiencing weight loss >7% of body weight on sertraline 3

Mechanism of SSRI-Associated Weight Gain

The paradoxical weight gain observed with SSRIs appears to involve complex interactions between serotonin and multiple mechanisms, with the extent of weight gain being dependent on subtle yet important pharmacological differences within the SSRI class 6.

Weight gain during antidepressant treatment can be either:

• A sign of improvement in patients who had weight loss as a symptom of depression
• A side effect of the medication itself, particularly when weight gain continues despite achieving full remission of depressive symptoms 7

In conclusion, while SSRIs as a class can cause weight gain, the effect varies significantly between different medications, with some causing weight gain (particularly paroxetine), others being relatively weight neutral (fluoxetine, sertraline), and non-SSRI options like bupropion potentially causing weight loss.