Which antidepressant, Lexapro (escitalopram) or Prozac (fluoxetine), is more likely to cause weight gain in a night shift worker?

Weight Gain: Lexapro vs Prozac

Lexapro (escitalopram) causes more weight gain than Prozac (fluoxetine), with escitalopram associated with modest weight gain while fluoxetine remains weight-neutral to slightly weight-reducing over time. 1

Direct Comparative Evidence

The most robust head-to-head data comes from a 2024 large-scale observational study of 183,118 patients across 8 U.S. health systems:

• Escitalopram was associated with 0.41 kg greater weight gain at 6 months compared to sertraline (the reference comparator), representing one of the higher weight-gain profiles among SSRIs 1
• Fluoxetine showed minimal weight change with a difference of -0.07 kg compared to sertraline (essentially weight-neutral) 1
• Escitalopram carried a 10-15% higher risk of gaining ≥5% of baseline body weight compared to reference treatment, while fluoxetine did not show this increased risk 1

FDA-Labeled Weight Effects

Escitalopram (Lexapro)

• "Increased weight" is listed as a metabolic/nutritional adverse event in FDA labeling 2
• Patients treated with escitalopram in controlled trials did not differ significantly from placebo regarding clinically important weight change during acute treatment, but weight gain emerged as a documented adverse event 2

Fluoxetine (Prozac)

• Weight loss is the predominant acute effect: 11% of fluoxetine-treated patients vs 2% of placebo patients reported anorexia/decreased appetite 3
• Patients on fluoxetine 60 mg lost an average of 0.45 kg compared to a 0.16 kg gain in placebo patients during 16-week trials 3
• Long-term data shows weight neutrality: After initial weight loss during acute treatment (mean 0.4 kg decrease in first 4 weeks), patients on fluoxetine continuation therapy showed similar weight gain to placebo over 50 weeks, with weight increase related to depression recovery rather than medication effect 4

Clinical Context for Night Shift Workers

For your night shift worker specifically:

• Night shift work independently increases obesity risk through circadian disruption and metabolic dysregulation
• Choose fluoxetine (Prozac) to avoid compounding weight gain risk in this already vulnerable population 1
• The weight-neutral to slightly weight-reducing profile of fluoxetine makes it preferable when metabolic concerns are present 3, 4

Mechanistic Considerations

• SSRIs vary in their weight effects despite similar mechanisms: The difference between escitalopram and fluoxetine likely relates to differential effects on appetite regulation and metabolic pathways beyond serotonin reuptake 5
• A 2011 head-to-head trial confirmed escitalopram causes minimal weight change (0.14 kg over 12 weeks), but this was still more than would be expected with fluoxetine based on comparative data 6

Alternative if Weight is Primary Concern

• Bupropion remains the only antidepressant consistently associated with weight loss (-0.22 kg difference vs sertraline at 6 months, with 15% reduced risk of ≥5% weight gain) 1
• Consider bupropion as first-line if weight gain is a critical concern, though it has different side effect profile (more activating, contraindicated in seizure disorders) 5

Monitoring Recommendations

• Weigh at baseline and monthly during the first 3 months of treatment 5
• Weight gain >2 kg in one month or ≥7% of baseline weight warrants intervention: consider switching medications or adding lifestyle modifications 5