What selective serotonin reuptake inhibitors (SSRIs) are considered weight-neutral?

Weight-Neutral SSRIs

Fluoxetine and sertraline are the weight-neutral SSRIs you should prescribe when weight concerns are a priority. 1, 2

First-Line SSRI Recommendations for Weight-Conscious Patients

• Fluoxetine is the preferred first choice among SSRIs, as it typically causes modest weight loss during initial treatment (first 6-12 weeks) followed by weight neutrality with long-term use 1, 2

• Sertraline is the second-line SSRI option, showing short-term weight loss that transitions to weight neutrality with chronic use 1, 2

• Both fluoxetine and sertraline demonstrate significantly better weight profiles than other SSRIs in head-to-head comparisons 3

SSRIs to Avoid Due to Weight Gain Risk

• Paroxetine has the highest risk of weight gain among all SSRIs and should be avoided when weight is a concern 1, 2, 4

• In a 26-32 week comparative trial, paroxetine-treated patients experienced significant weight increase, while fluoxetine-treated patients had modest weight decrease and sertraline-treated patients had minimal weight increase 3

• The number of patients gaining ≥7% of baseline weight was significantly greater with paroxetine compared to either fluoxetine or sertraline 3

Comparative Weight Effects Among Common Antidepressants

• Bupropion (not an SSRI) is the only antidepressant consistently associated with weight loss rather than weight gain, making it the optimal choice when weight concerns are paramount 1, 2

• In long-term trials (up to 6 months), 23% of bupropion-treated patients lost ≥5 lbs compared to only 11% on placebo 1, 5

• Bupropion promotes weight loss through appetite suppression and reduced food cravings 1

• However, bupropion should be avoided in patients with seizure disorders or eating disorders, as it lowers the seizure threshold 1

Clinical Algorithm for Antidepressant Selection When Weight Matters

1. If no contraindications exist (no seizure disorder, no eating disorder, no uncontrolled hypertension): Choose bupropion as first-line 1, 2

2. If an SSRI is specifically required or bupropion is contraindicated: Choose fluoxetine as first-line SSRI 1, 2

3. If fluoxetine is not tolerated or ineffective: Switch to sertraline as second-line SSRI 1, 2

4. Never use paroxetine when weight is a concern 1, 2, 4

Additional Weight-Neutral or Favorable Options

• Vortioxetine can be considered as a weight-neutral alternative if fluoxetine and sertraline are not appropriate 1

• Citalopram shows minimal weight change (0.12 kg difference vs sertraline at 6 months), making it relatively weight-neutral though less favorable than fluoxetine or sertraline 6

• Escitalopram is associated with slightly more weight gain than sertraline (0.41 kg difference at 6 months) and should be considered less favorable 6

Important Clinical Caveats

• Weight effects vary significantly within the SSRI class, emphasizing that not all SSRIs behave identically regarding metabolic effects 1, 2

• Individual variations can occur even with weight-neutral SSRIs, requiring monitoring 7

• Regular weight monitoring is essential if long-term SSRI treatment continues, particularly in pediatric patients: monitor at baseline, monthly for the first 3 months, then quarterly during continued treatment 1

• In pediatric populations, approximately 7% of children on sertraline experienced weight loss >7% of body weight compared to none on placebo, though this effect diminished with longer-term treatment 8

• The choice of agent must ultimately be guided by the specific type of depression or anxiety disorder being treated, but within appropriate options, weight profile should influence selection 2