Antidepressants with the lowest weight gain

Which antidepressants cause the least weight gain, and which cause the most. Bupropion is weight-neutral or causes weight loss. Mirtazapine causes the most among common antidepressants. Ranking and clinical decision framework.

Medically reviewed by Shariq Refai, MD, MBA Last reviewed: July 2026

Ranking (lowest to highest weight gain)

Weight-neutral or weight loss:

Bupropion (Wellbutrin, Zyban): mean weight loss of 1 to 3 kg in the first year. May improve weight in patients with binge eating pattern.

Minimal weight change:

Vortioxetine (Trintellix): minimal weight change in trials
Vilazodone (Viibryd): minimal weight change

Low weight gain:

Fluoxetine (Prozac): relatively weight-neutral short-term; long-term data mixed
Sertraline (Zoloft): minimal short-term; some long-term gain
Escitalopram (Lexapro): minimal short-term; some long-term gain
Citalopram (Celexa): similar

Moderate weight gain:

Duloxetine (Cymbalta): mean 1 to 2 kg first year
Venlafaxine (Effexor): similar
Desvenlafaxine (Pristiq): similar
Paroxetine (Paxil): highest weight gain among SSRIs
Trazodone (off-label): mild sedation-related weight gain

Higher weight gain:

Some TCAs (amitriptyline, doxepin, imipramine, clomipramine): via anticholinergic and antihistamine effects

Highest antidepressant weight gain:

Mirtazapine (Remeron): mean 3 to 4 kg in first year, often much more

Mechanisms

Bupropion mechanism (weight-neutral or weight loss): dopamine and norepinephrine reuptake inhibition without histamine or 5-HT2C effect. Increases dopamine, which reduces food-seeking behavior. Sometimes used specifically for weight management (Contrave, bupropion-naltrexone combination).

SSRIs and SNRIs (variable weight): 5-HT2C activation can produce satiety early, but chronic use may cause metabolic changes leading to gradual weight gain. Individual variability large.

Mirtazapine (high weight gain): strong H1 (histamine) antagonism increases appetite. 5-HT2C antagonism disinhibits food-seeking. Alpha-2 antagonism may play role. Combined mechanism makes mirtazapine an outlier for weight gain.

TCAs (moderate weight gain): H1 antagonism plus anticholinergic burden reducing energy expenditure.

Clinical decision framework

When weight is priority concern:

First choice: bupropion
Alternatives: fluoxetine, vortioxetine, vilazodone
Consider: sertraline or escitalopram if bupropion not appropriate

When weight gain would be beneficial (elderly with cachexia, anorexia comorbidity):

Mirtazapine (also aids sleep)
Certain TCAs (with anticholinergic burden considered)

Switching for weight reasons:

Existing SSRI → bupropion (or bupropion augmentation)
Existing SNRI → bupropion
Existing mirtazapine → bupropion or vortioxetine (large change likely)

Augmentation for weight:

Adding bupropion 150 to 300 mg to existing SSRI: modest weight loss effect and often helps sexual side effects too

Combination pharmacology for weight

Bupropion-naltrexone (Contrave) is FDA-approved specifically for weight loss. Uses subtherapeutic depression dose but is FDA-approved for the weight indication. Not universally covered by insurance.

GLP-1 receptor agonists (semaglutide, tirzepatide) for antipsychotic-induced weight gain are increasingly used. Off-label for antidepressant-induced weight gain, but rationale is similar. See weight gain side effect page.

Common questions

Which antidepressant causes the least weight gain? Bupropion. Mean weight loss of 1 to 3 kg in the first year.

Is Wellbutrin (bupropion) as effective as an SSRI? For depression, comparable efficacy in most head-to-head trials. Less effective for anxiety disorders (where it's not first-line). No good for OCD.

Does mirtazapine really cause 10+ pounds of weight gain? Mean 3 to 4 kg (7 to 9 pounds) in the first year but wide individual variation. Some patients gain 15+ pounds. Some minimal.

Are there weight-loss antidepressants? Bupropion can cause modest weight loss. No antidepressant is FDA-approved for weight loss (though bupropion-naltrexone is approved for the weight indication).

Do SSRIs cause weight gain long-term? Yes for many patients. 5 to 10 pounds over 1 to 2 years is typical. Paroxetine causes the most. Difference from short-term trials suggests longer-term follow-up matters.

Does dose reduction help weight gain? Sometimes. Weight gain is dose-related for most antidepressants. Lowest effective dose may reduce weight effect.

Can I add Wellbutrin to my current antidepressant? Yes, common augmentation strategy. Especially helpful when both weight and sexual side effects are concerns.

Does depression itself cause weight gain? Both directions. Depression can cause weight loss (reduced appetite, anhedonia) or weight gain (comfort eating, reduced activity, atypical depression). Improvement in depression may itself change weight regardless of medication.

Sources

Serretti A, Mandelli L. Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry. 2010;71(10):1259-1272.
Blumenthal SR, Castro VM, Clements CC, et al. An electronic health records study of long-term weight gain following antidepressant use. JAMA Psychiatry. 2014;71(8):889-896.
Anderson JW, Greenway FL, Fujioka K, Gadde KM, McKenney J, O'Neil PM. Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obes Res. 2002;10(7):633-641.
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