What medications are used to gain weight?

Medications for Weight Gain

For intentional weight gain in specific medical contexts, oxandrolone and megestrol acetate are FDA-approved options, while for unintentional weight loss prevention, switching to medications known to cause weight gain (such as certain antipsychotics, antidepressants, or antiepileptics) may be appropriate depending on the underlying condition being treated. 1, 2, 3

FDA-Approved Medications for Therapeutic Weight Gain

Oxandrolone

• Indicated as adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma, and in patients who fail to gain or maintain normal weight without definite pathophysiologic reasons 1
• Also used to offset protein catabolism associated with prolonged corticosteroid administration 1
• Dosing considerations: Lower doses are recommended in elderly patients (≥65 years) due to greater sensitivity to fluid retention and hepatic transaminase elevations 1
• Mean weight gain was similar across age groups in clinical trials, with treatment durations averaging 68.5 to 94.7 days 1
• Important monitoring: Requires periodic liver function tests due to hepatotoxicity risk, lipid level monitoring, and hemoglobin/hematocrit checks for polycythemia 1
• Significant drug interaction: Can cause unexpectedly large increases in INR/PT when combined with warfarin, requiring an approximately 80-85% reduction in warfarin dose 1

Megestrol Acetate

• Weight gain is a frequent side effect of this medication, associated with increased appetite rather than fluid retention 2
• Carries risks of thromboembolic phenomena (including fatal pulmonary embolism), glucocorticoid effects, heart failure, and hyperglycemia 2
• Should be used with caution given the serious adverse event profile 2

Medications That Cause Weight Gain as a Side Effect

When the goal is to counteract unintentional weight loss or when weight gain would be beneficial, consider switching to medications within the same therapeutic class that are associated with weight gain:

Antipsychotics

• Olanzapine, clozapine, quetiapine, and risperidone are consistently associated with substantial weight gain 4, 3
• Weight gain occurs partly through antagonism of hypothalamic H1 histamine receptors 4

Antidepressants

• Amitriptyline (tricyclic) has the highest association with weight gain among tricyclic antidepressants 4, 5, 6
• Mirtazapine and paroxetine (SSRI) also promote significant weight gain 4, 3, 6
• These medications affect appetite regulation through multiple mechanisms 5

Antiepileptic Agents

• Gabapentin, pregabalin, valproic acid, and carbamazepine are consistently associated with weight gain 4, 3
• In contrast, topiramate and zonisamide promote weight loss and should be avoided if weight gain is desired 4

Other Medication Classes

• Antihyperglycemics: Insulin and sulfonylureas (e.g., glyburide) promote weight gain 4
• Beta-blockers are associated with weight gain 4
• Progesterone-based contraceptives: Medroxyprogesterone acetate demonstrates evidence of weight gain 4
• Oral glucocorticoids are often cited as most likely to cause weight gain, though actual incidence is poorly defined 4
• Protease inhibitors (antiretroviral therapy) promote weight gain 4

Clinical Monitoring and Management

When Using Weight-Gain Promoting Medications

• Monitor weight trajectory regularly, particularly during initial months of treatment 4, 6
• Watch for unintentional weight gain >2 kg in a month or ≥7% increase from baseline body weight 4, 5, 6
• Assess for development of weight-related complications including cardiovascular disease, diabetes, and hepatic steatosis 4

Important Caveats

• Dose-dependent effects: Weight gain effects may be more significant with higher doses and long-term use 5
• Individual variability: Response to weight-gain promoting medications varies considerably between patients 4
• When prescribing medications that promote weight gain, use the lowest dose required for clinical efficacy for the shortest duration necessary if weight gain is not the therapeutic goal 4

Context-Specific Considerations

The appropriateness of using medications for weight gain depends entirely on the clinical context:

• For cachexia or post-surgical/trauma recovery: Oxandrolone is specifically FDA-approved for this indication 1
• For appetite stimulation: Megestrol acetate causes weight gain through increased appetite 2
• For psychiatric conditions with comorbid underweight: Switching to weight-gain promoting antipsychotics or antidepressants may address both conditions 3
• For seizure disorders with underweight: Selecting gabapentin, pregabalin, valproic acid, or carbamazepine over weight-neutral alternatives may be beneficial 4, 3