What medications, such as Megace (megesterol acetate) or Oxandrin (oxandrolone), can help stimulate appetite and gain weight?

Medications for Weight Gain and Appetite Stimulation

For cancer-related anorexia and cachexia, megestrol acetate 400-800 mg daily is the first-line pharmacological intervention, with robust evidence for appetite improvement and weight gain, though you must counsel patients about significant risks including thromboembolic events (1 in 6 patients) and increased mortality (relative risk 1.42). 1, 2

Primary Pharmacological Options

Megestrol Acetate (Megace) - First-Line for Cancer Cachexia

Efficacy:

• Patients are 2.57 times more likely to experience appetite improvement and 1.55 times more likely to gain weight compared to placebo. 2
• Approximately 1 in 4 patients will have increased appetite, and 1 in 12 will gain weight. 2
• Meta-analysis demonstrates clear benefit for appetite improvement and weight gain in cancer, AIDS, and other conditions. 3

Dosing:

• Start with 400-800 mg daily orally; the liquid formulation is preferred as it is less expensive and more bioavailable. 2, 4
• Higher doses (800 mg/day) show greater weight improvement, though doses above 480 mg/day show diminishing additional benefit. 2
• A reasonable alternative is starting at 160 mg/day and titrating to 480-800 mg/day based on response. 2

Critical Safety Warnings:

• Thromboembolic events (DVT, PE) occur with relative risk of 1.84 - approximately 1 in 6 patients will develop these complications. 2, 5
• Mortality risk is increased with relative risk of 1.42 - approximately 1 in 23 patients will die from treatment-related complications. 2
• Edema occurs with relative risk of 1.36. 2, 5
• Weight gain is primarily adipose tissue rather than skeletal muscle, which limits functional benefit. 1, 2, 5
• Adrenal suppression can occur with long-term use; monitor adrenal function. 1, 2
• May cause vaginal bleeding in women and impotence in men. 6, 4

Monitoring Requirements:

• Regular assessment for thromboembolic phenomena is essential. 2, 5
• Monitor weight changes to assess response. 2, 5
• Assess adrenal function in patients on long-term therapy. 2, 5
• Limit duration of therapy and regularly reassess whether continued treatment is warranted based on response and quality of life goals. 2, 6

Clinical Context:

• Most appropriate for patients with life expectancy measured in months rather than weeks where increased appetite is an important quality of life goal. 2, 6
• Should be avoided in bed-bound patients due to increased DVT risk. 7
• Consider combining with testosterone in men to offset hormonal effects. 7

Oxandrolone (Oxandrin) - Anabolic Alternative

FDA-Approved Indications:

• Adjunctive therapy to promote weight gain after extensive surgery, chronic infections, or severe trauma. 8
• For patients who fail to gain or maintain normal weight without definite pathophysiologic reasons. 8
• To offset protein catabolism associated with prolonged corticosteroid administration. 8

Comparative Efficacy:

• In HIV-related weight loss, oxandrolone 10 mg twice daily produces similar weight gain to megestrol acetate (2.5 kg vs 2.8 kg over 2 months), but with a higher proportion of lean body mass (56% vs 39%). 9
• Better for preserving or building muscle mass compared to megestrol acetate. 9

Practical Application:

• Oxandrolone should be reserved for patients with profound cachexia where lean body mass preservation is critical. 7
• Typical dosing is 10 mg twice daily. 9
• Well-tolerated with similar adverse event profile to megestrol acetate in comparative trials. 9

Alternative Options Based on Clinical Context

Corticosteroids (Dexamethasone) - For Shorter Life Expectancy

When to Use:

• Consider dexamethasone 2-8 mg daily as an alternative to megestrol acetate for patients with life expectancy of weeks to a couple months. 1, 2, 6
• Provides similar appetite stimulation to megestrol acetate but with different toxicity profile and lower cost. 2, 6
• Faster onset of action compared to megestrol acetate. 6

Limitations:

• Toxicities and decline in efficacy with long-term use limit their role. 1
• Should not be used for prolonged periods due to significant side effects. 6

Mirtazapine - For Elderly Patients with Depression

Specific Indication:

• Elderly patients with appetite loss and concurrent depression should receive mirtazapine 7.5-30 mg at bedtime, as it addresses both conditions simultaneously. 6
• Promotes sleep, appetite, and weight gain. 6

Dosing:

• Start with 7.5 mg at bedtime, maximum 30 mg at bedtime. 6
• Full therapeutic trial requires 4-8 weeks to assess efficacy. 6

Expected Outcomes:

• Mean weight gain of 1.9 kg at 3 months and 2.1 kg at 6 months, with approximately 80% experiencing some weight gain. 6

Important Caveat:

• Do NOT use in patients with dementia without depression - evidence shows no consistent benefit and potentially harmful side effects outweigh uncertain benefits. 6

Combination Therapy - Enhanced Efficacy

Megestrol Acetate + Olanzapine:

• Combination therapy with megestrol acetate plus olanzapine 5 mg daily showed superior weight gain (85% vs 41% achieving ≥5% weight gain) in one trial. 2, 5
• This approach requires further validation but represents a promising strategy. 2

Megestrol Acetate + Exercise:

• May be most effective when combined with exercise programs to maintain or increase lean body mass. 2
• However, megestrol acetate may attenuate benefits of resistance training, causing smaller gains or deterioration in muscle strength and functional performance. 6

Medications NOT Recommended

Cannabinoids (Dronabinol)

• Cannabinoids are inferior to megestrol acetate for appetite stimulation in cancer patients. 2
• Multiple guidelines conclude insufficient evidence to support routine use. 6
• Three placebo-controlled trials in dementia patients found no significant effect on body weight, BMI, or energy intake. 6

Other Agents with Insufficient Evidence

• Cyproheptadine, hydrazine sulfate, melatonin, TNF inhibitors, and insulin lack benefit or have insufficient evidence. 1
• Thalidomide has insufficient evidence to support use for cachexia management. 1

Clinical Decision Algorithm

Step 1: Identify the underlying condition and life expectancy

• Cancer cachexia with months of life expectancy → Megestrol acetate 400-800 mg daily 2
• Cancer cachexia with weeks of life expectancy → Dexamethasone 2-8 mg daily 1, 2
• Elderly with depression and poor appetite → Mirtazapine 7.5-30 mg at bedtime 6
• Post-surgical/trauma with need for lean mass → Oxandrolone 10 mg twice daily 8, 9

Step 2: Assess contraindications

• Bed-bound patients → Avoid megestrol acetate due to DVT risk 7
• History of thromboembolic disease → Consider alternatives to megestrol acetate 2
• Dementia without depression → Avoid all appetite stimulants 6

Step 3: Initiate therapy with appropriate monitoring

• Megestrol acetate: Monitor for thromboembolic events, edema, weight changes, adrenal function 2, 5
• Reassess benefit versus harm regularly, especially after 9 months of treatment 6

Step 4: Consider combination or alternative strategies if inadequate response

• Add olanzapine 5 mg daily to megestrol acetate 2, 5
• Switch to oxandrolone if lean mass preservation is priority 9
• Discontinue if no benefit after appropriate trial period 2, 6