Appetite Stimulant Selection in Patients with Constipation
In patients requiring appetite stimulation who also have constipation, use megestrol acetate or mirtazapine as first-line agents, while avoiding metoclopramide and corticosteroids due to their constipating effects.
Preferred Appetite Stimulants
Megestrol Acetate (First-Line Option)
- Megestrol acetate is an effective appetite stimulant that does not worsen constipation 1.
- Start at 160 mg daily (minimum effective dose), with optimal dosing at 400-800 mg daily for cancer-related anorexia 1.
- In clinical trials, 64% of patients on 800 mg daily gained ≥5 pounds, with mean weight increase of 7.8 pounds over 12 weeks 2.
- Appetite improvement occurs in 67-89% of patients depending on dose 2.
- Critical caveat: 1 in 6 patients develop thromboembolic phenomena, and careful monitoring is required 1.
Mirtazapine (Alternative First-Line)
- Mirtazapine increases appetite in 17% of patients (vs 2% placebo), with 7.5% achieving ≥7% body weight gain 3.
- Start at 15 mg at bedtime, can increase to 45 mg daily 3.
- Does not cause constipation, making it particularly suitable for this population 3.
- Additional benefit: may help with concurrent depression or anxiety 3.
- Main side effect is somnolence (54% of patients), which may limit daytime use 3.
Agents to AVOID in Constipated Patients
Metoclopramide
- While metoclopramide can be used for early satiety and gastroparesis, it is listed among anticholinergic drugs and antiemetics known to cause constipation 1.
- Should be reserved only for patients with documented gastroparesis requiring prokinetic therapy 1.
Corticosteroids (Dexamethasone)
- Corticosteroids are effective appetite stimulants (level B1 evidence) 1.
- However, corticosteroids are specifically listed among drugs known to cause constipation 1.
- Reserve for patients with weeks-to-days life expectancy where short-term appetite improvement outweighs constipation risk 1.
Dronabinol/Cannabinoids
- Limited efficacy compared to megestrol acetate (49% vs 75% weight gain) 1.
- No specific constipation benefit, and evidence for cancer-related anorexia is very limited 1.
Concurrent Constipation Management
When initiating appetite stimulants in constipated patients, simultaneously address the constipation:
First-Line Laxative Therapy
- Start prophylactic stimulant laxative (senna or bisacodyl) immediately 1.
- Senna: 8.6-17.2 mg daily, can increase as needed 1.
- Bisacodyl: 5-10 mg daily for short-term or rescue use 1.
- Evidence shows senna alone is as effective as senna-docusate combinations (stool softeners not necessary) 1.
Osmotic Laxatives as Adjuncts
- Polyethylene glycol (PEG) 17g daily: durable response over 6 months 1.
- Lactulose 15g daily if PEG fails or is not tolerated 1.
- Magnesium oxide 400-500 mg daily (avoid in renal insufficiency) 1.
For Persistent Constipation
- Add lubiprostone 24 mcg twice daily if over-the-counter agents fail 1.
- Consider prucalopride 1-2 mg daily or linaclotide 72-145 mcg daily for refractory cases 1.
Clinical Algorithm
- Assess constipation severity and treat proactively before or concurrent with appetite stimulant initiation 1.
- Initiate megestrol acetate 400-800 mg daily OR mirtazapine 15-45 mg at bedtime 1, 3.
- Start prophylactic senna or bisacodyl to prevent worsening constipation 1.
- Avoid metoclopramide and corticosteroids unless specific indications outweigh constipation risk 1.
- Monitor for thromboembolic events if using megestrol acetate 1.
- Escalate laxative therapy if constipation persists despite stimulant laxatives 1.
Important Pitfalls
- Do not assume all appetite stimulants are constipation-neutral: metoclopramide and corticosteroids worsen constipation 1.
- Do not delay laxative prophylaxis: initiate concurrent with appetite stimulant to prevent symptom escalation 1.
- Do not use dronabinol as first-line: inferior efficacy compared to megestrol acetate 1.
- Monitor for megestrol acetate complications: thromboembolic risk is significant (1 in 6 patients) 1.