Can mirtazapine (Remeron) be used for appetite stimulation?

Mirtazapine for Appetite Stimulation

Mirtazapine can be used for appetite stimulation, but its use should be reserved for specific clinical contexts where appetite loss coexists with depression or other targeted symptoms, rather than as a standalone appetite stimulant in otherwise healthy individuals. 1, 2

When Mirtazapine IS Appropriate for Appetite Stimulation

Depression with Appetite Loss (Primary Indication)

• Start mirtazapine 15 mg nightly when depression presents with appetite loss and weight loss, as this provides dual therapeutic benefit by treating both conditions simultaneously 1, 2
• The dose can be increased to 30 mg nightly after 2-4 weeks if inadequate response is observed 2
• At 30 mg daily, retrospective data shows mean weight gain of 1.9 kg at 3 months and 2.1 kg at 6 months, with approximately 80% of patients experiencing weight gain 3, 1
• Mirtazapine is uniquely positioned among antidepressants because bupropion causes weight loss and SSRIs are weight-neutral to weight-loss promoting 1

Short Bowel Syndrome with Insufficient Oral Intake

• Consider mirtazapine (along with olanzapine, dronabinol, or megestrol) in stable patients with short bowel syndrome-intestinal failure who have insufficient oral intake despite other interventions, particularly when stool output is <2 L/day 3

Gastroparesis and Functional Dyspepsia

• Mirtazapine has shown benefit in refractory gastroparesis by improving nausea, vomiting, and weight loss through its 5-HT3 receptor antagonism 1
• In functional dyspepsia, mirtazapine demonstrated improvement in weight loss, dyspeptic symptoms, and early satiety 1

Dementia with Concurrent Depression

• Mirtazapine may be used in dementia patients only when depression is also present, as it offers potential benefit for both conditions 3, 1

When Mirtazapine Should NOT Be Used

Dementia Without Depression (Strong Contraindication)

• Do NOT use mirtazapine or other appetite stimulants in persons with dementia who lack concurrent depression (Grade GPP recommendation, 89% consensus) 3, 1
• The potentially harmful side effects outweigh the very uncertain benefits for appetite and body weight in this population 3

Conditions Where Weight Gain Is Detrimental

• Exercise extreme caution or avoid mirtazapine in patients with obesity, cardiovascular disease, or metabolic syndrome where weight gain would be harmful 1, 4
• The FDA label specifically notes that 7.5% of patients experienced weight gain ≥7% of body weight in controlled trials, compared to 0% for placebo 4

Mechanism of Appetite Stimulation

• Histamine H1 receptor blockade is the primary mechanism driving appetite stimulation and weight gain 1
• Serotonin 5-HT2 and 5-HT3 receptor antagonism reduces nausea and early satiety, indirectly promoting increased food intake 1
• The appetite-stimulating effect occurs at doses as low as 15 mg daily 1

Dosing and Administration

• Start at 15 mg nightly (preferably at bedtime) as the initial dose 1, 4
• Effective daily dosage range is 15-45 mg 1
• The FDA label confirms that appetite increase was reported in 17% of mirtazapine-treated patients versus 2% for placebo 4

Critical Safety Considerations

Common Side Effects

• Somnolence occurs in 54% of patients (versus 18% for placebo) and resulted in discontinuation in 10.4% of cases 4
• Warn patients about impaired performance and avoid driving or operating machinery until effects are known 4
• Avoid concomitant use with benzodiazepines and alcohol 4

Serious Adverse Effects to Monitor

• Low white blood cell count (agranulocytosis): monitor for fever, sore throat, flu-like symptoms 4
• Serotonin syndrome when combined with other serotonergic drugs 4
• QTc prolongation and potential cardiac arrhythmias, particularly in overdose or with other QTc-prolonging medications 4
• Activation of mania/hypomania in patients with bipolar disorder (screen for personal/family history before initiating) 4

Discontinuation Syndrome

• Never abruptly discontinue mirtazapine—taper the dose slowly to avoid withdrawal symptoms 4, 5
• Discontinuation syndrome can occur even at low doses (15 mg/day), with symptoms including anxiety, nausea, tremor, loss of appetite, and weight loss occurring within 48 hours of stopping 5
• Symptoms may include dizziness, irritability, anxiety, sweating, seizures, confusion, and electric shock sensations 4

Evidence Quality and Limitations

• The evidence for mirtazapine as a standalone appetite stimulant in hospitalized patients is limited and shows no significant difference compared to other agents (dronabinol, megestrol) in improving meal intake or weight 6, 7
• Current data lack standardization and generalizability for the inpatient setting 7
• The strongest evidence supports its use when appetite stimulation is a secondary benefit in patients requiring antidepressant therapy 1, 2

Practical Algorithm

1. Assess for depression: If present with appetite loss → mirtazapine 15 mg nightly is first-line 1, 2
2. Assess for contraindications: Dementia without depression, conditions where weight gain is harmful → do NOT use 3, 1
3. Consider alternative diagnoses: Gastroparesis, functional dyspepsia → mirtazapine may provide dual benefit 1
4. Monitor response: Weekly weight and appetite checks initially, increase to 30 mg after 2-4 weeks if needed 1, 2
5. Plan discontinuation: Always taper slowly when stopping to avoid withdrawal syndrome 4, 5