Can Remeron (mirtazapine) be used to increase appetite?

Mirtazapine for Appetite Stimulation

Mirtazapine can be used to increase appetite, but only when depression is also present and requires treatment—it should not be used solely as an appetite stimulant in patients without depression. 1

Clinical Context and Evidence Base

FDA-Approved Effects on Appetite

The FDA label explicitly recognizes increased appetite and weight gain as established effects of mirtazapine 2:

• In controlled trials, appetite increase occurred in 17% of mirtazapine-treated patients versus 2% on placebo 2
• Weight gain ≥7% of body weight occurred in 7.5% of patients on mirtazapine versus 0% on placebo 2
• In pediatric trials, 49% experienced weight gain ≥7% compared to 5.7% on placebo 2
• 8% of patients discontinued mirtazapine specifically due to weight gain in premarketing studies 2

Mechanism of Appetite Stimulation

Mirtazapine increases appetite primarily through histamine H1 receptor blockade, with additional contributions from serotonin 5-HT2 and 5-HT3 receptor antagonism 3:

• H1 receptor blockade is the most significant contributor to appetite stimulation 3
• 5-HT3 antagonism reduces nausea and early satiety, indirectly promoting food intake 3
• These mechanisms explain why appetite stimulation is a consistent side effect rather than a therapeutic indication 4, 5

When Mirtazapine Is Appropriate for Appetite Stimulation

Depression with Appetite Loss (Primary Indication)

Start mirtazapine 15 mg nightly when a patient has both depression and appetite loss/weight loss requiring antidepressant therapy 3:

• This represents the only guideline-supported use for appetite stimulation 1
• Mirtazapine offers dual benefit: treating depression while addressing appetite loss 3
• One retrospective study in 22 dementia patients with depression showed mean weight gain of 1.9 kg at 3 months and 2.1 kg at 6 months on 30 mg daily, with 80% experiencing weight gain 1

Specific Clinical Scenarios Where Evidence Supports Use

Gastroparesis with nausea and weight loss: Mirtazapine improved nausea, vomiting, and weight loss through 5-HT3 antagonism 3

Functional dyspepsia with early satiety: Small studies showed improvement in weight loss, dyspeptic symptoms, and early satiety 3

Palliative care in end-stage cardiovascular disease: Used to stimulate appetite when depression coexists 3

When Mirtazapine Should NOT Be Used

Dementia Patients Without Depression

Do not use mirtazapine or any appetite stimulants in persons with dementia who do not have concurrent depression 1:

• This is a Grade GPP recommendation with 89% consensus 1
• Trials showed weak methodology and inconsistent effects 1
• Potentially harmful side effects outweigh uncertain benefits for appetite and weight 1

Patients Where Weight Gain Is Detrimental

Exercise extreme caution or avoid mirtazapine in patients with 3:

• Obesity
• Cardiovascular disease where weight gain worsens outcomes
• Metabolic syndrome
• Consider alternative antidepressants (sertraline is weight-neutral with lower cardiac risk) 6

Practical Dosing Algorithm

Starting Dose

Begin with 15 mg orally at bedtime 3, 2, 4:

• This dose demonstrates appetite-stimulating effects 3
• Take as a single daily dose, preferably in the evening 2
• The elimination half-life of 20-40 hours supports once-daily dosing 4

Dose Titration

If inadequate response after 2-4 weeks, increase to 30 mg nightly 3, 4:

• Maximum effective dose is 45 mg daily 3, 4
• Clinical antidepressant effect typically appears in 2-4 weeks, though sleep and anxiety may improve in week 1 4

Monitoring

• Monitor weight and appetite weekly initially 3
• Assess for excessive sedation (54% incidence vs 18% placebo) 2
• Check for QTc prolongation in patients with cardiovascular disease or family history of QT prolongation 2

Critical Safety Considerations

Common Adverse Effects That Limit Use

Somnolence is the most common limiting side effect 2:

• Occurred in 54% of patients versus 18% on placebo 2
• Led to discontinuation in 10.4% versus 2.2% on placebo 2
• Warn patients not to drive or operate machinery until they know how mirtazapine affects them 2
• Avoid concomitant benzodiazepines and alcohol 2

Serious but Rare Risks

QTc prolongation and cardiac arrhythmias: Cases of Torsades de Pointes, ventricular tachycardia, and sudden death reported, mostly with overdose or other risk factors 2

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Can be fatal; discontinue immediately if suspected 2

Serotonin syndrome: Risk increases with concomitant serotonergic drugs or MAOIs; contraindicated with MAOIs 2

Metabolic Effects

• Elevated cholesterol ≥20% above normal in 15% versus 7% placebo 2
• Triglycerides ≥500 mg/dL in 6% versus 3% placebo 2

Comparative Context

Mirtazapine is uniquely positioned among antidepressants for appetite stimulation 3:

• Bupropion causes weight loss 3
• SSRIs are weight-neutral to weight-loss promoting 3
• Tricyclic antidepressants cause weight gain but have worse anticholinergic and cardiac side effects 4, 5

In hospitalized patients, a retrospective study showed no significant difference between dronabinol, megestrol, and mirtazapine for meal intake or weight change, though all showed numerical improvements (mean 17.12% increase in meal intake) 7

Bottom Line Algorithm

1. Is depression present requiring antidepressant therapy?

   • Yes + appetite loss → Mirtazapine 15 mg nightly is appropriate 1, 3
   • No → Do not use mirtazapine solely for appetite 1

2. Are there contraindications to weight gain?

   • Obesity, cardiovascular disease, metabolic syndrome → Choose alternative antidepressant 3, 6

3. Monitor for limiting side effects:

   • Excessive sedation → May require discontinuation 2
   • Inadequate appetite response at 15 mg after 2-4 weeks → Increase to 30 mg 3, 4