What starting dose of mirtazapine (Remeron) is recommended to stimulate appetite in adults, including elderly or frail patients, with depression‑related or illness‑related weight loss?

Mirtazapine for Appetite Stimulation: Recommended Starting Dose

Start mirtazapine at 15 mg orally once daily at bedtime for appetite stimulation in adults with depression-related or illness-related weight loss. 1

Standard Dosing Protocol

• The FDA-approved starting dose is 15 mg once daily, preferably in the evening prior to sleep. 1
• For elderly or frail patients, consider initiating at 7.5 mg at bedtime to minimize sedation and other adverse effects. 2
• If inadequate response after 1–2 weeks, the dose may be increased to 30 mg once daily; the maximum dose is 45 mg per day. 1
• Dose changes should not be made more frequently than every 1–2 weeks to allow sufficient time to evaluate response. 1

Why This Dose Works for Appetite Stimulation

Mirtazapine's appetite-stimulating effects are mediated through histamine H₁ receptor blockade and 5-HT₂C receptor antagonism, which are prominent even at the 15 mg starting dose. 3, 4

• The drug promotes sleep, appetite, and weight gain, making it particularly suitable for patients with depression accompanied by insomnia or weight loss. 2, 5
• Common adverse effects include increased appetite (11% vs 2% placebo) and body weight gain (10% vs 1% placebo), which are therapeutic benefits in this context. 4
• Sedation is more pronounced at lower doses (15 mg) due to preferential H₁ antagonism; paradoxically, higher doses (30–45 mg) may be less sedating because increased noradrenergic activity counteracts histamine blockade. 6

Clinical Advantages in This Population

• Mirtazapine has a faster onset of action than some SSRIs (fluoxetine, paroxetine, sertraline), with significant improvements in depressive symptoms noted as early as 1 week. 2, 6
• The drug is especially effective for patients with depression and anorexia, particularly those with insomnia or sleep disturbances. 2
• Unlike SSRIs, mirtazapine has no sexual side effects and does not cause gastrointestinal adverse effects that might further suppress appetite. 3, 6

Special Population Considerations

Elderly and frail patients:

• Start at 7.5 mg at bedtime to reduce risk of excessive sedation, orthostatic hypotension, and falls. 2
• Steady-state concentrations are reached after 6 days in the elderly (versus 4 days in younger adults), requiring slower titration. 3

Hepatic or renal impairment:

• Mirtazapine clearance is reduced by hepatic or renal dysfunction; use lower starting doses and titrate cautiously with close monitoring. 4

Monitoring and Response Timeline

• Begin assessing appetite, weight, and therapeutic response within 1–2 weeks of treatment initiation. 2
• If inadequate response by 6–8 weeks at therapeutic doses, consider treatment modification (dose increase to 30–45 mg or alternative strategies). 2
• Continue treatment for 4–9 months after satisfactory response in first-episode depression; longer duration (≥1 year) is recommended for recurrent depression. 2

Critical Safety Screening

• Screen for personal or family history of bipolar disorder, mania, or hypomania before initiating mirtazapine, as antidepressants may precipitate manic episodes. 1
• At least 14 days must elapse between discontinuation of an MAOI and initiation of mirtazapine, and vice versa. 1
• Monitor for suicidal ideation, especially in patients younger than 24 years, during the first 1–2 months of therapy when risk is highest. 2

Common Pitfalls to Avoid

• Do not start at doses higher than 15 mg in treatment-naïve patients, as this increases sedation without improving appetite stimulation. 1, 4
• Do not discontinue abruptly; taper gradually to minimize withdrawal symptoms. 1
• Do not assume lack of efficacy before completing a 6–8 week trial at adequate doses. 2
• Do not overlook drug interactions with CYP3A4 inhibitors (ketoconazole, clarithromycin) or inducers (carbamazepine, phenytoin), which require dose adjustments. 1