What is the recommended starting dose of mirtazapine for an adult patient with insomnia and no significant medical history?

Mirtazapine Dosing for Sleep

For insomnia, start mirtazapine at 7.5 mg at bedtime, which can be increased to 15 mg if needed after 1-2 weeks, though this is a third-line option after FDA-approved hypnotics and cognitive behavioral therapy have been tried. 1, 2

Why Lower Doses for Sleep vs. Depression

• The sedating effects of mirtazapine are paradoxically stronger at lower doses (7.5-15 mg) than at antidepressant doses (15-45 mg). 3, 4
• At low doses, mirtazapine's antihistamine (H1 receptor antagonism) effects predominate, producing sedation without the full noradrenergic activation seen at higher doses. 3, 5
• The FDA-approved starting dose for depression is 15 mg once daily at bedtime, with a maximum of 45 mg per day, but for off-label insomnia use, clinicians commonly start at 7.5 mg. 6, 7

Critical Positioning in Treatment Algorithm

• Mirtazapine is explicitly a third-line agent for insomnia, only appropriate after benzodiazepine receptor agonists (zolpidem, eszopiclone, zaleplon) or ramelteon have failed. 2
• The American Academy of Sleep Medicine recommends sedating antidepressants like mirtazapine primarily when comorbid depression or anxiety is present, not for primary insomnia. 1, 2
• Cognitive Behavioral Therapy for Insomnia (CBT-I) must be initiated before or alongside mirtazapine, as it provides superior long-term outcomes. 2

Dosing Schedule and Titration

• Start at 7.5 mg (half of a 15 mg tablet) taken once nightly at bedtime. 1, 7
• If inadequate response after 1-2 weeks, increase to 15 mg nightly. 6, 7
• Do not make dose changes more frequently than every 1-2 weeks to allow sufficient time for evaluation of response. 6
• The elimination half-life of 20-40 hours allows once-daily bedtime dosing and requires several days to reach steady-state blood levels. 2, 3

Why NOT PRN (As-Needed) Dosing

• Mirtazapine cannot be taken PRN for insomnia—it requires nightly scheduled dosing to maintain therapeutic blood levels and sedating effects. 2
• With a 20-40 hour half-life, mirtazapine takes several days to reach steady state and cannot provide immediate "on-demand" sedation like short-acting hypnotics. 2, 3

Common Side Effects at Sleep Doses

• Sedation and drowsiness are the most common effects, which is the desired outcome for insomnia but may cause morning grogginess. 3, 4, 5
• Increased appetite and weight gain occur more commonly with mirtazapine than placebo. 3, 4, 5
• Dizziness is reported in approximately 3-5% of patients. 4, 5
• Unlike SSRIs and tricyclics, mirtazapine has minimal anticholinergic effects, no sexual dysfunction, and no gastrointestinal side effects. 3, 4

When Mirtazapine Is Most Appropriate

• Patients with comorbid depression and insomnia are ideal candidates, as mirtazapine addresses both conditions simultaneously. 1, 2
• Patients with comorbid anxiety and insomnia may benefit, as mirtazapine improves anxiety symptoms within the first week. 3, 4
• Patients who have failed first-line hypnotics (zolpidem, eszopiclone) and need an alternative approach. 2
• Patients who cannot tolerate the side effects of SSRIs or tricyclics (sexual dysfunction, GI upset, anticholinergic effects). 3, 4

Important Safety Considerations

• Screen for bipolar disorder before starting mirtazapine, as antidepressants can trigger manic episodes. 6
• Dose reduction may be needed in hepatic or renal impairment, as mirtazapine is extensively metabolized by the liver and excreted by the kidneys. 4
• Gradually taper mirtazapine rather than stopping abruptly to avoid withdrawal symptoms. 6
• Allow at least 14 days between discontinuing an MAOI and starting mirtazapine, and vice versa. 6

Drug Interactions Requiring Dose Adjustment

• Strong CYP3A4 inducers (carbamazepine, phenytoin, rifampin) may require increasing mirtazapine dose. 6
• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin) may require decreasing mirtazapine dose. 6
• Cimetidine increases mirtazapine levels and may require dose reduction. 6

Onset of Action

• Sleep disturbances and anxiety symptoms may improve within the first week of treatment. 3, 4
• Full antidepressant effects (if treating comorbid depression) typically require 2-4 weeks. 3, 4

Common Pitfalls to Avoid

• Do not use mirtazapine as first-line treatment for primary insomnia—try FDA-approved hypnotics or CBT-I first. 2
• Do not prescribe mirtazapine PRN—it requires nightly scheduled dosing. 2
• Do not start at antidepressant doses (15-45 mg) when targeting insomnia alone—start at 7.5 mg. 1, 7
• Do not continue long-term without periodic reassessment of need and effectiveness. 2
• Do not combine with other sedating medications without careful monitoring for additive effects. 2