What is the recommended dosage when using mirtazapine with fluoxetine?

Dosage Recommendations for Mirtazapine with Fluoxetine Combination

When combining mirtazapine with fluoxetine, start with mirtazapine 7.5 mg at bedtime and fluoxetine 10 mg every other morning, then titrate based on response and tolerability. 1

Dosing Guidelines

Initial Dosing

• Mirtazapine: 7.5 mg at bedtime 1
• Fluoxetine: 10 mg every other morning 1

Titration

• Mirtazapine: Increase by 7.5 mg increments every 5-7 days as tolerated
• Fluoxetine: Increase to 10 mg daily after 1-2 weeks, then to 20 mg daily if needed
• Allow 3-4 weeks between fluoxetine dose adjustments due to its very long half-life 1

Maximum Recommended Doses

• Mirtazapine: 30 mg at bedtime 1
• Fluoxetine: 20 mg every morning 1

Pharmacological Considerations

Drug Interactions

• Fluoxetine is a potent inhibitor of CYP2D6 and can increase mirtazapine blood levels 1
• This combination may require lower doses of mirtazapine than when used alone
• Monitor for increased side effects from elevated mirtazapine concentrations

Therapeutic Blood Levels (if monitoring)

• Mirtazapine: 40-80 ng/mL 1
• Fluoxetine plus norfluoxetine: 120-300 ng/mL 1

Clinical Benefits and Rationale

This combination provides complementary mechanisms:

• Mirtazapine: Promotes sleep, appetite, and weight gain 1
• Fluoxetine: More activating, with very long half-life 1
• Together they may address both insomnia/anxiety and depression-related apathy

Monitoring and Side Effect Management

Common Side Effects to Monitor

• Sedation (especially from mirtazapine)
• Weight gain (primarily from mirtazapine)
• Activation/insomnia (primarily from fluoxetine)
• Serotonergic effects (sweating, tremors, GI disturbances)

Important Cautions

• Give mirtazapine at bedtime to minimize daytime sedation
• Administer fluoxetine in the morning to minimize sleep disruption
• Due to fluoxetine's long half-life, side effects may not manifest for several weeks 1
• Monitor for serotonin syndrome, though risk is relatively low with this specific combination

Special Populations

• Elderly patients: Start with mirtazapine 7.5 mg and fluoxetine 10 mg every other day
• Hepatic impairment: Use lower doses of both medications and titrate more slowly
• Renal impairment: Lower doses may be required, especially for mirtazapine

Discontinuation

When discontinuing this combination:

• Taper gradually over 10-14 days to minimize withdrawal symptoms 1
• Fluoxetine can often be discontinued more rapidly due to its long half-life
• Mirtazapine should be tapered more gradually to prevent rebound insomnia

This combination can be particularly effective for patients with depression accompanied by significant sleep disturbance, anxiety, or poor appetite, but requires careful monitoring for combined side effects.