What is the recommended protocol for tapering mirtazapine (Remeron)?

Mirtazapine Tapering Protocol

Gradually reduce mirtazapine dosage rather than stopping abruptly, using a slow taper of approximately 10% of the current dose per month, with dose reductions made no more frequently than every 1-2 weeks. 1

FDA-Mandated Tapering Approach

The FDA label explicitly states that adverse reactions may occur upon discontinuation or dose reduction of mirtazapine, and clinicians should gradually reduce the dosage rather than stopping abruptly whenever possible. 1 This is the foundational guidance that supersedes all other recommendations.

Recommended Tapering Schedule

Initial Tapering Phase

• Reduce by 10% of the current dose every 1-2 weeks as a reasonable starting point, though slower tapers (10% per month) are often better tolerated, particularly for patients on long-term therapy. 2, 3
• Each new dose should be 90% of the previous dose, not a straight-line reduction from the original starting dose—this prevents disproportionately large reductions at lower doses. 4
• Do not make dose changes more frequently than every 1-2 weeks to allow sufficient time for evaluation of response. 1

For Long-Term Users

• Patients who have been on mirtazapine for more than one year should use an even slower taper of 10% per month rather than 10% every 1-2 weeks. 3
• The tapering process may take several months depending on initial dose and treatment duration. 4

Very Gradual Approach for High-Risk Patients

• If the patient is anxious about tapering or has previously experienced withdrawal symptoms, start with very small reductions of 5% of the current dose. 4
• For patients on higher doses, consider tapering to 50% of the original dose before implementing the slower 10% reduction schedule. 4

Managing Withdrawal Symptoms

Common Withdrawal Manifestations

• A case report documented severe, recurrent panic attacks occurring within 2 days of abrupt mirtazapine discontinuation after only 10 weeks of treatment at 30 mg/day, with attacks recurring every 1-2 hours for 5 days. 5
• Symptoms resolved only after reinstitution of mirtazapine, demonstrating that even medium-duration therapy requires gradual tapering. 5

Response to Withdrawal Symptoms

• If withdrawal symptoms become severe, temporarily return to the previous dose and then resume tapering at a slower rate. 4
• The taper rate must be determined by the patient's ability to tolerate reductions, not by a rigid schedule. 3
• Pauses in the taper are acceptable and often necessary when withdrawal symptoms emerge. 3

Symptomatic Management

• For insomnia during tapering, consider temporary use of alternative sleep aids. 4
• For anxiety or irritability, short-term supportive interventions may be beneficial. 4

Monitoring Requirements

• Follow up at least monthly during the taper, with more frequent contact needed during difficult phases. 3
• Monitor for withdrawal symptoms including anxiety, insomnia, mood changes, and panic symptoms. 3, 5
• Screen for depression, anxiety, and substance use disorders that may emerge during tapering. 3
• Advise patients of increased overdose risk if they return to previous doses after tolerance is lost. 3

Important Clinical Considerations

Target Endpoint

• The target dose may not necessarily be zero—some patients may benefit from continuing at a lower maintenance dose rather than complete discontinuation. 4
• Once the smallest available dose is reached, the interval between doses can be extended before complete cessation. 2

Concurrent Medication Management

• If the patient is also taking benzodiazepines, address the benzodiazepine taper first due to the higher risks associated with benzodiazepine withdrawal (including seizures and death). 3, 4
• Benzodiazepine withdrawal carries greater risks than antidepressant withdrawal and should take precedence. 3

Drug Interaction Adjustments

• Patients on strong CYP3A inducers (carbamazepine, phenytoin, rifampin) may need dosage increases during tapering. 1
• Patients on strong CYP3A inhibitors (ketoconazole, clarithromycin) or cimetidine may need dosage decreases. 1

Common Pitfalls to Avoid

• Never abruptly discontinue mirtazapine—even after relatively short treatment durations (10 weeks), abrupt cessation can cause severe withdrawal symptoms. 5
• Do not use rigid tapering schedules that ignore patient tolerance—the taper must be individualized based on symptom emergence. 3
• Avoid making dose reductions too frequently (more often than every 1-2 weeks), as this doesn't allow adequate time to assess tolerance. 1
• Do not taper too quickly to therapeutic minimum doses and stop—continue tapering to much lower doses to minimize withdrawal. 6