Mirtazapine Discontinuation Requires Gradual Tapering
Yes, mirtazapine requires a gradual taper when discontinuing—the FDA explicitly recommends gradually reducing the dosage rather than stopping abruptly whenever possible, as adverse reactions may occur upon discontinuation or dose reduction. 1
FDA-Mandated Tapering Guidance
The FDA drug label for mirtazapine clearly states that gradual dose reduction is preferred over abrupt cessation to minimize discontinuation-related adverse reactions. 1 This is not optional guidance—it represents the official prescribing information that clinicians should follow.
Evidence of Withdrawal Syndrome
Case reports demonstrate that abrupt mirtazapine discontinuation can cause severe withdrawal symptoms even after medium-duration treatment (10 weeks) and at standard doses (30 mg/day). 2
One documented case showed recurrent panic attacks beginning 48 hours after abrupt cessation, with attacks recurring every 1-2 hours for 5 days, only resolving after medication reinitiation. 2
Even low-dose mirtazapine (15 mg/day) can produce acute discontinuation syndrome within 48 hours, including anxiousness, nausea, tremor, loss of appetite, and significant weight loss. 3
Symptoms in this low-dose case persisted for 14 days and resolved immediately upon restarting the medication. 3
Recommended Tapering Approach
While the FDA label does not specify an exact tapering schedule for mirtazapine, evidence from antidepressant discontinuation research provides guidance:
Tapers should extend over weeks to months rather than days, with dose reductions of approximately 10-25% of the current dose every 1-2 weeks. 4, 5
For patients on mirtazapine for more than one year, consider extending the taper to 10% reductions per month. 6
The taper rate must be determined by the patient's tolerance of withdrawal symptoms, not by a rigid predetermined schedule. 6
Monitoring During Discontinuation
Follow up at least monthly during the taper, with more frequent contact during difficult phases when withdrawal symptoms emerge. 6
Monitor specifically for withdrawal symptoms including anxiety, nausea, tremor, dizziness, low mood, insomnia, and changes in appetite. 2, 3
Pauses in the taper are acceptable and often necessary when withdrawal symptoms emerge. 6
Critical Pitfalls to Avoid
Never discontinue mirtazapine abruptly—this is equivalent to suddenly stopping antihypertensives or antihyperglycemics and can cause significant patient harm. 6
Do not assume that lower doses (15 mg) or shorter treatment durations (10 weeks) eliminate the need for tapering. 2, 3
Distinguish withdrawal symptoms from relapse of depression, as withdrawal symptoms (low mood, anxiety) can be mistaken for return of the underlying condition. 4
Advise patients not to abruptly discontinue mirtazapine and to discuss any tapering regimen with their healthcare provider. 1