Mirtazapine Should Be Discontinued 5 Days Before Skin Allergy Testing
Mirtazapine will significantly interfere with skin allergy testing and should be discontinued for 5 days prior to testing if clinically safe to do so. The medication has potent antihistaminic properties that will suppress the normal wheal-and-flare response, rendering the test results unreliable or falsely negative.
Evidence for Significant Interference
The research evidence is clear and consistent: mirtazapine causes dose-dependent suppression of skin prick tests, with 83% of patients on mirtazapine showing negative histamine controls 1. This is one of the highest interference rates among all psychiatric medications studied.
In a comprehensive study examining which medications interfere with allergy testing, mirtazapine was specifically identified as a medication that should be discontinued temporarily if clinically able 2. The antihistaminic effect is substantial enough that skin testing has little meaning in patients treated with mirtazapine 1.
Why Mirtazapine Interferes
Mirtazapine's mechanism of action includes potent histamine H1-receptor antagonism, which is responsible for some of its therapeutic effects (sedation, appetite stimulation) but also directly blocks the histamine response needed for valid skin testing. This is fundamentally different from SSRIs, SNRIs, or benzodiazepines, which generally do not interfere with testing 1, 2.
Clinical Recommendation
- Discontinue mirtazapine 5 days before testing if the prescribing physician (you) determines it is safe to do so
- The 5-day washout period allows sufficient clearance of the drug and its antihistaminic effects
- Given that your patient has been on mirtazapine for over a year (indicating stability), a 5-day interruption is typically safe for most patients, though you should assess for:
- History of severe withdrawal symptoms with missed doses
- Severity of underlying depression
- Suicide risk
- Recent medication adjustments
Important Caveats
If discontinuation poses significant psychiatric risk, the allergy testing should either be:
- Postponed until a safer time for medication interruption
- Interpreted with extreme caution, understanding that negative results may be falsely negative due to medication interference
- Consider alternative testing methods such as serum-specific IgE testing (though this has lower sensitivity than skin testing for most allergens)
The odds ratio for a negative histamine test in patients taking atypical antidepressants/sedatives (which includes mirtazapine) was 3.11, meaning these patients are three times more likely to have falsely negative results 2.