Moderate
Amitriptyline × Mirtazapine
Tricyclic antidepressants (TCA)×Other antidepressants (NaSSA)
Mechanism
Additive sedation, anticholinergic effect, and weight gain. Mirtazapine's serotonergic effect (via α2-blockade) is not pronounced on a TCA.
Symptoms
Deep sedation, drowsiness, dry mouth, constipation, weight gain. Older patients: delirium and fall risk.
Management
Avoid the combination, especially in older patients. For resistant depression augmentation: mirtazapine + SSRI (sertraline, escitalopram) instead of a TCA. For neuropathic pain: gabapentin or pregabalin.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.