Alprazolam × Mirtazapine

Both drugs depress the central nervous system. Mirtazapine increases the sedative effect of benzodiazepines (mirtazapine SmPC), and together they impair attention and coordination more than either drug alone (mirtazapine label, US Food and Drug Administration, FDA). The alprazolam SmPC warns that combining it with antidepressants deepens CNS depression and raises the risk of respiratory depression, coma and death (alprazolam SmPC).

Drowsiness, dizziness, slowed reactions, impaired attention and coordination (mirtazapine SmPC). In older or debilitated patients alprazolam more often causes ataxia and oversedation (alprazolam SmPC). Marked CNS depression can lead to respiratory depression (alprazolam SmPC).

The combination is avoided where possible: the mirtazapine label approved by the US Food and Drug Administration (FDA) advises against taking it with benzodiazepines and names alprazolam. If both drugs are needed, the dose and duration of combined use are limited (alprazolam SmPC; alprazolam label, FDA). The alprazolam course is kept as short as possible, no longer than 2–4 weeks, and is not extended without reassessment (alprazolam SmPC). In older or debilitated patients alprazolam is started at 0.25 mg two or three times daily and kept at the lowest effective dose to avoid ataxia and oversedation (alprazolam SmPC). The patient is warned not to drive or operate machinery until it is clear how they tolerate the combination (mirtazapine SmPC; alprazolam label, FDA).