Mirtazapine-associated Movement Disorders: A Literature Review

Mirtazapine (MTZ) is an atypical antidepressant approved by the FDA, which mechanism of action involves the antagonism of alpha-2, H1, 5-HT2A, 5-HT2C, and 5-HT3 receptors. In this context, the aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms, and management of MTZ-associated movement disorders (MDs). Relevant reports of six databases were identified and assessed by two reviewers without language restriction. Fifty-two reports containing 179 cases from 20 countries were assessed. The mean age was 57 year (range, 17-85). The majority of the individuals were female (60%) and of European origin. The mean time from MTZ start to symptom onset was 7.54 days; the time from management to MD improvement was within one week in 82.60% of the individuals. The MDs associated with MTZ were 69 restless legs syndrome (RLS), 35 tremors, 10 akathisia (AKT), 9 periodic limb MD, 6 dystonia, 4 rapid eye movement sleep behavior disorders, 3 dyskinesia, 2 parkinsonism, and 1 tic, and in the group not clearly identified, 18 restlessness, 15 hyperkinesis, and 1 extrapyramidal symptom. In the literature, the majority of the reports lack important information about the neurological examination. The management should be the MTZ withdrawal, except in RLS that other options are possible. In AKT, the MTZ should not be rechallenge, and if available, the prescription of a benzodiazepine may reduce recovery time.