The nonselective
serotonin (5-HT)-2A antagonists
ritanserin,
mianserin, and
cyproheptadine were found efficacious in
neuroleptic-induced
akathisia (NIA).
Mirtazapine is structurally and pharmacologically similar to
mianserin, and the authors sought to determine its anti-NIA activity. Twenty-six
neuroleptic-treated schizophrenic patients with DSM-IV diagnosis of NIA received add-on
mirtazapine (15 mg/day) or placebo for 5 days in a double-blind design. Patients were assessed at baseline and days 3 and 5 with the Barnes
Akathisia Scale (BAS), Positive and Negative Symptom Scale, Hamilton Rating Scale for Depression, and Simpson-Angus Scale for
parkinsonism. Analysis of covariance with repeated measurements revealed significant group x time effects in favor of the
mirtazapine group in both completers (n = 10 in each group) and intent-to-treat analysis (n = 13 in each group) for the BAS global subscale (F [1, 17] = 14.87, p = 0.001, and F [1, 23] = 13.24, p = 0.01, respectively) and objective subscale (F [1, 17] = 8.25, p = 0.011, and F [1, 23] = 7.35, p = 0.012, respectively) and borderline significant superiority for the BAS subjective subscale (F [1, 17] = 4.39, p = 0.051, and F [1, 23] = 4.12, p = 0.054, respectively) and distress subscale (F [1, 17] = 4.21, p = 0.056, and F [1, 23] = 3.80, p = 0.064, respectively). Significantly more
mirtazapine-than placebo-treated patients (53.8% [7/13] vs. 7.7% [1/13], respectively; chi2 = 8.3, p = 0.004) met operational response criterion, a reduction of at least two points on the BAS global subscale.
Mirtazapine treatment was associated with modest improvement of psychotic and parkinsonian symptoms. Mild sedation was the only side effect. Our study demonstrated that
mirtazapine (15 mg/day) is an efficacious and well-tolerated therapeutic option in NIA. Marked 5HT2A/2C antagonistic activity of
mirtazapine apparently accounts for its anti-NIA activity. The role of
mirtazapine in the treatment of
akathisia induced by atypical
antipsychotic agents merits further investigation.