Sulpiride addition for the treatment of clozapine-induced hypersalivation: preliminary study.

BACKGROUND: Hypersalivation is a common, troublesome side effect of clozapine treatment. It occurs in 31-54% of clozapine treated patients. Management of this stigmatizing side effect may reduce noncompliance. Reports in the literature have shown beneficial clinical effects of combined clozapine-sulpiride therapy as measured by the Brief Psychiatric Rating Scale, and we found that this treatment combination also has very strong antisalivatory activity for clozapine-induced hypersalivation. METHODS: 18 patients (12 female, 6 male) with clozapine-induced hypersalivation received sulpiride (150-300 mg/day) in addition to ongoing clozapine treatment (from 100 mg/d to 800 mg/d). Baseline, 7 day and 21 day follow-up values were recorded for the 5-point Nocturnal Hypersalivation Rating Scale. RESULTS: At the end of the trial only 3 patients complained of minimal sialorrhea, and the mean Nocturnal Hypersalivation Rating Scale scale values showed a significant reduction in sialorrhea (delta baseline-endpoint -.2.78 +/- 0.87). CONCLUSIONS: Our findings support reports of the beneficial effect of clozapine-sulpiride combination therapy and suggest that sulpiride addition may contribute to the amelioration of clozapine-induced hypersalivation.

Efficacy of low-dose mirtazapine in neuroleptic-induced akathisia: a double-blind randomized placebo-controlled pilot study.

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.