A retrospective case notes review of the effectiveness and tolerability of metoclopramide in the treatment of clozapine-induced hypersalivation (CIH).

OBJECTIVE: The objective of the study is to explore the long-term effectiveness and tolerability of metoclopramide in the treatment of CIH. METHOD: This study is a retrospective, observational cohort study of patients prescribed metoclopramide for CIH at the South London & Maudsley (SLaM) NHS Foundation Trust. RESULTS: Of the 96 patients identified, 14 patients were eligible for inclusion in our study. Five patients continued treatment with a mean duration of 27 months (SD = 17.8), and one patient continued until transfer with a duration of 3 months. Eight patients discontinued treatment after a mean duration of 8 months. CONCLUSION: Metoclopramide may be an effective and tolerated drug in CIH, but more data is required to establish its place in the pharmacotherapy of this condition.

Correction to: Estimating the optimal dose of flupentixol decanoate in the maintenance treatment of schizophrenia-a systematic review of the literature.

An error in Fig. 3 was introduced in the production process which the authors have asked to be rectified. Below is the correct figure.

Estimating the optimal dose of flupentixol decanoate in the maintenance treatment of schizophrenia-a systematic review of the literature.

RATIONALE: The licensed dose range for the long-acting injectable antipsychotic flupentixol decanoate (Depixol®) in the treatment of schizophrenia is very broad. This provides little useful direction to prescribers and may ultimately result in patients receiving unnecessarily high doses. OBJECTIVES: We aimed to estimate the effect of dose of flupentixol decanoate on relapse rates in schizophrenia and on tolerability by expanding on an earlier review and including non-RCT and German-language studies, as well as using pharmacokinetic and pharmacodynamic data to offer guidance on dosing. METHODS: A literature review using EMBASE, Medline, PsycINFO and PubMed was conducted. Treatment success rates at 6 months were extracted or extrapolated from the studies and plotted against dose to estimate a dose-response curve. RESULTS: Data from 16 studies (n = 514) allowed estimation of a dose-response curve which rises steeply between the chosen placebo anchor (25% success rate) and 10 mg every 2 weeks before reaching a maximum between 20 and 40 mg every 2 weeks (80-95% success rates). Extrapyramidal side effects (EPSEs) were frequently seen (12-71% of participants) in that dose range. Two -weekly injections seem to provide the highest trough plasma concentration per dose administered and the lowest peak-to-trough concentration ratio. Plasma concentration varied up to 5-fold among individuals receiving the same dose. CONCLUSIONS: The optimal dose of flupentixol decanoate is likely to be between 20 mg and 40 mg every 2 weeks although higher doses may be required in some individuals owing to variation in drug handling. Doses of flupentixol should be individually established in the range of 10 to 40 mg every 2 weeks according to response and tolerability.

Factors predicting use of laxatives in outpatients stabilized on clozapine.

Constipation is a common and sometimes fatal side effect of clozapine treatment. In this study, we aimed to identify factors associated with clozapine-induced constipation. Data on 202 outpatients stabilized on clozapine treatment were collected. Of these, 71 patients (35%) had a current prescription for laxatives (a proxy for the presence of constipation). Mean clozapine dose was 400.4 mg/day in those prescribed laxatives and 390.1 mg/day in those not prescribed laxatives (p = 0.67), while mean clozapine plasma concentration was 0.53 mg/l and 0.49 mg/l, respectively (p = 0.29). Patients using laxatives had on average 29% higher norclozapine concentrations (mean = 0.34 mg/l) than those who did not use laxatives (mean = 0.27 mg/l; p = 0.046). Laxative use was more common in female patients (49.1%) than male patients (29.1%; p < 0.01). Prescribers should be vigilant for constipation at any dose or plasma concentration of clozapine and should be mindful that male patients may be undertreated. Norclozapine concentrations may predict clozapine-induced constipation.