Abstract
BackgroundClozapine is the only medication licensed for the treatment of resistant schizophrenia in the UK. Although efficacious, a common and unpopular side effect of clozapine treatment is clozapine-induced hypersalivation (CIH), which can contribute to non-adherence. The standard treatment for CIH in the UK is hyoscine hydrobromide but this may aggravate cognitive deficits in patients with schizophrenia while glycopyrrolate may be an effective alternative with a more tolerable side effect profile. There is currently no convincing evidence for hyoscine, or any other medication, as an effective treatment for CIH.Methods/designThis is a multicentre randomised, double-blind, placebo-controlled feasibility study of glycopyrronium bromide (glycopyrrolate) and hyoscine hydrobromide (hyoscine) in patients with clozapine-induced hypersalivation. We aim to recruit 42 patients who have been prescribed clozapine and are experiencing hypersalivation, and randomise them to one of three study arms (either hyoscine, glycopyrrolate or placebo). The primary outcome measures will be the participant recruitment and attrition rates, and the secondary outcome will be the metrics of the daytime hypersalivation measure. After a 1-week washout period (discontinuing CIH medication, if any), there will be a 4-week treatment period where participants will be titrated up to the maximum tolerated dose of hyoscine, glycopyrrolate or placebo. Measurements of daytime salivation, nocturnal salivation, cognition and side effects will be taken during home visits in week 2 and week 5. Information on salivation and side effects will also be taken through telephone calls in week 3 and week 4. To gather information on the experience of study participants, exit interviews will also be requested with all participants who drop out of the study and a sample of participants who complete the study.DiscussionThere is currently no convincing evidence for hyoscine, or any other medication, as an effective treatment for CIH. There is promising evidence that glycopyrrolate may be more successful in the treatment of CIH causing fewer cognitive side effects. We propose to conduct a randomised placebo-controlled feasibility study of glycopyrrolate and hyoscine in the treatment of clozapine-induced hypersalivation to inform the design of a future efficacy trial.Trial registrationClinicaltrials.gov NCT02613494, 23 November 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1678-5) contains supplementary material, which is available to authorized users.
Highlights
Clozapine is the only medication licensed for the treatment of resistant schizophrenia in the UK
There is promising evidence that glycopyrrolate may be more successful in the treatment of clozapine-induced hypersalivation (CIH) causing fewer cognitive side effects
We propose to conduct a randomised placebo-controlled feasibility study of glycopyrrolate and hyoscine in the treatment of clozapine-induced hypersalivation to inform the design of a future efficacy trial
Summary
Clozapine is the only medication licensed for the treatment of resistant schizophrenia in the UK. A common and unpopular side effect of clozapine treatment is clozapine-induced hypersalivation (CIH), which can contribute to non-adherence. The standard treatment for CIH in the UK is hyoscine hydrobromide but this may aggravate cognitive deficits in patients with schizophrenia while glycopyrrolate may be an effective alternative with a more tolerable side effect profile. Study rationale Clozapine is the only medication licensed for the treatment of resistant schizophrenia in the UK. Clozapine-induced hypersalivation (CIH) is a common side effect of clozapine treatment and occurs in up to 80% of patients [1, 2]. Adverse side effects may eventually lead to patients discontinuing clozapine treatment [6], considerably increasing the risk of relapse and hospitalisation. The effective treatment of CIH is vital to patient experience and continued wellbeing
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