Benzamide Derivates as Treatment of Clozapine-induced Hypersalivation

Study Overview
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Brief Summary
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Hypersalivation (sialorrhea or ptyalism) is known as a frequent, disturbing, uncomfortable adverse effect of clozapine therapy, and until now there is not enough effective treatment for this side effect leading to noncompliance. In previous studies it was found that substitute benzamide derivatives with higher selective binding to the D2/D3 dopamine receptor - amisulpride and sulpiride may be effective in treatment of clozapine-induced hypersalivation (CIH). Today, in psychiatric practice in Israel, there are four medications which belong to substitute benzamide derivatives group: amisulpride, sulpiride, tiapride and moclobemide. We hypothesized that antisalivation effect is universal for the whole group of benzamide. The aim of our study was to compare efficacy of amisulpride, moclobemide (reversible monoamine oxidase inhibitor-A (RIMAS)), and tiapride (dopamine D2 antagonist) as an additional possibility for management of CIH.

Detailed Description
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The pilot study will be conducted in two mental health centers. In order to examine our hypothesis, we will use an add-on design. Into the study will be enrolled 50 patients with schizophrenia and schizoaffective disorder (males and females, 19-60 years old), according to the DSM-IV criteria, treated with clozapine and suffering from hypersalivation.

Official Title
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Comparison of Benzamide Derivates (Amisulpride, Moclobemide and Tiapride) as Treatment of Clozapine-induced Hypersalivation: Pilot Double Phase Study: Open and Double-blind

Conditions
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Clozapine-induced Hypersalivation

Intervention / Treatment
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* Drug: Amisulpride, Moclobemide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-60 years, male or female DSM-IV criteria for schizophrenia Clozapine treatment At least 2 scores on the Nocturnal Hypersalivation Rating Scale (NHRS) Exclusion Criteria: Evidence of organic brain damage, mental retardation, alcohol or drug abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Moclobemide,<br>treatment during 2 weeks | Drug: Amisulpride, Moclobemide<br>* Amisulpride 400 mg/d; Moclobemide 300 mg/d every medication for 2 week aith 2 week washout<br>|
| Active Comparator: Amisulpride<br>Comparison | Drug: Amisulpride, Moclobemide<br>* Amisulpride 400 mg/d; Moclobemide 300 mg/d every medication for 2 week aith 2 week washout<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypersalivation will be assessed by subjective and objective tools. Clinical global impression (CGI) patient's self assessment will be taken as subjective tool and NHRS as an objective assessment tool. | NHRS, CGI | every two days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CGI, NHRS | CGI, NHRS | two weeks |