Clinical trial NCT00381589: Treatment of Clozapine-Induced Hypersalivation Ipratropium Bromide
Official title: Treatment of Clozapine-Induced Hypersalivation Ipratropium Bromide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypersalivation
Keywords: clozapine-induced hypersalivation
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
First posted: 2006-09-28
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Hypersalivation (Too much saliva) and drooling is a side effect experienced by 31% of people taking the antipsychotic clozapine. This study aims to determine if using the medication ipratropium bromide(IPB)at bedtime will reduce the amount of salivation and the distress people may feel.

Detailed description: With the recent questions regarding the effectiveness of newer atypical antipsychotic medications in treating schizophrenia, clozapine continues to remain the gold standard for treatment-refractory schizophrenia. However, treatment with clozapine continues to be limited by its many side effects. The second most common side effect, occurring in 31% of clozapine treated patients, is hypersalivation or sialorrhea. Sialorrhea can be profoundly stigmatizing and functionally disabling in certain patients, and may increase discontinuation rates in this high-risk patient population. Several studies have evaluated the efficacy of anticholinergic agents mainly in small, uncontrolled studies or anecdotal reports and are often complicated by difficulties in medication administration and systemic side effects. Open label and case series studies have demonstrated promising results with ipratropium bromide (IPB) treatment of clozapine-induced hypersalivation, acting on anticholinergic receptors with minimal systemic absorption. However, no randomized controlled trials have evaluated IPB in the treatment of this problematic side effect.The primary goals of this study is to determine the efficacy of ipratropium bromide in reducing clozapine-induced hypersalivation, as per the Toronto Nocturnal Hypersalivation Scale, which is a modified hypersalivation scale incorporating the Drooling Severity Scale and the Nocturnal Hypersalivation Rating Scale, and reduced measurements on visual analogue scales for hypersalivation distress and severity. Our hypothesis that Ipratropium bromide use at bedtime will result in a significant reduction in nocturnal clozapine-induced hypersalivation as measured by the Toronto Nocturnal Hypersalivation Scale (TNHS) through its local anticholinergic activity.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of schizophrenia or schizoaffective disorder as per DSM IV-TR criteria
* Receiving clozapine for at least 2 months
* No change in their clozapine dose for at least 2 weeks
* Have a Clinical Global Impression scale score for hypersalivation of greater than or equal to 4
* Have the capacity to provide voluntary, informed consent
* Able to speak English
* Have a minimum score of 2 on the TNHS prior to study entry
* No change in medications for at least 2 weeks

Exclusion Criteria:

* Subjects with co-morbid medical conditions that could influence hypersalivation (e.g. Idiopathic Parkinson's Disease)
* Subjects currently receiving ipratropium bromide for the treatment of hypersalivation or other medical conditions
* History of narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction
* History of an allergic reaction to ipratropium bromide

Primary outcomes:
measure: Toronto Nocturnal Hypersalivation Scale scores
timeFrame: intermittent
measure: Visual Analogue Scale - Severity
timeFrame: intermittent
measure: Visual Analogue Scale - Distress
timeFrame: Intermittent
measure: Simpson-Angus Rating Scale
timeFrame: Each study visit
measure: Clinical Global Improvement Scale
timeFrame: Each study visit
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Gary Remington, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sockalingam S, Shammi C, Remington G. Treatment of clozapine-induced hypersalivation with ipratropium bromide: a randomized, double-blind, placebo-controlled crossover study. J Clin Psychiatry. 2009 Aug;70(8):1114-9. doi: 10.4088/JCP.08m04495.