Official Title: “Treatment of Clozapine-Induced Hypersalivation Ipratropium Bromide”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment, Safety/Efficacy Study

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.

Intervention(s) in this Clinical Trial

• Drug: ipratropium bromide 0.03% spray

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Random assignment to investigational spray

Primary Measures

• Toronto Nocturnal Hypersalivation Scale scores
  • Time Frame: intermittent
    Safety Issue?: No
• Visual Analogue Scale - Severity
  • Time Frame: intermittent
    Safety Issue?: No
• Visual Analogue Scale - Distress
  • Time Frame: Intermittent
    Safety Issue?: No
• Simpson-Angus Rating Scale
  • Time Frame: Each study visit
    Safety Issue?: No
• Clinical Global Improvement Scale
  • Time Frame: Each study visit
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Centre for Addiction and Mental Health

Overall Clinical Trial Officials and Contacts

Gary Remington, MD Principal Investigator Centre for Addiction and Mental Health  

Overall Contact: Gary Remington, MD 416-535-8501 gary_remington@camh.net

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00381589

Study ID Number: 150/2006

ClinicalTrials.gov Identifier: NCT00381589

Health Authority: Canada: Health Canada