Glycopyrrolate for treatment of clozapine-induced sialorrhea in three adolescents
ABSTRACT The aim of this case study was to report preliminary data on the effectiveness and tolerability of glycopyrrolate for the treatment of clozapine-induced sialorrhea, or excessive flow of saliva, in an adolescent population.
Three adolescent females (age 13-16), who developed sialorrhea secondary to clozapine treatment, received an open-label trial of glycopyrrolate (4-8 mg) during inpatient hospitalization for treatment-resistant psychotic illness.
The target symptom of sialorrhea was improved in all three cases, with patient self-reports of decreased production of saliva confirmed by staff observation. Glycopyrrolate was generally well tolerated by the patients. One patient reported constipation, which improved with symptomatic treatment. A second patient reported dry mouth, which improved with a reduction in dose of glycopyrrolate.
These three cases provide support for the potential effectiveness and tolerability of glycopyrrolate for clozapine-induced sialorrhea in adolescents. Further controlled studies are required to determine the safety, efficacy and tolerability of glycopyrrolate in this age group and in adults for clozapine-induced sialorrhea.
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ABSTRACT: Clozapine-induced hypersalivation (CIH) occurs in up to 57% of treated patients and can be the source of considerable subjective distress. Previous open-label studies suggest that sublingual ipratropium bromide may be effective in treating CIH. We conducted a randomized, double-blind, placebo-controlled crossover trial to evaluate the efficacy of ipratropium in 20 individuals with CIH between September 2006 and August 2007. This study was 5 to 6 weeks in duration, based on the participants' clozapine blood-monitoring schedule, and it consisted of two 2-week crossover phases separated by a 1- or 2-week washout period. Primary outcome measures included the reduction in the Toronto Nocturnal Hypersalivation Scale (TNHS) and the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales. Secondary outcomes included visual analog scales assessing hypersalivation severity (VAS-S) and distress (VAS-D). No significant reduction in CIH was found on the TNHS (P = .379), CGI-S (P = .266), or CGI-I (P = .599). Moreover, no difference was noted between study groups on the VAS-S (P = .969) and VAS-D (P = .527). There was no difference in the number of CIH responders at the conclusion of the 2-week placebo (40%, n = 8) and ipratropium (45%, n = 9) study phases (45%, n = 9) according to the TNHS. Randomization order did not have a significant effect on TNHS, CGI-S, or CGI-I scores. Tolerability was comparable between groups, with dry mouth occurring in 1 placebo group subject and 2 ipratropium group subjects. Despite the reports of some preliminary studies that ipratropium is an efficacious treatment for CIH, ipratropium failed to demonstrate significant clinical effect in comparison to placebo. Further research should explore the efficacy of other locally acting anticholinergic agents or other classes of medications. clinicaltrials.gov Identifier: NCT00381589.The Journal of Clinical Psychiatry 08/2009; 70(8):1114-9. DOI:10.4088/JCP.08m04495 · 5.14 Impact Factor
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ABSTRACT: Children with autism and autism spectrum disorders have a high rate of irritability and aggressive symptoms. In one study up to 20% of children with autism have symptoms of irritability and aggression including aggression, severe tantrums, and deliberate self injurious behavior (Lecavalier  J. Autism Dev. Disord. 36:1101-1114.). These symptoms can lead to impairment and distress in both home and school settings. Medications to treat the irritability will be discussed across categories of antipsychotics, antidepressants, antihypertensive agents, and others. Emphasis will be placed on medications with the most safety and efficacy and FDA approval.Developmental Disabilities Research Reviews 01/2010; 16(3):258-64. DOI:10.1002/ddrr.118 · 0.29 Impact Factor
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ABSTRACT: Clozapine-induced sialorrhea (CIS) is a subjective distressing adverse effect and occurs in 31%-57% of schizophrenic patients receiving clozapine therapy. Current pharmacotherapy on CIS has focused on anticholinergic agents, even though they may impair cognitive function. Previous case reports have suggested the benefit of glycopyrrolate or biperiden in treating this condition, but no randomized controlled trial has provided evidence. The objective of our study was to evaluate the efficacy and impact on cognition of glycopyrrolate and biperiden treatments for schizophrenic patients suffering from CIS. Patients who satisfied the inclusion criteria entered a 12-week, randomized, double-blind, crossover, fixed-dose trial. The study consisted of two 4-week crossover phases, which were separated by a 4-week washout period. Sialorrhea and global cognitive function were assessed by using a Drooling Rating Scale (DRS) and the Mini Mental State Examination (MMSE), respectively. Throughout the study, patients treated with glycopyrrolate or biperiden had significantly reduced DRS scores. Moreover, the DRS scores were significantly lower with glycopyrrolate treatment than with biperiden. In other respects, there were no significant differences in MMSE scores in patients treated with glycopyrrolate. However, we found a significant reduction in MMSE scores in patients treated with biperiden. We provide evidence, for the first time, of the efficacy of glycopyrrolate and biperiden in the treatment of CIS. Furthermore, glycopyrrolate displays less impact on cognitive function. Consequently, glycopyrrolate can become a valid option for treating CIS. Observations from our study serve as a springboard for additional large-scale prospective trials.Schizophrenia Research 03/2010; 119(1-3):138-44. DOI:10.1016/j.schres.2010.02.1060 · 4.43 Impact Factor