Clinical Trial: Anticholinergic Burden in Schizophrenia

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Anticholinergic Burden in Schizophrenia

Brief Summary: Anticholinergic antiparkinsonian agents often cause side-effects including cognitive impairment, dry mouth, and constipation while they diminish antipsychotic-induced parkinsonian symptoms. The introduction of second generation antipsychotics (SGA) brought fewer neurological side effects. However, anticholinergic coprescription rates are still as high as 12-65% in patients on SGA that are much higher than the incidence of EPS reported in clinical trials (3-20%). This apparently discrepancy is likely explained, in part, by the established tradition of routine use of this medications. Older patients are particularly sensitive to anticholinergic side-effects due to age-related changes in pharmacokinetics and pharmacodynamics. In this study, we will examine the safety and benefits of reducing the dose of a frequently prescribed anticholinergics, benztropine, on cognitive function, extrapyramidal symptoms, and psychotic symptoms in older subjects with a primary psychotic disorder.

Detailed Summary:

Anticholinergic antiparkinsonian agents (AAAs) are frequently prescribed in patients with a primary psychotic disorder either to treat or prevent the emergence of antipsychotic induced extrapyramidal symptoms (EPS). Second generation antipsychotics (SGAs) are by definition associated with fewer neurological side effects. This would be expected to be associated with a lower use of AAAs. However, in a recent prescription survey, Park and colleagues found that while the rate of concomitant use of antiparkinsonian agents dropped by 9.2% in patients with schizophrenia after changing their antipsychotic from typical antipsychotics to SGAs, 30% of prescriptions for SGAs included a concomitant antiparkinsonian agent. This is consistent with the results of other cross-sectional surveys demonstrating anticholinergic co-prescription rates of 12 - 65% in patients treated with SGA. These high rates are remarkable especially when one considers that the incidence of EPS reported in past clinical trials using SGAs (3 - 20%) is much lower than this reported co-prescription rate. This apparent discrepancy is likely explained, in part, by the established tradition of prophylactic (or routine) use of AAAs for patients starting antipsychotic drugs.

The adverse effects of AAAs are well known, and are particularly significant clinically in the elderly, who are at high risk of cognitive impairment with AAAs. Anticholigergic effects have been reported to impair cognitive function both globally as well as in specific domains, including memory and executive functioning. The association between anticholinergic activity and cognitive performance are also strongly supported by recent studies measuring serum anticholinergic activity (SAA).

Furthermore, in addition to their well-known side effects such as dry mouth, blurred vision, and constipation, they
Sponsor: Centre for Addiction and Mental Health

Current Primary Outcome: percentage of participants who successfully withdraw from anticholinergic antiparkinsonian agents. [ Time Frame: at the end of the study ]

Original Primary Outcome: Same as current

Current Secondary Outcome: effect of reducing the dose of benztropine on EPS and anticholinergic side-effects including cognitive impairments. [ Time Frame: intermittent ]

Original Secondary Outcome: Same as current

Information By: Centre for Addiction and Mental Health

Dates:
Date Received: July 11, 2008
Date Started: June 2007
Date Completion:
Last Updated: August 21, 2015
Last Verified: August 2015