Association of 9-hydroxy risperidone concentrations with risk of switching or
discontinuation in the clinical antipsychotic trial of intervention
effectiveness-Alzheimer's disease trial.
Author(s): Wessels AM, Pollock BG, Anyama NG, Schneider LS, Lieberman JA, Marder SR, Bies
RR.
Affiliation(s): Division of Clinical Pharmacology, Wishard Memorial Hospital, 1001 West 10th St,
WD Meyers Building, W7123, Indianapolis, IN 46202, USA. awessels@iupui.edu
Publication date & source: 2010, J Clin Psychopharmacol. , 30(6):683-7
Risperidone has been used to treat behavioral symptoms, such as delusions and
agitation, in people with Alzheimer's disease. The relationship between magnitude
and variability of risperidone and 9-hydroxy risperidone exposure and the
relationship with time to discontinuation of the medication were explored.
Sixty-five subjects from the Clinical Antipsychotic Trial of Intervention
Effectiveness-Alzheimer's Disease Trial that received risperidone were included
in this study. Eighteen subjects completed the study without switching medication
(completers on risperidone), whereas 47 discontinued the medication. Those who
discontinued were divided into 2 groups according to responsiveness to therapy.
Using Cox proportional survival regression analysis, we estimated time to
discontinuation and factors associated with treatment discontinuation including
age, dose, body mass index, neuropsychiatric inventory baseline score, and
average exposure (area under the curve [AUC]) to risperidone and 9-hydroxy
risperidone. Twenty-four and 17 subjects discontinued therapy because of
inadequate therapeutic effect and side effects, respectively (6 subjects were
excluded because of missing information about reason for switching or
discontinuation). Discontinuation hazards for those with a higher than median AUC
of the metabolite were 2.54 (P = 0.029; inadequate and side effect group
combined) and 3.48 (P = 0.025; inadequate effect group) times that of those in
the lower than median AUC group. None of the other covariates contributed
significantly to the switching hazard. Risperidone metabolite, 9-hydroxy
risperidone concentrations, correlated with the risk of switching or
discontinuing the medication, suggesting that 9-hydroxy risperidone contributes
to adverse events and intolerability in dementia patients.
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