Switching Patients with Schizophrenia to Aripiprazole from Other Antipsychotics: A Randomized, Open-label Comparison of Fast versus Slow Switching Strategies
Date Issued
2011
Date
2011
Author(s)
Lo, Wei-Ming
Abstract
Background: The development of atypical antipsychotics has markedly improved the treatment of schizophrenia; however, somnolence, metabolic syndrome, hyperprolactinemia and QTc prolongation are their main adverse events. Aripiprazole, the first D2 partial agonist effect antipsychotics, is proposed to reduce such adverse events. Furthermore, the 5HT1A partial agonist and 5HT2A antagonist effect may improve negative and cognitive symptoms. When patients are willing to switch from other antipsychotics to aripiprazole, “cross-tapering” are considered during the switching period. It may reduce the worsening psychosis and unpleasant side effects. Besides, the individual phenotype of CYP2D6 and CYP3A4 may influence the pharmacokinetics of aripiprazole.
Objectives: To evaluate the efficacy and safety in different switching strategies and determine which strategy is more appropriate to implement in clinical practice.
Methods: This was a block randomization, open-label, parallel assignment, phase IV and 8-week study conducted at 3 hospitals in Taiwan between September 2007 to July 2009. Patients with a primary DSM-IV diagnosis of schizophrenia and schizoaffective disorder were randomly assigned to either fast-switch or slow-switch group. Efficacy measurements included Positive and Negative Symptom Scales and Clinical Global Impressions. Safety measurements included Simpson-Angus Scale, Barnes Akathisia Rating Scale and abnormal Involuntary Movement Scale. Patients were also taken blood samples for the measurement of metabolic profile, drug concentration, and cytochrome P450 CYP2D6 and CYP3A4 genotypes.
Results: In a total of 79 patients, 52 (66%) completed the 8-week trial. The fast switching group (n = 29) and the slow switching group (n = 23) were comparable in the demographic features and previous medications. PANSS negative score was significantly improved in both groups over the 8 weeks of treatment (both p < .05), Meanwhile, extrapyramidal symptom, metabolic profile, electrocardiogram and the prolactin level were maintained or somewhat improved as well. The prolactin level in almost all patients returned to normal range by the endpoint. After switching to aripiprazole from other antipsychotics, the symptoms of extrapyramidal symptoms did not increase. The serum concentrations of aripiprazole reached a stable level at day14, and did not significantly change at day 56 for both groups. After grouping by different CYP2D6 and CYP3A4 genotypes for all the subjects, only the CYP2D6*10 variant was associated with a lower serum concentration of aripiprazole as compared with those without the variant.
Conclusions: This study provided empirical clinical experience in the treatment of switching patients to aripiprazole from other antipsychotics. Compared with the slow switching strategy, the fast switching strategy has similar efficacy and safety in the 8-week treatment of patients with schizophrenia.
Subjects
Schizophrenia
Aripiprazole
Switching Strategies
Type
thesis
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