We sought to identify baseline predictors of response to clozapine.
Data were from a 15-site randomized clinical trial comparing clozapine and haloperidol in hospitalized patients with refractory schizophrenia (n = 423). Three-month outcomes were analyzed with the full sample (n = 368 due to attrition). Because of crossovers, analyses of 12-month outcomes were conducted with crossovers excluded (n = 291). Clinical predictors included age, race, diagnosis (current substance abuse, paranoid subtype of schizophrenia, or depressive syndrome), severity of symptoms, quality of life, age at onset of schizophrenia, extrapyramidal symptoms, and VA compensation payment. Multiple regression analysis was used to examine the interaction of treatment condition and each of these variables in predicting outcomes for symptoms, quality of life, side effects, and days hospitalized.
Patients with higher quality of life at baseline (p = .04) and higher symptoms (p = .02) had relatively smaller declines in hospital days at 6 months. In the 12-month sample patients with higher levels of symptoms had greater symptom reductions at 12 months (p = .03) and greater improvement in quality of life (p = .004).
Although high levels of symptoms were associated with greater improvement on clozapine, these findings are not robust enough to suggest that any specific, clinically defined subgroup of refractory patients should be preferentially targeted for clozapine treatment.
"The variable responses to antipsychotic drugs in the treatment of schizophrenia still present obstacles to tailoredmedicine . Early efforts to identify the predictors of antipsychotic drug response focused on clinical variables and showed only limited success (Baker et al., 2002; Moeller et al., 1995; Rosenheck et al., 1998; Salin-Pascual et al., 2004; Yoshimura et al., 2003). Recent advances in molecular genetics have provided a novel method for identifying genetic variables influencing clinical responses to antipsychotic drugs and have led to intensive pharmacogenetic research. "
[Show abstract][Hide abstract] ABSTRACT: We investigated whether the clinical response to aripiprazole differed according to the Taq1A polymorphism in the dopamine D2 receptor (DRD2) gene. In this 26-week, prospective, open-label, double-blind, parallel-group study, 90 patients with schizophrenia, schizoaffective disorder, or schizophreniform disorder were recruited and divided into two groups according to their DRD2 genotype (A1A1, n=14; A1A2+A2A2, n=76). The efficacy assessment included Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression (CGI) scores. Extrapyramidal symptoms were assessed using the Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), and Barnes Akathisia Rating Scale (BAS). Plasma prolactin levels were also measured. Patients with the A1A1 genotype showed a more favorable therapeutic response to aripiprazole when assessed using the PANSS ratio. The changes in the SAS score from baseline to week 4 also differed according to the genotype group. There were no significant differences in the changes in the CGI, AIMS, and BAS scores or plasma prolactin level between the two genotype groups. The results suggest an association between the DRD2 Taq1A polymorphism status and the variation in the clinical response to aripiprazole.
European Neuropsychopharmacology 10/2008; 18(12):897-907. DOI:10.1016/j.euroneuro.2008.07.010 · 4.37 Impact Factor
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