Dataset Information

D2 receptor genetic variation and clinical response to antipsychotic drug treatment: a meta-analysis.

ABSTRACT:

Objective

Several lines of evidence suggest that antipsychotic drug efficacy is mediated by dopamine type 2 (D(2)) receptor blockade. Therefore, it seems plausible that variation in the DRD(2) gene is associated with clinical response to antipsychotic drug treatment. The authors conducted the first meta-analysis to examine the relationship between DRD2 polymorphisms and antipsychotic drug response.

Method

A MEDLINE search of articles available up to December 31, 2008, yielded 18 prospective studies examining DRD2 gene variation and antipsychotic response in schizophrenia patients; of which, 10 independent studies met criteria for inclusion. Clinical response to antipsychotic treatment was defined as a 50% reduction of either the Brief Psychiatric Rating Scale total score or Positive and Negative Syndrome Scale total score at approximately 8 weeks of follow-up evaluation. Odds ratio was the primary effect-size measure and computed for each polymorphism in each study. Sufficient data were available for two DRD2 polymorphisms: -141C Ins/Del and Taq1A.

Results

Six studies reported results for the -141C Ins/Del polymorphism (total sample size: N=687). The Del allele carrier was significantly associated with poorer antipsychotic drug response relative to the Ins/Ins genotype. Eight studies assessed the Taq1A polymorphism and antipsychotic response (total sample size: N=748). There was no significant difference in the response rate among A1 allele carriers relative to individuals with the A2/A2 genotype or A2 allele carriers relative to individuals with the A1/A1 genotype.

Conclusions

The DRD2 genetic variation is associated with clinical response to antipsychotic drug treatment. These data may provide proof-of-principle for pharmacogenetic studies in schizophrenia.

SUBMITTER: Zhang JP

PROVIDER: S-EPMC2896457 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Publications

D2 receptor genetic variation and clinical response to antipsychotic drug treatment: a meta-analysis.

Zhang Jian-Ping JP Lencz Todd T Malhotra Anil K AK

The American journal of psychiatry 20100301 7

<h4>Objective</h4>Several lines of evidence suggest that antipsychotic drug efficacy is mediated by dopamine type 2 (D(2)) receptor blockade. Therefore, it seems plausible that variation in the DRD(2) gene is associated with clinical response to antipsychotic drug treatment. The authors conducted the first meta-analysis to examine the relationship between DRD2 polymorphisms and antipsychotic drug response.<h4>Method</h4>A MEDLINE search of articles available up to December 31, 2008, yielded 18 p ...[more]

PMID: 20194480

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Project description:Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic review and dose-response meta-analysis. We searched multiple electronic databases up to 20.02.2023 for fixed-dose studies investigating 16 second-generation antipsychotics and haloperidol (all formulations and administration routes) in adults with acute exacerbations of schizophrenia. The primary outcome was the number of participants receiving antiparkinsonian medication, and if not available, the number of participants with extrapyramidal side-effects (EPS) and the mean scores of EPS rating scales were used as proxies. The effect-size was odds ratio (ORs) compared with placebo. One-stage random-effects dose-response meta-analyses with restricted cubic splines were conducted to estimate the dose-response curves. We also examined the relationship between dopamine D2 receptor (D2R) occupancy and ORs by estimating occupancies from administrated doses. We included data from 110 studies with 382 dose arms (37193 participants). Most studies were short-term with median duration of 6 weeks (range 3-26 weeks). Almost all antipsychotics were associated with dose-dependent EPS with varied degrees and the maximum ORs ranged from OR = 1.57 95%CI [0.97, 2.56] for aripiprazole to OR = 7.56 95%CI [3.16, 18.08] for haloperidol at 30 mg/d. Exceptions were quetiapine and sertindole with negligible risks across all doses. There was very low quality of findings for cariprazine, iloperidone, and zotepine, and no data for clozapine. The D2R occupancy curves showed that the risk increased substantially when D2R occupancy exceeded 75-85%, except for D2R partial agonists that had smaller ORs albeit high D2R occupancies. In conclusion, we found that the risk of EPS increases with rising doses and differs substantially in magnitude among antipsychotics, yet exceptions were quetiapine and sertindole with negligible risks. Our data provided additional insights into the current D2R therapeutic window for EPS.

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Dataset Information

D2 receptor genetic variation and clinical response to antipsychotic drug treatment: a meta-analysis.

Objective

Method

Results

Conclusions

Publications

D2 receptor genetic variation and clinical response to antipsychotic drug treatment: a meta-analysis.

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