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BDNF Val66Met polymorphism and antipsychotic-induced tardive dyskinesia occurrence and severity: a meta-analysis.

ABSTRACT: Tardive dyskinesia (TD) is a serious long-term consequence of antipsychotic treatment. Since brain-derived neurotrophic factor (BDNF) has potent neurotrophic activity, genetic alterations in the BDNF gene may affect antipsychotic-induced TD.Searching PubMed and Web of Science until 05/31/13, we conducted a systematic review and a meta-analysis of the effects of BDNF Val66Met polymorphism on antipsychotic-induced TD. Pooled odds ratio was calculated to assess the effects of BDNF Val66Met polymorphism on TD occurrence. Additionally, pooled standardized mean differences (Hedges' g) were calculated to assess the effects on Abnormal Involuntary Movement Scale (AIMS) total score.Out of 699 potentially eligible hits, 6 studies (N=1740, mean age=46.0±10.4years; males=73.1%; Asians=80.5%, Caucasians=19.5%; schizophrenia=96.2%) were included in this meta-analysis. Pooling data from all studies, no significant associations were found between BDNF Val66Met polymorphism and TD (p=0.82) or AIMS total scores (p=0.11). However, in studies including only Caucasians (n=339), Met allele carriers had significantly higher AIMS total scores (Hedges' g=0.253, 95% confidence interval=0.030 to 0.476, p=0.026) and non-significantly higher TD occurrence (p=0.127). Conversely, there was no association between BDNF and AIMS scores (p=0.57) or TD (p=0.65) in Asians.Although there was no significant association between BDNF Val66Met polymorphism and TD or AIMS scores across all patients, our results suggest that BDNF Val66Met polymorphism affects severity and, possibly, TD development in Caucasians. Since the number of studies and patients was still small, additional data are needed to confirm genotype-racial interactions. Furthermore, BDNF enhancing treatments for TD may require further study, especially in Caucasians.

SUBMITTER: Miura I

PROVIDER: S-EPMC4010225 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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BDNF Val66Met polymorphism and antipsychotic-induced tardive dyskinesia occurrence and severity: a meta-analysis.

Miura Itaru I Zhang Jian-Ping JP Nitta Masahiro M Lencz Todd T Kane John M JM Malhotra Anil K AK Yabe Hirooki H Correll Christoph U CU

Schizophrenia research 20140107 2-3

<h4>Background</h4>Tardive dyskinesia (TD) is a serious long-term consequence of antipsychotic treatment. Since brain-derived neurotrophic factor (BDNF) has potent neurotrophic activity, genetic alterations in the BDNF gene may affect antipsychotic-induced TD.<h4>Methods</h4>Searching PubMed and Web of Science until 05/31/13, we conducted a systematic review and a meta-analysis of the effects of BDNF Val66Met polymorphism on antipsychotic-induced TD. Pooled odds ratio was calculated to assess th ...[more]

PMID: 24411528

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Project description:BackgroundData are limited on the benefits and risks of dose reduction in managing side effects associated with antipsychotic treatment. As an example, antipsychotic dose reduction has been recommended in the management of tardive dyskinesia (TD), yet the benefits of lowering doses are not well studied. However, stable maintenance treatment is essential to prevent deterioration and relapse in schizophrenia.MethodsA retrospective cohort study was conducted to analyze the healthcare burden of antipsychotic dose reduction in patients with schizophrenia. Medical claims from six US states spanning a six-year period were analyzed for ≥10% or ≥ 30% antipsychotic dose reductions compared with those from patients receiving a stable dose. Outcomes measured were inpatient admissions and emergency room (ER) visits for schizophrenia, all psychiatric disorders, and all causes, and TD claims.ResultsA total of 19,556 patients were identified with ≥10% dose reduction and 15,239 patients with ≥30% dose reduction. Following a ≥ 10% dose reduction, the risk of an all-cause inpatient admission increased (hazard ratio [HR] 1.17; 95% confidence interval [CI] 1.11, 1.23; P < 0.001), and the risk of an all-cause ER visit increased (HR 1.09; 95% CI 1.05, 1.14; P < 0.001) compared with controls. Patients with a ≥ 10% dose reduction had an increased risk of admission or ER visit for schizophrenia (HR 1.27; 95% CI 1.19, 1.36; P < 0.001) and for all psychiatric disorders (HR 1.16; 95% CI 1.10, 1.23; P < 0.001) compared with controls. A dose reduction of ≥30% also led to an increased risk of admission for all causes (HR 1.23; 95% CI 1.17, 1.31; P < 0.001), and for admission or ER visit for schizophrenia (HR 1.31; 95% CI 1.21, 1.41; P < 0.001) or for all psychiatric disorders (HR 1.21; 95% CI 1.14, 1.29; P < 0.001) compared with controls. Dose reductions had no significant effect on claims for TD.ConclusionPatients with antipsychotic dose reductions showed significant increases in both all-cause and mental health-related hospitalizations, suggesting that antipsychotic dose reductions may lead to increased overall healthcare burden in some schizophrenia patients. This highlights the need for alternative strategies for the management of side effects, including TD, in schizophrenia patients that allow for maintaining effective antipsychotic treatment.

Project description:(1) Introduction: Extrapyramidal disorders form the so-called extrapyramidal syndrome (EPS), which is characterized by the occurrence of motor disorders as a result of damage to the basal ganglia and the subcortical-thalamic connections. Often, this syndrome develops while taking medications, in particular antipsychotics (APs). (2) Purpose: To review studies of candidate genes encoding dopamine receptors as genetic predictors of development of AP-induced parkinsonism (AIP) and AP-induced tardive dyskinesia (AITD) in patients with schizophrenia. (3) Materials and Methods: A search was carried out for publications of PubMed, Web of Science, Springer, and e-Library databases by keywords and their combinations over the last 10 years. In addition, the review includes earlier publications of historical interest. Despite extensive searches of these commonly used databases and search terms, it cannot be ruled out that some publications were possibly missed. (4) Results: The review considers candidate genes encoding dopamine receptors involved in pharmacodynamics, including genes DRD1, DRD2, DRD3, and DRD4. We analyzed 18 genome-wide studies examining 37 genetic variations, including single nucleotide variants (SNVs)/polymorphisms of four candidate genes involved in the development of AIP and AITD in patients with schizophrenia. Among such a set of obtained results, only 14 positive associations were revealed: rs1799732 (141CIns/Del), rs1800497 (C/T), rs6275 (C/T), rs6275 (C/T) DRD2; rs167771 (G/A) DRD3 with AIP and rs4532 (A/G) DRD1, rs6277 (C/T), rs6275 (C/T), rs1800497 (C/T), rs1079597 (A/G), rs1799732 (141CIns/Del), rs1045280 (C/G) DRD2, rs6280 (C/T), rs905568 (C/G) DRD3 with AITD. However, at present, it should be recognized that there is no final or unique decision on the leading role of any particular SNVs/polymorphisms in the development of AIP and AITD. (5) Conclusion: Disclosure of genetic predictors of the development of AIP and AITD, as the most common neurological adverse drug reactions (ADRs) in the treatment of patients with psychiatric disorders, may provide a key to the development of a strategy for personalized prevention and treatment of the considered complication of AP therapy for schizophrenia in real clinical practice.

Project description:BackgroundTardive dyskinesia (TD) is a movement disorder resulting from treatment with typical and atypical antipsychotics. An estimated 16-50% of patients treated with antipsychotics have TD, but this number may be underestimated. The objectives of this study were to build an algorithm for use in electronic health records (EHRs) for the detection and characterization of TD patients, and to estimate the prevalence of TD in a population of patients exposed to antipsychotic medications.MethodsThis retrospective observational study included patients identified in the Optum EHR Database who received a new or refill prescription for an antipsychotic medication between January 2011 and December 2015 (follow-up through June 2016). TD mentions were identified in the natural language-processed clinical notes, and an algorithm was built to classify the likelihood that the mention represented documentation of a TD diagnosis as probable, possible, unlikely, or negative. The final TD population comprised a subgroup identified using this algorithm, with ≥1 probable TD mention (highly likely TD).Results164,417 patients were identified for the antipsychotic population, with1,314 comprising the final TD population. Conservatively, the estimated average annual prevalence of TD in patients receiving antipsychotics was 0.8% of the antipsychotic user population. The average annual prevalence may be as high as 1.9% per antipsychotic user per year, allowing for a more-inclusive algorithm using both probable and possible TD. Most TD patients were prescribed atypical antipsychotics (1049/1314, 79.8%). Schizophrenia (601/1314, 45.7%), and paranoid and schizophrenia-like disorders (277/1314, 21.1%) were more prevalent in the TD population compared with the entire antipsychotic drug cohort (13,308/164,417; 8.1% and 19,359/164,417; 11.8%, respectively).ConclusionsDespite a lower TD prevalence than previously estimated and the predominant use of atypical antipsychotics, identified TD patients appear to have a substantial comorbidity burden that requires special treatment and management consideration.

Dataset Information

BDNF Val66Met polymorphism and antipsychotic-induced tardive dyskinesia occurrence and severity: a meta-analysis.

Publications

BDNF Val66Met polymorphism and antipsychotic-induced tardive dyskinesia occurrence and severity: a meta-analysis.

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