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Clinical significance of pharmacogenomic studies in tardive dyskinesia associated with patients with psychiatric disorders.

ABSTRACT: Pharmacogenomics is the study of the effects of genetic polymorphisms on medication pharmacokinetics and pharmacodynamics. It offers advantages in predicting drug efficacy and/or toxicity and has already changed clinical practice in many fields of medicine. Tardive dyskinesia (TD) is a movement disorder that rarely remits and poses significant social stigma and physical discomfort for the patient. Pharmacokinetic studies show an association between cytochrome P450 enzyme-determined poor metabolizer status and elevated serum antipsychotic and metabolite levels. However, few prospective studies have shown this to correlate with the occurrence of TD. Many retrospective, case-control and cross-sectional studies have examined the association of cytochrome P450 enzyme, dopamine (receptor, metabolizer and transporter), serotonin (receptor and transporter), and oxidative stress enzyme gene polymorphisms with the occurrence and severity of TD. These studies have produced conflicting and confusing results secondary to heterogeneous inclusion criteria and other patient characteristics that also act as confounding factors. This paper aims to review and summarize the pharmacogenetic findings in antipsychotic-associated TD and assess its clinical significance for psychiatry patients. In addition, we hope to provide insight into areas that need further research.

SUBMITTER: Chang FC

PROVIDER: S-EPMC4207069 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Clinical significance of pharmacogenomic studies in tardive dyskinesia associated with patients with psychiatric disorders.

Chang Florence Cf FC Fung Victor Sc VS

Pharmacogenomics and personalized medicine 20141013

Pharmacogenomics is the study of the effects of genetic polymorphisms on medication pharmacokinetics and pharmacodynamics. It offers advantages in predicting drug efficacy and/or toxicity and has already changed clinical practice in many fields of medicine. Tardive dyskinesia (TD) is a movement disorder that rarely remits and poses significant social stigma and physical discomfort for the patient. Pharmacokinetic studies show an association between cytochrome P450 enzyme-determined poor metaboli ...[more]

PMID: 25378945

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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.

Project description:OBJECTIVE:We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD. METHOD:This analysis compared 200 patients with DSM-IV-defined schizophrenia and TD and 997 patients without TD, all of whom were randomly assigned to receive one of 4 second-generation antipsychotics. The primary clinical outcome measure was time to all-cause treatment discontinuation, and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups. Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores were compared using mixed models and analysis of variance. Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline. Percentages of patients meeting criteria for TD postbaseline or showing changes in AIMS scores were evaluated with ?(2) tests. Data were collected from January 2001 to December 2004. RESULTS:Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups (?(2)(1) = 0.11, P = .743). Changes in PANSS scores were not significantly different (F(1,974) = 0.82, P = .366), but patients with TD showed less improvement in neurocognitive scores (F(1,359) = 6.53, P = .011). Among patients with TD, there were no significant differences between drugs in the decline in AIMS scores (F(3,151) = 0.32, P = .811); 55% met criteria for TD at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all postbaseline visits, 24% did not meet criteria for TD at any subsequent visit, 32% showed a ? 50% decrease in AIMS score, and 7% showed a ? 50% increase in AIMS score. CONCLUSIONS:Schizophrenia patients with and without TD were similar in time to discontinuation of treatment for any cause and improvement in psychopathology, but differed in neurocognitive response. There were no significant differences between treatments in the course of TD, with most patients showing either persistence of or fluctuation in observable symptoms. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00014001.

Project description:OBJECTIVE:To evaluate the effects of once-daily valbenazine (40 or 80 mg/d) in older and younger adults with tardive dyskinesia (TD). METHODS:Data were pooled from three 6-week, randomized, double-blind, placebo-controlled (DBPC) studies (KINECT [NCT01688037], KINECT 2 [NCT01733121], and KINECT 3 [NCT02274558]) and two long-term studies (KINECT 3 extension and KINECT 4 [NCT02405091]). Outcomes analyzed in older and younger participants (55 years or older and younger than 55 years, respectively) included Abnormal Involuntary Movement Scale (AIMS) response (threshold of greater than or equal to 50% improvement from baseline in total score [items 1 to 7]) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) response (score 2 or less ["very much improved" or "much improved"]). Safety assessments included treatment-emergent adverse events (TEAEs). RESULTS:At week 6 (end of DBPC treatment), the percentage of participants who met the AIMS response threshold was higher with valbenazine versus placebo in both subgroups: 55 years or older (80 mg/d, 39.7% [P < .001]; 40 mg/d, 28.6% [P < .01]; placebo, 9.7%); younger than 55 years (80 mg/d, 39.5% [P < .001]; 40 mg/d, 20.0% [P > .05]; placebo, 10.8%). The percentage of participants with CGI-TD response was also higher with valbenazine versus placebo: 55 years or older (80 mg/d, 41.3% [P < .01]; 40 mg/d, 30.2% [P > .05]; placebo, 19.4%); younger than 55 years (80 mg/d, 39.5% [P < .05]; 40 mg/d, 35.3% [P < .05]; placebo, 18.5%). Responses at week 48 (end of long-term treatment, combined doses) were as follows: 55 years or older (AIMS, 70.7%; CGI-TD, 82.8%); younger than 55 years (AIMS, 58.7%; CGI-TD, 72.3%). No significant differences between older and younger subgroups were found for AIMS or CGI-TD response. No new safety signals or TEAEs of clinical concern were found in older participants who received long-term treatment. CONCLUSIONS:Valbenazine improved TD and was generally well tolerated in older and younger adults.

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Clinical significance of pharmacogenomic studies in tardive dyskinesia associated with patients with psychiatric disorders.

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Clinical significance of pharmacogenomic studies in tardive dyskinesia associated with patients with psychiatric disorders.

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