Which gene is not associated with risk for the development of TD? What is the prevalence of TD in patients with schizophrenia treated with antipsychotics? Those questions and more in this quiz.
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The correct answer is B. 20% to 25%.
Kane and Smith1 reviewed 56 studies published between 1959 and 1979, and found a mean 20% prevalence of TD. A meta-analysis of 41 studies performed during the period of second-generation antipsychotic use found a 25% prevalence of TD.2 In the latter study, the prevalence of TD was lower in patients treated with second- versus first-generation antipsychotics (21% versus 30%).
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The correct answer is D. CYP3A4.
A meta-analytic review of 20 studies found that carriers of the Met allele of the COMT (Catechol-O-Methyltransferase) Val158Met polymorphism had significant decreased risk of TD.3 This review also found a significant protective effect of Val carriers of the MnSOD (Manganese Superoxide Dismutase) Ala-9Val polymorphism.
By contrast, the A2 variant of the Taq1A polymorphism in DRD2 (Dopamine Receptor D2) was associated with increased risk of TD. Another meta-analysis found that certain “loss of function” alleles for CYP2D6 (Cytochrome P450 2D6) confer increased risk of TD.4 There is also evidence of associations between CYP1A2, but not CYP3A4 and risk of TD.3
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The correct answer is C. Male sex.
Tenbeck and colleagues performed a meta-analysis of risk factors for TD in 8 prospective studies of patients with schizophrenia.5 Statistically significant risk factors identified included non-white ethnicity (RR=1.8), early EPS (RR=1.6), and increasing age (RR=1.02). The association with increasing age may be a proxy for cumulative lifetime antipsychotic exposure. By contrast, sex, antipsychotic dose, and akathisia were not significant predictors of TD based on this review.
1. Kane JM, Smith JM. Tardive Dyskinesia Prevalence and Risk Factors, 1959 to 1979. Arch Gen Psychiatry. 1982;39:473-481.
2. Carbon M, Hsieh CH, Kane JM, Correll CU. Tardive Dyskinesia Prevalence in the Period of Second-Generation Antipsychotic Use: A Meta-Analysis. J Clin Psychiatry 2017;78:e264-e278.
3. Bakker PR, van Harten PN, van Os J. Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions. Mol Psychiatry 2008; 13(5): 544-556.
4. Patsopoulos NA, Ntzani EE, Zintzaras E, Ioannidis JP. CYP2D6 polymorphisms and the risk of tardive dyskinesia in schizophrenia: a meta-analysis. Pharmacogenet Genomics 2005;15:151-158.
5. Tenback DE, van Harten PN, van Os J. Non-therapeutic risk factors for onset of tardive dyskinesia in schizophrenia: a meta-analysis. Movement Disord. 2009;24:2309-2315.