Abstract
Background
Tardive dyskinesia (TD) is a severe condition that can affect almost 1 out of 4 patients
on current or previous antipsychotic treatment, including both first-generation antipsychotics
(FGAs) and second-generation antipsychotics (SGAs). While two novel vesicular monoamine
transporter inhibitors, deutetrabenazine and valbenazine, have shown acute efficacy
for TD, the majority of patients do not remit, and TD appears to recur once treatment
is withdrawn. Hence, prevention of TD remains a crucial goal.
Methods
We provide a clinically oriented overview of risk factors for TD, dividing them into
patient-, illness- and treatment-related variables, as well as nonmodifiable and modifiable
factors.
Results
Unmodifiable patient-related and illness-related risk factors for TD include older
age, female sex, white and African descent, longer illness duration, intellectual
disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive
symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism
and dopamine functioning. Modifiable comorbidity-related and treatment-related factors
include diabetes, smoking, and alcohol and substance abuse, FGA vs SGA treatment,
higher cumulative and current antipsychotic dose or antipsychotic plasma levels, early
parkinsonian side effects, anticholinergic co-treatment, akathisia, and emergent dyskinesia.
Discussion
Clinicians using dopamine antagonists need to consider risk factors for TD to minimize
TD and its consequences.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the Neurological SciencesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Tardive dyskinesia prevalence in the period of second-generation antipsychotic use: a meta-analysis.J. Clin. Psychiatry. 2017; 78: e264-e278https://doi.org/10.4088/JCP.16r10832
- Epidemiology, prevention, and assessment of tardive dyskinesia and advances in treatment.J. Clin. Psychiatry. 2017; https://doi.org/10.4088/JCP.tv17016ah4c
- Abnormal Involuntary Movement Scale (117-AIMS), in ECDEU Assessment Manual for Psychopharmacology.1976: 534-537
- Manual for the extrapyramidal symptom rating scale (ESRS).Schizophr. Res. 2005; 76: 247-265https://doi.org/10.1016/j.schres.2005.02.013
- Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 1: pathophysiology and mechanisms of induction.Can. J. Psychiatr. 2005; 50: 541-547https://doi.org/10.1177/070674370505000907
- Randomized controlled trial of deutetrabenazine for tardive dyskinesia: the ARM-TD study.Neurology. 2017; 88: 2003-2010https://doi.org/10.1212/WNL.0000000000003960
Anderson KE, Stamler D, Davis MD, et al. Deutetrabenazine for the treatment of tardive dyskinesia: Results from an open-label, long-term study. P7-009. The American Psychiatric Association 2017 Annual Meeting. San Diego, California, USA, 2017.
Anderson KE, Stamler D, Davis MD, et al. Long-term safety of deutetrabenazine for the treatment of tardive dyskinesia: Results from an open-label, long-term study. P07-010. The American Psychiatric Association 2017 Annual Meeting. San Diego, California, USA, 2017.
- Valbenazine for tardive dyskinesia: a systematic review of the efficacy and safety profile for this newly approved novel medication-what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?.Int. J. Clin. Pract. 2017; 71https://doi.org/10.1111/ijcp.12964
- Deutetrabenazine for tardive dyskinesia: a systematic review of the efficacy and safety profile for this newly approved novel medication-what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?.Int. J. Clin. Pract. 2017; https://doi.org/10.1111/ijcp.13030
- KINECT 3: a phase 3 randomized, double-blind, placebo-controlled trial of valbenazine for tardive dyskinesia.Am. J. Psychiatry. 2017; 174: 476-484https://doi.org/10.1176/appi.ajp.2017.16091037
- Efficacy of valbenazine (NBI-98854) in subjects with tardive dyskinesia: results of a long-term study (KINECT 3 Extension) (S56.005).Neurology. 2017; 88
- Efficacy of Valbenazine (NBI-98854) in treating subjects with tardive dyskinesia and schizophrenia or schizoaffective disorder.Psychopharmacol. Bull. 2017; 47: 69-76
- Long-term safety and tolerability of Valbenazine (NBI-98854) in subjects with tardive dyskinesia and a diagnosis of schizophrenia or mood disorder.Psychopharmacol. Bull. 2017; 47: 61-68
- Efficacy of Valbenazine (NBI-98854) in treating subjects with tardive dyskinesia and mood disorder.Psychopharmacol. Bull. 2017; 47: 53-60
- Quality of life in schizophrenia: relationship to sociodemographic factors, symptomatology and tardive dyskinesia.Acta Psychiatr. Scand. 1996; 94: 118-124
- Tardive dyskinesia associated with higher mortality in psychiatric patients: results of a meta-analysis of seven independent studies.J. Clin. Psychopharmacol. 2000; 20: 188-194
- Prospective study of tardive dyskinesia in the elderly: rates and risk factors.Am. J. Psychiatry. 1998; 155: 1521-1528https://doi.org/10.1176/ajp.155.11.1521
- Risk of tardive dyskinesia in older patients. A prospective longitudinal study of 266 outpatients.Arch. Gen. Psychiatry. 1995; 52: 756-765
- Incidence of tardive dyskinesia with risperidone or olanzapine in the elderly: results from a 2-year, prospective study in antipsychotic-naive patients.Neuropsychopharmacology. 2011; 36: 1738-1746https://doi.org/10.1038/npp.2011.55
- Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies.Am. J. Psychiatry. 2004; 161: 414-425https://doi.org/10.1176/appi.ajp.161.3.414
- Tardive dyskinesia and new antipsychotics.Curr. Opin. Psychiatry. 2008; 21: 151-156https://doi.org/10.1097/YCO.0b013e3282f53132
- Gender differences in tardive dyskinesia: a critical review of the literature.Schizophr. Bull. 1992; 18: 701-715
- Non-therapeutic risk factors for onset of tardive dyskinesia in schizophrenia: a meta-analysis.Mov. Disord. 2009; 24: 2309-2315https://doi.org/10.1002/mds.22707
- Drug-drug interactions with antipsychotics.CNS Spectr. 2007; 12: 6-9
- Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions.Mol. Psychiatry. 2008; 13: 544-556https://doi.org/10.1038/sj.mp.4002142
- The clinical effectiveness and cost-effectiveness of testing for cytochrome P450 polymorphisms in patients with schizophrenia treated with antipsychotics: a systematic review and economic evaluation.Health Technol. Assess. 2010; 14 (iii): 1-157https://doi.org/10.3310/hta14030
- Cytochrome P450 testing for prescribing antipsychotics in adults with schizophrenia: systematic review and meta-analyses.Pharm. J. 2010; 11 (iii): 1-14https://doi.org/10.1038/tpj.2010.73
- Genetics of common antipsychotic-induced adverse effects.Mol. Neuropsychiatry. 2016; 2: 61-78https://doi.org/10.1159/000445802
- The association between COMT Val158Met gene polymorphism and antipsychotic-induced tardive dyskinesia risk.Int. J. Neurosci. 2016; 126: 1044-1050https://doi.org/10.3109/00207454.2015.1089504
- Association study of the vesicular monoamine transporter gene SLC18A2 with tardive dyskinesia.J. Psychiatr. Res. 2013; 47: 1760-1765https://doi.org/10.1016/j.jpsychires.2013.07.025
- BDNF Val66Met polymorphism and antipsychotic-induced tardive dyskinesia occurrence and severity: a meta-analysis.Schizophr. Res. 2014; 152: 365-372https://doi.org/10.1016/j.schres.2013.12.011
- Polymorphisms of dopamine degradation enzyme (COMT and MAO) genes and tardive dyskinesia in patients with schizophrenia.Psychiatry Res. 2004; 127: 1-7https://doi.org/10.1016/j.psychres.2004.03.011
- Antipsychotic-induced tardive dyskinesia and the Ser9Gly polymorphism in the DRD3 gene: a meta analysis.Schizophr. Res. 2006; 83: 185-192https://doi.org/10.1016/j.schres.2006.01.010
- Oxidative stress and tardive dyskinesia: pharmacogenetic evidence.Prog. Neuro-Psychopharmacol. Biol. Psychiatry. 2013; 46: 207-213https://doi.org/10.1016/j.pnpbp.2012.10.018
- Clinical correlates of tardive dyskinesia in schizophrenia: baseline data from the CATIE schizophrenia trial.Schizophr. Res. 2005; 80: 33-43https://doi.org/10.1016/j.schres.2005.07.034
- Tardive dyskinesia outcomes: clinical and pharmacologic correlates of remission and persistence.Neuropsychopharmacology. 1993; 8: 233-239https://doi.org/10.1038/npp.1993.26
- On the use of antipsychotic medication in an intellectual disability (ID) community caseload.Psychiatr. Danub. 2017; 29: 578-583
- Antipsychotic use trends in youth with autism Spectrum disorder and/or intellectual disability: a meta-analysis.J. Am. Acad. Child Adolesc. Psychiatry. 2016; 55 (e4): 456-468https://doi.org/10.1016/j.jaac.2016.03.012
- Risk factors for tardive dyskinesia in adults with intellectual disability, comorbid psychopathology, and long-term psychotropic use.Res. Dev. Disabil. 2010; 31: 108-116https://doi.org/10.1016/j.ridd.2009.08.002
- Tardive dyskinesia: who is at risk?.Acta Psychiatr. Scand. 1997; 96: 206-216
- Tardive dyskinesia and deficit schizophrenia.Acta Psychiatr. Scand. 2011; 124: 357-362https://doi.org/10.1111/j.1600-0447.2011.01751.x
- Frequency and correlates of tardive dyskinesia in Indian patients with type I bipolar disorder.Asian J. Psychiatr. 2017; 32: 92-98https://doi.org/10.1016/j.ajp.2017.12.001
- Tardive dyskinesia: prevalence, incidence, and risk factors.Psychopharmacology Suppl. 1985; 2: 72-78
- As a predictor in the development of tardive dyskinesia.Biol. Psychiatry. 1984; 19: 441-444
- Tardive dyskinesia and the primary psychiatric diagnosis.Psychosomatics. 1984; 25: 135-138https://doi.org/10.1016/S0033-3182(84)73083-0
- Cognitive functions in tardive dyskinesia.Psychol. Med. 1983; 13: 671-674
- Tardive dyskinesia is associated with greater cognitive impairment in schizophrenia.Prog. Neuro-Psychopharmacol. Biol. Psychiatry. 2013; 46: 71-77https://doi.org/10.1016/j.pnpbp.2013.06.013
- Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: a systematic review and large scale meta-analysis.World Psychiatry. 2016; 15: 166-174https://doi.org/10.1002/wps.20309
- Physical multimorbidity and psychosis: comprehensive cross sectional analysis including 242,952 people across 48 low- and middle-income countries.BMC Med. 2016; 14: 189https://doi.org/10.1186/s12916-016-0734-z
- Tardive dyskinesia and diabetes mellitus.Psychopharmacol. Bull. 1992; 28: 281-286
- A combined analysis of worldwide studies demonstrates an association between bipolar disorder and tobacco smoking behaviors in adults.Bipolar Disord. 2015; 17: 575-597https://doi.org/10.1111/bdi.12319
- Smoking and tardive dyskinesia in male patients with chronic schizophrenia.Prog. Neuro-Psychopharmacol. Biol. Psychiatry. 2011; 35: 1765-1769https://doi.org/10.1016/j.pnpbp.2011.06.006
- Does the degree of smoking effect the severity of tardive dyskinesia? A longitudinal clinical trial.Eur. Psychiatry. 2009; 24: 33-40https://doi.org/10.1016/j.eurpsy.2008.07.007
- Substance misuse in patients with schizophrenia: epidemiology and management.Drugs. 2002; 62: 743-755
- Prevalence of comorbid bipolar and substance use disorders in clinical settings, 1990-2015: systematic review and meta-analysis.J. Affect. Disord. 2016; 206: 331-349https://doi.org/10.1016/j.jad.2016.07.011
- Comorbid substance use disorder in schizophrenia: a selective overview of neurobiological and cognitive underpinnings.Psychiatry Clin. Neurosci. 2013; 67: 367-383https://doi.org/10.1111/pcn.12072
- Increased tardive dyskinesia in alcohol-abusing schizophrenic patients.Compr. Psychiatry. 1992; 33: 121-122
- Substance abuse is associated with increased extrapyramidal symptoms in schizophrenia: a meta-analysis.Schizophr. Res. 2009; 113: 181-188https://doi.org/10.1016/j.schres.2009.06.010
- Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial.Lancet Psychiatry. 2017; 4: 595-604https://doi.org/10.1016/S2215-0366(17)30236-5
- side effects are unacceptable.Eur. Neuropsychopharmacol. 2001; 11: S397-403
- Early extrapyramidal side-effects as risk factors for later tardive dyskinesia: a prospective study.Aust. N Z J. Psychiatry. 2004; 38: 445-449https://doi.org/10.1080/j.1440-1614.2004.01382.x
- Evidence that early extrapyramidal symptoms predict later tardive dyskinesia: a prospective analysis of 10,000 patients in the European schizophrenia outpatient health outcomes (SOHO) study.Am. J. Psychiatry. 2006; 163: 1438-1440https://doi.org/10.1176/ajp.2006.163.8.1438
- diagnoses for tardive dyskinesia.Arch. Gen. Psychiatry. 1982; 39: 486-487
- Withdrawal-emergent dyskinesia in patients with schizophrenia during antipsychotic discontinuation.Biol. Psychiatry. 1995; 38: 713-719https://doi.org/10.1016/0006-3223(95)00082-8
- Risk factors for tardive dyskinesia among long-term outpatients maintained with neuroleptic medications. Results of the Yale tardive dyskinesia study.Arch. Gen. Psychiatry. 1993; 50: 723-733
- Patterns of psychotropic drug use and tardive dyskinesia.J. Clin. Psychopharmacol. 1984; 4: 41-45
- Prevalence and risk factors associated with tardive dyskinesia among Indian patients with schizophrenia.Asian J. Psychiatr. 2014; 9: 31-35https://doi.org/10.1016/j.ajp.2013.12.010
- Intermittent neuroleptic treatment and risk for tardive dyskinesia: curacao extrapyramidal syndromes study III.Am. J. Psychiatry. 1998; 155: 565-567https://doi.org/10.1176/ajp.155.4.565
- Anticholinergic medication for neuroleptic-induced tardive dyskinesia.Cochrane Database Syst. Rev. 2000; 2CD000204https://doi.org/10.1002/14651858.CD000204
- Effect of anticholinergics on tardive dyskinesia. A controlled discontinuation study.Br. J. Psychiatry. 1984; 145: 304-310
- Anticholinergics in the era of atypical antipsychotics: short-term or long-term treatment?.J. Psychopharmacol. 2012; 26: 1167-1174https://doi.org/10.1177/0269881112447988
- Systematic review of interventions for treating or preventing antipsychotic-induced tardive dyskinesia.Health Technol. Assess. 2017; 21: 1-218https://doi.org/10.3310/hta21430
- Practice Guidelines for the Treatment of Psychiatric Disorders: Compendium 2000.2000
- Smoking and mental illness: a population-based prevalence study.JAMA. 2000; 284: 2606-2610
- Comparison of olanzapine to risperidone in substance-abusing individuals with schizophrenia.Am. J. Addict. 2007; 16: 260-268https://doi.org/10.1080/10550490701389658
- Differences in craving for cannabis between schizophrenia patients using risperidone, olanzapine or clozapine.J. Psychopharmacol. 2012; 26: 189-195https://doi.org/10.1177/0269881111408957
- Antipsychotics for primary alcohol dependence: a systematic review and meta-analysis of placebo-controlled trials.J Clin Psychiatry. 2013; 74: e642-54https://doi.org/10.4088/JCP.12r08178
- Are people with schizophrenia adherent to diabetes medication? A comparative meta-analysis.Psychiatry Res. 2017; 250: 17-24https://doi.org/10.1016/j.psychres.2017.01.049
- Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large-scale meta-analysis of 3,211,768 patients and 113,383,368 controls.World Psychiatry. 2017; 16: 163-180https://doi.org/10.1002/wps.20420
- Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review.Ther. Clin. Risk Manag. 2017; 13: 757-777https://doi.org/10.2147/TCRM.S117321
- Antipsychotic plasma levels in the assessment of poor treatment response in schizophrenia.Acta Psychiatr. Scand. 2017; https://doi.org/10.1111/acps.12825
- Application of plasma levels of olanzapine and N-desmethyl-olanzapine to monitor metabolic parameters in patients with schizophrenia.Schizophr. Res. 2017; https://doi.org/10.1016/j.schres.2017.07.022
- Treatment outcome with clozapine in tardive dyskinesia, neuroleptic sensitivity, and treatment-resistant psychosis.J Clin Psychiatry. 1987; 48: 263-267
- Clozapine treatment for neuroleptic-induced tardive dyskinesia, parkinsonism, and chronic akathisia in schizophrenic patients.J Clin Psychiatry. 1997; 58: 318-322
- Tardive dyskinesia, clozapine, and treatment response.Prog. Neuro-Psychopharmacol. Biol. Psychiatry. 1998; 22: 567-573
- Clozapine-induced tardive dyskinesia in schizophrenic patients taking clozapine as a first-line antipsychotic drug.World J. Biol. Psychiatry. 2009; 10: 919-924https://doi.org/10.1080/15622970802481895
Article info
Publication history
Published online: February 05, 2018
Accepted:
February 2,
2018
Received:
January 3,
2018
Footnotes
☆This article is part of the Special Issue Tardive Syndromes and Their Management edited by Robert A. Hauser and Daniel D. Truong.
Identification
Copyright
© 2018 Elsevier B.V. All rights reserved.
