Abstract
Rationale
Though clozapine is recommended for treatment of tardive dyskinesia (TD) relating to the use of antipsychotic medications, studies comprehensively investigating the treatment effect of clozapine on TD are still limited.
Objectives
This review examines the effectiveness of clozapine as an intervention for tardive dyskinesia and dystonia in patients with all psychiatric conditions. Effectiveness of clozapine, duration to exert the effect and dosage used were also analysed.
Methods
A search in the PubMed, PsycINFO and clinicaltrials databases was performed, using the search terms “Clozapine” AND “dyskinesia” OR “dystonia”. Full-text articles that reported the use of clozapine to treat abnormal involuntary movements and were written in English were included.
Results
A total of 48 studies were identified, of which 13 were clinical trials and 35 were case reports. Significant improvement was seen in 86.7% of patients with schizophrenia spectrum disorders (average dose of clozapine = 355 mg/day) and 93% of patients with other psychiatric disorders (average dose of clozapine = 152.5 mg/day). Patients with other psychiatric diagnoses had faster improvement than the patients with schizophrenia spectrum disorders. Variation in improvements and dosage were also seen in the clinical trials.
Conclusion
Results suggested an overall effectiveness of clozapine in the treatment of TD for patients with a range of psychiatric conditions. Different response time and clozapine dosage were seen in patients with different psychiatric conditions, suggesting different treatment protocols are required for different conditions. Most of the studies identified are of inadequate qualities, highlighting the need for high quality studies to provide clearer evidence.
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References
Adityanjee EAB (1996) Successful treatment of tardive dystonia with clozapine. Biol Psychiatry 39:1064–1065
Arya D, Khan T, Margolius AJ, Fernandez HH (2019) Tardive dyskinesia: treatment update. Curr Neurol Neurosci Rep 19:69
Baptista T, de Leon J (2018) Positive response to clozapine augmentation in a patient with obsessive-compulsive disorder complicated by a tardive movement disorder. Braz J Psychiatry 40:229–230
Bassitt DP, Louzã Neto MR (1998) Clozapine efficacy in tardive dyskinesia in schizophrenic patients. Eur Arch Psychiatry Clin Neurosci 248:209–211
Bhidayasiri R, Fahn S, Weiner WJ et al (2013) Evidence-based guideline: treatment of tardive syndromes: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 81:463–469
Carroll BJ, Curtis GC, Kokmen E (1977) Paradoxical response to dopamine agonists in tardive dyskinesia. Am J Psychiatry 134:785–789
Chakrabarti SCPK (2002) Lithium - induced tardive dystonia. Neurol India 50:473
Conus P, Zullino D, Baumann P (2002) Clozapine is more efficacious for tongue dystonia than olanzapine. Psychopharmacology 162:89
Dalack GW, Becks L, Meador-Woodruff JH (1998) Tardive dyskinesia, clozapine, and treatment response. Prog Neuropsychopharmacol Biol Psychiatry 22:567–573
Delecluse F, Elosegi JA, Gérard JM (1998) A case of tardive tremor successfully treated with clozapine. Mov Disord 13:846–847
Duggal HS, Mendhekar DN (2006) Atypical antipsychotics, tardive dyskinesia, and D(2) receptors. Am J Psychiatry 163:1449–1450
Fariba K, Estevez R (2021) Tardive dystonia. In: StatPearls. StatPearls Publishing, Treasure Island (FL)
Frei K (2019) Tardive dyskinesia: who gets it and why. Parkinsonism Relat Disord 59:151–154
Friedman JH (1994) Clozapine treatment of psychosis in patients with tardive dystonia: report of three cases. Mov Disord 9:321–324
Gagnier JJ, Kienle G, Altman DG et al (2013) The CARE guidelines: consensus-based clinical case reporting guideline development. Glob Adv Health Med 2:38–43
Gerbino C (1980) Clozapine in the treatment of tardive dyskinesia: an interim report. Tardive dyskinesia, research and treatment 475–489
Glazer WM, Morgenstern H, Doucette JT (1993) Predicting the long-term risk of tardive dyskinesia in outpatients maintained on neuroleptic medications. J Clin Psychiatry 54:133–139
Gowda GS, Sastry Nagavarapu LS, Reddy Mukku SS, Farooq Ali S (2019) Amisulpride induced oropharyngeal dyskinesia in a patient with schizophrenia: a case report and review of literature. Asian J Psychiatr 41:78–81
Grover S, Hazari N, Kate N et al (2014) Management of tardive syndromes with clozapine: a case series. Asian J Psychiatr 8:111–114
Haile K, Umer H (2019) The use of clozapine and clonazepam co-administration in the treatment of a severe tardive dyskinesia: a case report. SAGE Open Med Case Rep 7:2050313X19833254
Hazari N, Kate N, Grover S (2013) Clozapine and tardive movement disorders: a review. Asian J Psychiatr 6:439–451
Jaffe E, Trémeau F, Sharif Z, Reider R (1995) Clozapine in tardive Tourette syndrome. Biol Psychiatry 38:196–197
Joe S, Park J, Lim J et al (2015) Remission of irreversible aripiprazole-induced tardive dystonia with clozapine: a case report. BMC Psychiatry 15:253
Kalian M, Lerner V, Goldman M (1993) Atypical variants of tardive dyskinesia, treated by a combination of clozapine with propranolol and clozapine with tetrabenazine. J Nerv Ment Dis 181:649–651
Kanodia S, Guha S (2018) Tardive dyskinesia responsive to deep brain stimulation. Aust N Z J Psychiatry 52:717
Kimiagar I, Dobronevsky E, Prokhorov T et al (2012) Rapid improvement of tardive dyskinesia with tetrabenazine, clonazepam and clozapine combined: a naturalistic long-term follow-up study. J Neurol 259:660–664
Kwan Y, Sim K (2010) Resolution of tardive dystonia in a patient with bipolar disorder treated with clozapine: a case report. Prog Neuropsychopharmacol Biol Psychiatry 34:238–239
Lamberti JS, Bellnier T (1993) Clozapine and tardive dystonia. J Nerv Ment Dis 181:137–138
Lee D, Baek JH, Bae M et al (2019) Long-term response to clozapine and its clinical correlates in the treatment of tardive movement syndromes: a naturalistic observational study in patients with psychotic disorders. J Clin Psychopharmacol 39:591–596
Lenders MWPM, Buschman HPJ, Vergouwen MDI et al (2005) Long term results of unilateral posteroventral pallidotomy for antipsychotic drug induced tardive dyskinesia. J Neurol Neurosurg Psychiatry 76:1039
Levkovitch Y, Kronenberg J, Kayser N et al (1995) Clozapine for tardive dyskinesia in adolescents. Brain Dev 17:213–215
Lieberman JA, Saltz BL, Johns CA et al (1991) The effects of clozapine on tardive dyskinesia. Br J Psychiatry 158:503–510
Louzã MR, Bassitt DP (2005) Maintenance treatment of severe tardive dyskinesia with clozapine: 5 years’ follow-up. J Clin Psychopharmacol 25:180–182
Ma C-H, Chien Y-L, Liu C-C et al (2016) A case of tardive dystonia associated with long-acting injectable paliperidone palmitate. Eur Neuropsychopharmacol 26:1251–1252
Margolese HC, Ferreri F (2007) Management of conventional antipsychotic-induced tardive dyskinesia. J Psychiatry Neurosci 32:72
Mendhekar DN (2005) Ziprasidone-induced tardive dyskinesia. Can J Psychiatry 50:567–568
Mentzel TQ, van der Snoek R, Lieverse R, et al (2018) Clozapine monotherapy as a treatment for antipsychotic-induced tardive dyskinesia: a meta-Analysis. J Clin Psychiatry 79.: https://doi.org/10.4088/JCP.17r11852
Mereu A, Serra G, Vicari S, Zanna V (2019) Bipolar disorder in a young woman with preexisting rapid-onset dystonia-parkinsonism and successful treatment with clozapine and lithium. J Clin Psychopharmacol 39:277–279
Moher D, Liberati A, Tetzlaff J et al (2010) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 8:336–341
Moore NC, Lewitt PA, Gershon S (1992) Reduction of dyskinesias and psychiatric disability with clozapine over different time courses. J Psychopharmacol 6:514–518
Pardis P, Remington G, Panda R et al (2019) Clozapine and tardive dyskinesia in patients with schizophrenia: a systematic review. J Psychopharmacol 33:1187–1198
Pierce A, Coker D (2019) Tardive dyskinesia suppression seen during a catatonic state: a case report. Psychosomatics 60:428–431
Poyurovsky M (2008) Clozapine in treatment-refractory obsessive-compulsive disorder with comorbid schizotypal personality disorder. Isr J Psychiatry Relat Sci 45:219–220
Ranjan R, Meltzer HY (1996) Acute and long-term effectiveness of clozapine in treatment-resistant psychotic depression. Biol Psychiatry 40:253–258
Ricciardi L, Pringsheim T, Barnes TRE et al (2019) Treatment recommendations for tardive dyskinesia. Can J Psychiatry 64:388–399
Roerig JL (2019) Clozapine augmentation strategies. Ment Health Clin 9:336–348
Sangroula D, Virk I, Mohammad W, Kahn DA (2017) Clozapine treatment of olanzapine-induced tardive dyskinesia: a case report. J Psychiatr Pract 23:53–59
Scheepers FE, de Wied CC, Hulshoff Pol HE et al (2001) The effect of clozapine on caudate nucleus volume in schizophrenic patients previously treated with typical antipsychotics. Neuropsychopharmacology 24:47–54
Sevincok L, Balci V, Akyildiz U (2008) Tardive dystonia associated with low-dose of amisulpride: a case report. J Clin Psychopharmacol 28:573–574
Simpson GM, Lee JH, Shrivastava RK (1978) Clozapine in tardive dyskinesia. Psychopharmacology 56:75–80
Singh S, Gupta A, Kuppili PP et al (2016) Paliperidone palmitate-associated severe refractory tardive dyskinesia with tardive dystonia: management and six-months follow-up. J Clin Psychopharmacol 36:391–393
Small JG, Milstein V, Marhenke JD et al (1987) Treatment outcome with clozapine in tardive dyskinesia, neuroleptic sensitivity, and treatment-resistant psychosis. J Clin Psychiatry 48:263–267
Spivak B, Mester R, Abesgaus J et al (1997) Clozapine treatment for neuroleptic-induced tardive dyskinesia, parkinsonism, and chronic akathisia in schizophrenic patients. J Clin Psychiatry 58:318–322
Stegmayer K, Walther S, van Harten P (2018) Tardive dyskinesia associated with atypical antipsychotics: prevalence, mechanisms and management strategies. CNS Drugs 32:135–147
Sterne JA, Hernán MA, Reeves BC et al (2016) ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 355:i4919
Trugman JM, Leadbetter R, Zalis ME et al (1994) Treatment of severe axial tardive dystonia with clozapine: case report and hypothesis. Mov Disord 9:441–446
Turan AB, Akkaya C, Eker SS et al (2011) Ziprasidone and tardive dystonia: a case report and literature review. Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology 21:242–245
Uzun O, Cansever A, Ozsahin A (2001) A case of relapsed tardive dyskinesia due to clozapine dose reduction. Int Clin Psychopharmacol 16:369–371
Van Harten PN, Kampuis DJ, Matroos GE (1996) Use of clozapine in tardive dystonia. Prog Neuropsychopharmacol Biol Psychiatry 20:263–274
Van Putten T, Wirshing WC, Marder SR (1990) Tardive Meige syndrome responsive to clozapine. J Clin Psychopharmacol 10:381–382
Walters VL, Tognolini RZ, Rueda HM et al (1997) New strategies for old problems: tardive dyskinesia (TD) review and report on severe TD cases treated with clozapine, with 12, 8 and 5 years of video follow-up. Schizophr Res 28:231–246
Ward KM, Citrome L (2018) Antipsychotic-related movement disorders: drug-induced parkinsonism vs. tardive dyskinesia-key differences in pathophysiology and clinical management. Neurol Ther 7:233–248
Wei H-T, Lai Y-W, Chen M-H, Chen Y-S (2012) Oral-paliperidone-induced tardive dyskinesia: a case report. Gen Hosp Psychiatry 34:578.e5–6
Yassa R, Jeste DV (1992) Gender differences in tardive dyskinesia: a critical review of the literature. Schizophr Bull 18:701–715
Yero T, Rey JA (2008) Tetrabenazine (xenazine), an FDA-approved treatment option for Huntington’s disease-related chorea. P T 33:690–694
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Wong, J., Pang, T., Cheuk, N.K.W. et al. A systematic review on the use of clozapine in treatment of tardive dyskinesia and tardive dystonia in patients with psychiatric disorders. Psychopharmacology 239, 3393–3420 (2022). https://doi.org/10.1007/s00213-022-06241-2
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DOI: https://doi.org/10.1007/s00213-022-06241-2