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Antipsychotic-Associated Symptoms of Tourette Syndrome: A Systematic Review

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Abstract

Background

Although antipsychotics are used to treat Tourette syndrome, there have been reports of paradoxical induction of tics by first- and second-generation antipsychotics.

Objective

The objective of this systematic review was to better characterize tics as the potential adverse effect of antipsychotics.

Methods

A literature search was performed, with no language restriction, using the MEDLINE, EMBASE, and PsycINFO databases for all publications up to January 2018. To be included, studies utilizing any study design had to meet the following criteria: (1) a temporal association of tics with antipsychotic use where tics emerged during treatment or after discontinuation and (2) no diagnosis of Tourette syndrome before tic emergence. More stringent criteria were used for individuals under 18 years of age that included (1) no personal or family history of primary tic disorder and either (2) tics occurring during antipsychotic treatment improved significantly upon discontinuation or dose reduction or (3) tics emerged after discontinuation of at least 3 months of antipsychotic treatment. Data were extracted according to: age, sex, diagnosis, personal history of motor symptoms or family history of tics, antipsychotic type and dose, treatment duration, types of symptoms emerged, treatment strategies, and follow-up. A Fisher’s exact test was used to compare the occurrence of symptoms between first- and second-generation antipsychotic users.

Results

The search identified 1290 articles, of which 92 full-text articles were assessed leading to the inclusion of 50 articles. Most of the included articles were case reports or series, involving a total of 60 cases. Thirty cases were associated with treatment with first-generation antipsychotics, 27 with second-generation antipsychotics, and three with a combination of first- and second-generation antipsychotics. Antipsychotics were being used to treat schizophrenia in 60% of the cases and other indications included developmental, behavioral, and mood or anxiety disorders. Tics occurred during treatment (n = 44) or following treatment discontinuation (n = 16). The occurrence of vocal tics with or without motor tics was significantly higher in the first- vs. second-generation antipsychotic users (p < 0.0001). Significantly higher occurrences were also noted in the first- vs. second-generation antipsychotic users for specific types of vocal tics (i.e., barking and coprolalia) and other concurrent motor symptoms (i.e., tardive dyskinesia). In the cases identified, antipsychotic-associated tics were treated by (1) discontinuing the offending antipsychotic, reducing its dose, or switching to different antipsychotics for tics occurring during treatment, (2) reinitiating antipsychotic treatment for tics occurring following discontinuation, or (3) using non-antipsychotic agents. It should be noted that symptoms were not always fully reversible and recurred at times.

Conclusion

Tics can be a disturbing adverse effect of antipsychotics. Clinicians need to be particularly vigilant when initiating and modifying antipsychotic regimens.

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Authors and Affiliations

  1. Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada

    David D. Kim & Alasdair M. Barr

  2. British Columbia Children’s Hospital Research Institute, Vancouver, BC, Canada

    Yunsun Chung & Bruce C. Carleton

  3. Faculty of Medicine and Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada

    Jessica W. Y. Yuen

  4. Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada

    Mahyar Etminan

  5. Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada

    Bruce C. Carleton

  6. Pharmaceutical Outcomes Programme, British Columbia Children’s Hospital, Vancouver, BC, Canada

    Bruce C. Carleton

  7. Department of Psychiatry, University of British Columbia, Room A3-111, 938 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada

    Randall F. White, William G. Honer & Ric M. Procyshyn

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Correspondence to Ric M. Procyshyn.

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No sources of funding were used to assist with the preparation of this article.

Conflict of interest

Alasdair M. Barr has received grants from Bristol-Myers Squibb and the Canadian Institutes of Health Research. Bruce C. Carleton is part of the Pharmaceutical Outcomes Programme and has received financial support for its pharmacoepidemiological research from the British Columbia Provincial Health Services Authority; he also serves on a data safety board for AEVI Genomic Medicine. Randall F. White has received consulting fees or sat on paid advisory boards for: Janssen, Lundbeck, and Otsuka; and has received a grant from ThermoFisher/Affymetrix. William G. Honer has received consulting fees or sat on paid advisory boards for: the Canadian Agency for Drugs and Technology in Health, the Centre for Drug Research and Development, AlphaSights, In Silico (unpaid), and Otsuka/Lundbeck. Ric M. Procyshyn has received consulting fees or sat on paid advisory boards for: Janssen, Lundbeck, and Otsuka; is on the speaker’s bureau for Janssen, Lundbeck, and Otsuka; and has received grants from the Canadian Institutes of Health Research. David D. Kim, Yunsun Chung, Jessica W.Y. Yuen, and Mahyar Etminan have no conflicts of interest directly relevant to the contents of this article.

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Kim, D.D., Barr, A.M., Chung, Y. et al. Antipsychotic-Associated Symptoms of Tourette Syndrome: A Systematic Review. CNS Drugs 32, 917–938 (2018). https://doi.org/10.1007/s40263-018-0559-8

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