David D Kim1, Alasdair M Barr1, Yunsun Chung2, Jessica W Y Yuen3, Mahyar Etminan4, Bruce C Carleton2,5,6, Randall F White7, William G Honer7, Ric M Procyshyn8. 1. Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada. 2. British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada. 3. Faculty of Medicine and Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada. 4. Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada. 5. Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada. 6. Pharmaceutical Outcomes Programme, British Columbia Children's Hospital, Vancouver, BC, Canada. 7. Department of Psychiatry, University of British Columbia, Room A3-111, 938 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. 8. Department of Psychiatry, University of British Columbia, Room A3-111, 938 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada. rprocyshyn@bcmhs.bc.ca.
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.
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.