591915 research-article2015
TPP0010.1177/2045125315591915Therapeutic Advances in PsychopharmacologyK. Nath et al.
Therapeutic Advances in Psychopharmacology
Letter to the Editor
Paradoxical worsening of tics with haloperidol Kamal Nath, Arnab Bhattacharya, Susmita Hazarika, Debjit Roy and Samir Kumar Praharaj
Tourette’s syndrome (TS) is a common childhood onset neuropsychiatric disorder with multiple motor and one or more vocal tics that endure for more than a year [Cath et al. 2011]. Dopamine receptor blocking drugs are an efficacious treatment for tics in TS [Roessner et al. 2011]. Here we present a case of TS which was worsened on haloperidol despite its known efficacy for treating the disorder. Case report A 12-year-old boy presented with multiple motor tics in the form of eye blinking, grimacing movements, and sudden jerky contractions of the neck muscles and a squeaking sound for a period of 12 months. The tics disappeared during sleep. There was no history of birth trauma, seizure, head injury or family history of tics, movement disorder or any other neuropsychiatric disorders. He had not received treatment for his tics in the past. On the Yale Global Tic Severity Scale (YGTSS) [Leckman et al. 1989], the score was 37. He was prescribed haloperidol (5 drops of 2 mg/ml oral solution) daily. After 2 days there was a worsening of the tics which involved the shoulders, upper limb and the trunk, causing marked distress. The vocal tic changed from a squeaking sound to a grunting sound. His deep tendon jerks were brisk but the plantar reflex was flexor in response bilaterally. He was afebrile with clear consciousness. On YGTSS, the score was 73. Haloperidol was discontinued and he was put on tablet clonazepam 1 mg/day. After 5 days, his vocal tic came down to earlier levels and the severity of motor tics was now less than what he presented with in the first visit. He was discharged on the same medication and maintains well a year later. On the Naranjo adverse events probability scale [Naranjo et al. 1981], the score was 8, which is suggestive of a probable association.
Discussion The pathology underlying TS involves a derangement in a number of neurotransmitters [Singer and Minzer, 2003]. Among them, dopamine has a primary role as suggested by nuclear imaging and treatment response studies with neuroleptics [Wolf et al. 1996]. Evidence suggests a hyperdopaminergic state in the striatum in patients with TS and haloperidol, a potent post-synaptic dopamine receptor blocker is effective in its treatment. But in our case and in another earlier report [Diaz et al. 1992] a pre-existing tic was worsened and new tics emerged when put on haloperidol. However, the previous case involved an adult subject whereas our patient was a pre-adolescent boy. Moreover, the earlier patient developed worsening after a week of therapy but our subject suffered an exacerbation within 24 hours of initiation of the medication, thus making it plausible that our patient suffered an idiosyncratic adverse effect but the earlier case had a more gradual and possibly dose dependent one.
Ther Adv Psychopharmacol 2015, Vol. 5(5) 314–315 DOI: 10.1177/ 2045125315591915 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Correspondence to: Samir Kumar Praharaj, MBBS, MD, DPM Assistant Professor, Department of Psychiatry, Kasturba Medical College, Manipal, Karnataka, 576104, India [email protected] Kamal Nath, MBBS, MD Susmita Hazarika, MBBS, DPM Debjit Roy, MBBS, MD Department of Psychiatry, Silchar Medical College and Hospital, Silchar, Assam, India Arnab Bhattacharya, MBBS, MD, DPM Tata Motors Hospital, Jamshedpur, India
In TS patients treated with neuroleptics, exacerbation of tics has been reported along with other extrapyramidal symptoms [Bruun, 1988]. The probable mechanism is a presynaptic dopamine receptor blockade [Gualtieri and Patterson, 1986] which increases the dopamine release at the synapse. This is supported by the fact that dopamine agonists which preferentially activate presynaptic dopamine receptors have found to be beneficial [Feinberg and Carroll, 1979]. A probable explanation in our case was presynaptic dopamine receptor blockade which led to an increase in the dopamine release, further aggravating the existing hyperdopaminergic state. In conclusion, clinicians need to have a high index of suspicion for this rare paradoxical adverse effect of haloperidol which can sometimes worsen tics in TS, a condition it normally improves.
314 http://tpp.sagepub.com
K Nath, A Bhattacharya et al. Funding This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors.
Gualtieri, C. and Patterson, D. (1986) Neuroleptic induced tics in two hyperactive children. Am J Psychiatry 143: 1176–1177.
Conflict of interest statement The authors declare no conflict of interest in writing this letter.
Leckman, J., Riddle, M., Hardin, M., Ort, S., Swartz, K., Stevenson, J. et al. (1989) The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. J Am Acad Child Adolesc Psychiatry 28: 566–573.
References
Naranjo, C., Busto, U., Sellers, E., Sandor, P., Ruiz, I., Roberts, E. et al. (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30: 239–245.
Bruun, R. (1988) Subtle and under recognized side effects of neuroleptic treatment in children with Tourette’s disorder. Am J Psychiatry 145: 621–624. Cath, D., Hedderly, T., Ludolph, A., Stern, J., Murphy, T., Hartmann, A. et al. (2011) European clinical guidelines for Tourette syndrome and other tic disorders. Part I: assessment. Eur Child Adolesc Psychiatry 20: 155–171. Diaz, J., Smith, K. and Maccario, M. (1992) Exacerbation of motor tic and induction of new tic by haloperidol use. West J Med 156: 198–199. Feinberg, M. and Carroll, B. (1979) Effects of dopamine agonists and antagonists in Tourette’s disease. Arch Gen Psychiatry 36: 979–985.
Roessner, V., Plessen, K., Rothenberger, A., Ludolph, A., Rizzo, R., Skov, L. et al. (2011) European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment. Eur Child Adolesc Psychiatry 20: 173–196. Singer, H. and Minzer, K. (2003) Neurobiology of Tourette syndrome: concepts of neuroanatomical localization and neurochemical abnormalities. Brain Dev 25(Suppl.): S70–SS84. Wolf, S., Jones, D., Knable, M., Gorey, J., Lee, K., Hyde, T. et al. (1996) Tourette syndrome: prediction of phenotypic variation in monozygotic twins by caudate nucleus D2 receptor binding. Science 273: 1225–1227.
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SAGE journals
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TPP0010.1177/2045125315591915Therapeutic Advances in PsychopharmacologyK. Nath et al.
Therapeutic Advances in Psychopharmacology
Letter to the Editor
Paradoxical worsening of tics with haloperidol Kamal Nath, Arnab Bhattacharya, Susmita Hazarika, Debjit Roy and Samir Kumar Praharaj
Tourette’s syndrome (TS) is a common childhood onset neuropsychiatric disorder with multiple motor and one or more vocal tics that endure for more than a year [Cath et al. 2011]. Dopamine receptor blocking drugs are an efficacious treatment for tics in TS [Roessner et al. 2011]. Here we present a case of TS which was worsened on haloperidol despite its known efficacy for treating the disorder. Case report A 12-year-old boy presented with multiple motor tics in the form of eye blinking, grimacing movements, and sudden jerky contractions of the neck muscles and a squeaking sound for a period of 12 months. The tics disappeared during sleep. There was no history of birth trauma, seizure, head injury or family history of tics, movement disorder or any other neuropsychiatric disorders. He had not received treatment for his tics in the past. On the Yale Global Tic Severity Scale (YGTSS) [Leckman et al. 1989], the score was 37. He was prescribed haloperidol (5 drops of 2 mg/ml oral solution) daily. After 2 days there was a worsening of the tics which involved the shoulders, upper limb and the trunk, causing marked distress. The vocal tic changed from a squeaking sound to a grunting sound. His deep tendon jerks were brisk but the plantar reflex was flexor in response bilaterally. He was afebrile with clear consciousness. On YGTSS, the score was 73. Haloperidol was discontinued and he was put on tablet clonazepam 1 mg/day. After 5 days, his vocal tic came down to earlier levels and the severity of motor tics was now less than what he presented with in the first visit. He was discharged on the same medication and maintains well a year later. On the Naranjo adverse events probability scale [Naranjo et al. 1981], the score was 8, which is suggestive of a probable association.
Discussion The pathology underlying TS involves a derangement in a number of neurotransmitters [Singer and Minzer, 2003]. Among them, dopamine has a primary role as suggested by nuclear imaging and treatment response studies with neuroleptics [Wolf et al. 1996]. Evidence suggests a hyperdopaminergic state in the striatum in patients with TS and haloperidol, a potent post-synaptic dopamine receptor blocker is effective in its treatment. But in our case and in another earlier report [Diaz et al. 1992] a pre-existing tic was worsened and new tics emerged when put on haloperidol. However, the previous case involved an adult subject whereas our patient was a pre-adolescent boy. Moreover, the earlier patient developed worsening after a week of therapy but our subject suffered an exacerbation within 24 hours of initiation of the medication, thus making it plausible that our patient suffered an idiosyncratic adverse effect but the earlier case had a more gradual and possibly dose dependent one.
Ther Adv Psychopharmacol 2015, Vol. 5(5) 314–315 DOI: 10.1177/ 2045125315591915 © The Author(s), 2015. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Correspondence to: Samir Kumar Praharaj, MBBS, MD, DPM Assistant Professor, Department of Psychiatry, Kasturba Medical College, Manipal, Karnataka, 576104, India [email protected] Kamal Nath, MBBS, MD Susmita Hazarika, MBBS, DPM Debjit Roy, MBBS, MD Department of Psychiatry, Silchar Medical College and Hospital, Silchar, Assam, India Arnab Bhattacharya, MBBS, MD, DPM Tata Motors Hospital, Jamshedpur, India
In TS patients treated with neuroleptics, exacerbation of tics has been reported along with other extrapyramidal symptoms [Bruun, 1988]. The probable mechanism is a presynaptic dopamine receptor blockade [Gualtieri and Patterson, 1986] which increases the dopamine release at the synapse. This is supported by the fact that dopamine agonists which preferentially activate presynaptic dopamine receptors have found to be beneficial [Feinberg and Carroll, 1979]. A probable explanation in our case was presynaptic dopamine receptor blockade which led to an increase in the dopamine release, further aggravating the existing hyperdopaminergic state. In conclusion, clinicians need to have a high index of suspicion for this rare paradoxical adverse effect of haloperidol which can sometimes worsen tics in TS, a condition it normally improves.
314 http://tpp.sagepub.com
K Nath, A Bhattacharya et al. Funding This research received no specific grant from any funding agency in the public, commercial, or notfor-profit sectors.
Gualtieri, C. and Patterson, D. (1986) Neuroleptic induced tics in two hyperactive children. Am J Psychiatry 143: 1176–1177.
Conflict of interest statement The authors declare no conflict of interest in writing this letter.
Leckman, J., Riddle, M., Hardin, M., Ort, S., Swartz, K., Stevenson, J. et al. (1989) The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. J Am Acad Child Adolesc Psychiatry 28: 566–573.
References
Naranjo, C., Busto, U., Sellers, E., Sandor, P., Ruiz, I., Roberts, E. et al. (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30: 239–245.
Bruun, R. (1988) Subtle and under recognized side effects of neuroleptic treatment in children with Tourette’s disorder. Am J Psychiatry 145: 621–624. Cath, D., Hedderly, T., Ludolph, A., Stern, J., Murphy, T., Hartmann, A. et al. (2011) European clinical guidelines for Tourette syndrome and other tic disorders. Part I: assessment. Eur Child Adolesc Psychiatry 20: 155–171. Diaz, J., Smith, K. and Maccario, M. (1992) Exacerbation of motor tic and induction of new tic by haloperidol use. West J Med 156: 198–199. Feinberg, M. and Carroll, B. (1979) Effects of dopamine agonists and antagonists in Tourette’s disease. Arch Gen Psychiatry 36: 979–985.
Roessner, V., Plessen, K., Rothenberger, A., Ludolph, A., Rizzo, R., Skov, L. et al. (2011) European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment. Eur Child Adolesc Psychiatry 20: 173–196. Singer, H. and Minzer, K. (2003) Neurobiology of Tourette syndrome: concepts of neuroanatomical localization and neurochemical abnormalities. Brain Dev 25(Suppl.): S70–SS84. Wolf, S., Jones, D., Knable, M., Gorey, J., Lee, K., Hyde, T. et al. (1996) Tourette syndrome: prediction of phenotypic variation in monozygotic twins by caudate nucleus D2 receptor binding. Science 273: 1225–1227.
Visit SAGE journals online http://tpp.sagepub.com
SAGE journals
http://tpp.sagepub.com 315
