- Email: [email protected]
TREATMENT OF WITHDRAWAL DYSKINESIA
LETTERS TO THE EDITOR
fluphenazine, none of which abated his psychotic symptoms. Significantly, loxapine was administered before he came under our care and he suffered an acute dystonic reaction, after which the loxapine was discontinued. S.D.’s baseline mental status has progressively deteriorated during the course of his illness and his schizophrenic symptoms have persisted throughout all therapeutic attempts. During S.D.’s most recent hospital admission, his medications were olanzapine 5 mg orally in the morning + 15 mg orally at bedtime and oxcarbamazepine 300 mg orally in the morning + 150 mg orally at bedtime. This regimen was clearly not working, and he was deteriorating during the 3 months that he was hospitalized. S.D.’s psychotic symptoms had been refractory to all atypical, typical, and intramuscular medications tried thus far. It is known from the literature that clozapine can help with psychotic symptoms in many patients who do not respond to other neuroleptic drugs (Ciapparelli et al., 2003; Naber and Hippius, 1990). Therefore, S.D.’s family elected to try a trial of clozapine in the hopes of achieving some symptomatic relief. Before starting S.D. on clozapine, his oxcarbamazepine was decreased to 150 mg and olanzapine was titrated to 10 mg daily. Also, a full baseline neurological workup, including metabolics, magnetic resonance imaging, and EEG, was grossly normal. S.D. was given his first dose of clozapine 12.5 mg orally at 10:00 A.M. on a Friday along with 5 mg intramuscular olanzapine for agitation. In the early afternoon, he became quite somnolent and slept for several hours. Around 6 P.M., the staff noticed that S.D. looked flushed (particularly at the ears), vacant, and confused, and appeared to be less responsive than normal. Cogwheeling of his arms was present and his vitals were as follows: temperature 38.2°C, heart rate 120, respiratory rate 20, blood pressure 140/100. Blood work was not done during the weekend; however, the creatine kinase (CK) level measured 3 days later was elevated at 411. The fact that after initiating clozapine, S.D. developed fever, autonomic changes, muscle rigidity, and an elevated CK level raised concern for a neuroleptic malignant syndrome (NMS) diagnosis. This case is an interesting one because NMS caused by clozapine is considered to be rare and the clinical picture developed at a low dose within 8 hours of initiation of treatment. Although we do believe that this reaction was NMS, there may also be an alternate explanation for S.D.’s symptoms. His symptoms of rigidity and mild hypertension may have been an acute dystonic reaction to the clozapine together with the anticholinergic effects from the olanzapine. The elevated CK value may be attributed to the intramuscular olanzapine that S.D. received on Friday morning with his clozapine. In the literature, there have been 21 cases of NMS caused by clozapine reported, a similar number to cases of NMS caused by risperidone (23) and olanzapine (19; Ananth
1102
et al., 2004). For clozapine, the mean age of the patients who had NMS was 40.2 years (SD = 17.1) and the mean dose of clozapine was 318 mg daily (SD = 299; Ananth et al., 2004). Eleven of the cases were taking increasing doses of clozapine, and the other 10 were taking stable doses (Ananth et al., 2004). The mean number of days to onset of NMS was 218 days, the mean CK during NMS was 1,571, and the mean temperature was 38.7°C. Another interesting point with this case is that the patient had a previous adverse dystonic reaction to loxapine. Although their pharmacodynamics are different, loxapine and clozapine have similar molecular structures, loxapine being of the dibenzoxazepine class of drugs and clozapine a dibenzodiazepine. One might wonder whether there is a connection between the adverse reactions that our patient experienced with the two different drugs. Mia Skarpathiotakis, M.Sc. University of Toronto Toronto Neal Westreich, M.D., F.R.C.P.C. Sunnybrook and Women’s College Health Sciences Center Toronto Disclosure: The authors have no financial relationships to disclose.
Ananth J, Parameswaran S, Gunatilake S, Burgoyne K, Sidhom T (2004), Neuroleptic malignancy syndrome and atypical antipsychotic drugs. J Clin Psychiatry 65:464–470 Ciapparelli A, Dell’Osso L, Bandettini di Poggio A, Carmassi C, Cecconi D, Fenzi M, et al. (2003), Clozapine in treatment-resistant patients with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder: a naturalistic 48-month follow-up study. J Clin Psychiatry 64:451–458 Naber D, Hippius H (1990), The European experience with use of clozapine. Hosp Community Psychiatry 41:886–890 DOI: 10.1097/01.chi.0000177328.92333.2b
TREATMENT OF WITHDRAWAL DYSKINESIA To the Editor: Second-generation antipsychotic medications (SGAs) are used increasingly in children and adolescents to treat a wide variety of disorders. Although better tolerated and with a lower rate of inducing movement disorders than neuroleptics (at least in adults), the risk of tardive dyskinesia (TD), a potentially disfiguring movement disorder, still exists. Most of the dyskinesias reported in children and adolescents became evident only upon withdrawal of the antipsychotic medication. Kumra and colleagues (1998) reported that withdrawal
J. AM. ACAD. CHILD ADOLESC. PSYCHIATR Y, 44:11, NOVEMB ER 2005
LETTERS TO THE EDITOR
dyskinesia developed in 28% of the patients taken off their antipsychotic medication for a period of 14 to 28 days as part of NIMH studies. This rate is consistent with the withdrawal dyskinesia rate of 29.7% reported by Campbell and colleagues (1997) in their large prospective study of children with autism. Children and adolescents with dyskinetic movements may refuse to go to school or interact with other children because of legitimate concerns about being ridiculed. Therefore, a tolerable and effective treatment for these movements may return a patient to functioning before the complete resolution of movements. Significant reductions of dyskinetic movements after treatment with a mixture of branched-chain amino acids (BCAA)—L-valine, L-isoleucine, and L-leucine, a medical food marketed as Tarvil—were reported in a doubleblind, placebo-controlled study of adult males with tardive dyskinesia (Richardson et al., 2003). Mild gastrointestinal symptoms were the most common adverse event. We report a case of medication-related dyskinesia in an adolescent to alert child and adolescent psychiatrists to a novel treatment for medication-related movement disorders using BCAAs. The patient is a 17-year-old white male who has had three hospitalizations since the age of 15 as a result of bipolar disorder type I. He initially responded to lithium monotherapy, but after his second hospitalization, aripiprazole was added to treat hallucinations. He was stable on lithium 900 mg/day and aripiprazole 12.5 mg/day for more than 6 months. Adverse effects included mild urinary hesitancy, slight sedation, and occasional shoulder shrugging (rated as ‘‘minimal’’ movements of his neck and shoulders, on the Abnormal Involuntary Movements Scale [Rapoport et al., 1985]). During a recent rehospitalization because of a suicide attempt, his aripiprazole dose was gradually decreased during a 2-week period and quetiapine was started. Three weeks after discontinuing aripiprazole, he presented with noticeable abnormal movements of his jaw, tongue, and hands as well as facial twitches. On the Modified Simpson Dyskinesia Scale (Simpson and Angus, 1970), he received ratings of ‘‘moderate’’ on global lip movement and choreoathetoid movements of his left upper extremity and ratings of ‘‘mild’’ on global facial expression and lateral jaw movements. On the Abnormal Involuntary Movements Scale, he was found to have moderate movements of his facial expression muscles, as well as mild lip and jaw movements. The patient began treatment with three packs per day of a BCAA mixture (176 mg BCAA/kg) and was increased to
five packs per day (293 mg BCAA/kg). One week later, there was noticeable improvement in the dyskinesias. When he surreptitiously skipped several doses, the movements worsened. Three weeks later, the movements were no longer evident and he returned to school. He is tolerating the BCAA mixture well except for some complaints of dyspepsia. He was treated for 12 weeks, coinciding with the end of the school year. His dyskinetic movements (facial tics, lip movements, and choreoathetoid movements of the fingers rated as ‘‘questionable’’ on the Modified Simpson Dyskinesia Scale) worsened slightly after discontinuing the BCAA mixture but were not significant enough to warrant restarting BCAA. We believe that treatment with the BCAA mixture allowed our patient to resume his usual activities more rapidly and to adhere to his medication regimen of lithium, divalproex, and quetiapine. Vivian Kafantaris, M.D. Judith Hirsch, M.D. Ema Saito, M.D. Natasha Bennett, M.A. The Zucker Hillside Hospital Glen Oaks, NY Disclosure: The distributor of the BCAA mixture has donated a 3-month supply of their product for use by this patient. Tarvil is available at www.tarvil.com. Dr. Kafantaris has received research funding from Lilly and Pfizer and research support in the form of study medication donations from AstraZeneca, GlaxoSmithKline, Janssen, Lilly, and Pfizer. The other authors have no financial relationships to disclose. Campbell M, Armenteros JL, Malone RP, Adams PB, Eisenberg ZW, Overall JE (1997), Neuroleptic-related dyskinesias in autistic children; a prospective longitudinal study. J Am Acad Child Adolesc Psychiatry 36:835–843 Kumra S, Jacobsen L, Lenane M, Smith A, Lee P, Malanga CJ, et al. (1998), Case series: spectrum of neuroleptic-induced movement disorders and extrapyramidal side effects in childhood-onset schizophrenia. J Am Acad Child Adolesc Psychiatry 37:221–227 Rapoport J, Connors C, Reatig N (1985), Rating scales and assessment instruments for use in pediatric psychopharmacology research. Psychopharmacol Bull 21:713–111 Richardson MA, Bevans ML, Read LL, Read LL, Chao HM, Clelland JD, et al. (2003), Efficacy of the branched-chain amino acids in the treatment of tardive dyskinesia in men. Am J Psychiatry 160:(6):1117–1124 Simpson GM, Angus JWS (1970), A rating scale for extrapyramidal side effects. Acta Psychiatr Scand 212(suppl 44):11–19 DOI: 10.1097/01.chi.0000177329.69462.5f All statements expressed in this column are those of the authors and do not reflect the opinions of the Journal or the American Academy of Child and Adolescent Psychiatry. See the Instructions for Authors for information about the preparation and submission of Letters to the Editor.
J. AM. ACAD. CH ILD ADO LE SC. PSY CH IAT RY, 44:11, NO VEM BER 2 005
1103
fluphenazine, none of which abated his psychotic symptoms. Significantly, loxapine was administered before he came under our care and he suffered an acute dystonic reaction, after which the loxapine was discontinued. S.D.’s baseline mental status has progressively deteriorated during the course of his illness and his schizophrenic symptoms have persisted throughout all therapeutic attempts. During S.D.’s most recent hospital admission, his medications were olanzapine 5 mg orally in the morning + 15 mg orally at bedtime and oxcarbamazepine 300 mg orally in the morning + 150 mg orally at bedtime. This regimen was clearly not working, and he was deteriorating during the 3 months that he was hospitalized. S.D.’s psychotic symptoms had been refractory to all atypical, typical, and intramuscular medications tried thus far. It is known from the literature that clozapine can help with psychotic symptoms in many patients who do not respond to other neuroleptic drugs (Ciapparelli et al., 2003; Naber and Hippius, 1990). Therefore, S.D.’s family elected to try a trial of clozapine in the hopes of achieving some symptomatic relief. Before starting S.D. on clozapine, his oxcarbamazepine was decreased to 150 mg and olanzapine was titrated to 10 mg daily. Also, a full baseline neurological workup, including metabolics, magnetic resonance imaging, and EEG, was grossly normal. S.D. was given his first dose of clozapine 12.5 mg orally at 10:00 A.M. on a Friday along with 5 mg intramuscular olanzapine for agitation. In the early afternoon, he became quite somnolent and slept for several hours. Around 6 P.M., the staff noticed that S.D. looked flushed (particularly at the ears), vacant, and confused, and appeared to be less responsive than normal. Cogwheeling of his arms was present and his vitals were as follows: temperature 38.2°C, heart rate 120, respiratory rate 20, blood pressure 140/100. Blood work was not done during the weekend; however, the creatine kinase (CK) level measured 3 days later was elevated at 411. The fact that after initiating clozapine, S.D. developed fever, autonomic changes, muscle rigidity, and an elevated CK level raised concern for a neuroleptic malignant syndrome (NMS) diagnosis. This case is an interesting one because NMS caused by clozapine is considered to be rare and the clinical picture developed at a low dose within 8 hours of initiation of treatment. Although we do believe that this reaction was NMS, there may also be an alternate explanation for S.D.’s symptoms. His symptoms of rigidity and mild hypertension may have been an acute dystonic reaction to the clozapine together with the anticholinergic effects from the olanzapine. The elevated CK value may be attributed to the intramuscular olanzapine that S.D. received on Friday morning with his clozapine. In the literature, there have been 21 cases of NMS caused by clozapine reported, a similar number to cases of NMS caused by risperidone (23) and olanzapine (19; Ananth
1102
et al., 2004). For clozapine, the mean age of the patients who had NMS was 40.2 years (SD = 17.1) and the mean dose of clozapine was 318 mg daily (SD = 299; Ananth et al., 2004). Eleven of the cases were taking increasing doses of clozapine, and the other 10 were taking stable doses (Ananth et al., 2004). The mean number of days to onset of NMS was 218 days, the mean CK during NMS was 1,571, and the mean temperature was 38.7°C. Another interesting point with this case is that the patient had a previous adverse dystonic reaction to loxapine. Although their pharmacodynamics are different, loxapine and clozapine have similar molecular structures, loxapine being of the dibenzoxazepine class of drugs and clozapine a dibenzodiazepine. One might wonder whether there is a connection between the adverse reactions that our patient experienced with the two different drugs. Mia Skarpathiotakis, M.Sc. University of Toronto Toronto Neal Westreich, M.D., F.R.C.P.C. Sunnybrook and Women’s College Health Sciences Center Toronto Disclosure: The authors have no financial relationships to disclose.
Ananth J, Parameswaran S, Gunatilake S, Burgoyne K, Sidhom T (2004), Neuroleptic malignancy syndrome and atypical antipsychotic drugs. J Clin Psychiatry 65:464–470 Ciapparelli A, Dell’Osso L, Bandettini di Poggio A, Carmassi C, Cecconi D, Fenzi M, et al. (2003), Clozapine in treatment-resistant patients with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder: a naturalistic 48-month follow-up study. J Clin Psychiatry 64:451–458 Naber D, Hippius H (1990), The European experience with use of clozapine. Hosp Community Psychiatry 41:886–890 DOI: 10.1097/01.chi.0000177328.92333.2b
TREATMENT OF WITHDRAWAL DYSKINESIA To the Editor: Second-generation antipsychotic medications (SGAs) are used increasingly in children and adolescents to treat a wide variety of disorders. Although better tolerated and with a lower rate of inducing movement disorders than neuroleptics (at least in adults), the risk of tardive dyskinesia (TD), a potentially disfiguring movement disorder, still exists. Most of the dyskinesias reported in children and adolescents became evident only upon withdrawal of the antipsychotic medication. Kumra and colleagues (1998) reported that withdrawal
J. AM. ACAD. CHILD ADOLESC. PSYCHIATR Y, 44:11, NOVEMB ER 2005
LETTERS TO THE EDITOR
dyskinesia developed in 28% of the patients taken off their antipsychotic medication for a period of 14 to 28 days as part of NIMH studies. This rate is consistent with the withdrawal dyskinesia rate of 29.7% reported by Campbell and colleagues (1997) in their large prospective study of children with autism. Children and adolescents with dyskinetic movements may refuse to go to school or interact with other children because of legitimate concerns about being ridiculed. Therefore, a tolerable and effective treatment for these movements may return a patient to functioning before the complete resolution of movements. Significant reductions of dyskinetic movements after treatment with a mixture of branched-chain amino acids (BCAA)—L-valine, L-isoleucine, and L-leucine, a medical food marketed as Tarvil—were reported in a doubleblind, placebo-controlled study of adult males with tardive dyskinesia (Richardson et al., 2003). Mild gastrointestinal symptoms were the most common adverse event. We report a case of medication-related dyskinesia in an adolescent to alert child and adolescent psychiatrists to a novel treatment for medication-related movement disorders using BCAAs. The patient is a 17-year-old white male who has had three hospitalizations since the age of 15 as a result of bipolar disorder type I. He initially responded to lithium monotherapy, but after his second hospitalization, aripiprazole was added to treat hallucinations. He was stable on lithium 900 mg/day and aripiprazole 12.5 mg/day for more than 6 months. Adverse effects included mild urinary hesitancy, slight sedation, and occasional shoulder shrugging (rated as ‘‘minimal’’ movements of his neck and shoulders, on the Abnormal Involuntary Movements Scale [Rapoport et al., 1985]). During a recent rehospitalization because of a suicide attempt, his aripiprazole dose was gradually decreased during a 2-week period and quetiapine was started. Three weeks after discontinuing aripiprazole, he presented with noticeable abnormal movements of his jaw, tongue, and hands as well as facial twitches. On the Modified Simpson Dyskinesia Scale (Simpson and Angus, 1970), he received ratings of ‘‘moderate’’ on global lip movement and choreoathetoid movements of his left upper extremity and ratings of ‘‘mild’’ on global facial expression and lateral jaw movements. On the Abnormal Involuntary Movements Scale, he was found to have moderate movements of his facial expression muscles, as well as mild lip and jaw movements. The patient began treatment with three packs per day of a BCAA mixture (176 mg BCAA/kg) and was increased to
five packs per day (293 mg BCAA/kg). One week later, there was noticeable improvement in the dyskinesias. When he surreptitiously skipped several doses, the movements worsened. Three weeks later, the movements were no longer evident and he returned to school. He is tolerating the BCAA mixture well except for some complaints of dyspepsia. He was treated for 12 weeks, coinciding with the end of the school year. His dyskinetic movements (facial tics, lip movements, and choreoathetoid movements of the fingers rated as ‘‘questionable’’ on the Modified Simpson Dyskinesia Scale) worsened slightly after discontinuing the BCAA mixture but were not significant enough to warrant restarting BCAA. We believe that treatment with the BCAA mixture allowed our patient to resume his usual activities more rapidly and to adhere to his medication regimen of lithium, divalproex, and quetiapine. Vivian Kafantaris, M.D. Judith Hirsch, M.D. Ema Saito, M.D. Natasha Bennett, M.A. The Zucker Hillside Hospital Glen Oaks, NY Disclosure: The distributor of the BCAA mixture has donated a 3-month supply of their product for use by this patient. Tarvil is available at www.tarvil.com. Dr. Kafantaris has received research funding from Lilly and Pfizer and research support in the form of study medication donations from AstraZeneca, GlaxoSmithKline, Janssen, Lilly, and Pfizer. The other authors have no financial relationships to disclose. Campbell M, Armenteros JL, Malone RP, Adams PB, Eisenberg ZW, Overall JE (1997), Neuroleptic-related dyskinesias in autistic children; a prospective longitudinal study. J Am Acad Child Adolesc Psychiatry 36:835–843 Kumra S, Jacobsen L, Lenane M, Smith A, Lee P, Malanga CJ, et al. (1998), Case series: spectrum of neuroleptic-induced movement disorders and extrapyramidal side effects in childhood-onset schizophrenia. J Am Acad Child Adolesc Psychiatry 37:221–227 Rapoport J, Connors C, Reatig N (1985), Rating scales and assessment instruments for use in pediatric psychopharmacology research. Psychopharmacol Bull 21:713–111 Richardson MA, Bevans ML, Read LL, Read LL, Chao HM, Clelland JD, et al. (2003), Efficacy of the branched-chain amino acids in the treatment of tardive dyskinesia in men. Am J Psychiatry 160:(6):1117–1124 Simpson GM, Angus JWS (1970), A rating scale for extrapyramidal side effects. Acta Psychiatr Scand 212(suppl 44):11–19 DOI: 10.1097/01.chi.0000177329.69462.5f All statements expressed in this column are those of the authors and do not reflect the opinions of the Journal or the American Academy of Child and Adolescent Psychiatry. See the Instructions for Authors for information about the preparation and submission of Letters to the Editor.
J. AM. ACAD. CH ILD ADO LE SC. PSY CH IAT RY, 44:11, NO VEM BER 2 005
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