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High-dose ziprasidone-induced acute dystonia
Progress in Neuro-Psychopharmacology & Biological Psychiatry 31 (2007) 546 – 547 www.elsevier.com/locate/pnpbp
Case report
High-dose ziprasidone-induced acute dystonia Paul J. Rosenfield, Ragy R. Girgis ⁎, Roberto Gil Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and New York State Psychiatric Institute, 1051 Riverside Drive, Box 109, New York, NY 10032, USA Received 12 August 2006; received in revised form 23 September 2006; accepted 9 October 2006 Available online 22 November 2006
Abstract There are few clinical data describing the relative risks of extrapyramidal symptoms (EPS) at higher doses of ziprasidone (i.e., greater than 160 mg/day) when compared to lower doses. We report on a patient who displayed no EPS with ziprasidone 160 mg/day for several months, but did display marked, acute dystonic reactions on ziprasidone 240 mg/day. The observations from the present case indicate that high-dose, ziprasidone-induced acute dystonia may occur even if no such side effects have been experienced at doses up to and including 160 mg/day. © 2006 Elsevier Inc. All rights reserved. Keywords: Acute dystonia; Extrapyramidal symptoms (EPS); High-dose; Schizophrenia; Side effects; Ziprasidone
1. Introduction In order to improve response in patients with persistent psychotic symptoms, some clinicians have prescribed higher than Food and Drug Administration-recommended doses of the second-generation antipsychotic ziprasidone. Potential risks include QTc prolongation and increased extrapyramidal symptoms (EPS). There are few clinical data describing the relative risks of EPS at higher doses of ziprasidone when compared to lower doses. A study of 15 inpatients receiving 240–320 mg/day demonstrated minimal increases in QTc from baseline (i.e., average 3.4 ms after removing an outlier), with none of the patients approaching the 500 ms threshold of concern (Levy et al., 2004); however, the occurrence of EPS was not reported. At doses of 160 mg/day and under, ziprasidone has been found to have low rates of EPS (Daniel et al., 1999). However, there are case reports of ziprasidone-induced acute dystonia (Mason et al., 2005), oculogyric crisis in a child (Ramos et al., 2003), and Pisa syndrome (Ziegenbein et al., 2003). These doses of ziprasidone have also been associated with tardive dyskinesia (Keck et al., 2004) and tardive dystonia (Papapetropoulos et al., 2005). Less is known about the clinical characteristics of ziprasidone at doses above 160 mg/day. Accounts of overdose have described cliniAbbreviations: EPS, extrapyramidal symptoms. ⁎ Corresponding author. Tel.: +1 212 305 2913; fax: +1 212 305 9213. E-mail address: [email protected] (R.R. Girgis). 0278-5846/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2006.10.005
cally significant EPS, although in a minority of cases (Arbuck, 2005; Gomez-Criado et al., 2005). One recent report described acute dystonia in a ziprasidone-naïve patient after rapid dose escalation (i.e., over 3 days) to 200 mg/day (Weinstein et al., 2006), and another reported akathisia after dose reduction from 240 mg/day in two patients (Oral et al., 2006). We report a patient who displayed no EPS with ziprasidone 160 mg/day for several months, but did display marked, acute dystonic reactions on ziprasidone 240 mg/day. 2. Case report Ms. A was a 31-year-old female with schizophrenia and persistent psychotic symptoms despite multiple antipsychotic regimens and reliable adherence. She had previously experienced acute dystonia with haloperidol and mild EPS with risperidone (requiring adjunctive benztropine). The patient had most recently been on monotherapy with ziprasidone 160 mg/ day and had not experienced any EPS. Because of her persistent psychosis, the patient had agreed to a trial of ziprasidone 240 mg/day, divided twice daily. Within 2 days of this dose increase, she experienced transient tongue dystonia, general body stiffness, and conjugate eye deviation in her home on two separate occasions. She did not tell her psychiatrist about these side effects or discontinue her medications. In the morning on day 4 of her dose increase, she took her complete dose of ziprasidone 240 mg at once, along with bismuth subsalicylate
P.J. Rosenfield et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry 31 (2007) 546–547
for concomitant diarrhea. Several hours later, and upon arrival at her clinic for a scheduled appointment, she had a severe, acute dystonic reaction including oculogyric crisis, lock jaw, tongue protrusion, generalized and severe total body stiffness, and respiratory difficulty. She fell on the floor and was unable to move. She did not experience laryngeal dystonia or loss of consciousness. She did not respond to two doses of intramuscular diphenhydramine 25 mg, both given within 10 min of symptom onset. Her symptoms completely resolved, however, when intravenous diphenhydramine 50 mg was given. Admission physical examination, laboratories, and EKG were all within normal limits. Ziprasidone was discontinued and aripiprazole was initiated without further EPS. 3. Discussion The present case illustrates that the occurrence of significant ziprasidone-induced acute dystonic reactions are still possible with higher doses (i.e., greater than 160 mg/day), even if no EPS have been experienced at doses up to and including 160 mg/day. It is possible that the EPS in the case described above were the result of the magnitude of the dose of ziprasidone. In addition, the more marked EPS experienced by the patient on the fourth day of her dose increase may have been related to the fact that on that day she took the whole 240 mg dose at once instead of in divided doses as she had been prescribed and had done the previous days. The risk of EPS has generally been observed to occur in a dose-dependent manner for both conventional and atypical agents (Casey, 1997; Tandon and Jibson, 2002). Further, while the low risk of EPS associated with atypical antipsychotics is considered to be a major advantage over conventional agents, one meta-analysis showed that this differential risk may be mitigated when lower doses (i.e., less than 600 mg/ day chlorpromazine equivalents) of low-potency conventional agents are used as comparator drugs (Leucht et al., 2003). However, as suggested in other reports (Mason et al., 2005; Weinstein et al., 2006), it remains possible that the EPS were at least partly the result of the dose escalation, rather than just the magnitude of the dose itself. Clinically, the onset of dystonia often occurs within hours to days of initiation or the rapid dose increase of antipsychotic medications (Pierre, 2005; van Harten et al., 1999). The possible contribution of the speed of dose escalation to the appearance of acute dystonia is illustrated by one case report of a 34 year-old male who had no EPS after being gradually titrated to a dose of 3 mg twice daily of risperidone on two separate occasions (Brody, 1996). However, on the third occasion the patient was more rapidly titrated to 3 mg twice daily of risperidone and he experienced a marked dystonic reaction (Brody, 1996). This case report, however, was limited by the patient's recent use of cocaine (Brody, 1996). The contribution of bismuth subsalicylate to the scenario described above is unclear as the patient was experiencing EPS before taking bismuth subsalicylate and blood levels of ziprasidone were not available. However, certain liquid formula-
547
tions of bismuth subsalicylate have been reported to affect blood levels of certain medications (Healy et al., 1997). 4. Conclusion The observations from the present case indicate that highdose (i.e., greater than 160 mg/day), ziprasidone-induced EPS may occur even if no such side effects have been experienced at doses up to and including 160 mg/day. However, as few reports of EPS at higher doses of ziprasidone exist, it remains unclear whether such symptoms are the result of the velocity or magnitude of dose titration, or both. Longitudinal studies are needed before conclusions can be drawn regarding the relative risks of ziprasidone-induced EPS at higher doses when compared with lower doses. References Arbuck DM. 12,800-mg ziprasidone overdose without significant ECG changes. Gen Hosp Psychiatry 2005;27:222–3. Brody AL. Acute dystonia induced by rapid increase in risperidone dosage. J Clin Psychopharmacol 1996;16:461–2. Casey DE. The relationship of pharmacology to side effects. J Clin Psychiatry 1997;58(Suppl 10):55–62. Daniel DG, Zimbroff DL, Potkin SG, Reeves KR, Harrigan EP, Lakshminarayanan M. Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial. Ziprasidone Study Group. Neuropsychopharmacology 1999;20:491–505. Gomez-Criado MS, Bernardo M, Florez T, Gutierrez JR, Gandia R, Ayani I. Ziprasidone overdose: cases recorded in the database of Pfizer-Spain and literature review. Pharmacotherapy 2005;25:1660–5. Healy DP, Dansereau RJ, Dunn AB, Clendening CE, Mounts AW, Deepe Jr GS. Reduced tetracycline bioavailability caused by magnesium aluminum silicate in liquid formulations of bismuth subsalicylate. Ann Pharmacother 1997;31:1460–4. Keck ME, Muller MB, Binder EB, Sonntag A, Holsboer F. Ziprasidone-related tardive dyskinesia. Am J Psychiatry 2004;161:175–6. Leucht S, Wahlbeck K, Hamann J, Kissling W. New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet 2003;361:1581–9. Levy WO, Robichaux-Keene NR, Nunez C. No significant QTc interval changes with high-dose ziprasidone: a case series. J Psychiatr Pract 2004;10:227–32. Mason MN, Johnson CE, Piasecki M. Ziprasidone-induced acute dystonia. Am J Psychiatry 2005;162:625–6. Oral ET, Altinbas K, Demirkiran S. Sudden akathisia after a ziprasidone dose reduction. Am J Psychiatry 2006;163:546. Papapetropoulos S, Wheeler S, Singer C. Tardive dystonia associated with ziprasidone. Am J Psychiatry 2005;162:2191. Pierre JM. Extrapyramidal symptoms with atypical antipsychotics: incidence, prevention and management. Drug Saf 2005;28:191–208. Ramos AE, Shytle RD, Silver AA, Sanberg PR. Ziprasidone-induced oculogyric crisis. J Am Acad Child Adolesc Psychiatry 2003;42:1013–4. Tandon R, Jibson MD. Extrapyramidal side effects of antipsychotic treatment: scope of problem and impact on outcome. Ann Clin Psychiatry 2002;14:123–9. van Harten PN, Hoek HW, Kahn RS. Acute dystonia induced by drug treatment. BMJ 1999;319:623–6. Weinstein SK, Adler CM, Strakowski SM. Ziprasidone-induced acute dystonic reactions in patients with bipolar disorder. J Clin Psychiatry 2006;67:327–8. Ziegenbein M, Schomerus G, Kropp S. Ziprasidone-induced Pisa syndrome after clozapine treatment. J Neuropsychiatry Clin Neurosci 2003;15:458–9.
Case report
High-dose ziprasidone-induced acute dystonia Paul J. Rosenfield, Ragy R. Girgis ⁎, Roberto Gil Department of Psychiatry, College of Physicians and Surgeons, Columbia University, and New York State Psychiatric Institute, 1051 Riverside Drive, Box 109, New York, NY 10032, USA Received 12 August 2006; received in revised form 23 September 2006; accepted 9 October 2006 Available online 22 November 2006
Abstract There are few clinical data describing the relative risks of extrapyramidal symptoms (EPS) at higher doses of ziprasidone (i.e., greater than 160 mg/day) when compared to lower doses. We report on a patient who displayed no EPS with ziprasidone 160 mg/day for several months, but did display marked, acute dystonic reactions on ziprasidone 240 mg/day. The observations from the present case indicate that high-dose, ziprasidone-induced acute dystonia may occur even if no such side effects have been experienced at doses up to and including 160 mg/day. © 2006 Elsevier Inc. All rights reserved. Keywords: Acute dystonia; Extrapyramidal symptoms (EPS); High-dose; Schizophrenia; Side effects; Ziprasidone
1. Introduction In order to improve response in patients with persistent psychotic symptoms, some clinicians have prescribed higher than Food and Drug Administration-recommended doses of the second-generation antipsychotic ziprasidone. Potential risks include QTc prolongation and increased extrapyramidal symptoms (EPS). There are few clinical data describing the relative risks of EPS at higher doses of ziprasidone when compared to lower doses. A study of 15 inpatients receiving 240–320 mg/day demonstrated minimal increases in QTc from baseline (i.e., average 3.4 ms after removing an outlier), with none of the patients approaching the 500 ms threshold of concern (Levy et al., 2004); however, the occurrence of EPS was not reported. At doses of 160 mg/day and under, ziprasidone has been found to have low rates of EPS (Daniel et al., 1999). However, there are case reports of ziprasidone-induced acute dystonia (Mason et al., 2005), oculogyric crisis in a child (Ramos et al., 2003), and Pisa syndrome (Ziegenbein et al., 2003). These doses of ziprasidone have also been associated with tardive dyskinesia (Keck et al., 2004) and tardive dystonia (Papapetropoulos et al., 2005). Less is known about the clinical characteristics of ziprasidone at doses above 160 mg/day. Accounts of overdose have described cliniAbbreviations: EPS, extrapyramidal symptoms. ⁎ Corresponding author. Tel.: +1 212 305 2913; fax: +1 212 305 9213. E-mail address: [email protected] (R.R. Girgis). 0278-5846/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2006.10.005
cally significant EPS, although in a minority of cases (Arbuck, 2005; Gomez-Criado et al., 2005). One recent report described acute dystonia in a ziprasidone-naïve patient after rapid dose escalation (i.e., over 3 days) to 200 mg/day (Weinstein et al., 2006), and another reported akathisia after dose reduction from 240 mg/day in two patients (Oral et al., 2006). We report a patient who displayed no EPS with ziprasidone 160 mg/day for several months, but did display marked, acute dystonic reactions on ziprasidone 240 mg/day. 2. Case report Ms. A was a 31-year-old female with schizophrenia and persistent psychotic symptoms despite multiple antipsychotic regimens and reliable adherence. She had previously experienced acute dystonia with haloperidol and mild EPS with risperidone (requiring adjunctive benztropine). The patient had most recently been on monotherapy with ziprasidone 160 mg/ day and had not experienced any EPS. Because of her persistent psychosis, the patient had agreed to a trial of ziprasidone 240 mg/day, divided twice daily. Within 2 days of this dose increase, she experienced transient tongue dystonia, general body stiffness, and conjugate eye deviation in her home on two separate occasions. She did not tell her psychiatrist about these side effects or discontinue her medications. In the morning on day 4 of her dose increase, she took her complete dose of ziprasidone 240 mg at once, along with bismuth subsalicylate
P.J. Rosenfield et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry 31 (2007) 546–547
for concomitant diarrhea. Several hours later, and upon arrival at her clinic for a scheduled appointment, she had a severe, acute dystonic reaction including oculogyric crisis, lock jaw, tongue protrusion, generalized and severe total body stiffness, and respiratory difficulty. She fell on the floor and was unable to move. She did not experience laryngeal dystonia or loss of consciousness. She did not respond to two doses of intramuscular diphenhydramine 25 mg, both given within 10 min of symptom onset. Her symptoms completely resolved, however, when intravenous diphenhydramine 50 mg was given. Admission physical examination, laboratories, and EKG were all within normal limits. Ziprasidone was discontinued and aripiprazole was initiated without further EPS. 3. Discussion The present case illustrates that the occurrence of significant ziprasidone-induced acute dystonic reactions are still possible with higher doses (i.e., greater than 160 mg/day), even if no EPS have been experienced at doses up to and including 160 mg/day. It is possible that the EPS in the case described above were the result of the magnitude of the dose of ziprasidone. In addition, the more marked EPS experienced by the patient on the fourth day of her dose increase may have been related to the fact that on that day she took the whole 240 mg dose at once instead of in divided doses as she had been prescribed and had done the previous days. The risk of EPS has generally been observed to occur in a dose-dependent manner for both conventional and atypical agents (Casey, 1997; Tandon and Jibson, 2002). Further, while the low risk of EPS associated with atypical antipsychotics is considered to be a major advantage over conventional agents, one meta-analysis showed that this differential risk may be mitigated when lower doses (i.e., less than 600 mg/ day chlorpromazine equivalents) of low-potency conventional agents are used as comparator drugs (Leucht et al., 2003). However, as suggested in other reports (Mason et al., 2005; Weinstein et al., 2006), it remains possible that the EPS were at least partly the result of the dose escalation, rather than just the magnitude of the dose itself. Clinically, the onset of dystonia often occurs within hours to days of initiation or the rapid dose increase of antipsychotic medications (Pierre, 2005; van Harten et al., 1999). The possible contribution of the speed of dose escalation to the appearance of acute dystonia is illustrated by one case report of a 34 year-old male who had no EPS after being gradually titrated to a dose of 3 mg twice daily of risperidone on two separate occasions (Brody, 1996). However, on the third occasion the patient was more rapidly titrated to 3 mg twice daily of risperidone and he experienced a marked dystonic reaction (Brody, 1996). This case report, however, was limited by the patient's recent use of cocaine (Brody, 1996). The contribution of bismuth subsalicylate to the scenario described above is unclear as the patient was experiencing EPS before taking bismuth subsalicylate and blood levels of ziprasidone were not available. However, certain liquid formula-
547
tions of bismuth subsalicylate have been reported to affect blood levels of certain medications (Healy et al., 1997). 4. Conclusion The observations from the present case indicate that highdose (i.e., greater than 160 mg/day), ziprasidone-induced EPS may occur even if no such side effects have been experienced at doses up to and including 160 mg/day. However, as few reports of EPS at higher doses of ziprasidone exist, it remains unclear whether such symptoms are the result of the velocity or magnitude of dose titration, or both. Longitudinal studies are needed before conclusions can be drawn regarding the relative risks of ziprasidone-induced EPS at higher doses when compared with lower doses. References Arbuck DM. 12,800-mg ziprasidone overdose without significant ECG changes. Gen Hosp Psychiatry 2005;27:222–3. Brody AL. Acute dystonia induced by rapid increase in risperidone dosage. J Clin Psychopharmacol 1996;16:461–2. Casey DE. The relationship of pharmacology to side effects. J Clin Psychiatry 1997;58(Suppl 10):55–62. Daniel DG, Zimbroff DL, Potkin SG, Reeves KR, Harrigan EP, Lakshminarayanan M. Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial. Ziprasidone Study Group. Neuropsychopharmacology 1999;20:491–505. Gomez-Criado MS, Bernardo M, Florez T, Gutierrez JR, Gandia R, Ayani I. Ziprasidone overdose: cases recorded in the database of Pfizer-Spain and literature review. Pharmacotherapy 2005;25:1660–5. Healy DP, Dansereau RJ, Dunn AB, Clendening CE, Mounts AW, Deepe Jr GS. Reduced tetracycline bioavailability caused by magnesium aluminum silicate in liquid formulations of bismuth subsalicylate. Ann Pharmacother 1997;31:1460–4. Keck ME, Muller MB, Binder EB, Sonntag A, Holsboer F. Ziprasidone-related tardive dyskinesia. Am J Psychiatry 2004;161:175–6. Leucht S, Wahlbeck K, Hamann J, Kissling W. New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet 2003;361:1581–9. Levy WO, Robichaux-Keene NR, Nunez C. No significant QTc interval changes with high-dose ziprasidone: a case series. J Psychiatr Pract 2004;10:227–32. Mason MN, Johnson CE, Piasecki M. Ziprasidone-induced acute dystonia. Am J Psychiatry 2005;162:625–6. Oral ET, Altinbas K, Demirkiran S. Sudden akathisia after a ziprasidone dose reduction. Am J Psychiatry 2006;163:546. Papapetropoulos S, Wheeler S, Singer C. Tardive dystonia associated with ziprasidone. Am J Psychiatry 2005;162:2191. Pierre JM. Extrapyramidal symptoms with atypical antipsychotics: incidence, prevention and management. Drug Saf 2005;28:191–208. Ramos AE, Shytle RD, Silver AA, Sanberg PR. Ziprasidone-induced oculogyric crisis. J Am Acad Child Adolesc Psychiatry 2003;42:1013–4. Tandon R, Jibson MD. Extrapyramidal side effects of antipsychotic treatment: scope of problem and impact on outcome. Ann Clin Psychiatry 2002;14:123–9. van Harten PN, Hoek HW, Kahn RS. Acute dystonia induced by drug treatment. BMJ 1999;319:623–6. Weinstein SK, Adler CM, Strakowski SM. Ziprasidone-induced acute dystonic reactions in patients with bipolar disorder. J Clin Psychiatry 2006;67:327–8. Ziegenbein M, Schomerus G, Kropp S. Ziprasidone-induced Pisa syndrome after clozapine treatment. J Neuropsychiatry Clin Neurosci 2003;15:458–9.