Journal of Clinical Psychopharmacology
&
Volume 35, Number 1, February 2015
clozapine are the result of aspiration, we recommend measuring the peripheral eosinophil concentration to rule out EP. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Naoki Hashimoto, MD, PhD Department of Psychiatry Hokkaido University Graduate School of Medicine Sapporo, Japan Child and Adolescent Psychiatry Department of Psychiatry University of California San Francisco San Francisco, CA [email protected]
Tamaki Maeda, MD Koyogaoka Hospital Abashiri, Hokkaido, Japan
Ryo Okubo, MD Hisashi Narita, MD Ichiro Kusumi, MD, PhD Department of Psychiatry Hokkaido University Graduate School of Medicine Sapporo, Japan
REFERENCES 1. Taylor DM, Douglas-Hall P, Olofinjana B, et al. Reasons for discontinuing clozapine: matched, case-control comparison with risperidone long-acting injection. Br J Psychiatry. 2009; 194:165Y167. 2. Abdelmawla N, Ahmed MI. Clozapine and risk of pneumonia. Br J Psychiatry. 2009;194:468Y469. 3. Cottin V, Cordier JF. Eosinophilic pneumonias. Allergy. 2005;60:841Y857. 4. Lo¨ffler W. Zur differential-Diagnose der ¨ ber fluchtige Lungeninfiltierungen. II U Succedan-Infiltrate (mir Eosinophilia). Beitr Klin Tuberk. 1932;79:368Y392. 5. Liebow AA, Carrington CB. The eosinophilic pneumonias. Medicine (Baltimore). 1969;48: 251Y285. 6. Solomon J, Schwarz M. Drug-, toxin-, and radiation therapy-induced eosinophilic pneumonia. Semin Respir Crit Care Med. 2006;27:192Y197. 7. Gallagher RM, Kirkham JJ, Mason JR, et al. Development and inter-rater reliability of the Liverpool adverse drug reaction causality assessment tool. PLoS One. 2011;6:e28096. 8. Nielsen J, Correll CU, Manu P, et al. Termination of clozapine treatment due to medical reasons: when is it warranted and how can it be avoided? J Clin Psychiatry. 2013;74:603Y613. 9. Roberts CE, Mortenson LY, Merrill DB, et al. Successful rechallenge with clozapine after eosinophilia. Am J Psychiatry. 2011;168:1147Y1151.
Blonanserin Ameliorated the Tendency Toward QTc Prolongation Associated With Risperidone in a Patient With Schizophrenia To the Editors: T prolongation is reported to induce ventricular tachyarrhythmia and torsade de pointes.1 Psychiatric patients who take a moderate dose of an antipsychotic (Q100 mg thioridazine equivalent) are reported to have a 2.39 times higher risk of sudden cardiac death than comparable nonusers.2 Blonanserin (BNS) has a D2 receptorblocking activity comparable with that of haloperidol, as well as potent 5HT-2A receptor-blocking activity and weak 5HT2C, D1, and >1 receptor-blocking activities; it is also almost devoid of histamine H1 and muscarinic M1 antagonist activity.3,4 Blonanserin is reported to be effective in the treatment of both positive and negative symptoms of schizophrenia.5,6 Blonanserin is the atypical antipsychotic least frequently discontinued for intolerability.7 We present a case in which BNS ameliorated the tendency toward QT prolongation associated with risperidone (RIS). A 25-year-old woman started to have auditory hallucinations, persecution mania, and compulsive laughter. She was admitted to our hospital and started on 4 mg/d of RIS. Her positive symptoms diminished. However, because she did not have insight and became aware of her own heartbeat, she often stopped RIS and relapsed. At the age of 32, she had a severe recurrence associated with the discontinuation of RIS, and she was admitted to our hospital. She had no electrolyte abnormality. We manually calculated the QTc interval (QTc) using both Bazett (QTcB) and Fridericia (QTcF) method. QTcB was 446 milliseconds, and QTcF was 428 milliseconds before administration of RIS on the day of hospitalization. On the seventh day of administration of 6 mg/d RIS, she felt her heart beating, and her QTcB was prolonged to 474 milliseconds and QTcF to 452 milliseconds. We consulted the cardiology department and were advised to change her medication because RIS might be causing the tendency toward QTc prolongation. We started a gradual change from RIS to BNS. On the 14th day after the first administration of RIS, she was taking 4 mg/d of RIS and 4 mg/d of BNS, but her QTcB was still 462 milliseconds and QTcF was 446 milliseconds. We stopped RIS on the 15th day after the administration began. When she
Q
* 2015 Wolters Kluwer Health, Inc. All rights reserved.
Letters to the Editors
reached a dose of 12 mg/d BNS on the 8th day after stopping RIS, her QTcB was normalized to 420 milliseconds and QTcF to 432 milliseconds. Awareness of her heartbeat was diminished. Although we increased BNS to 24 mg/d due to residual auditory hallucinations, her QTcB was 415 milliseconds, and QTcF was 403 milliseconds. Risperidone was reported to have low risk of QTc prolongation8 or the same risk of QTc prolongation as BNS.9 On the other hand, RIS was reported to induce QTc prolongation.10,11 One of the myocardial ion channels under control of the human ether-a`-go-goYrelated gene (hERG) was reported to be involved in QTc prolongation associated with antipsychotics.12 Blonanserin at 0.1 KM was reported to cause a 22.1% blockade of hERG and BNS at 1 KM to cause an 81.9% blockade of hERG (Pharmaceuticals Medical Devices Agency, Japan. Drug-related information: submission overview of approved products. Blonanserin: Lonasen tablets 2 mg/Lonasen tablets 4 mg/Lonasen powder 2%. Available at: http://www.info.pmda.go.jp/shinyaku/ P200800002/index.html). Based on the logistic regression, the hERG IC50 of BNS is supposed to be about 0.3. The IC50 of RIS is reported to be 0.148 KM or half that of BNS. This may be one reason that the QTc interval was reduced in our case. The hERG IC50 of BNS is higher than that of haloperidol (0.0268 KM), olanzapine (0.231 KM), and thioridazine (0.033 KM). It was reported that BNS has a lower risk of QTc prolongation than haloperidol.9 There are some limitations to this study. It may not have been necessary to change the medication because the treatment with RIS induced a maximal QTcB value of 474 milliseconds and QTcF of 452 milliseconds, which are not considered ‘‘prolonged’’ but barely ’’borderline’’ (QTc Q460 milliseconds, for other authors to 500 milliseconds). There are many other risk factors such as age, female sex, bradycardia, electrolytic disorders (hypokalemia and hypomagnesaemia), previous heart disorders, sodium channel mutations, and congenital long QT syndrome.13 In general, although laboratory investigations showed a dose-related inhibition of iKr channels associated with different neuroactive drugs, there are no definitive data regarding the effective incidence of life-threatening arrhythmias related to long QTc interval in patients treated with a therapeutic dosage of antipsychotics.14 Concomitant risk factors may be responsible for the arrhythmic episodes, and antipsychotics should be avoided in these patients. When we see a case of QTc prolongation associated with antipsychotics, switching to BNS may be 1 option. www.psychopharmacology.com
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
101
Journal of Clinical Psychopharmacology
Letters to the Editors
ACKNOWLEDGMENT This study was partly supported by a grant from Zikei Institute of Psychiatry. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Yutaka Mizuki, MD Department of Neuropsychiatry Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences Okayama, Japan
Manabu Takaki, MD, PhD Department of Neuropsychiatry Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences Okayama, Japan [email protected]
REFERENCES 1. Reilly JG, Ayis SA, Ferrier IN, et al. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet. 2000;355:1048Y1052. 2. Ray WA, Meredith S, Thapa PB, et al. Antipsychotics and the risk of sudden cardiac death. Arch Gen Psychiatry. 2001;58: 1161Y1167. 3. Deeks ED, Keating GM. Blonanserin: a review of its use in the management of schizophrenia. CNS Drugs. 2010;24:65Y84. 4. Noda Y, Kurumiya S, Miura Y, et al. Comparative study of 2-(4-ethyl-1-piperazinyl)4-(fluorophenyl)-5,6,7,8,9, 10-hexahydrocycloocta[b]pyridine (AD-5423) and haloperidol for their pharmacological activities related to antipsychotic efficacy and/or adverse side-effects. J Pharmacol Exp Ther. 1993;265:745Y751. 5. Garcia E, Robert M, Peris F, et al. The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: a randomized, double-blind, placebo-controlled, multicentre study. CNS Drugs. 2009;23: 615Y625. 6. Yang J, Bahk WM, Cho HS, et al. Efficacy and tolerability of blonanserin in the patients with schizophrenia: a randomized, double-blind, risperidone-compared trial. Clin Neuropharmacol. 2010;33:169Y175. 7. Takaki M, Okahisa Y, Kodama M, et al. Efficacy and tolerability of blonanserin in 48 patients with intractable schizophrenia. Acta Neuropsychiatr. 2012;24:380Y383. 8. Vieweg WV, Hasnain M, Hancox JC, et al. Risperidone, QTc interval prolongation, and torsade de pointes: a systematic review of case reports. Psychopharmacology (Berl). 2013;228:515Y524. 9. Kishi T, Matsuda Y, Iwata N. Cardiometabolic risks of blonanserin and perospirone in the management of schizophrenia: a systematic
102
www.psychopharmacology.com
review and meta-analysis of randomized controlled trials. PLoS One. 2014;9:e88049. 10. US Food and Drug Administration Advisory Committee. Zeldox Capsules (ziprasidone): Summary of Efficacy and Safety and Overall Benefit Risk Relationship. Bethesda, MD: US Food and Drug Administration; 2000. 11. Harrigan EP, Miceli JJ, Anziano R, et al. A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition. J Clin Psychopharmacol. 2004;24:62Y69. 12. Crumb WJ Jr, Ekins S, Sarazan RD, et al. Effects of antipsychotic drugs on I(to), I (Na), I (sus), I (K1), and hERG: QT prolongation, structure activity relationship, and network analysis. Pharm Res. 2006;23:1133Y1143. 13. Vieweg WV. New generation antipsychotic drugs and QTc interval prolongation. Prim Care Companion J Clin Psychiatry. 2003;5: 205Y215. 14. Killeen MJ. Antipsychotic-induced sudden cardiac death: examination of an atypical reaction. Expert Opin Drug Saf. 2009;8: 249Y252.
Under Arrest The Use of Amantadine for Treatment-Refractory Mood Lability and Aggression in a Patient With Traumatic Brain Injury To the Editors: raumatic brain injury (TBI) is a complex condition with high prevalence, mortality, and morbidity. In the United States alone, more than 50,000 people die of TBI every year1 and more than 5 million TBI survivors are living with permanent disabilities.2 Patients with TBI often struggle with myriad cognitive and psychiatric symptoms. Rates of mood lability and aggression in patients with TBI are high, ranging from 20% to 73%.3Y6 Clinicians prescribe a wide range of medications for the treatment of mood lability and aggression secondary to TBI, including anticonvulsants, mood stabilizers, antidepressants, antipsychotics, psychostimulants, and antihypertensives, among other medication subtypes. In clinical practice, patients presenting with this TBI-associated symptom cluster often report previous trials on multiple medications. We describe the case of a 52-year-old man with treatment-refractory mood lability and aggression secondary to TBI and treated with amantadine on 2 separate occasions, both before and after being lost to follow-up because of incarceration.
T
&
Volume 35, Number 1, February 2015
CASE REPORT Mr A was a 52-year-old man with a history of hepatitis C, hypertension, hypercholesterolemia, and TBI, who presented to the psychiatric clinic for evaluation of severe, daily emotional lability, aggression, and insomnia. Eighteen months before presentation, the patient was attacked and sustained a severe TBI, comprising a right temporofrontal skull fracture, subdural hematoma, and subarachnoid hemorrhage. His psychiatric history included opioid use disorder, which was in complete remission for 4 years at the time of presentation. The patient had a history of selling illicit substances for more than 5 years before presentation but had no history of mood lability or violent behavior before sustaining the TBI. Mr A seemed to be of average intellectual ability, had a ninth-grade education, and had most recently worked as a logger before sustaining the brain injury. At the time of presentation, Mr A’s complete list of medications included 250 mg of divalproex sodium by mouth twice daily (for mood stabilization because the patient had no known history of seizures), 20 mg of ziprasidone by mouth at night, and 1 mg of clonazepam by mouth every 6 hours as needed for agitation. The patient had previous trials of quetiapine, lithium, risperidone, citalopram, and paliperidone but had experienced breakthrough aggression, lability, and/or adverse effects on each. At this initial visit, the team increased the patient’s divalproex sodium to 250 mg by mouth in the morning and 500 mg by mouth at night while continuing his other psychotropic medications. At week 4, divalproex sodium was discontinued because of thrombocytopenia and leukopenia, both of which are known adverse effects. The patient subsequently underwent a trial on ziprasidone (titrated to a dose of 40 mg by mouth in the morning and 80 mg by mouth at night), which was ineffective and caused severe akathisia. Next, the patient was tried on propranolol (up to a dose of 20 mg by mouth 3 times daily) but experienced severe breakthrough symptoms of mood lability and aggression. The team added olanzapine to the patient’s regimen (2.5 mg by mouth in the morning and 5 mg by mouth at night), which resulted in the patient’s admission to the inpatient neurology service because of severe hypotension. Mr A was reassessed in the clinic at week 13, and the treatment team considered various options. The team chose to avoid carbamazepine because of the patient’s risk for developing leukopenia
* 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
&
Volume 35, Number 1, February 2015
clozapine are the result of aspiration, we recommend measuring the peripheral eosinophil concentration to rule out EP. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Naoki Hashimoto, MD, PhD Department of Psychiatry Hokkaido University Graduate School of Medicine Sapporo, Japan Child and Adolescent Psychiatry Department of Psychiatry University of California San Francisco San Francisco, CA [email protected]
Tamaki Maeda, MD Koyogaoka Hospital Abashiri, Hokkaido, Japan
Ryo Okubo, MD Hisashi Narita, MD Ichiro Kusumi, MD, PhD Department of Psychiatry Hokkaido University Graduate School of Medicine Sapporo, Japan
REFERENCES 1. Taylor DM, Douglas-Hall P, Olofinjana B, et al. Reasons for discontinuing clozapine: matched, case-control comparison with risperidone long-acting injection. Br J Psychiatry. 2009; 194:165Y167. 2. Abdelmawla N, Ahmed MI. Clozapine and risk of pneumonia. Br J Psychiatry. 2009;194:468Y469. 3. Cottin V, Cordier JF. Eosinophilic pneumonias. Allergy. 2005;60:841Y857. 4. Lo¨ffler W. Zur differential-Diagnose der ¨ ber fluchtige Lungeninfiltierungen. II U Succedan-Infiltrate (mir Eosinophilia). Beitr Klin Tuberk. 1932;79:368Y392. 5. Liebow AA, Carrington CB. The eosinophilic pneumonias. Medicine (Baltimore). 1969;48: 251Y285. 6. Solomon J, Schwarz M. Drug-, toxin-, and radiation therapy-induced eosinophilic pneumonia. Semin Respir Crit Care Med. 2006;27:192Y197. 7. Gallagher RM, Kirkham JJ, Mason JR, et al. Development and inter-rater reliability of the Liverpool adverse drug reaction causality assessment tool. PLoS One. 2011;6:e28096. 8. Nielsen J, Correll CU, Manu P, et al. Termination of clozapine treatment due to medical reasons: when is it warranted and how can it be avoided? J Clin Psychiatry. 2013;74:603Y613. 9. Roberts CE, Mortenson LY, Merrill DB, et al. Successful rechallenge with clozapine after eosinophilia. Am J Psychiatry. 2011;168:1147Y1151.
Blonanserin Ameliorated the Tendency Toward QTc Prolongation Associated With Risperidone in a Patient With Schizophrenia To the Editors: T prolongation is reported to induce ventricular tachyarrhythmia and torsade de pointes.1 Psychiatric patients who take a moderate dose of an antipsychotic (Q100 mg thioridazine equivalent) are reported to have a 2.39 times higher risk of sudden cardiac death than comparable nonusers.2 Blonanserin (BNS) has a D2 receptorblocking activity comparable with that of haloperidol, as well as potent 5HT-2A receptor-blocking activity and weak 5HT2C, D1, and >1 receptor-blocking activities; it is also almost devoid of histamine H1 and muscarinic M1 antagonist activity.3,4 Blonanserin is reported to be effective in the treatment of both positive and negative symptoms of schizophrenia.5,6 Blonanserin is the atypical antipsychotic least frequently discontinued for intolerability.7 We present a case in which BNS ameliorated the tendency toward QT prolongation associated with risperidone (RIS). A 25-year-old woman started to have auditory hallucinations, persecution mania, and compulsive laughter. She was admitted to our hospital and started on 4 mg/d of RIS. Her positive symptoms diminished. However, because she did not have insight and became aware of her own heartbeat, she often stopped RIS and relapsed. At the age of 32, she had a severe recurrence associated with the discontinuation of RIS, and she was admitted to our hospital. She had no electrolyte abnormality. We manually calculated the QTc interval (QTc) using both Bazett (QTcB) and Fridericia (QTcF) method. QTcB was 446 milliseconds, and QTcF was 428 milliseconds before administration of RIS on the day of hospitalization. On the seventh day of administration of 6 mg/d RIS, she felt her heart beating, and her QTcB was prolonged to 474 milliseconds and QTcF to 452 milliseconds. We consulted the cardiology department and were advised to change her medication because RIS might be causing the tendency toward QTc prolongation. We started a gradual change from RIS to BNS. On the 14th day after the first administration of RIS, she was taking 4 mg/d of RIS and 4 mg/d of BNS, but her QTcB was still 462 milliseconds and QTcF was 446 milliseconds. We stopped RIS on the 15th day after the administration began. When she
Q
* 2015 Wolters Kluwer Health, Inc. All rights reserved.
Letters to the Editors
reached a dose of 12 mg/d BNS on the 8th day after stopping RIS, her QTcB was normalized to 420 milliseconds and QTcF to 432 milliseconds. Awareness of her heartbeat was diminished. Although we increased BNS to 24 mg/d due to residual auditory hallucinations, her QTcB was 415 milliseconds, and QTcF was 403 milliseconds. Risperidone was reported to have low risk of QTc prolongation8 or the same risk of QTc prolongation as BNS.9 On the other hand, RIS was reported to induce QTc prolongation.10,11 One of the myocardial ion channels under control of the human ether-a`-go-goYrelated gene (hERG) was reported to be involved in QTc prolongation associated with antipsychotics.12 Blonanserin at 0.1 KM was reported to cause a 22.1% blockade of hERG and BNS at 1 KM to cause an 81.9% blockade of hERG (Pharmaceuticals Medical Devices Agency, Japan. Drug-related information: submission overview of approved products. Blonanserin: Lonasen tablets 2 mg/Lonasen tablets 4 mg/Lonasen powder 2%. Available at: http://www.info.pmda.go.jp/shinyaku/ P200800002/index.html). Based on the logistic regression, the hERG IC50 of BNS is supposed to be about 0.3. The IC50 of RIS is reported to be 0.148 KM or half that of BNS. This may be one reason that the QTc interval was reduced in our case. The hERG IC50 of BNS is higher than that of haloperidol (0.0268 KM), olanzapine (0.231 KM), and thioridazine (0.033 KM). It was reported that BNS has a lower risk of QTc prolongation than haloperidol.9 There are some limitations to this study. It may not have been necessary to change the medication because the treatment with RIS induced a maximal QTcB value of 474 milliseconds and QTcF of 452 milliseconds, which are not considered ‘‘prolonged’’ but barely ’’borderline’’ (QTc Q460 milliseconds, for other authors to 500 milliseconds). There are many other risk factors such as age, female sex, bradycardia, electrolytic disorders (hypokalemia and hypomagnesaemia), previous heart disorders, sodium channel mutations, and congenital long QT syndrome.13 In general, although laboratory investigations showed a dose-related inhibition of iKr channels associated with different neuroactive drugs, there are no definitive data regarding the effective incidence of life-threatening arrhythmias related to long QTc interval in patients treated with a therapeutic dosage of antipsychotics.14 Concomitant risk factors may be responsible for the arrhythmic episodes, and antipsychotics should be avoided in these patients. When we see a case of QTc prolongation associated with antipsychotics, switching to BNS may be 1 option. www.psychopharmacology.com
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
101
Journal of Clinical Psychopharmacology
Letters to the Editors
ACKNOWLEDGMENT This study was partly supported by a grant from Zikei Institute of Psychiatry. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Yutaka Mizuki, MD Department of Neuropsychiatry Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences Okayama, Japan
Manabu Takaki, MD, PhD Department of Neuropsychiatry Okayama University Graduate School of Medicine Dentistry, and Pharmaceutical Sciences Okayama, Japan [email protected]
REFERENCES 1. Reilly JG, Ayis SA, Ferrier IN, et al. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet. 2000;355:1048Y1052. 2. Ray WA, Meredith S, Thapa PB, et al. Antipsychotics and the risk of sudden cardiac death. Arch Gen Psychiatry. 2001;58: 1161Y1167. 3. Deeks ED, Keating GM. Blonanserin: a review of its use in the management of schizophrenia. CNS Drugs. 2010;24:65Y84. 4. Noda Y, Kurumiya S, Miura Y, et al. Comparative study of 2-(4-ethyl-1-piperazinyl)4-(fluorophenyl)-5,6,7,8,9, 10-hexahydrocycloocta[b]pyridine (AD-5423) and haloperidol for their pharmacological activities related to antipsychotic efficacy and/or adverse side-effects. J Pharmacol Exp Ther. 1993;265:745Y751. 5. Garcia E, Robert M, Peris F, et al. The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: a randomized, double-blind, placebo-controlled, multicentre study. CNS Drugs. 2009;23: 615Y625. 6. Yang J, Bahk WM, Cho HS, et al. Efficacy and tolerability of blonanserin in the patients with schizophrenia: a randomized, double-blind, risperidone-compared trial. Clin Neuropharmacol. 2010;33:169Y175. 7. Takaki M, Okahisa Y, Kodama M, et al. Efficacy and tolerability of blonanserin in 48 patients with intractable schizophrenia. Acta Neuropsychiatr. 2012;24:380Y383. 8. Vieweg WV, Hasnain M, Hancox JC, et al. Risperidone, QTc interval prolongation, and torsade de pointes: a systematic review of case reports. Psychopharmacology (Berl). 2013;228:515Y524. 9. Kishi T, Matsuda Y, Iwata N. Cardiometabolic risks of blonanserin and perospirone in the management of schizophrenia: a systematic
102
www.psychopharmacology.com
review and meta-analysis of randomized controlled trials. PLoS One. 2014;9:e88049. 10. US Food and Drug Administration Advisory Committee. Zeldox Capsules (ziprasidone): Summary of Efficacy and Safety and Overall Benefit Risk Relationship. Bethesda, MD: US Food and Drug Administration; 2000. 11. Harrigan EP, Miceli JJ, Anziano R, et al. A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition. J Clin Psychopharmacol. 2004;24:62Y69. 12. Crumb WJ Jr, Ekins S, Sarazan RD, et al. Effects of antipsychotic drugs on I(to), I (Na), I (sus), I (K1), and hERG: QT prolongation, structure activity relationship, and network analysis. Pharm Res. 2006;23:1133Y1143. 13. Vieweg WV. New generation antipsychotic drugs and QTc interval prolongation. Prim Care Companion J Clin Psychiatry. 2003;5: 205Y215. 14. Killeen MJ. Antipsychotic-induced sudden cardiac death: examination of an atypical reaction. Expert Opin Drug Saf. 2009;8: 249Y252.
Under Arrest The Use of Amantadine for Treatment-Refractory Mood Lability and Aggression in a Patient With Traumatic Brain Injury To the Editors: raumatic brain injury (TBI) is a complex condition with high prevalence, mortality, and morbidity. In the United States alone, more than 50,000 people die of TBI every year1 and more than 5 million TBI survivors are living with permanent disabilities.2 Patients with TBI often struggle with myriad cognitive and psychiatric symptoms. Rates of mood lability and aggression in patients with TBI are high, ranging from 20% to 73%.3Y6 Clinicians prescribe a wide range of medications for the treatment of mood lability and aggression secondary to TBI, including anticonvulsants, mood stabilizers, antidepressants, antipsychotics, psychostimulants, and antihypertensives, among other medication subtypes. In clinical practice, patients presenting with this TBI-associated symptom cluster often report previous trials on multiple medications. We describe the case of a 52-year-old man with treatment-refractory mood lability and aggression secondary to TBI and treated with amantadine on 2 separate occasions, both before and after being lost to follow-up because of incarceration.
T
&
Volume 35, Number 1, February 2015
CASE REPORT Mr A was a 52-year-old man with a history of hepatitis C, hypertension, hypercholesterolemia, and TBI, who presented to the psychiatric clinic for evaluation of severe, daily emotional lability, aggression, and insomnia. Eighteen months before presentation, the patient was attacked and sustained a severe TBI, comprising a right temporofrontal skull fracture, subdural hematoma, and subarachnoid hemorrhage. His psychiatric history included opioid use disorder, which was in complete remission for 4 years at the time of presentation. The patient had a history of selling illicit substances for more than 5 years before presentation but had no history of mood lability or violent behavior before sustaining the TBI. Mr A seemed to be of average intellectual ability, had a ninth-grade education, and had most recently worked as a logger before sustaining the brain injury. At the time of presentation, Mr A’s complete list of medications included 250 mg of divalproex sodium by mouth twice daily (for mood stabilization because the patient had no known history of seizures), 20 mg of ziprasidone by mouth at night, and 1 mg of clonazepam by mouth every 6 hours as needed for agitation. The patient had previous trials of quetiapine, lithium, risperidone, citalopram, and paliperidone but had experienced breakthrough aggression, lability, and/or adverse effects on each. At this initial visit, the team increased the patient’s divalproex sodium to 250 mg by mouth in the morning and 500 mg by mouth at night while continuing his other psychotropic medications. At week 4, divalproex sodium was discontinued because of thrombocytopenia and leukopenia, both of which are known adverse effects. The patient subsequently underwent a trial on ziprasidone (titrated to a dose of 40 mg by mouth in the morning and 80 mg by mouth at night), which was ineffective and caused severe akathisia. Next, the patient was tried on propranolol (up to a dose of 20 mg by mouth 3 times daily) but experienced severe breakthrough symptoms of mood lability and aggression. The team added olanzapine to the patient’s regimen (2.5 mg by mouth in the morning and 5 mg by mouth at night), which resulted in the patient’s admission to the inpatient neurology service because of severe hypotension. Mr A was reassessed in the clinic at week 13, and the treatment team considered various options. The team chose to avoid carbamazepine because of the patient’s risk for developing leukopenia
* 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
