CASE REPORT
Electroconvulsive in a Schizophrenic Patient With Neuroleptic Malignant Syndrome and Rhabdomyolysis Maria Chona P. San Gabriel, MD, Bharathi Eddula-Changala, MD, Yonghong Tan, MD, and Carrol T. Longshore, MD
Abstract: We present the case of a middle-aged man with a chronic history of schizoaffective disorder, depressed type, stable on a secondgeneration antipsychotic. Psychotic symptoms recurred contingent to medication noncompliance necessitating hospitalization. Treatment was complicated by the development of neuroleptic malignant syndrome (NMS). In addition, subsequent medication rechallenges failed because of recurrent rhabdomyolysis and atypical NMS. Electroconvulsive therapy (ECT) treatment was initiated, affording remission of psychotic symptoms and nonrecurrence of NMS and rhabdomyolysis. Our experience confirmed the efficacy of ECT treatment in providing symptom relief of psychosis complicated by recurrent episodes of NMS and atypical NMS. Likewise, it illustrated the efficacy of ECT treatment for rhabdomyolysis. Key Words: electroconvulsive therapy, ECT, neuroleptic malignant syndrome, NMS, rhabdomyolysis, atypical NMS, schizophrenia (J ECT 2015;31: 197–200)
S
ince the advent of the first antipsychotic, chlorpromazine, in 1950, treatment regimens for major psychiatric disorders have improved. In 1988, the treatment armamentarium continued to expand upon the introduction of the second-generation antipsychotics in the market. However, medication adverse effects including neuroleptic malignant syndrome (NMS) became evident. Initially described by Delay et al1 in the 1960s, NMS is an idiosyncratic yet potentially fatal adverse response to antipsychotics. Classically, it is characterized by hyperthermia, severe muscle rigidity, autonomic instability, and mental status changes particularly delirium. However, studies have revealed the predilection of second-generation antipsychotics to present atypically.2 This include clozapine presenting with less rigidity and short induction period with delayed rise in creatine phosphokinase (CPK) levels, risperidone and aripiprazole with lower-grade fever, and aripiprazole being less likely to present with mental status alteration.3 Pathophysiologic mechanisms posit the theory of dopamine dysfunction resulting in abrupt and extensive D2 blockade and hyperactivity of the peripheral sympathetic system.4 Alternative theories include primary skeletal muscle defects, direct toxic effects on the skeletal muscle, as well as molecular and genetic defects.5 According to Trollor et al,2 symptom onset typically occurs within 2 weeks of psychotropic initiation. Proposed risk factors include male sex, preexisting medical and neurologic conditions,
From the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, Elmhurst Hospital Center, Elmhurst, NY. Received for publication May 10, 2014; accepted August 14, 2014. Reprints: Maria Chona P. San Gabriel, MD, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, Elmhurst Hospital Center, 79-01 Broadway, Elmhurst, NY 11373 (e‐mail: [email protected]). The authors have no conflicts of interest or financial disclosures to report. Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/YCT.0000000000000184
extrapyramidal syndromes (EPS), mental retardation, agitation, as well as recent use of restraint. Additional predisposing factors include iron deficiency and medication factors, namely, depot administration and rapid up-titration of medication dosage and environmental factors such as humidity and elevated ambient temperature.6 Although no specific laboratory test or biomarker is predictive of the syndrome, several laboratory abnormalities have been implicated. This includes metabolic acidosis, hypoxia, decreased serum iron concentration,7 as well as elevated catecholamine and CPK levels.8 In 90% of cases, CPK elevation peaks on day 2 of fever onset and subsides on day 12.9 On the basis of the literature, incidence rates range from 0.01% to 0.02%, with the highest incident rate of 3%,10 whereas mortality rate range from 10% to 55%.11 Although declining in occurrence, the potential fatal adverse effect of the illness with varied manifestations warrants a high index of suspicion for prompt diagnosis and timely intervention. The presence of 7 different NMS guidelines with points of disagreement makes diagnosis a challenge. Points of dissimilarity include hyperthermia, presence of EPS, symptom onset, accurate definition of hypertension, and the presence of additional features such as elevated CPK and symptoms of autonomic instability.12 Symptom onset of less than 7 days from treatment initiation is specified by the guideline of Caroff and Mann.13 Hyperthermia is defined as a temperature of 37.5°C or higher by Pope et al,14 Addonizio et al,15 and Levenson.16 Meanwhile, a specified temperature of 38°C or higher is set by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition,8 Caroff and Mann,13 as well as Friedman et al.17 Adityanjee et al,18 on the other hand, defined it as temperature of 39°C or higher. The presence of severe EPS is required by Friedman et al,17 whereas its consideration is suggested by Pope et al.14 Furthermore, emphasis on symptom onset of 7 days or less after medication initiation is indicated in the guideline by Caroff and Mann.13 Whereas blood pressure elevation is defined by Addonizio et al15 (blood pressure, 150/100 mm Hg), others described it as an abnormal or labile blood pressure.9,14,16,18 Meanwhile, Friedman et al17 excluded it from their guideline. Creatine phosphokinase elevation is a major factor for Levenson16 but is supportive for the other guidelines.18,19 Given the unresolved differences and the absence of an objective test or biological marker with the potential fatal adverse effect of the illness, a consensus regarding the diagnostic criteria for NMS using the Delphi technique was developed. On the basis of the consensus, diagnostic criterion for NMS includes exposure to dopamine antagonist or dopamine agonist withdrawal within the past 72 hours; hyperthermia of higher than 100.4°F or higher than 38.0°C on at least 2 occasions (orally measured); rigidity; mental status alteration; creatinine kinase elevation (at least 4 times the upper limit of the normal); sympathetic nervous system lability (blood pressure elevation of ≥25% for either systolic or diastolic blood pressures above baseline or blood pressure fluctuation of ≥20-mm Hg diastolic change or ≥25-mm Hg systolic change within 24 hours), diaphoresis, urinary incontinence; hypermetabolism (heart rate
Journal of ECT • Volume 31, Number 3, September 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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increase of ≥25% above baseline and respiratory rate increase of ≥50% above baseline); and negative workup for infectious, toxic, metabolic, or neurologic causes.20 An equally fatal consequence of antipsychotic use is rhabdomyolysis. This results from sarcolemmal injury leading to muscle enzyme elevation to potential life-threatening complications such as acute renal failure. Because of its varied clinical manifestations, no definite criteria have been set for the diagnosis of rhabdomyolysis. However, CPK elevation of at least 5-fold from the normal limit is a primary diagnostic indicator.21 Other possible etiologies include trauma, alcohol and drug abuse, prolonged immobilization, exercise, as well as exertion.22
CASE REPORT The patient is a 42-year-old Russian man, married with 2 children, employed, and domiciled living with his family. He was diagnosed with chronic schizoaffective disorder, depressed type, stable on olanzapine for the past 10 years. His chief complaint was “I was tired of taking medications for so long.” He was brought in by the emergency medical service after a referral from his psychologist because of insomnia and bizarre behavior contingent to medication noncompliance. At the psychiatric emergency room, he was observed to be emotionally labile, withdrawn, and, at times, internally preoccupied and paranoid. He reported feeling guilty for his perceived actions with poor insight. Subsequently, he was admitted to the inpatient psychiatry service and was restarted on 20 mg of olanzapine at bedtime and 0.5 mg of clonazepam bid. The patient was first diagnosed with mental illness at the age of 26 years with 2 past hospitalizations (ages 26 and 32 years). Upon discharge from his first hospitalization, he was maintained on olanzapine of unrecalled dosage. At the age of 30 years, he was briefly treated with risperidone and benztropine of unknown dosages but was noncompliant. A month after, he was shifted to 5 mg of fluphenazine daily for 10 days and was bridged to fluphenazine decanoate intramuscularly; benztropine continued at 1 mg bid. He remained stable until 2 years later (age, 32 years) when he became noncompliant with treatment because he wanted to have a child. Subsequently, he relapsed and was admitted for 20 days. Retrial with olanzapine (up to a total dose of 10 mg bid) was initiated, but he remained nonresponsive. He was shifted to ziprasidone with dosage titrated up to 80 mg bid and 1 mg of benztropine bid. Upon discharge, he remained stable. For unclear reason, the following year (age, 33 years), the patient was shifted to olanzapine, clonazepam, and citalopram, leading to psychiatric stabilization until his most recent relapse. During the course of his treatment, he underwent other antidepressant trials, namely, amitriptyline (1998) and paroxetine. The extent of his depressive symptoms was unclear, but no history of manic episodes or use of mood stabilizer was documented. During his illness, the patient had episodes of treatment noncompliance, but since the age of 34 years, he has been compliant until the recent admission. He denied any substance history and reported only history of hypertriglyceridemia before admission. He was not maintained on statins or other medication. He denied history of surgery, head trauma, or allergy. Likewise, he had no history of drug reaction, rhabdomyolysis, NMS, catatonia, or serotonin syndrome (SS). Upon admission, laboratory tests, namely, complete blood cell count, basic metabolic panel, erythrocyte sedimentation rate, and thyroid function test were within reference range. The result of urine toxicology was negative, and cranial computed tomographic scan and chest x-ray were not significant. The patient was born and raised in Russia. He was born term, with no complications, and milestones were attained at par with
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age. He claimed to have been raised in a loving and supportive family; he is 1 of 3 siblings. He finished 11th grade and decided to start his career as a barber. In his 20s, he got married, and in 1996, he moved to the United States with his wife for a better future. Currently, he has 2 daughters (17 and 15 years old) and continues to work as a barber. His parents are now residing in Flushing, New York, and his sister is residing in New Jersey, whom he visits intermittently. According to his wife, his brother committed suicide, the detail of which is unknown. It is unclear whether his brother had a psychiatric history. At present, he denied any legal issues. Upon admission, the patient was noted to be uncooperative, affectively labile, and internally preoccupied. He was continued on 20 mg of olanzapine at bedtime and 0.5 mg of clonazepam twice a day (bid) for the next 4 days. During that time, he episodically manifested disorganized and aggressive behaviors that required multiple administrations of oral neuroleptics. On days 5 and 6, his behavior escalated, necessitating administration of additional doses of medications. Cumulative statistics medications administered were 5 mg of haloperidol orally and 15 mg intramuscularly, 2 mg of lorazepam orally and 5 mg intramuscularly, as well as 100 mg of chlorpromazine intramuscularly. Likewise, a mechanical 5-point restraint was needed 4 times for a total duration of 5 hours. Review of medication revealed the following medication regimen: 20 mg of olanzapine daily, 1 mg of clonazepam three times a day, and 500 mg of valproic acid at bedtime. Over the ensuing hours, he was noted to be tachycardic (heart rate of 107 beats per minute) and febrile (temperature of 38.3°C) with rigidity. Laboratory tests revealed leukocytosis of 14.7 K/mcL (white blood cell reference range of 4.5–11.0 K/mcL) and CPK elevation up to 19,792 U/L (reference range of 21–232 U/L) with normal renal function (creatinine of 0.9 mg/dL; reference range of 0.4–1.6 mg/dL). Because of the suspicion for NMS, medications were discontinued. Later that day, his fever subsided, but he remained to be tachycardic (heart rate of 120 beats per minute) with persistent CPK elevation (27,847 U/L). Complete blood cell count, creatinine level, and liver profile were within normal levels. He was transferred to medicine service for possible NMS versus SS. He remained off antipsychotics and was only given lorazepam for intermittent episodes of aggressiveness. Aggressive intravenous hydration and monitoring of laboratory tests were done, which revealed down-trending CPK levels. He also had elevated liver profile (aspartate aminotransferase of 386 U/L with reference range of 5–40 U/L; alanine aminotransferase of 131 U/L with reference range of 5–50 U/L; lactate dehydrogenase of 1370 U/L with reference range of 90–225 U/L) that eventually trended down to normal. The patient continued to respond to supportive care and aggressive hydration, and on day 11, he was deemed medically stable and was transferred back to psychiatry service. He was given a final diagnosis of NMS with CPK level down to 553 U/L. Upon readmission to psychiatry service, the patient was noted to be calm and cooperative but with minimized symptoms. He denied any psychotic symptoms but was noted to be internally preoccupied. Likewise, he denied suicidal or homicidal ideations. The following day, he was started on 50 mg of quetiapine daily and was slowly up-titrated to 100 mg of quetiapine daily for the next 3 days. Eventually, he reported anxiety symptoms and was given lorazepam. On day 16 (September 16, 2013), his CPK level was 40,000 U/L, and, on repeat, 6 hours after, peaked to 200,000 U/L with elevation in the liver function tests (aspartate aminotransferase, 1338 U/L; alanine aminotransferase, 356 U/L; lactate dehydrogenase, 3762 U/L). Our patient denied any symptoms with no rigidity or alteration in mental status noted. Vitals signs remained stable. Quetiapine was discontinued, and he was © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Journal of ECT • Volume 31, Number 3, September 2015
transferred back to medicine service later that day. Aggressive fluid treatment was instituted, and his CPK level down-trended to 948 U/L by September 26, 2013. Eventually, he stabilized and was transferred back to psychiatry service. On October 7, 2013 (day 12 from second admission in medicine service), the patient was rechallenged with clozapine. He was started on 12.5 mg of clozapine and was slowly titrated (in 20 days) to a total daily dose of 175 mg of clozapine. Despite slow titration, CPK level monitoring revealed abrupt elevation. The next day, he was noted to be tachycardic at 101 beats per minute and serial CPK level determinations revealed consistent rising values with a level of 300 U/L on October 25, 2013; 8634 U/L on October 27, 2013, with repeat later that day of 21,584 U/L; and 24,905 U/L with repeat of 27,966 U/L (reference range of 21–232 U/L) on October 28, 2013. Urine myoglobin was elevated at 210,000 μg/L (normal value of
Electroconvulsive in a Schizophrenic Patient With Neuroleptic Malignant Syndrome and Rhabdomyolysis Maria Chona P. San Gabriel, MD, Bharathi Eddula-Changala, MD, Yonghong Tan, MD, and Carrol T. Longshore, MD
Abstract: We present the case of a middle-aged man with a chronic history of schizoaffective disorder, depressed type, stable on a secondgeneration antipsychotic. Psychotic symptoms recurred contingent to medication noncompliance necessitating hospitalization. Treatment was complicated by the development of neuroleptic malignant syndrome (NMS). In addition, subsequent medication rechallenges failed because of recurrent rhabdomyolysis and atypical NMS. Electroconvulsive therapy (ECT) treatment was initiated, affording remission of psychotic symptoms and nonrecurrence of NMS and rhabdomyolysis. Our experience confirmed the efficacy of ECT treatment in providing symptom relief of psychosis complicated by recurrent episodes of NMS and atypical NMS. Likewise, it illustrated the efficacy of ECT treatment for rhabdomyolysis. Key Words: electroconvulsive therapy, ECT, neuroleptic malignant syndrome, NMS, rhabdomyolysis, atypical NMS, schizophrenia (J ECT 2015;31: 197–200)
S
ince the advent of the first antipsychotic, chlorpromazine, in 1950, treatment regimens for major psychiatric disorders have improved. In 1988, the treatment armamentarium continued to expand upon the introduction of the second-generation antipsychotics in the market. However, medication adverse effects including neuroleptic malignant syndrome (NMS) became evident. Initially described by Delay et al1 in the 1960s, NMS is an idiosyncratic yet potentially fatal adverse response to antipsychotics. Classically, it is characterized by hyperthermia, severe muscle rigidity, autonomic instability, and mental status changes particularly delirium. However, studies have revealed the predilection of second-generation antipsychotics to present atypically.2 This include clozapine presenting with less rigidity and short induction period with delayed rise in creatine phosphokinase (CPK) levels, risperidone and aripiprazole with lower-grade fever, and aripiprazole being less likely to present with mental status alteration.3 Pathophysiologic mechanisms posit the theory of dopamine dysfunction resulting in abrupt and extensive D2 blockade and hyperactivity of the peripheral sympathetic system.4 Alternative theories include primary skeletal muscle defects, direct toxic effects on the skeletal muscle, as well as molecular and genetic defects.5 According to Trollor et al,2 symptom onset typically occurs within 2 weeks of psychotropic initiation. Proposed risk factors include male sex, preexisting medical and neurologic conditions,
From the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, Elmhurst Hospital Center, Elmhurst, NY. Received for publication May 10, 2014; accepted August 14, 2014. Reprints: Maria Chona P. San Gabriel, MD, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, Elmhurst Hospital Center, 79-01 Broadway, Elmhurst, NY 11373 (e‐mail: [email protected]). The authors have no conflicts of interest or financial disclosures to report. Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/YCT.0000000000000184
extrapyramidal syndromes (EPS), mental retardation, agitation, as well as recent use of restraint. Additional predisposing factors include iron deficiency and medication factors, namely, depot administration and rapid up-titration of medication dosage and environmental factors such as humidity and elevated ambient temperature.6 Although no specific laboratory test or biomarker is predictive of the syndrome, several laboratory abnormalities have been implicated. This includes metabolic acidosis, hypoxia, decreased serum iron concentration,7 as well as elevated catecholamine and CPK levels.8 In 90% of cases, CPK elevation peaks on day 2 of fever onset and subsides on day 12.9 On the basis of the literature, incidence rates range from 0.01% to 0.02%, with the highest incident rate of 3%,10 whereas mortality rate range from 10% to 55%.11 Although declining in occurrence, the potential fatal adverse effect of the illness with varied manifestations warrants a high index of suspicion for prompt diagnosis and timely intervention. The presence of 7 different NMS guidelines with points of disagreement makes diagnosis a challenge. Points of dissimilarity include hyperthermia, presence of EPS, symptom onset, accurate definition of hypertension, and the presence of additional features such as elevated CPK and symptoms of autonomic instability.12 Symptom onset of less than 7 days from treatment initiation is specified by the guideline of Caroff and Mann.13 Hyperthermia is defined as a temperature of 37.5°C or higher by Pope et al,14 Addonizio et al,15 and Levenson.16 Meanwhile, a specified temperature of 38°C or higher is set by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition,8 Caroff and Mann,13 as well as Friedman et al.17 Adityanjee et al,18 on the other hand, defined it as temperature of 39°C or higher. The presence of severe EPS is required by Friedman et al,17 whereas its consideration is suggested by Pope et al.14 Furthermore, emphasis on symptom onset of 7 days or less after medication initiation is indicated in the guideline by Caroff and Mann.13 Whereas blood pressure elevation is defined by Addonizio et al15 (blood pressure, 150/100 mm Hg), others described it as an abnormal or labile blood pressure.9,14,16,18 Meanwhile, Friedman et al17 excluded it from their guideline. Creatine phosphokinase elevation is a major factor for Levenson16 but is supportive for the other guidelines.18,19 Given the unresolved differences and the absence of an objective test or biological marker with the potential fatal adverse effect of the illness, a consensus regarding the diagnostic criteria for NMS using the Delphi technique was developed. On the basis of the consensus, diagnostic criterion for NMS includes exposure to dopamine antagonist or dopamine agonist withdrawal within the past 72 hours; hyperthermia of higher than 100.4°F or higher than 38.0°C on at least 2 occasions (orally measured); rigidity; mental status alteration; creatinine kinase elevation (at least 4 times the upper limit of the normal); sympathetic nervous system lability (blood pressure elevation of ≥25% for either systolic or diastolic blood pressures above baseline or blood pressure fluctuation of ≥20-mm Hg diastolic change or ≥25-mm Hg systolic change within 24 hours), diaphoresis, urinary incontinence; hypermetabolism (heart rate
Journal of ECT • Volume 31, Number 3, September 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.ectjournal.com
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increase of ≥25% above baseline and respiratory rate increase of ≥50% above baseline); and negative workup for infectious, toxic, metabolic, or neurologic causes.20 An equally fatal consequence of antipsychotic use is rhabdomyolysis. This results from sarcolemmal injury leading to muscle enzyme elevation to potential life-threatening complications such as acute renal failure. Because of its varied clinical manifestations, no definite criteria have been set for the diagnosis of rhabdomyolysis. However, CPK elevation of at least 5-fold from the normal limit is a primary diagnostic indicator.21 Other possible etiologies include trauma, alcohol and drug abuse, prolonged immobilization, exercise, as well as exertion.22
CASE REPORT The patient is a 42-year-old Russian man, married with 2 children, employed, and domiciled living with his family. He was diagnosed with chronic schizoaffective disorder, depressed type, stable on olanzapine for the past 10 years. His chief complaint was “I was tired of taking medications for so long.” He was brought in by the emergency medical service after a referral from his psychologist because of insomnia and bizarre behavior contingent to medication noncompliance. At the psychiatric emergency room, he was observed to be emotionally labile, withdrawn, and, at times, internally preoccupied and paranoid. He reported feeling guilty for his perceived actions with poor insight. Subsequently, he was admitted to the inpatient psychiatry service and was restarted on 20 mg of olanzapine at bedtime and 0.5 mg of clonazepam bid. The patient was first diagnosed with mental illness at the age of 26 years with 2 past hospitalizations (ages 26 and 32 years). Upon discharge from his first hospitalization, he was maintained on olanzapine of unrecalled dosage. At the age of 30 years, he was briefly treated with risperidone and benztropine of unknown dosages but was noncompliant. A month after, he was shifted to 5 mg of fluphenazine daily for 10 days and was bridged to fluphenazine decanoate intramuscularly; benztropine continued at 1 mg bid. He remained stable until 2 years later (age, 32 years) when he became noncompliant with treatment because he wanted to have a child. Subsequently, he relapsed and was admitted for 20 days. Retrial with olanzapine (up to a total dose of 10 mg bid) was initiated, but he remained nonresponsive. He was shifted to ziprasidone with dosage titrated up to 80 mg bid and 1 mg of benztropine bid. Upon discharge, he remained stable. For unclear reason, the following year (age, 33 years), the patient was shifted to olanzapine, clonazepam, and citalopram, leading to psychiatric stabilization until his most recent relapse. During the course of his treatment, he underwent other antidepressant trials, namely, amitriptyline (1998) and paroxetine. The extent of his depressive symptoms was unclear, but no history of manic episodes or use of mood stabilizer was documented. During his illness, the patient had episodes of treatment noncompliance, but since the age of 34 years, he has been compliant until the recent admission. He denied any substance history and reported only history of hypertriglyceridemia before admission. He was not maintained on statins or other medication. He denied history of surgery, head trauma, or allergy. Likewise, he had no history of drug reaction, rhabdomyolysis, NMS, catatonia, or serotonin syndrome (SS). Upon admission, laboratory tests, namely, complete blood cell count, basic metabolic panel, erythrocyte sedimentation rate, and thyroid function test were within reference range. The result of urine toxicology was negative, and cranial computed tomographic scan and chest x-ray were not significant. The patient was born and raised in Russia. He was born term, with no complications, and milestones were attained at par with
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age. He claimed to have been raised in a loving and supportive family; he is 1 of 3 siblings. He finished 11th grade and decided to start his career as a barber. In his 20s, he got married, and in 1996, he moved to the United States with his wife for a better future. Currently, he has 2 daughters (17 and 15 years old) and continues to work as a barber. His parents are now residing in Flushing, New York, and his sister is residing in New Jersey, whom he visits intermittently. According to his wife, his brother committed suicide, the detail of which is unknown. It is unclear whether his brother had a psychiatric history. At present, he denied any legal issues. Upon admission, the patient was noted to be uncooperative, affectively labile, and internally preoccupied. He was continued on 20 mg of olanzapine at bedtime and 0.5 mg of clonazepam twice a day (bid) for the next 4 days. During that time, he episodically manifested disorganized and aggressive behaviors that required multiple administrations of oral neuroleptics. On days 5 and 6, his behavior escalated, necessitating administration of additional doses of medications. Cumulative statistics medications administered were 5 mg of haloperidol orally and 15 mg intramuscularly, 2 mg of lorazepam orally and 5 mg intramuscularly, as well as 100 mg of chlorpromazine intramuscularly. Likewise, a mechanical 5-point restraint was needed 4 times for a total duration of 5 hours. Review of medication revealed the following medication regimen: 20 mg of olanzapine daily, 1 mg of clonazepam three times a day, and 500 mg of valproic acid at bedtime. Over the ensuing hours, he was noted to be tachycardic (heart rate of 107 beats per minute) and febrile (temperature of 38.3°C) with rigidity. Laboratory tests revealed leukocytosis of 14.7 K/mcL (white blood cell reference range of 4.5–11.0 K/mcL) and CPK elevation up to 19,792 U/L (reference range of 21–232 U/L) with normal renal function (creatinine of 0.9 mg/dL; reference range of 0.4–1.6 mg/dL). Because of the suspicion for NMS, medications were discontinued. Later that day, his fever subsided, but he remained to be tachycardic (heart rate of 120 beats per minute) with persistent CPK elevation (27,847 U/L). Complete blood cell count, creatinine level, and liver profile were within normal levels. He was transferred to medicine service for possible NMS versus SS. He remained off antipsychotics and was only given lorazepam for intermittent episodes of aggressiveness. Aggressive intravenous hydration and monitoring of laboratory tests were done, which revealed down-trending CPK levels. He also had elevated liver profile (aspartate aminotransferase of 386 U/L with reference range of 5–40 U/L; alanine aminotransferase of 131 U/L with reference range of 5–50 U/L; lactate dehydrogenase of 1370 U/L with reference range of 90–225 U/L) that eventually trended down to normal. The patient continued to respond to supportive care and aggressive hydration, and on day 11, he was deemed medically stable and was transferred back to psychiatry service. He was given a final diagnosis of NMS with CPK level down to 553 U/L. Upon readmission to psychiatry service, the patient was noted to be calm and cooperative but with minimized symptoms. He denied any psychotic symptoms but was noted to be internally preoccupied. Likewise, he denied suicidal or homicidal ideations. The following day, he was started on 50 mg of quetiapine daily and was slowly up-titrated to 100 mg of quetiapine daily for the next 3 days. Eventually, he reported anxiety symptoms and was given lorazepam. On day 16 (September 16, 2013), his CPK level was 40,000 U/L, and, on repeat, 6 hours after, peaked to 200,000 U/L with elevation in the liver function tests (aspartate aminotransferase, 1338 U/L; alanine aminotransferase, 356 U/L; lactate dehydrogenase, 3762 U/L). Our patient denied any symptoms with no rigidity or alteration in mental status noted. Vitals signs remained stable. Quetiapine was discontinued, and he was © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Journal of ECT • Volume 31, Number 3, September 2015
transferred back to medicine service later that day. Aggressive fluid treatment was instituted, and his CPK level down-trended to 948 U/L by September 26, 2013. Eventually, he stabilized and was transferred back to psychiatry service. On October 7, 2013 (day 12 from second admission in medicine service), the patient was rechallenged with clozapine. He was started on 12.5 mg of clozapine and was slowly titrated (in 20 days) to a total daily dose of 175 mg of clozapine. Despite slow titration, CPK level monitoring revealed abrupt elevation. The next day, he was noted to be tachycardic at 101 beats per minute and serial CPK level determinations revealed consistent rising values with a level of 300 U/L on October 25, 2013; 8634 U/L on October 27, 2013, with repeat later that day of 21,584 U/L; and 24,905 U/L with repeat of 27,966 U/L (reference range of 21–232 U/L) on October 28, 2013. Urine myoglobin was elevated at 210,000 μg/L (normal value of
