295
ANZJP Correspondence
Late onset myocarditis with clozapine use Lip Hong Tan1, Shuichi Suetani2,3, Scott Clark2,3 and Douglas Wilson3 1University
of Adelaide, Adelaide, Australia of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia 3Central Adelaide Local Health Network, Western Community Mental Health Centre, Adelaide, Australia 2Discipline
Corresponding author: Shuichi Suetani, University of Adelaide, Registrar, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville, SA 5011, Australia. Email: [email protected] DOI: 10.1177/0004867414557162
To the Editor Myocarditis is a serious complication of clozapine therapy with a reported incidence between 0.7% to 1.2% (Layland et al., 2009). The majority of cases occur within two months of commencement (Layland et al., 2009) with occasional reports after long-term therapy (Lang et al., 2008). The exact mechanism underlying clozapine-related myocarditis is unknown. Hypotheses include: IgEmediated hypersensitivity, increased plasma catecholamine, cytochrome P450 1A2 enzyme deficiency, blockade of calcium-dependent ion channels, increased production of inflammatory cytokines, and low serum selenium levels (Layland et al., 2009).
Towards more rational prescribing of antidementia drugs Kevin T Ong1, Shirantha G Adikari1 and Edward Strivens1,2 1Older
Persons, Sub-Acute and Rehabilitation Services, Cairns and Hinterland Hospital and Health Service, Cairns, Australia 2James Cook University School of Medicine and Dentistry, James Cook University, Townsville, Australia
We report two cases of myocarditis after long-term clozapine therapy identified during routine monitoring. Mr R, a 62-year-old male nursing home resident, was treated with clozapine (500mg/day) from 1997 for schizophrenia. He has a background of diabetes, hyperlipidaemia and peripheral vascular disease. He presented with lethargy, temperature of 38.3º C, CRP 200mg/L and troponin T 276ng/L. Serial ECG showed T wave inversion with variable broadening of QRS complex. His echocardiogram revealed moderate systolic dysfunction and ejection fraction of 33% with global hypokinesis. A diagnosis of clozapineinduced myocarditis was made after excluding alternative aetiologies. Clozapine was ceased and he was commenced on olanzapine 5mg. He made good clinical recovery and was discharged two weeks later but died seven weeks later due to renal failure. Mr S, a 52-year-old male with a 24-year history of schizophrenia was treated on 500mg/day of clozapine since 2009. His clozapine levels ranged from 146-910µg/L suggesting longterm partial compliance. His medical history includes hyperlipidaemia and diabetes. He presented with a twoweek history of exertional dyspnoea without chest pain. ECG showed new onset atrial flutter 2:1 with sinus tachycardia, troponin T 294ng/L, CRP 25mg/L. Echocardiogram revealed systolic dysfunction with an ejection fraction of 35% and global hypokinesis. He was diagnosed with myocarditis secondary to clozapine. Clozapine was ceased, and olanzapine 10mg was
initiated. He was discharged home one week later following clinical recovery. His cardiac condition remains stable four months after discharge. These cases meet the criteria for clozapine-related myocarditis but occur outside the initial high-risk period following commencement (Ronaldson et al., 2010) suggesting the need for ongoing clinical vigilance for symptoms suggestive of myocarditis for the duration of clozapine treatment. Suspicion should lead to prompt investigation with troponin T, CRP and ECG to facilitate early identification and treatment of myocarditis.
Corresponding author: Kevin T Ong, Older Persons, Sub-Acute and Rehabilitation Services, Cairns and Hinterland Hospital and Health Service, Cairns, QLD 4870, Australia. Email: [email protected]
nine months. He had anomia of familiar people, word finding difficulties, and lacked motivation to keep in touch with his children. Although more lethargic, he was still independent with all activities of daily living. There were no concerns with his driving, nutrition, continence, mobility, or mood. He scored 27/30 in the mini-mental state examination (MMSE), and 9/18 in the frontal assessment battery (FAB). Physical examination revealed bilateral
DOI: 10.1177/0004867414557681
To the Editor A 69 year old man presented to our regional memory clinic with gradual decline in short term memory over
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Declaration of interest In the last year DW has given talks for Pfizer, Astra Zeneca and Eli-Lilly. Previously DW has given talks for JanssenCilag, Bristol-Myer-Squib, Sanofi, Novartis, Lunbeck, Wyeth and Boehringer.
References Lang UE, Willbring M, Von Golitschek R, et al. (2008) Clozapine-induced myocarditis after long term treatment: case presentation and clinical perspectives. Journal of Psychopharmacology 22: 576–580. Layland JL, Liew D and Prior DL (2009) Clozapineinduced cardiotoxicity: a clinical update. Medical Journal of Australia. 190: 190–192. Ronaldson KJ, Taylor AJ, Fitzgerald PB, et al. (2010) Diagnostic characteristics of clozapineinduced myocarditis identified by an analysis of 38 cases and 47 controls. Journal of Clinical Psychiatry 71: 976–981.
Australian & New Zealand Journal of Psychiatry, 49(3)
Downloaded from anp.sagepub.com at PURDUE UNIV LIBRARY TSS on May 19, 2015
296
ANZJP Correspondence
palmomental reflexes, more significant decline in encoding than retrieval, and paucity of speech which was almost stuttering. The rest of his examination and routine bloods work-up were unremarkable. His CT brain showed frontal atrophy only. Upon his request and consent, 5mg rivastigmine patch daily was trialled for three weeks. At three weeks he reported increased frequency in bowel habits and urination, but cognition and function did not improve at all. Given the predominant frontal features and poor response to rivastigmine, there was a high index of suspicion of underlying frontotemporal dementia (FTD). Although there are conflicting reports about memantine use in FTD, and memantine is only approved for moderate to severe Alzheimer’s disease (AD), he was more alert and assertive after trialling memantine, which pleased him and his wife. Repeat MMSE and FAB scores improved to 28/30 and 14/18 respectively. Memantine has been shown to increase metabolism in the salience network in FTD (Chow et al., 2011), a network associated with
social emotional function and hypometabolism in FTD. There is consensus that early diagnosis and management of dementia improve quality of life, which delays residential care placement, and so is very cost effective. Anti-dementia drugs (ADD) like acteylcholinesterase inhibitors (AChEI) and memantine are not disease modifying therapies, but they do improve quality of life in some AD cases. AChEI also has benefit in Lewy body dementia sufferers (McKeith et al., 2005). However subsidies for ADD use in Australia are approved only in AD sufferers, based on MMSE cut-off scores. Dementia neuropathologies may have different local and distant topographical effects cerebrally (La Joie et al., 2012). Hence cognitive screening cut-off scores, which have not been validated by gold standard histopathological diagnoses, are less important than deficit patterns on scores in determining underlying neuropathology, which may better guide management, like in this patient. Finally initial prescriptions of ADD
could be worth considering when potential benefits might outweigh the risk, even if off label or an out of pocket fee applies.
Understanding the interplay between motivation and social cognition performance in schizophrenia Urvakhsh Meherwan Mehta1,2, Haralahalli D Bhagyavathi1 and Jagadisha Thirthalli1
To the Editor
(processing speed, verbal/visual learning and memory, planning, and cognitive flexibility), symptoms (Positive and Negative Syndrome Scale), and motivation (motivation item, Quality of Life Scale). Global SC and neurocognitive scores were computed as averages of the z-scores corresponding to each subdomain. We observed significant direct correlations between motivation, and global SC (r=0.448, p
ANZJP Correspondence
Late onset myocarditis with clozapine use Lip Hong Tan1, Shuichi Suetani2,3, Scott Clark2,3 and Douglas Wilson3 1University
of Adelaide, Adelaide, Australia of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia 3Central Adelaide Local Health Network, Western Community Mental Health Centre, Adelaide, Australia 2Discipline
Corresponding author: Shuichi Suetani, University of Adelaide, Registrar, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville, SA 5011, Australia. Email: [email protected] DOI: 10.1177/0004867414557162
To the Editor Myocarditis is a serious complication of clozapine therapy with a reported incidence between 0.7% to 1.2% (Layland et al., 2009). The majority of cases occur within two months of commencement (Layland et al., 2009) with occasional reports after long-term therapy (Lang et al., 2008). The exact mechanism underlying clozapine-related myocarditis is unknown. Hypotheses include: IgEmediated hypersensitivity, increased plasma catecholamine, cytochrome P450 1A2 enzyme deficiency, blockade of calcium-dependent ion channels, increased production of inflammatory cytokines, and low serum selenium levels (Layland et al., 2009).
Towards more rational prescribing of antidementia drugs Kevin T Ong1, Shirantha G Adikari1 and Edward Strivens1,2 1Older
Persons, Sub-Acute and Rehabilitation Services, Cairns and Hinterland Hospital and Health Service, Cairns, Australia 2James Cook University School of Medicine and Dentistry, James Cook University, Townsville, Australia
We report two cases of myocarditis after long-term clozapine therapy identified during routine monitoring. Mr R, a 62-year-old male nursing home resident, was treated with clozapine (500mg/day) from 1997 for schizophrenia. He has a background of diabetes, hyperlipidaemia and peripheral vascular disease. He presented with lethargy, temperature of 38.3º C, CRP 200mg/L and troponin T 276ng/L. Serial ECG showed T wave inversion with variable broadening of QRS complex. His echocardiogram revealed moderate systolic dysfunction and ejection fraction of 33% with global hypokinesis. A diagnosis of clozapineinduced myocarditis was made after excluding alternative aetiologies. Clozapine was ceased and he was commenced on olanzapine 5mg. He made good clinical recovery and was discharged two weeks later but died seven weeks later due to renal failure. Mr S, a 52-year-old male with a 24-year history of schizophrenia was treated on 500mg/day of clozapine since 2009. His clozapine levels ranged from 146-910µg/L suggesting longterm partial compliance. His medical history includes hyperlipidaemia and diabetes. He presented with a twoweek history of exertional dyspnoea without chest pain. ECG showed new onset atrial flutter 2:1 with sinus tachycardia, troponin T 294ng/L, CRP 25mg/L. Echocardiogram revealed systolic dysfunction with an ejection fraction of 35% and global hypokinesis. He was diagnosed with myocarditis secondary to clozapine. Clozapine was ceased, and olanzapine 10mg was
initiated. He was discharged home one week later following clinical recovery. His cardiac condition remains stable four months after discharge. These cases meet the criteria for clozapine-related myocarditis but occur outside the initial high-risk period following commencement (Ronaldson et al., 2010) suggesting the need for ongoing clinical vigilance for symptoms suggestive of myocarditis for the duration of clozapine treatment. Suspicion should lead to prompt investigation with troponin T, CRP and ECG to facilitate early identification and treatment of myocarditis.
Corresponding author: Kevin T Ong, Older Persons, Sub-Acute and Rehabilitation Services, Cairns and Hinterland Hospital and Health Service, Cairns, QLD 4870, Australia. Email: [email protected]
nine months. He had anomia of familiar people, word finding difficulties, and lacked motivation to keep in touch with his children. Although more lethargic, he was still independent with all activities of daily living. There were no concerns with his driving, nutrition, continence, mobility, or mood. He scored 27/30 in the mini-mental state examination (MMSE), and 9/18 in the frontal assessment battery (FAB). Physical examination revealed bilateral
DOI: 10.1177/0004867414557681
To the Editor A 69 year old man presented to our regional memory clinic with gradual decline in short term memory over
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Declaration of interest In the last year DW has given talks for Pfizer, Astra Zeneca and Eli-Lilly. Previously DW has given talks for JanssenCilag, Bristol-Myer-Squib, Sanofi, Novartis, Lunbeck, Wyeth and Boehringer.
References Lang UE, Willbring M, Von Golitschek R, et al. (2008) Clozapine-induced myocarditis after long term treatment: case presentation and clinical perspectives. Journal of Psychopharmacology 22: 576–580. Layland JL, Liew D and Prior DL (2009) Clozapineinduced cardiotoxicity: a clinical update. Medical Journal of Australia. 190: 190–192. Ronaldson KJ, Taylor AJ, Fitzgerald PB, et al. (2010) Diagnostic characteristics of clozapineinduced myocarditis identified by an analysis of 38 cases and 47 controls. Journal of Clinical Psychiatry 71: 976–981.
Australian & New Zealand Journal of Psychiatry, 49(3)
Downloaded from anp.sagepub.com at PURDUE UNIV LIBRARY TSS on May 19, 2015
296
ANZJP Correspondence
palmomental reflexes, more significant decline in encoding than retrieval, and paucity of speech which was almost stuttering. The rest of his examination and routine bloods work-up were unremarkable. His CT brain showed frontal atrophy only. Upon his request and consent, 5mg rivastigmine patch daily was trialled for three weeks. At three weeks he reported increased frequency in bowel habits and urination, but cognition and function did not improve at all. Given the predominant frontal features and poor response to rivastigmine, there was a high index of suspicion of underlying frontotemporal dementia (FTD). Although there are conflicting reports about memantine use in FTD, and memantine is only approved for moderate to severe Alzheimer’s disease (AD), he was more alert and assertive after trialling memantine, which pleased him and his wife. Repeat MMSE and FAB scores improved to 28/30 and 14/18 respectively. Memantine has been shown to increase metabolism in the salience network in FTD (Chow et al., 2011), a network associated with
social emotional function and hypometabolism in FTD. There is consensus that early diagnosis and management of dementia improve quality of life, which delays residential care placement, and so is very cost effective. Anti-dementia drugs (ADD) like acteylcholinesterase inhibitors (AChEI) and memantine are not disease modifying therapies, but they do improve quality of life in some AD cases. AChEI also has benefit in Lewy body dementia sufferers (McKeith et al., 2005). However subsidies for ADD use in Australia are approved only in AD sufferers, based on MMSE cut-off scores. Dementia neuropathologies may have different local and distant topographical effects cerebrally (La Joie et al., 2012). Hence cognitive screening cut-off scores, which have not been validated by gold standard histopathological diagnoses, are less important than deficit patterns on scores in determining underlying neuropathology, which may better guide management, like in this patient. Finally initial prescriptions of ADD
could be worth considering when potential benefits might outweigh the risk, even if off label or an out of pocket fee applies.
Understanding the interplay between motivation and social cognition performance in schizophrenia Urvakhsh Meherwan Mehta1,2, Haralahalli D Bhagyavathi1 and Jagadisha Thirthalli1
To the Editor
(processing speed, verbal/visual learning and memory, planning, and cognitive flexibility), symptoms (Positive and Negative Syndrome Scale), and motivation (motivation item, Quality of Life Scale). Global SC and neurocognitive scores were computed as averages of the z-scores corresponding to each subdomain. We observed significant direct correlations between motivation, and global SC (r=0.448, p
