Massive serum creatine kinase increases with atypical antipsychotic drugs: what is the mechanism and the message?

Meltzer, Herbert Y.

doi:10.1007/s002130000465

Cited by 59 publications

(34 citation statements)

References 18 publications

(16 reference statements)

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“…Neuroleptics can induce a myopathy with high levels of CK that is different of the neuroleptic malignant syndrome 13 . Serum CK levels may increase in as many as 10% of patients treated with atypical antipsychotic drugs 14 . Blockade of the serotonin 5-HT receptors on the sarcolemma is probably behind this type of TM 14 .…”

Section: Cresyl Violetmentioning

confidence: 99%

“…Serum CK levels may increase in as many as 10% of patients treated with atypical antipsychotic drugs 14 . Blockade of the serotonin 5-HT receptors on the sarcolemma is probably behind this type of TM 14 . Drug-induced hypokalemia may produce a reversible vacuolar myopathy, generally as a consequence of prolonged potassium serum levels below 2 mmol/L 15 .…”

Section: Cresyl Violetmentioning

confidence: 99%

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Toxic myopathies: muscle biopsy features

Scola

Pereira

Lorenzoni

et al. 2007

Arq. Neuro-Psiquiatr.

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-Several drugs and toxic substances can cause muscular abnormalities and are frequent causes of acquired myopathies. We present a series of 32 patients, predominance of young adult patients, diagnosed with toxic myopathy. The most common substances inducing myopathy were corticosteroids (56.2%) followed by the propoxyphene, neuroleptics, zidovudine and drug-induced hypokalemia. The investigation showed normal serum creatine kinase levels in 65.4%, myopathic pattern of the needle electromyography in 40% and the more frequent histological diagnosis of the muscle biopsy was type 2 fiber atrophy (59.3%). Clinical features, etiology, course of the disease, serum levels of muscular enzymes, electromyographic features and, especially, muscle biopsy features are discussed.KEY WORDS: myopathy, drug, iatrogenic myopathy, toxic myopathy, muscle biopsy.Miopatia tóxica: biópsia muscular RESUMO -Diversos medicamentos e substâncias tóxicas podem causar alterações musculares e são causas freqüentes de miopatia adquirida. Apresentamos uma série de 32 pacientes, predomínio de pacientes adulto jovens, com miopatia tóxica. As substâncias mais relacionadas com a miopatia foram os corticosteróides (56,2%) seguidos pelo propoxifeno, neurolépticos, zidovudina e drogas indutoras de hipocalemia. A investigação mostrou níveis normais de creatino quinase sérica em 65,4%, eletromiografia de agulha com padrão miopático em 40% e o mais freqüente diagnóstico histológico da biópsia muscular foi atrofia de fibras do tipo 2 (59,3%). As manifestações clínicas, etiologia, tempo de evolução, nível sérico das enzimas musculares, alterações da eletroneuromiografia e, especialmente, da biópsia muscular são discutidos. PALAVRAS-CHAVE: miopatias, drogas, miopatia iatrogênica, miopatia tóxica, biópsia muscular.

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Section: Cresyl Violetmentioning

confidence: 99%

Section: Cresyl Violetmentioning

confidence: 99%

Toxic myopathies: muscle biopsy features

Scola

Pereira

Lorenzoni

et al. 2007

Arq. Neuro-Psiquiatr.

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“…A few case reports describe an increase in serum creatine kinase [28,29,30] during treatment with typical neuroleptics or atypical antipsychotics and hence suggest a drug-related adverse effect on skeletal muscle that is probably more complex than mere interference with glucose transporters (i.e. temporary change of cell membrane permeability).…”

Section: Introductionmentioning

confidence: 99%

“…temporary change of cell membrane permeability). For example, there may be a relation between antagonism at the serotoninergic receptor 5-HT 2A and influence on muscle fiber function [29]. We decided to extend our study to include the effects of clozapine compared to haloperidol, which has a quite different receptor binding profile, on differentiated myotubes.…”

Section: Introductionmentioning

confidence: 99%

Clozapine-Induced Alteration of Glucose Homeostasis in the Rat: The Contribution of Hypothalamic-Pituitary-Adrenal Axis Activation

et al. 2007

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Background/Aims: To our knowledge, a suitable animal model to investigate how atypical antipsychotics may induce diabetes in patients has not received much attention. Methods: We investigated the effects of acute as well as subchronic administration of clozapine on food intake, body weight gain, glucose tolerance and insulin secretion in response to glucose in Sprague-Dawley rats. We then evaluated the effects of clozapine on corticosterone secretion and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and phosphoenolpyruvate carboxykinase (PEPCK) expression in the liver. We investigated the in vitro effects of clozapine on glucose uptake and development of differentiated myotubes in skeletal muscle cell (C2C12) cultures. Results: Clozapine administration caused hyperglycemia (p < 0.05) in female rats. In male rats, the increase of plasma glucose levels after clozapine injection was not statistically significant. The increase of plasma insulin concentrations and the intraperitoneal glucose tolerance test results proved that clozapine reduced insulin sensitivity in female rats. These endocrine and metabolic effects of clozapine were not related to changes in feeding behavior of fat accumulation. We observed a stimulatory effect of clozapine on corticosterone (p < 0.01) secretion in both female and male rats. Chronic clozapine administration upregulated PEPCK and 11β-HSD-1 expression in rat liver. Clozapine did not inhibit basal and insulin-induced glucose transport in murine myotubes but it was able to antagonize the stimulatory effect of α-methyl-5-hydroxytryptamine on glucose uptake. Conclusion: Clozapine induces sex-related alterations of glucose homeostasis and insulin sensitivity in rodents. We discussed the possible contribution of clozapine-induced activation of HPA and clozapine antagonistic activity at peripheral 5-HT_2A receptors to the observed metabolic alterations.

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“…(5) In conclusion, even in patients receiving long-term olanzapine treatment, the possibility of delayed-onset rhabdomyolysis should be considered. If clinical manifestations such as muscle weakness, fever or alternations in consciousness occur, monitoring of serum CK is required.…”

Section: E T T E R T O T H E E D I T O R 279mentioning

confidence: 98%

Delayed-onset rhabdomyolysis related to olanzapine: a case report

Lee

Mao

Tai

et al. 2016

smedj

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L e t t e r t o t h e E d i t o r 279Dear Sir, Olanzapine is a widely used, atypical antipsychotic. Few reports on the association between regular dosage of olanzapine and rhabdomyolysis have been published to date. The present case report draws attention to delayed-onset rhabdomyolysis, a rare adverse effect of olanzapine therapy, and discusses its possible mechanisms.The patient, a 62-year-old man, had a history of chronic schizophrenia, with his first episode of auditory hallucination and persecutory delusion occurring at 25 years of age. Between the ages of 30 and 60 years, the patient was repeatedly hospitalised due to psychotic exacerbations. About two years prior to the current presentation, he was receiving rehabilitation in a halfway house and treated with olanzapine 10 mg/day, valproate 500 mg/day, estazolam 2 mg/day and benzhexol hydrochloride 2 mg/day.The patient was sent to our emergency department when he could not get up from the floor due to generalised weakness and paralysis. On presentation, he was conscious, and had decreased muscle power but no extrapyramidal symptoms. His creatine kinase (CK) level was high (13,046 U/L), but troponin, heart type creatine kinase isoenzyme, blood urea nitrogen, creatinine, complete blood count, electrolytes, C-reactive protein and glucose levels were all normal. Rhabdomyolysis was diagnosed.On suspicion of its contribution to rhabdomyolysis, olanzapine was stopped. Following hydration, the patient's CK level fell to 11,407 U/L three days later and he was discharged back to the rehabilitation facility on the fifth day. At the one-month outpatient follow-up, his CK level was within normal limits.The patient had no evidence of seizure on clinical presentation. He also did not have fever or muscle rigidity, making neuroleptic malignant syndrome unlikely. The causal relationship suggesting that olanzapine was the probable cause of rhabdomyolysis was supported by a score of 5 in the Naranjo Adverse Drug Reaction Probability Scale.(1) There have been previous case reports of olanzapineinduced elevation of serum CK level occurring within seven weeks of administration.(2,3) In our case, olanzapine 10 mg/day was administered for nearly two years without dose titration, which could have led to delayed-onset, olanzapine-related rhabdomyolysis. However, the combined effects of polypharmacy might also be a contributory factor, since olanzapine was used concomitantly with other medications like valproate, estazolam and benzhexol hydrochloride. The patient might have been vulnerable to some incipient muscle changes related to the use of olanzapine or the combination of medications over the two years, prior to the occurrence of drug-induced rhabdomyolysis.Although unclear, the mechanism of olanzapine-related rhabdomyolysis might be drug-related myopathy. Olanzapine is an atypical antipsychotic with a high affinity for histamine-H1, 5-hydroxytryptamine 2A (5-HT2A) and dopamine D2. H1-receptor antihistamines, acting on the sarcolemma, may facilitate sodium flux into the cells, t...

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Massive serum creatine kinase increases with atypical antipsychotic drugs: what is the mechanism and the message?

Cited by 59 publications

References 18 publications

Toxic myopathies: muscle biopsy features

Toxic myopathies: muscle biopsy features

Clozapine-Induced Alteration of Glucose Homeostasis in the Rat: The Contribution of Hypothalamic-Pituitary-Adrenal Axis Activation

Delayed-onset rhabdomyolysis related to olanzapine: a case report

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