Olanzapine overdose presenting with acute muscle toxicity

Keyal, Niraj Kumar; Shrestha, Gentle Sunder; Pradhan, Saurabh; Maharjan, Ramesh Kumar; Acharya, Subhash Prasad; Marhatta, Moda Nath

doi:10.4103/2229-5151.201962

Cited by 9 publications

(4 citation statements)

References 7 publications

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“…Interestingly, the muscle transcript data from this study further suggested a transition from slow muscle fibers to fast-glycolytic fibers that are more susceptible to atrophy. Accordingly, acute muscle toxicity has been reported following high-dose OLZ administration in humans (Keyal et al, 2017; Waring et al, 2006). These data highlight excessive adipose accretion and muscle impairment as important metabolic abnormalities associated with OLZ use, even in the absence of weight gain.…”

Section: Discussionmentioning

confidence: 99%

Samidorphan mitigates olanzapine-induced weight gain and metabolic dysfunction in rats and non-human primates

et al. 2019

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Background: Olanzapine, regarded as one of the most efficacious antipsychotic medications for the treatment of schizophrenia, is associated with a high risk of weight gain and metabolic dysfunction. ALKS 3831, a clinical candidate for treatment of schizophrenia, is a combination of olanzapine and samidorphan, an opioid receptor antagonist. The addition of samidorphan is intended to mitigate weight gain and the metabolic dysregulation associated with the use of olanzapine. Methods: Non-clinical studies were conducted to assess the metabolic effects of olanzapine and samidorphan alone and in combination at clinically relevant exposure levels. Results: Chronic olanzapine administration in male and female rats shifted body composition by increasing adipose mass, which was accompanied by an increase in the rate of weight gain in female rats. Co-administration of samidorphan normalized body composition in both sexes and attenuated weight gain in female rats. In hyperinsulinemic euglycemic clamp experiments conducted prior to measurable changes in weight and/or body composition, olanzapine decreased hepatic insulin sensitivity and glucose uptake in muscle while increasing uptake in adipose tissue. Samidorphan appeared to normalize glucose utilization in both tissues, but did not restore hepatic insulin sensitivity. In subsequent studies, samidorphan normalized olanzapine-induced decreases in whole-body glucose clearance following bolus insulin administration. Results from experiments in female monkeys paralleled the effects in rats. Conclusions: Olanzapine administration increased weight gain and adiposity, both of which were attenuated by samidorphan. Furthermore, the combination of olanzapine and samidorphan prevented olanzapine-induced insulin insensitivity. Collectively, these data indicate that samidorphan mitigates several metabolic abnormalities associated with olanzapine in both the presence and the absence of weight gain.

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Section: Discussionmentioning

confidence: 99%

Samidorphan mitigates olanzapine-induced weight gain and metabolic dysfunction in rats and non-human primates

et al. 2019

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“…Muscle (*) -Olanzapine Brain stem (Anwar et al, 2016) Acute muscle toxicity (Keyal et al, 2017) Pancreatitis (Kerr et al, 2007) Repatha (Evolocumab) -Muscle-related statin Intolerance (Nissen et al, 2016) -Risedronate (actonel) Ocular myasthenia (Raja et al, 2007) Muscle weakness (Badayan and Cudkowicz, 2009) Gastrointestinal cancer (Vinogradova et al, 2013) Sofosbuvir Ocular surface (Salman, 2016) Myositis (Patel et al, 2015) Pancreatitis (Margapuri and Jubbal, 2019) Teriparatide -Muscle cramp (Kakaria et al, 2005) Pancreatitis (*) *Reported side effects.…”

Section: Cisplatinmentioning

confidence: 99%

Universal Nature of Drug Treatment Responses in Drug-Tissue-Wide Model-Animal Experiments Using Tensor Decomposition-Based Unsupervised Feature Extraction

Taguchi

Turki

2020

Front. Genet.

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Gene expression profiles of tissues treated with drugs have recently been used to infer clinical outcomes. Although this method is often successful from the application point of view, gene expression altered by drugs is rarely analyzed in detail, because of the extremely large number of genes involved. Here, we applied tensor decomposition (TD)-based unsupervised feature extraction (FE) to the gene expression profiles of 24 mouse tissues treated with 15 drugs. TD-based unsupervised FE enabled identification of the common effects of 15 drugs including an interesting universal feature: these drugs affect genes in a gene-group-wide manner and were dependent on three tissue types (neuronal, muscular, and gastroenterological). For each tissue group, TD-based unsupervised FE enabled identification of a few tens to a few hundreds of genes affected by the drug treatment. These genes are distinctly expressed between drug treatments and controls as well as between tissues in individual tissue groups and other tissues. We also validated the assignment of genes to individual tissue groups using multiple enrichment analyses. We conclude that TD-based unsupervised FE is a promising method for integrated analysis of gene expression profiles from multiple tissues treated with multiple drugs in a completely unsupervised manner.

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“…Olanzapine is an antipsychotic drug, classified within the atypical antipsychotics. The psychiatrists use olanzapine to manage schizophrenia (especially the negative symptoms) ( 9 ) and bipolar disorder ( 10 ). Side effects include extrapyramidal and anticholinergic symptoms ( 9 , 11 ), weight gain, hypertriglyceridemia, hypercholesterolemia, hyperglycemia in patients with diabetes mellitus, galactorrhea, amenorrhea, gynecomastia, erectile dysfunction, neutropenia, seizure threshold lowering, personality changes and suicidality ( 10 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

“…The psychiatrists use olanzapine to manage schizophrenia (especially the negative symptoms) ( 9 ) and bipolar disorder ( 10 ). Side effects include extrapyramidal and anticholinergic symptoms ( 9 , 11 ), weight gain, hypertriglyceridemia, hypercholesterolemia, hyperglycemia in patients with diabetes mellitus, galactorrhea, amenorrhea, gynecomastia, erectile dysfunction, neutropenia, seizure threshold lowering, personality changes and suicidality ( 10 , 12 ). In case of overdose, patients may suffer from tachycardia, agitation, hyperpyrexia, leukocytosis, elevated creatine phosphokinase levels, paradoxical miosis mimicking opioid or α2-agonist intoxication ( 13 ), dysarthria, low level of consciousness, dry mouth, ataxia and coma.…”

Section: Introductionmentioning

confidence: 99%

Patient Survival After Acute Voluntary Poisoning With a Huge Dose of Oxcarbazepine and Olanzapine

et al. 2018

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Introduction:Oxcarbazepine is a carbamazepine pre-drug with less drug interactions. Its adverse effects, including hyponatremia, somnolence and ataxia, are dose dependent. Olanzapine is an atypical antipsychotic drug most commonly used to manage psychoses and symptoms of irritability and aggressive behavior. Main side effects include extrapyramidal and anticholinergic symptoms, weight gain, and hyperglycemia.Case Report:In this manuscript a case of oxcarbazepine and olanzapine intoxication is discussed. A 45-year-old woman, previously diagnosed with bipolar disorder and chronic alcoholism, was presented two hours after ingestion of 30,000mg of oxcarbazepine and 140 mg of olanzapine, combined with alcohol. She was immediately treated with gastric lavage and administration of activated charcoal. During her hospitalization she was hemodynamically and respiratory stable with no neurological signs and symptoms except for somnolence. Another side effect was hyponatremia. She was discharged from our department in stable clinical condition after being evaluated by a psychiatrist.Conclusion:Early approach is crucial for the management of drug intoxication. Late symptoms can be avoided through close monitoring of vital signs, mental status and laboratory values. Psychiatric consultation is essential for a better long-term outcome.

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Olanzapine overdose presenting with acute muscle toxicity

Cited by 9 publications

References 7 publications

Samidorphan mitigates olanzapine-induced weight gain and metabolic dysfunction in rats and non-human primates

Samidorphan mitigates olanzapine-induced weight gain and metabolic dysfunction in rats and non-human primates

Universal Nature of Drug Treatment Responses in Drug-Tissue-Wide Model-Animal Experiments Using Tensor Decomposition-Based Unsupervised Feature Extraction

Patient Survival After Acute Voluntary Poisoning With a Huge Dose of Oxcarbazepine and Olanzapine

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