quetiapine-fumarate and Cardiomyopathies

We describe a case of cardiomyopathy due to quetiapine. Atypical antipsychotics are known for their multiple and sometimes dangerous side effects. Various studies showed increased sudden cardiac death and sudden unexpected deaths. Quetiapine can cause tachycardia and QT prolongation, alongside a broad list of other side effects. Cardiomyopathy has been reported, but a causative relation was doubted. We report a case of a 37-year-old woman developing a cardiomyopathy under high doses of quetiapine. Symptoms and ultrasound signs largely recovered in the course of the next months after quetiapine was stopped.

Topics: Adult; Antipsychotic Agents; Cardiomyopathies; Female; Humans; Quetiapine Fumarate

Atypical antipsychotic medications (second-generation antipsychotics) have been increasingly used in the treatment of a number of psychotic disorders since their introduction in 1988, with the newest medication introduced in 2002. Justification for their use includes claims of equal or improved antipsychotic activity over first-generation antipsychotics, increased tolerability, and decreased side effects. However, there are still significant adverse effects and toxicities with this class of medications. Toxicologic exposures and fatalities associated with atypical antipsychotics continue to increase in the United States, with 32,422 exposures and 72 deaths in 2003. There have also been Food and Drug Administration warnings in the past year about how some atypical antipsychotics have been marketed to minimize the potentially fatal risks and claiming superior safety to other atypical antipsychotics without adequate substantiation, indicating the toxicologic potential of these agents may be underestimated.. Continued research to evaluate adverse effects and tolerability of atypical antipsychotics compared with first-generation antipsychotics and each other is reviewed. This article also reviews the pharmacodynamics, pharmacokinetics, and drug interactions with these medications. New therapeutic monitoring recommendations for this class of medications have also been proposed. Finally, clinical toxicity in overdose and management are reviewed.. While new atypical antipsychotic medications may have a safer therapeutic and overdose profile than first-generation antipsychotic medications, many adverse and toxic effects still need to be considered in therapeutic monitoring and overdose management.

Topics: Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Cardiomyopathies; Child; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Drug Interactions; Drug Overdose; Dry Eye Syndromes; Humans; Hyperlipidemias; Hypotension; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Seizures; Thiazoles

Quetiapine is a common atypical antipsychotic used to treat mental disorders such as schizophrenia, bipolar disorder, and major depressive disorder. There has been increasing number of reports describing its cardiotoxicity. However, the molecular mechanisms underlying quetiapine-induced myocardial injury remain largely unknown. Herein, we reported a novel cell death type, quetiapine-induced necroptosis, which accounted for quetiapine cardiotoxicity in mice and proposed novel therapeutic strategies. Quetiapine-treated hearts showed inflammatory infiltration and evident fibrosis after 21-day continuous injection. The specific increases of protein levels of RIP3, MLKL and the phosphorylation of MLKL showed that quetiapine induced necroptotic cell death both in vivo and in vitro. Pharmacologic blockade of necroptosis using its specific inhibitor Necrostatin-1 attenuated quetiapine-induced myocardial injury in mice. In addition, quetiapine imbalanced the endocannabinoid system and caused opposing effects on two cannabinoid receptors (CB1R and CB2R). Specific antagonists of CB1R (AM 281, Rimonabant), but not its agonist ACEA significantly ameliorated the heart histopathology induced by chronic quetiapine exposure. By contrast, specific agonists of CB2R (JWH-133, AM 1241), but not its antagonist AM 630 exerted beneficial roles against quetiapine cardiotoxicity. The protective agents (AM 281, Rimonabant, AM 1241, and JWH-133) consistently inactivated the quetiapine-induced necroptosis signaling. Quetiapine bidirectionally regulates cannabinoid receptors and induces myocardial necroptosis, leading to cardiac toxic effects. Therefore, pharmacologic inhibition of CB1R or activation of CB2R represents promising therapeutic strategies against quetiapine-induced cardiotoxicity.

Topics: Animals; Antipsychotic Agents; Apoptosis; Cannabinoid Receptor Agonists; Cannabinoid Receptor Antagonists; Cardiomyopathies; Cardiotoxicity; Cell Line; Endocannabinoids; Male; Mice, Inbred BALB C; Myocytes, Cardiac; Necrosis; Quetiapine Fumarate; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Signal Transduction

Several detailed case reports have described cardiac muscle disorders (cardiomyopathy and myocarditis) in patients treated with quetiapine, some of which have been fatal. The symptoms included shortness of breath and oedema. The disorders sometimes resolved on withdrawal of quetiapine. Quetiapine is chemically similar to clozapine and olanzapine, which are known to sometimes provoke this type of adverse effect. In practice, a patient who develops dyspnoea or other signs of heart failure during quetiapine therapy may benefit if the drug's role is recognised and quetiapine withdrawn.

Topics: Antipsychotic Agents; Cardiomyopathies; Clozapine; Dibenzothiazepines; Dyspnea; Edema; Humans; Myocarditis; Quetiapine Fumarate