Antipsychotic Use and the Risk of Rhabdomyolysis

Abstract

Rhabdomyolysis is not a well-understood adverse effect of antipsychotic use. Proposed mechanisms suggest involvement of serotoninergic and/or dopaminergic blockade. The purpose of this study was to describe the relationship between antipsychotic use and rhabdomyolysis. Patients admitted with rhabdomyolysis and taking an antipsychotic from January 2009 to October 2011 were included. Background demographics, laboratory data, medical and physical history, concomitant medications, and hospital course data were collected. Of the 673 cases admitted with rhabdomyolysis, 71 (10.5%) were on an antipsychotic. This is significantly greater when compared to the general US population, where only 1.3% of individuals take an antipsychotic drug (P < .0001). Cause of rhabdomyolysis was not documented in 38% of cases, and antipsychotic use was suspected in 10% of cases. No significant correlations were found between antipsychotic type and other patient-specific parameters. Seventeen (25%) of these patients were taking 2 or more antipsychotics. The largest percentage was on quetiapine (Seroquel(®); AstraZeneca, Wilmington, Delaware), the most commonly prescribed antipsychotic in the United States. Antipsychotic use is a risk factor for rhabdomyolysis and seems to be more common in those taking multiple agents. More research needs to be done to determine which antipsychotics have a higher risk and which receptors are involved. Providers should be aware of rhabdomyolysis associated with antipsychotic use.

Severe rhabdomyolysis induced by quetiapine and mirtazapine in a French military soldier

“…Antipsychotic drugs are an important cause of an increase in CK levels and are the leading cause of drug-induced rhabdomyolysis 5. Only few cases of quetiapine-induced rhabdomyolysis have been described in the literature 6. Even small doses could induce CK levels increase, yet, it seems that the CK elevation mechanism following the use of quetiapine is not dose dependent 7…”

Safety and Tolerability of Antipsychotics

“…However, later case reports included low to modest antipsychotic doses (Stephanie and Trenkwalder 2010 ). Clinical symptoms that preceded recognition of Rhab were muscle and abdominal pain, generalized weakness, and dark urine (Packhard et al 2014 ). The pathophysiology of antipsychotic-induced Rhab may be associated with increased skeletal muscle membrane permeability involving the 5HT2A receptor antagonism (Packhard et al 2014 ).…”

“…Clinical symptoms that preceded recognition of Rhab were muscle and abdominal pain, generalized weakness, and dark urine (Packhard et al 2014 ). The pathophysiology of antipsychotic-induced Rhab may be associated with increased skeletal muscle membrane permeability involving the 5HT2A receptor antagonism (Packhard et al 2014 ). Blockade of the 5HT2A receptor may impact glucose uptake in the skeletal muscle increasing CK permeability leading to the muscle breakdown.…”

“…The mechanism of antipsychotic-induced Rhab remains unknown (Packhard et al 2014 ). Although Rhab is commonly associated with NMS (see Sect.…”

“…At this time, Rhab has been reported with each antipsychotic agent except the newer agents lurasidone, asenapine, and iloperidone as only time on the market for these agents will determine whether or not Rhab occurs. Two risk factors were identifi ed as contributing to Rhab that included polytherapy (>2 antipsychotics) and dose as most of the reported cases took place with antipsychotic overdose situations (Packhard et al 2014 ).…”