Risperidone ( Risperdal ) is an atypical antipsychotic agent indicated for the treatment or management of schizophrenia, inappropriate behaviour associated with severe dementia and manic episodes associated with bipolar I disorder.
All atypical antipsychotics, including risperidone, can trigger neuroleptic malignant syndrome ( NMS ), and rhabdomyolysis can be part of this syndrome.

Rhabdomyolysis refers to the disintegration of striated muscle and the consequent release of muscular cell contents such as myoglobin into extracellular fluid and circulation. Myoglobin is normally bound to plasma globulins, of which a small amount may be excreted in the urine. When a massive amount of myoglobin is released, and the binding capacity of plasma proteins is surpassed, myoglobin is filtered by the glomeruli and eventually reaches the tubules, where it can cause obstruction and may lead to renal failure.
Clinical signs and symptoms of rhabdomyolysis include muscle pain, weakness, and dark red-coloured urine. Serum creatine phosphokinase ( CPK ) levels are also typically markedly elevated and can be used to assess the presence and intensity of muscle damage.

Other atypical antipsychotics including Clozapine, Olanzapine, Quetiapine, Aripiprazole and one Paliperidone product are currently labelled for the risk of rhabdomyolysis independent of neuroleptic malignant syndrome, as well as part of NMS, in their respective Canadian product monographs.
Risperidone and Ziprasidone are not labelled for the risk of rhabdomyolysis independent of neuroleptic malignant syndrome.
Health Canada has received 5 reports of rhabdomyolysis independent of neuroleptic malignant syndrome suspected of being associated with Risperidone. All but one patient had recovered at the time of reporting. No deaths were reported.

Reports of significant and transient elevation of CPK in stable patients without the presence of neuroleptic malignant syndrome involving Risperidone and other antipsychotics have been described in the literature. However, the exact pathophysiological mechanism that mediates this association remains unclear. There are individual vulnerability factors involved in the development of rhabdomyolysis in the presence of antipsychotics. It has also been proposed, based on animal studies, that the accumulation of serotonin in skeletal muscle can play a role in the development of muscle injury.

Source: Health Canada – CARN, 2013

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