Patient Education About Rhabdomyolysis and Antipsychotics Can Help Prevent Acute Complications
Mention drug-induced rhabdomyolysis and statins immediately come to mind; yet, in the past, antipsychotics actually caused more cases than statins. Few studies have explored the association between antipsychotics and muscle necrosis, but enough evidence exists to show that the risk is higher than some health care professionals may realize.
This is when pharmacists need to take the lead. In some cases, you may be the only health care provider who is aware of the problem, which means it’s essential to counsel patients when you dispense antipsychotics. You can help prevent a potentially life-threatening side effect by simply teaching patients to not ignore rhabdomyolysis symptoms.
Overview of Rhabdomyolysis
Rhabdomyolysis begins when skeletal muscles are injured. The damage triggers a cascade of events inside muscle cells, ultimately leading to excessive intracellular calcium, mitochondrial dysfunction, production of reactive oxygen species, and death of muscle cells. As cell integrity is breached, intracellular constituents are released into the bloodstream, causing high levels of myoglobin, creatine kinase, lactate dehydrogenase, aldolase, and electrolytes.
Complications initially arise from low blood levels of calcium and potassium, then they can progress to acute kidney injury as excess myoglobin obstructs renal tubules and becomes toxic. An estimated 10 to 40 percent of patients with rhabdomyolysis develop acute renal failure, but in children the percentage may be higher.1
While patients may experience the classic triad of symptoms—myalgia, weakness and dark red or brown urine due to myoglobinuria—it’s important to know that more than half of them don’t complain about muscle pain or weakness. Instead, they’re motivated to see a doctor when they notice discolored urine. High levels of creatine kinase—5 times its normal value or higher—confirm the diagnosis.
The many possible causes of rhabdomyolysis explain why prevalence is so hard to pin down. The short list includes2:
- Trauma and muscle compression – Crush syndrome, fractures, electrical injury, extensive burns and prolonged immobilization.
- Exertion – Athletic endeavors, especially when performed under hot or humid conditions. Most often occurs in competitive athletes, military recruits and untrained individuals. Higher risk is associated with use of nutritional supplements and in people with sickle cell.
- Infection – A large number of viruses and bacteria can damage muscles. Viral-induced myositis is common etiology in children younger than 9 years.
- Metabolic and genetic conditions – A variety of health conditions can cause rhabdomyolysis, including those that affect energy production and cause enzyme deficiencies or electrolyte imbalances.
- Drugs and toxins – In addition to antipsychotics, statins, selective serotonin reuptake inhibitors, colchicine, lithium, zidovudine, alcohol, and illegal drugs are associated with rhabdomyolysis.
Association of Rhabdomyolysis and Antipsychotics
As an adverse effect of antipsychotic medications, rhabdomyolysis is not widely studied. As a result, it’s not well understood, according to a report in the October 2014 issue of the Journal of Pharmacy Practice.3 But pharmacists can be guided by solid information available from this and a few other studies.
In the 2014 study, researchers reviewed records from 673 patients who were admitted to the hospital with rhabdomyolysis. They concluded that providers should be more concerned about patients using antipsychotics, based on the following results:
- 5 percent took antipsychotics, which is significant compared to antipsychotic use in only 1.3 percent of the general population.
- 25 percent of the patients used two or more antipsychotics.
- More than one-third of the cases didn’t indicate the cause of rhabdomyolysis—antipsychotic use was suspected in 10 percent of them.
Additional insight is gained from a report published in the Journal of Child and Adolescent Psychopharmacology in 2012.4 In this study, investigators reviewed data on patients aged 17 years or younger in the WHO database of individual case safety reports. They identified eight different antipsychotics associated with rhabdomyolysis:
For most of the patients, onset of rhabdomyolysis occurred within two months of starting antipsychotic treatment, but in several cases it was triggered by changes in therapy. The experts concluded that providers should be especially vigilant about rhabdomyolysis when the dose is increased, when a new antipsychotic drug is added, or the type of antipsychotic medication is switched.
Finally, a study published in 2005 found that antipsychotics were responsible for more cases of prescription drug-induced rhabdomyolysis than statins.5 While use of both drug classes has increased since then, it’s likely that antipsychotics still rank as one of the top causes. The researchers reported the following statistics based on 475 patients hospitalized for rhabdomyolysis at Johns Hopkins Hospital:
- Half of patients developed acute renal failure—in this group, antipsychotic use was the only risk factor.
- 10 percent of patients treated with antipsychotics experienced recurrent episodes of elevated creatine kinase.
- Neuroleptic malignant syndrome (NMS), a rare side effect of antipsychotic medications, was the fourth cause of rhabdomyolysis in this population—rhabdomyolysis recurred in 26 percent of those with NMS.
Pharmacist Counseling Can Help Prevent Adverse Effects of Antipsychotics
Antipsychotics are used in adults diagnosed with schizophrenia and bipolar disorder. In children, adolescents and young adults, they’re primarily used to treat ADHD, autism, disruptive behaviors, and aggression. It’s a good time to put rhabdomyolysis on your radar because the number of antipsychotic prescriptions for adolescents and young adults continues to rise.6 The key role for pharmacists is to teach patients and their parents about the serious nature of rhabdomyolysis. Impress upon them the importance of watching for muscle pain, weakness and dark urine and the need to call the doctor should symptoms arise. Your counseling diligence fills the information gap and helps to ensure your patients’ safety and health.
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- “Rhabdomyolysis: Pathogenesis, Diagnosis, and Treatment,” Spring 2015, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365849/ ↩
- “Rhabdomyolysis,” November 2016, http://emedicine.medscape.com/article/1007814-overview ↩
- “Antipsychotic Use and the Risk of Rhabdomyolysis,” October 2014, https://www.ncbi.nlm.nih.gov/pubmed/24429293 ↩
- “Rhabdomyolysis Reported for Children and Adolescents Treated with Antipsychotic Medicines: A Case Series Analysis,” December 2012, https://www.ncbi.nlm.nih.gov/pubmed/23234587 ↩
- “Rhabdomyolysis: An Evaluation of 475 Hospitalized Patients,” November 2005, http://journals.lww.com/md-journal/Fulltext/2005/11000/Rhabdomyolysis__An_Evaluation_of_475_Hospitalized.5.aspx ↩
- “Treatment of Young People With Antipsychotic Medications in the United States,” September 2015, http://jamanetwork.com/journals/jamapsychiatry/fullarticle/2339963 ↩