Many children with sickle cell disease experience frequent and severe pain episodes, which require emergency room visits or hospitalization. Now, researchers have discovered that adding a low dose of the drug methadone to standard treatment can limit pain.
“More than half of sickle cell patients have at least one episode of significant pain every year, and about 20 percent experience multiple episodes each year that require hospital stays,” says Jennifer Horst, an instructor of pediatrics at the Washington University in St. Louis School of Medicine and an emergency room physician at St. Louis Children’s Hospital.
“In this study, the pediatric patients who received a one-time dose of methadone rated their pain levels much lower than those who took standard pain-killing drugs. In many cases, their pain went away, so we believe methadone has the potential to make life better for these pediatric patients.”
Patients are treated with pain-killing drugs, usually opioids such as morphine, until their pain is under control. For the new study, published in the journal Pediatric Blood & Cancer, researchers followed 24 children and 23 adults who were hospitalized after suffering episodes of severe sickle cell pain.
Half of the patients were given a single, low dose of the long-duration opioid methadone. The result was that many of them then needed lower amounts than usual of other opioid drugs to control their pain.
Severe pain occurs when the shape of red blood cells becomes sickle-like in shape, making it more difficult for the cells to flow through blood vessels. As a result, the red blood cells don’t supply enough oxygen to tissues in the body that need it.
Horst and senior investigator Evan D. Kharasch, professor of anesthesiology, compared pain relief in patients given morphine with pain relief in those whose treatments were supplemented with methadone.
Rate your pain
Morphine is the standard painkiller prescribed to sickle cell patients. Methadone also frequently is used to treat pain, particularly in patients having surgery or those with cancer. The latter drug also is used in detoxification and maintenance therapy for individuals who are dependent on opioid drugs, including heroin.
Study patients who did not receive methadone were given morphine to treat their pain. All of the patients in the study were able to regulate the amount of pain-killing drugs they received.
The children who received methadone rated their pain lower on a standard scale that indicated no pain to severe pain. They also rated their pain relief as better, at 7 to 8 on a scale of 1 to 10, while those who didn’t get methadone rated their pain relief at around 4 or 5 during the first 72 hours of their hospital stays.
In adults, however, pain relief linked to methadone was not statistically significant, perhaps because the doses were too low, says Kharasch—also a professor of biochemistry and molecular biophysics.
“Because adult patients have lived with sickle cell disease their entire lives, it’s possible they develop a tolerance to pain medications, and pain-killing drugs, including methadone, become generally less effective. However, we wanted to make sure methadone was safe to use in sickle cell patients, so we actually gave very low doses of the drug. That might be why the adults didn’t register the same improvements in pain scores.”
How it might work
Methadone may help relieve pain from sickle cell disease because the drug has pain-killing properties that are different from morphine and because it remains in the body longer, the researchers say.
“Methadone has a faster onset and lasts longer than other, typical pain medicines, so we think it may be useful in getting some patients relief before they have to be hospitalized,” Horst says. “We’d like to treat pain more quickly, especially in children, so that their pain crises can be resolved more quickly and they can go home sooner. Children who come in several times a year can miss a lot of school. That affects their quality of life.”
The researchers believe they have demonstrated that the drug can be used safely in children but say they will have to study larger numbers of kids and adults before determining whether methadone can be incorporated as a standard treatment for sickle cell-related pain.
Further, larger studies could help establish the most effective doses of the drug in children and adults. In addition, they plan to evaluate whether treating patients with methadone in the emergency department might potentially prevent the need for hospitalization in some patients.
The National Institute on Drug Abuse, the National Center for Research Resources of the National Institutes of Health, and the Doris Duke Foundation funded the work.
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