Sickle cell pain & methadone

09/28/16 • 3 min

BioMed Radio - Washington University School of Medicine in St. Louis

Children with sickle cell disease frequently have painful episodes that can require hospitalization for a few days. Physicians want to treat those episodes quickly to eliminate pain and get a child back home and back to school as quickly as possible, and now, researchers at Washington University School of Medicine in St. Louis have found that using the drug methadone might eliminate the pain more quickly. Methadone frequently is used to treat cancer pain and is a well-known treatment for addiction. But it also may be useful treating the severe pain associated with sickle cell disease.

TREATING PAIN FROM SICKLE CELL DISEASE CAN BE DIFFICULT. CHILDREN WITH THE DISEASE OFTEN HAVE SEVERE PAIN EPISODES THAT CAN REQUIRE HOSPITALIZATION. BUT NOW RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE AND ST. LOUIS CHILDRENS HOSPITAL HAVE FOUND THAT ADDING METHADONE TO OTHER PAIN KILLERS CAN RELIVE SICKLE CELL PAIN MORE QUICKLY IN CHILDREN AND MAY BE ABLE TO HELP YOUNGER PATIENTS GET HOME FROM THE HOSPITAL SOONER. JIM DRYDEN HAS THE STORY

ITS NOT UNCOMMON FOR PATIENTS WITH SICKLE CELL DISEASE TO HAVE PAIN EPISODES THAT LAND THEM IN THE HOSPITAL. SIXTY PERCENT HAVE AT LEAST ONE SUCH EPISODE, CALLED A VASO-OCCLUSIVE EPISODE, EACH YEAR. ABOUT ONE IN FIVE HAVE MULTIPLE EPISODES ANNUALLY THAT REQUIRE HOSPITALIZATION. BECAUSE THE DRUG METHADONE HAS BEEN EFFECTIVE AS A TREATMENT FOR CANCER PAIN, WASHINGTON UNIVERSITY EMERGENCY MEDICINE SPECIALIST JENNIFER HORST AND HER COLLEAGUES DECIDED TO SEE HOW IT WORKED IN PATIENTS WITH PAIN FROM SICKLE CELL DISEASE.

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Methadone is a medication that is used a lot with patients with other types of chronic pain, such as cancer patients. There are some patients with sickle cell disease who have received methadone, but its a small minority. And its not one of the typical pain medications.

CHILDREN, AND ADULTS, WITH SICKLE CELL DISEASE HAVE VASO-OCCLUSIVE EPISODES WHEN THE SHAPE OF THEIR RED BLOOD CELLS BECOMES ALTERED.

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There is a problem with their red blood cells, and under certain circumstances such as illness or dehydration or, sometimes, of unknown causes the red blood cells change shape. And we call it sickle; theyre in a sickle shape. And whenever the red blood cells change shape, they do not flow through the blood vessels as well and cannot give oxygen to the tissue as well, and thats what causes pain.

HORST WORKED WITH WASHINGTON UNIVERSITY ANESTHESIOLOGIST EVAN KHARASCH IN TESTING METHADONE IN SICKLE CELL PATIENTS. THEY FOLLOWED 24 CHILDREN AND ANOTHER 23 ADULTS WHO HAD BEEN HOSPITALIZED FOR PAIN. EVERYONE GOT STANDARD PAIN-KILLING DRUGS, BUT HALF OF THE KIDS AND ADULTS ALSO GOT A SINGLE, LOW DOSE OF METHADONE ON THEIR FIRST DAY IN THE HOSPITAL.

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Because this pain medication has a faster onset and lasts longer than other, typical pain medicines, we hoped that we would be able to either prevent them from being admitted to the hospital which would be the most ideal thing, that theyd be able to go home or that if they had to be admitted, they would be able to resolve their pain crises more quickly and be discharged home.

IN THE CHILDREN, THE SINGLE, LOW DOSE OF METHADONE RESULTED IN BETTER PAIN RELIEF THAN THE STANDARD PAIN-KILLING DRUGS THAT KIDS NORMALLY GET.

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There is not a lot of data on how methadone works in children, and so that was one of the things we were looking at. What we have found is that methadone is longer lasting than other pain medicines that would typically be used, and also has a faster onset. And so, the pain could be treated more quickly, and the pain relief would last longer.

BUT IN ADULTS, HORST SAYS, THERE WASNT AS MUCH OF A DIFFERENCE BETWEEN PATIENTS WHO GOT METHADONE AND THOSE WHO DIDNT.

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Part of the study was to make sure that we could give this medication in a safe manner, and so we used lower doses than one would probably typically give to treat pain. And so that might be why the adults did not have the improvement in pain scores that we would liked to have seen.

THE NEW STUDY IS PUBLISHED IN THE JOURNAL PEDIATRIC BLOOD & CANCER. IM JIM DRYDEN...

RUNS 3:00

(act) :16 o/c pain medications

CHILDREN, AND ADULTS, WITH SICKLE CELL DISEASE HAVE VASO-OCCLUSIVE EPISODES WHEN THE SHAPE OF THEIR RED BLOOD CELLS BECOMES ALTERED.

(act) :25 o/c causes pain

(act) :21 o/c discharged home

IN THE CHILDREN, THE SINGLE, LOW DOSE OF METHADONE RESULTED IN BETTER PAIN RELIEF THAN THE STANDARD PAIN-KILLING DRUGS THAT KIDS NORMALLY GET.

(act) :23 o/c last longer

BUT IN ADULTS, HORST SAYS, THERE WASNT AS MUCH OF A DIFFERENCE BETWEEN PATIENTS WHO GOT METHADONE AND THOSE WHO DIDNT.

(act) :15 o/c have seen

THE NEW STUDY IS PUBLISHED IN THE JOURNAL PEDIATRIC BLOOD & CANCER. IM JIM DRYDEN...

RUNS 3:00

Previous Episode

ABCD study

Researchers at Washington University School of Medicine in St. Louis will play a major role in the largest long-term study of brain development and child health in U.S. history. The landmark study will follow the biological and behavioral development of more than 10,000 children, beginning when the kids are 9 to 10 years old. Scientists studying the adolescents will use advanced brain imaging, interviews and behavioral testing to see how childhood experiences can affect a childs changing biology, brain development and, ultimately, social, behavioral, academic and health outcomes. If the researchers can get a better understanding of the relationships between such factors, they may be able to predict and prevent, or even reverse, potential problems in development.

WE ARENT BORN WITH FULLY-DEVELOPED BRAINS. IN FACT, BRAIN DEVELOPMENT CONTINUES FOR YEARS. AND RESEARCHERS AT WASHINGTON UNIVERSITY IN ST. LOUIS WILL PLAY A BIG ROLE IN A NEW NIH-FUNDED STUDY OF BRAIN DEVELOPMENT IN ADOLESCENTS. THE SO-CALLED ABCD STUDY WILL BE THE LARGEST OF ITS KIND EVER, FOLLOWING MORE THAN 10,000 CHILDREN FROM AGE 9 OR 10 INTO EARLY ADULTHOOD. JIM DRYDEN REPORTS

A WHOLE LOT OF THINGS INFLUENCE BRAIN DEVELOPMENT: FAMILY BACKGROUND, SOCIO-ECONOMIC GROUP, AND A GREAT DEAL OF GROWTH AND DEVELOPMENT OCCURS DURING ADOLESCENCE. NOW, THE NIH HAS LAUNCHED AN AMBITIOUS PROJECT TO KEEP TRACK OF SOME OF THE THINGS THAT INFLUENCE HEALTHY, AND UNHEALTHY, BRAIN DEVELOPMENT. RESEARCHERS AT 19 CENTERS, INCLUDING WASHINGTON UNIVERSITY, WILL SCAN THE BRAINS OF YOUNG PEOPLE, CONDUCT INTERVIEWS AND DO BEHAVIORAL TESTING TO LEARN HOW ENVIRONMENT, BEHAVIOR AND GENETICS INTERACT TO INFLUENCE BRAIN DEVELOPMENT. WASHINGTON UNIVERSITY NEUROSCIENTIST DEANNA BARCH SAYS THEYLL BE LOOKING AT

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Factors that promote both health brain development in children and the factors that lead brain development to go awry and to put kids at risk for a variety of mental health or other challenges later in life.

AND BARCH SAYS THE RESEARCHERS WILL CONSIDER PRETTY MUCH EVERYTHING.

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Things like peers and social supports and families, and how those help promote healthy brain development; factors related to the activities that kids engage in sports and music and after-school activities but to also try to understand what happens when kids engage in behaviors that may be less good for them. You know, if they use substances or other things that might interfere with healthy brain development and behavior.

ONE KEY PART OF THE STUDY WILL INVOLVE FOLLOWING TWINS. THE WASHINGTON UNIVERSITY TEAM IS ONE OF FOUR INVOLVED IN THIS STUDY THAT IS SPECIFICALLY RECRUITING PAIRS OF TWINS. BY STUDYING THE BRAINS AND BEHAVIOR OF THOSE TWIN PAIRS, AND BY RECRUITING TWINS OF EVERY RACE, ETHNICITY AND ECONOMIC BACKGROUND, WASHINGTON UNIVERSITY GENETICS RESEARCHER ANDREW HEATH SAYS THE PROJECT SHOULD BE ABLE TO LEARN A GREAT DEAL ABOUT HOW GENETICS INFLUENCE BRAIN DEVELOPMENT.

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We are going to be able to achieve a breadth of race and ethnic diversity that has never before been possible: Hispanic pairs, African-American pairs, Asian pairs, as well as white non-Hispanic pairs. Thats a really exciting aspect of this study. Its going to allow us to look at the genetics of brain development in a truly diverse sample.

THE IDEA, SAYS WASHINGTON UNIVERSITY RESEARCHERS PAMELA MADDEN IS TO GET A LARGE, AND REPRESENTATIVE SAMPLE OF KIDS.

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In addition to twins throughout the state, we are reaching more locally to school districts. We are interested in coming up with a representative sample of the St. Louis, and the broader Missouri region.

BUT WHEN ITS ALL SAID AND DONE, HEATH SAYS THE PROJECT SHOULD HELP RESEARCHERS LEARN WHAT CONSTITUTES NORMAL BRAIN DEVELOPMENT SO THAT THEY MAY BE ABLE TO SPOT AT-RISK KIDS AT VERY YOUNG AGES.

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Who are the high-risk kids? What are the factors that identify someone, when theyre 9 or 10? I think that, in itself, is going to be very helpful to advance our understanding. Who are the high-risk kids? Because once we know that, we can do much more to understand how do we help the high-risk kids?

THE ABCD, THATS ADOLESCENT BRAIN COGNITIVE DEVELOPMENT, STUDY WILL FOLLOW THE CHILDREN FOR AT LEAST 10 YEARS. IM JIM DRYDEN...

RUNS 3:00

Next Episode

PCORI depression grant

Treatment-resistant depression is a big problem for older adults. More than half of seniors with clinical depression dont get relief from standard antidepressant medications. To address that problem, psychiatrists at Washington University School of Medicine in St. Louis are helming a multicenter study to evaluate the efficacy of supplementing current therapies with additional drugs, or changing medications altogether. The study will follow 1,500 people with depression from St. Louis and rural Missouri, Los Angeles, Western Pennsylvania, New York City, Toronto and rural Ontario. Study subjects will be 60 or older, and all will have failed to respond to treatment involving at least two antidepressants. Some subjects will take additional drugs during the study, and others will be switched to different medications. After treatment, the researchers will attempt to evaluate which types of patients respond best to specific treatment strategies.

TREATMENT-RESISTANT DEPRESSION IS A PARTICULAR PROBLEM FOR OLDER ADULTS. LESS THAN HALF OF SENIORS WITH CLINICAL DEPRESSION RESPOND COMPLETELY TO THE MOST COMMONLY USED ANTIDEPRESSANT DRUGS. SO NOW, RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS ARE LEADING A STUDY TO IDENTIFY BETTER WAYS TO PROVIDE RELIEF FOR THOSE WHO DONT CURRENTLY GET COMPLETE RELIEF FROM COMMON ANTIDEPRESSANT MEDICATIONS. JIM DRYDEN HAS THE STORY

ITS CALLED THE OPTIMUM STUDY AN ACRONYM FOR OPTIMIZING OUTCOMES OF TREATMENT-RESISTANT DEPRESSION IN OLDER ADULTS AND RESEARCHERS ARE RECRUITING 1500 PEOPLE OVER THE AGE OF 60 WHOSE DEPRESSION HASNT RESPONDED COMPLETELY TO DRUGS CALLED SELECTIVE SEROTONIN REUPTAKE INHIBITORS, OR SSRIs. WASHINGTON UNIVERSITY PSYCHIATRIST ERIC LENZE IS LEADING THE OPTIMUM STUDY.

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Most older adults get either an incomplete benefit or an insufficient benefit. Youll almost always receive a medication that we call an SSRI. These are medications like Prozac or Paxil or Zoloft or Lexapro. Half, or more, of older adults will have, as I said, either an incomplete or a very insufficient benefit from these medications.

SOME PEOPLE IN THE STUDY WILL REMAIN ON WHATEVER DRUG THEYRE CURRENTLY USING, AND A SECOND DRUG WILL BE ADDED, TOO. ADDING A SECOND DRUG IS KNOWN AS AUGMENTATION, AND LENZE SAYS ITS A COMMON WAY TO TREAT MANY DISORDERS.

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Many people might have high blood pressure or diabetes, and they take one medication for it. And that helps some but not enough, so they need to take a second medication. So in depression treatment, if one treatment isnt enough, add a second one that seems to work well with that first one.

OTHERS IN THE STUDY WILL GET A DIFFERENT DRUG ENTIRELY. THATS A STRATEGY THAT LENZE CALLS A SWITCH.

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The other line of thinking is, well if this medication isnt working, dont stay on that medication because its not working very well. So try switching to a different kind of medication.

THE REASON SWITCHING IS ATTRACTIVE, PARTICULARLY FOR OLDER ADULTS, IS THAT IT LIMITS THE NUMBER OF PILLS A PATIENT HAS TO TAKE.

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If you get augmentation treatment, that means youre going to be on two medications, so you might have more side effects. You might have more risks, simply because youre on two Medications, and right now, we dont know which is the best thing to do.

THE AUGMENTATION AND SWITCH PATIENTS WILL BE EVALUATED AFTER 10 WEEKS OF TREATMENT, AND IF SOME STILL HAVE DEPRESSION, THEYLL BE PLACED INTO ANOTHER ARM OF THE STUDY IN WHICH OLDER, HARDER-TO-USE DRUGS MAY BE INTRODUCED AS TREATMENTS.

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You might benefit from your doctor adding lithium. And in fact, decades ago, thats what psychiatrists used to do. And this isnt done very much anymore, in part because lithium can be difficult to prescribe. You need to check someones kidney function. You need to do blood levels of the medication, instruct them on how to stay hydrated, and things like that.

OTHERS IN THE STUDY WILL GET AN OLDER TYPE OF ANTIDEPRESSANT DRUG CALLED NORTRIPTYLINE. LENZE SAYS THE RESEARCHERS HOPE THAT BY STUDYING ALL OF THESE DIFFERENT COMBINATIONS OF AUGMENTATION AND SWITCHING, THEY MAY BE ABLE TO IDENTIFY EFFECTIVE THERAPIES THAT CAN BE PERSONALLY TAILORED TO INDIVIDUAL PATIENTS. IM JIM DRYDEN...

RUNS 2:56