Zofran and Pain Management: Old Drug May Provide New Relief from Symptoms of Opioid Addiction

Fear of addiction often is a barrier to adequate pain relief, especially for people with cancer. According to the World Health Organization, when used correctly, "analgesic drug therapy is capable of relieving pain in more than 90% of cancer patients." Yet many patients suffer. The WHO states that this is because "health care workers as well as patients believe that there is a significant risk of addiction when using opioids." Common opioids include codeine, morphine, oxycodone, fentanyl and methadone. Now scientists at Stanford University School of Medicine have found that ondansetron, frequently sold under the brand name Zofran, "can prevent symptoms of withdrawal from opioids with little likelihood of serious side effects."

Zofran, the ondansetron brand developed by GlaxcoSmithKline, is an anti-emetic. It is used to prevent nausea and vomiting after chemotherapy, radiation and surgery. According to the Pharmaceutical Business Review, "over 500,000 Americans received chemotherapy in 2004, and the majority of these patients received an anti-emetic such as ondansetron." In 2005, Zofran had annual sales of approximately $225 million. That year, Zofran also went off patent. Generic versions of Zofran were developed by Kali Laboratories and Hana Biosciences.

In the Stanford study, scientists discovered Zofran's ability to block opioid withdrawal symptoms in a round-about way. Scientists noticed that, after giving morphine to mice for some time and then stopping the drug, mice exhibited symptoms of withdrawal. Science Daily explains that, for mice, opioid withdrawal symptoms included the mice jumping into the air and becoming extra sensitive to pain.

Researchers then observed that some of the mice were much more likely than other mice to exhibit opioid withdrawal symptoms when morphine was no longer administered. Some mice also were more likely than other mice to exhibit severe, or intense, reactions to the withdrawal of morphine.

What was behind this intense addiction behavior in some mice? The Stanford researchers turned to a powerful computational tool called "haplotype-based" genetic mapping. Science Daily states that genetic mapping produced "an unambiguous result: One particular gene determined the severity of withdrawal." This was the clue scientists were looking for.

The gene determining the severity of withdrawal, and thus potentially influencing the individual's risk of addiction, codes for a protein known as the 5-HT3 receptor. The scientists then looked for a drug that blocked 5-HT3 receptors. That drug was ondansetron.

When the morphine-addicted mice received ondansetron, their withdrawal behaviors---jumping into the air and extra pain sensitivity---substantially diminished.

This is where researchers received another lucky break. In many studies using laboratory animals, the laboratory findings cannot easily or quickly be tested in humans. Here, however, both the addictive opioid, morphine, and the 5-HT3 receptor blocker, ondansetron (Zofran), were approved for human use.

Non-addicted, healthy humans were administered a single dose of morphine. Later they were administered morphine and ondansetron, either before or with the opioid. Like the mice, people who took ondansetron had substantially reduced signs of opioid withdrawal. Stanford professor of anesthesia J. David Clark said, "A major accomplishment of this study was to take lab findings and translate them to humans."

Clark also cautioned that using ondansetron to block opioid withdrawal symptoms "is not a cure for addiction." It is, however, a potentially valuable tool for patients, such as those with cancer, who need strong pain management, but who fear addiction and the additional physical suffering it can cause.

Recently, the FDA sought more stringent regulation of opioid painkillers. Specifically, the FDA is targeting morphine, oxycodone, fentanyl and methadone, both brand-name and generic versions. According to Dr. John Jenkins, director of the FDA's Office of New Drugs, "approximately 21 million prescriptions for 3.7 millions patients were issued in 2007" for these medications. Because "the rates of misuse and abuse [of opiates] have risen over the last decade," Jenkins said the FDA would implement "a relatively massive new program" to manage the medications' risks.

Medicine Net states that addiction to opioids is "liked being hooked on heroin." Withdrawal can cause muscle and bone pain, vomiting, diarrhea, insomnia and cold flashes.

The National Institutes of Health recognizes that cancer patients, in particular, often need round-the-clock pain management. The World Health Organization, as well as experts such as Barry Stimmel, author of Pain and Its Relief Without Addiction, explain that patients need not suffer pain out of fear of suffering addiction and its associated withdrawal syndromes. The ability to manage withdrawal symptoms with an available, effective and safe drug such as Zofran (ondansetron) may help patients and their physicians strike a better balance between appropriate use of opioid pain relievers and fear of their side effects.

Sources:

"Fear of Addiction: Confronting A Barrier to Cancer Pain Relief," World Health Organization.

"Commonly Available Drug Found To Treat Opioid Addiction," Science Daily.

"GlaxoSmithKline: Zofran sales set for off-Par performance," Pharmaceutical Business Review.

"FDA Seeks Better Regulation of Painkillers," Medline Plus.

"Prescription Pain Relievers: The Buzz Can Kill You," Medicine Net.

Barry Stimmel, "Pain and Its Relief Without Addiction," Google Books.