OPIOID ROTATION TO METHADONE FOR CHRONIC NON-MALIGNANT PAIN AND CANCER PAIN: A COMMUNITY-BASED EXPERIENCEThe challenges experienced by physicians who prescribe Methadone for chronic non-malignant pain and cancer pain are diverse and complex. There is a sense of foreboding initially that is difficult to put your finger on. Perhaps it is the isolation of the clinician, and uncertainty of what he or she can expect to see and experience when starting patients on Methadone, or the hesitation among colleagues who may be reluctant to "go there" for any number of reasons. The literature also does little to clarify what may be the "best approach" for physicians. For example, there are many different protocols that vary considerably in their dosing frequency and drug potency.1,2,3 How could one drug create so much confusion? In spite of its recent insurgency, Methadone is not a new drug. It is a synthetic opioid agonist which was developed by German chemists in the 1940's during WW II as an alternative to morphine.4 Because its potency was unclear it was withdrawn from the market when a number of individuals unexpectantly died from respiratory depression.5 It resurfaced in the 70's but was primarily used for the treatment of opioid addiction which, up until recently has unfairly stigmatized the drug. Methadone's use in chronic pain and palliative care is helping to clarify its role in pain management allowing us to better understand its analgesic potency and equianalgesic ratios, but it still has a way to go. Methadone has unique properties which make it an attractive option in the treatment of complex pain syndromes such as neuropathic pain. This historically has been a challenge for clinicians to manage, due to the high doses needed when using "traditional" opioids such as Morphine, Hydromorphone and Fentanyl, which often result in opioid toxicity.6 Because Methadone's metabolites are not neuroactive, there is a reduced incidence of neurotoxicity (Myoclonus, delirium, opioid induced hyperalgesia) in these patients and more effective pain control.7,8 It is a is a combined mu-agonist and N-Methyl-D-Asparate (NMDA) antagonist that provides a dual mechanism of action that has been shown to reduce the hyperalgesia and "wind-up" sometimes seen with other opioids.9,10 Methadone also increases the availability of two central nervous system neurotransmitters, serotonin and norepinephrine comparable to that seen with the Selective serotonin reuptake inhibitors. This may have some benefit on a patient's mood, though this role is unclear and controversial, especially in the opioid naïve patient.11 Methadone is rapidly absorbed from the GI tract with an analgesic effect in 30 minutes to an hour, which is similar to morphine. It is a highly lipophylic drug with few active metabolites and is absorbed from many different routes (oral, sublingual, rectal). At present we do not have a parental form available in Canada but the drug can be given in a concentrated form sublingually as a liquid or lozenge, and rectally as a suppository in adjustable strengths, which is convenient near the end of life. The major challenge for clinicians who use Methadone, with its unpredictable and long half life, is adjusting the analgesia benefit.12 Sedation, which may appear days after a successful conversion, appears to be the most common side effect seen, but can be minimized with a slow and patient titration of the drug.13 The conversion to Methadone from traditional opioids can be surprisingly easy, and does not require complicated drug calculations. At our institution we adapted "The Simplified Protocol" developed by Dr. Bruneo Gagnon and his colleagues at McGill University, but soon made some adaptations to fit with our experience.14 Using a gradual reduction of the original opioid by one third over three days, while giving Methadone every 8 hours starting at a 2.5 mg to 5 mg dose and adjusting this daily, appears to be most effective in establishing a regular dosing regimen for Methadone. (See Table 1-1 for examples of a conversion to Methadone in an opioid naïve and opioid tolerant patient). Dosing increases are based on the patient's pain control as well as any indication of excessive sedation. Recently, Cancer Care Nova Scotia, in their Interprofessional core curriculum, recommended a helpful method of calculating a Methadone target when attempting to convert a patient over to Methadone, based on the Morphine equivalent dose of the original opioid used by the patient.15 Clinicians convert the original opioid used by the patient to the morphine equivalent. If the Morphine equivalent was < 500mg in 24 hours, the estimated Methadone equivalent is one-tenth the Morphine equivalent. For example, a patient on Hydromorphone Cont 60 mg in 24 hours has a Morphine equivalent of 300 mg, which would be equivalent to a maximum dose of 30 mg of Methadone in 24 hours, divided over 8 hours. In patients with a Morphine equivalent >500mg the estimated Methadone equivalent would be one-twentieth the Morphine equivalent. The NS Cancer Society suggests a more aggressive dosing schedule in achieving this maximum Methadone equivalent dosing, when transitioning the patient to methadone, however some patients do not tolerate these higher doses, and until it becomes easier to tease out what groups of patients may benefit from the more aggressive dosing, we have, in our institution, continued to use a more gradual dosing increase based on individual patient response. The real challenge is in determining what opioid is best to use for breakthrough pain while transitioning patients over to Methadone, and what to use if the patient's pain becomes unstable. The literature suggests that Methadone can be used for breakthrough pain; however our experience when using it this way has not been positive, especially during the initial conversion from the original opioid to Methadone. We have found that using 10% of the original opioid (adding both the long acting and short acting formulations of the original opioid together to get the 10% total) to be more effective for breakthrough pain, especially in patients with unstable disease. Trying to balance the analgesic benefit of methadone, with its long half life and ensuing sedation, especially in the elderly who often hit "a wall" 5 days into the conversion, is difficult. Methadone for breakthrough pain is more effective when the patient's symptoms have stabilized, after successful conversion. With this group, 5%-10% of the total Methadone dose may be used for breakthrough. There is very little literature that supports the conversion of patients to Methadone at home.16,17 We initially introduced our community based Methadone protocol through our Hospital In The Home program (HITH) and recently have expanded it to some areas of Cape Breton using Home Care Nova Scotia. Setting up the program required ongoing education and support for nurses, physicians and pharmacists within the community. A protocol was drafted which was then circulated to the primary stakeholders. We found that the palliative care population was the most challenging to convert to Methadone, mainly due to the unstable nature of their disease. These patients often required dose adjustments, while those patients with chronic non-malignant pain required very little drug adjustment and were much easier to stabilize. The role of the (HITH) nurses was primarily to monitor patients and provide education prior to and during the methadone conversion. Drug orders were reviewed with the pharmacist, patient and nurses, and a letter was sent to the family physician outlining the opioid switch. The family physicians were asked to obtain a Methadone license so as to be able to prescribe for their patients once they were discharged from the service. However, these physicians continue to receive support from St Martha's on an "as needed" basis. During the conversion process we called the patient's home on a daily basis to monitor the process and the nurses made frequent home visits. To date our institution has successfully converted 15 patients to methadone, at home, using this policy, and no significant issues have occurred. Challenges do occur however when a patient's disease becomes unstable but this can be managed adequately through effective communication with the palliative care team. In summary, Methadone is a safe opioid analgesic that can be reliable, and easily initiated at home, if the proper supports and education are provided to caregivers and health care professionals. Because of initial dosing adjustments, it is important that the conversion to methadone be supervised by a physician who is experienced in its use. However, once a patient is successfully transitioned over to Methadone, family physicians can safely and effectively prescribe and monitor these patients. Thanks to Dr. Michael MacKenzie, Director of the Palliative Care Department at St. Martha's Regional Hospital in Antigonish, Nova Scotia, for reviewing the draft copy of this article. References:
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