Methadone Regulation; The Dual Diagnosis of Pain & Addiction

When it comes to prescribing methadone for pain or addiction, an important consideration may lead you that old adage; Which came first, the chicken or the egg?  If you would like to refresh yourself about methadone’s pharmacological mechanisms and its intricate dosing, please check out Treatment of Neuropathic Pain and Mathematical Model for Methadone Conversion Examined. But today, we discuss the dilemma that comes when the use of methadone for pain versus methadone for opioid use disorder overlap.

Methadone has analgesic activity due to both opioid and non-opioid mechanisms which collectively make this drug useful for both analgesia and opioid use disorder (OUD). Methadone has FDA indications for BOTH pain management and opioid use disorder. Methadone clinics certified for OUD are not permitted to prescribe methadone for pain, and prescribers who are not connected with a certified methadone clinic are only permitted to prescribe methadone for pain, not OUD. So, you can see where a problem may arise if a patient presents with both pain and OUD.  Similarly, in today’s climate, many chronic pain patients have had their opioids significantly reduced or discontinued, and some have taken to the streets to obtain illicit opioids, while others have latched onto various other substances that are legal in some states and not others, such as kratom, or marijuana. These patients are labeled to have OUD, however even if in treatment, their chronic pain is likely still an issue.  For many medical providers, this line may be gray.

The other problem dually diagnosed patients face is that methadone dosing for pain is individually tailored to each patient, and usually dosed multiple times per day. While patients in methadone clinics typically receive once daily dosing.  Additionally, this once daily dose is regimented as enrolled methadone maintenance patients have to physically go to the clinic to take their observed dose, with the exception of patients that have earned the right to take home a week or month supply at a time.  These variations in regulation are somewhat state dependent but do have overarching Federal Regulations.  The dosing and pharmacokinetics of methadone are very complicated with half-life varying tremendously between patients. One methadone dose has analgesic properties for approximately 3-6 hours and usually requires dosing 3-4 times per day. For methadone maintenance patients requiring analgesia, non-opioid analgesics such as acetaminophen, non-steroidal anti-inflammatories, antidepressants, and anticonvulsants with analgesia properties may be used adjunctively to help control the pain throughout day. Certain medication options, most often antidepressants with norepinephrine reuptake blockade properties (i.e. venlafaxine, duloxetine, milnicipran) that could be used adjunctively with methadone may have drug-drug interactions due to overlapping serotonergic properties, and/or prolongation of the QTc interval that could adversely affect cardiac conductivity. This would require careful monitoring by the prescribers and possibly more procedures such as ECGs.

Utilizing complementary and alternative medicine strategies is key in providing the most well-rounded pain management. These types of strategies include massage therapy, physical therapy, and acupuncture. While these are extremely beneficial components of treatment, there may be patients who cannot afford or do not have access to these strategies.

How do we treat patients who have documented, understood pain, but are also diagnosed with OUD? There is not a clear answer, but it is certain that the patients’ addiction and pain treatment should include coordination of their primary care provider, addiction provider, and possibly a pain management provider if available, especially if there is an acute injury requiring that a second opioid be used in addition to methadone. The differences in treatment approaches for different patients will be analyzed in the following cases.

A 42-year old female presents to a pain management doctor following an accident at work. The accident left her unable to work with significant back pain, two failed back surgeries, bilateral leg neuropathies, and radicular pain throughout her lumbar region. She has tried and failed hydrocodone/acetaminophen and morphine ER. In an effort to find an opioid that works for the patient, the pain provider sent in a prescription for oxycodone CR 30 mg. The medication was rejected by worker’s compensation and the pain provider attempted to do a prior authorization. The worker’s compensation adjuster explained to the provider that the only long acting opioid that is covered is methadone, due to its low cost. The worker’s compensation company is clearly mistaken. While methadone has quite a long half-life, its analgesic activity is relatively short. The pain provider sent a prescription for methadone low dose three times daily for pain benefit as a trial. 

A 57-year old patient is referred to the methadone clinic by his primary care provider. The patient has been seeing a pain management provider who has been prescribing him high doses of opioids for the last 10 years. The patient has pain pathology that justifies the opioids. Over time, he has required higher doses due to tolerance and has become increasingly more dependent on these medications. He even has a history of overdoses due to the patient taking increased amounts of his opioids because of what he describes as unbearable, uncontrolled pain. The pain management provider is not comfortable with continuing opioid therapy in this patient and recommended that the patient be assessed for, and begin treatment for opioid use disorder. The patient understands that he has become increasingly dependent on opioids and is afraid of the possibility of overdosing in the future but is frustrated due to his need for pain management. This patient was started in a methadone maintenance program, however other adjuvant analgesics have yet to be started by his provider.

A 53-year old patient has been treated for OUD at a methadone clinic for 5 years after falling dependent to opioids during treatment of his chronic pain. He is being weaned off of methadone. He’s extremely concerned about how his pain will be managed once he is not taking methadone.  As a patient with a history of opioid use disorder, he will most likely be barred from obtaining opioids moving forward to control his pain given his history. What options does this patient have for pain management? Where can patients then turn if they are truly in successful recovery, however still suffer from chronic pain? There is a unique opioid, buprenorphine, that could be the answer to this patient’s dilemma.

Fast forward a few months and this patient’s pain has still gone untreated due mostly to fear of his abuse history.  The patient feels there is no other choice but to turn to heroin to treat his untreated pain.  The patient is soon admitted to the emergency department for a heroin overdose.   Given his history, comorbidities, and current state where do we turn next?  A practitioner may administer or dispense (but not prescribe) an opioid such as methadone as emergent treatment for heroin overdose in a hospital setting. Treatment may not be carried out for more than three days or be renewed or extended. It may legally only be used while arrangements are being made for referral for treatment.  This option assumes that the patient who is admitted for an overdose has already agreed to and is ready for addiction treatment.

It is critical to have non-opioid medications and non-pharmacologic therapies that we know may be effective in treating pain on board for these patients. There is also the option of transitioning a patient to buprenorphine therapy! Providers with DATA-200 waivers, also known as X DEA numbers can prescribe Suboxone and similar buprenorphine products for OUD, but are not permitted to write bupenorphine under their waver for a pain patient. They can however prescribe other forms of buprenorphine for a patient, just like any other prescriber. Non x-waivered clinicians can in fact legally prescribe Suboxone and similar products to treat pain OFF LABEL, which is completely opposite than what is allowable with methadone.  Moreover, whether x-waivered or not, all clinicians that hold a DEA license can prescribe Butrans, Belbuca, and Buprenex as indicated in their corresponding FDA-approved package inserts, for pain. All of these buprenorphine therapies could be good options for pain management in these patients. Given the pain crisis we are facing, providers also need to be well versed in the unique properties of methadone and understand that an OUD patient on methadone may have underlying chronic pain needs after OUD treatment is complete.  What we don’t want is for this group of patients to be in recovery, and then relapse again due to inadequately addressed pain and poor or no access to behavior health and counseling.

After these authors spoke with both buprenorphine and methadone prescribers, the dilemma is clear.  Some patients have legitimate pain and are on OUD therapy, however legally the methadone or buprenorphine dose cannot be increased for pain.  These therapies are indicated to prevent withdrawal and relapse and not pain as discussed above.  The argument could be made that untreated pain can lead to relapse. It takes dedicated providers, patients, and a lot of effort from all involved to treat the dual diagnosis of opioid use disorder and chronic debilitating pain. A comprehensive knowledge of the regulations governing prescriptions for both methadone and buprenorphine are essential to properly approach patients with the dual diagnosis of pain and opioid use disorder!

Always, comments are welcomed with enthusiasm!

Drs. Alexa Daley and Lydia Mackie graduated with their PharmD’s in May 2019 from Albany College of Pharmacy and Health Sciences. Both completed a pain-focused rotation under the mentorship of Dr. Jacqueline Cleary (listed below) at Saratoga Community Health Center in Saratoga Springs, NY.

 

 

 

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References:

1. Toombs JD, Kral LA. Methadone Treatment for Pain States [Internet]. Am Fam Physician. 2005 Apr 1;71(7):1353-1358. Available from: https://www.aafp.org/afp/2005/0401/p1353.html
2. Methadone [Internet]. Substance Abuse and Mental Health Services Administration; 2015 [cited 2019 March 11]. Available from: https://www.samhsa.gov/medication-assisted-treatment/treatment/methadone
3. Prescriptions [Internet]. U.S. Department of Justice, Drug Enforcement Administration; 2019 [cited 2019 March 11]. Available from: https://www.deadiversion.usdoj.gov/faq/prescriptions.htm#rx-8
4. Trafton JA, Ramani A. Methadone: a new old drug with promises and pitfalls. Curr Pain Headache Rep. 2009;13(1):24–30.
5. Methadone. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc; 2018 [updated 18 May 2018; cited 7 March 2019]. Available from: http://online.lexi.com Subscription required to view.
6. Zorn KE, Fudin J. Treatment of Neuropathic Pain: The Role of Unique Opioid Agents. Practical Pain Management. 2016; 11(4).
7. Title 21 Code of Federal Regulations. Drug Enforcement Administration; Diversion Control Division; 2019. [cited 2019 March 24]. Available from: https://www.deadiversion.usdoj.gov/21cfr/cfr/1306/1306_07.htm
8. McCarberg B, Bainbridge J, Fudin J. OPTIMIZING CHRONIC PAIN MANAGEMENT: INTEGRATING PHARMACOKINETICS AND PHARMACODYNAMICS. Clinical Courier. 2019 June; Volume 27 (Issue 3)
9. Eap CB, Buclin T, Baumann P. Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Clin Pharmacokinet. 2002;41:1153–93
10. Methadone. In: Quick Answers; Drug-Drug Interactions [database on the Internet]. Greenwood Village (CO): Truven Health Analytics; 2019 [cited 2019 March 15]. Available from: www.micromedexsolutions.com. Subscription required to view.