- Alcohol and MMT
- MMT Patients and The Perils of Pain
- From the Editor
- Events to Note
- The Naltrexone Nexus Part 1
- Where to Get Info
- Readers Survey Response Coke Confounds MMT
Alcohol & MMT
Booze Begets Challenges
Alcohol drinking disorders have been estimated to affect from 50% [1,2,3] up to 70%  of all patients in methadone maintenance treatment (MMT) programs. This engenders various behavioral and psychosocial challenges potentially impacting response to treatment.
Reported problems among either alcohol-abusing or dependent patients have included: higher rates of medical illness and death, greater criminality, greater use of illicit substances during treatment, poorer social functioning, depression, obsessive-compulsive disorders, phobic anxiety, and psychosis. 
However, it has been stressed that patients in MMT programs can be treated for their alcohol drinking disorders without first withdrawing them from methadone. The policy of some alcohol treatment programs to first detoxify patients from methadone has important public health implications, since as many as 55% to 80% of patients will relapse to illicit IV drug use within two years with increased risks for hepatitis and HIV/AIDS. 
There has been some concern regarding adverse interactions between methadone and sedatives during alcohol detoxification, and between methadone and disulfiram (Antabuse) for long-term therapy. However, research indicates such concerns are unfounded, and no modifications in dosages are required for any of the drugs. 
Curiously, numerous animal experiments have found that morphine and other opiates actually suppress alcohol drinking.  The propensity for morphine, heroin and methadone to satisfy cravings for alcohol in humans has also been observed, and opiate treatment once was proposed for intractable cases of alcohol dependency.  Indeed, laudanum, an opium and alcohol mixture, was used early in this century in sanatoria providing “acute-alcoholism cures.”
Long-term use of opiates to treat alcohol dependence has never been pursued in opiate-naïve patients, since the treatment would likely create dependency on the opiates. Further, the exact mechanisms by which opiates reduce alcohol craving are not fully understood, and are apparently mercurial in nature, considering the high prevalence of alcohol abuse among opiate addicts and the failure of methadone to automatically curtail excessive drinking. There might be a dose/response relationship in methadone’s ability to decrease alcohol consumption, whereby higher doses are beneficial, but this has not been reported as yet.
According to the National Institute on Alcohol Abuse & Alcoholism (NIAAA), 90% to 100% of heavy drinkers have fatty livers to some extent, the earliest signs of liver disease. About 10% to 30% develop alcoholic hepatitis, and 10% to 20% develop cirrhosis, end-stage liver disease.  Some researchers have observed that chronic liver disease is the most common medical problem seen in heroin addicts, and 50% to 60% of those entering MMT have evidence of chronic liver disease. 
Extensive studies of MMT patients with liver disease have not been conducted, but methadone itself is not hepatotoxic, even in patients with severe chronic liver disease. However, the liver has a primary role in methadone metabolism, clearance, and drug storage methadone can persist in the liver unchanged for up to six weeks. Severe liver disease, or sudden changes in liver function, may cause significant alterations in methadone metabolism and release affecting serum concentrations so methadone dose may need appropriate adjustment. 
Alcohol (ethanol) consumption does not prevent hepatic uptake of methadone but has a biphasic effect on its metabolism.  When ethanol is present in large amounts, methadone metabolism is inhibited, resulting in higher serum concentrations and possibly symptomatic drowsiness. But when ethanol is no longer present following an acute drinking episode (or after discontinuing chronic use of large quantities), methadone metabolism is accelerated, possibly causing opiate withdrawal symptoms.
Research studies on the impact of alcohol in MMT have been inconsistent; some finding alcohol dependency associated with treatment failures; others showing it unrelated to treatment outcomes. To clarify the relationship between alcohol use and response to methadone treatment, during 1990-93 a group of MMT patients classified as alcohol-dependent (according to DSM-III-R criteria) was compared to a sample of “heavy-drinking” patients without dependency symptoms.  There was no non-drinking control group for comparison.
As might be expected, the results found that alcohol-dependent heroin addicts were likely to have more psychological and legal problems, increased family dysfunction, and poorer peer relations at admission to the MMT program. Surprisingly, however, they were also more likely to remain in treatment longer than nondependent alcohol drinkers. The researchers speculated that this may have been due to alcohol-dependent patients’ significant experiences with self-help groups, which aided them in overcoming denial, becoming more amenable to treatment, and able to focus more intensely on opiate dependency issues.
The researchers concluded that recognizing different types of alcohol drinking patterns especially dependent versus nondependent among MMT patients may help clinicians plan more effective treatments. Nondependent “heavy drinkers” may need special attention to help break down their denial about alcohol-related problems. The dependent-identified group should benefit from alcohol-specific interventions such as required attendance at AA.
In a follow-up to the above research, a selection of study participants were interviewed about one year after discharge from MMT.  Alcohol-dependent patients were found to have benefited from treatment more than those who were non dependent in terms of decreased opiate use, fewer alcohol-related symptoms, improved peer relations, and improved psychological functioning.
As a result of treatment, the dependent patients also had significantly fewer associations with problem-causing or criminally involved peers, increased self-esteem, lower depression, and responses suggesting improved social skills. The authors contended that this study demonstrated the feasibility and value of establishing the alcohol dependency status of heavy drinking clients at the time of admission to MMT so multiple drug dependencies can be identified and treated appropriately.
1. Chatham L, Rown-Szal G, Joe GW, Brown BS, Simpson DD. Heavy drinking in a population of methadone maintained clients. J Stud Alcohol. 1995;56:417-422.
2. Stine SM, Kosten TR. Methadone dose in the treatment of opiate dependence. Medscape Mental Health. 1997;2(11). Available online:http:www.medscape.com. Accessed: November 27, 1997.
3. Methadone maintenance and patients in alcoholism treatment. Alcohol Alert. Washington, DC: National Institute on Alcohol Abuse and Alcoholism. August 1988;1. Available online at: http://www.niaaa.nih.gov/publications/aa01.htm. Accessed February 10, 1998.
4. Miller S. The Integration of Pharmacological and Nonpharmacological Treatments in Drug/Alcohol Addictions. New York, NY; Haworth Medical Press: 1997.
5. Sinclair D. Development in Finland of the extinction treatment for with naltrexone. Psychiatria Fennica. In press, 1997.
6. Siegel S. Alcohol and opiate dependence: Re-evaluation of the Victorian perspective. In: Cappell HD, et al. eds. Research Advances in Alcohol and Drug Problems, 9. New York, NY; Plenum Publishing Corp.: 1986.
7. Kurtzweil P. Medications can aid recovery from alcoholism. FDA Consumer Magazine. May 1996.
8. Chatham, L.R., et al. Heavy drinking, alcohol-dependent vs. nondependent methadone-maintenance clients: A follow-up study. Addictive Behaviors. 1996;22(1):69-80.
MMT Patients and The Perils of Pain
The management of acute and chronic pain in methadone maintenance treatment patients is an ongoing concern. It has been observed that unrelieved pain has numerous negative health consequence, including: increases in stress, metabolic rate, blood clotting and water retention; delayed healing; hormonal imbalances; impaired immune system and gastrointestinal functioning; decreased mobility; and interference with appetite and sleep. Such pain can also produce psychological problems, such as: feelings of powerlessness, hopelessness, low self-esteem, and depression. 
Since A.T. Forum first addressed this topic over two years ago [Vol V, #1, Winter 1996], there have been two conferences on the subject and other commentary worth noting.
Last winter, a second conference on Pain Management and Chemical Dependency (PMCD) was held January 15-17, 1998, in New York City. According to Herman Joseph, PhD Executive Chair of the Conference and Researcher, Bureau of Methadone Planning & Policy, New York State Office of Alcoholism & Substance Abuse Services (OASAS) there were over 500 attendees representing 23 countries; most (86%) were physicians and nurses. The first conference was held in fall 1996 and another, the third, will be held in New York in late January 1999.
Presenter Russell Portenoy, MD, noted that “substance abuse” and the more serious “substance dependence” should be used in place of “addiction” to define the degree to which a person might exhibit aberrant drug-related behavior. While there is a broad range of behaviors that might be considered problematic by physicians, many factors might enter into a differential diagnosis of true dependency. 
He stressed that the different behavioral manifestations of drug abuse and drug dependence are often confused with the pharmacologic phenomena of tolerance and physical dependence. Such tolerance and physical dependence normally occur during pain treatment with opioid medications, and in those experiencing chronic pain are not indicators of what is normally thought of as drug addiction.
Portenoy proposed the term “pseudo addiction” as the development of aberrant behaviors in response to unrelieved pain. If analgesia is improved, those behaviors cease. Similarly, Herman Joseph mentioned that MMT patients may temporarily resort to illicit heroin to self-medicate unrelieved pain, but later cease such activity if adequate analgesia is provided.
The crucial point is that there is a tendency for the medical profession to label as “addicts” all persons with past histories of either drug abuse or dependency and subsequently to provide inappropriate or inadequate analgesia. As Seddon Savage, MD noted: “[Prior] addiction to opioids or other drugs does not preclude the successful use of opioids for the treatment of pain but requires careful assessment and management of both addiction and pain by an experienced treatment team.” 
The most commonly used guideline for analgesic selection is the three-step “Analgesic Ladder” published by the World Health Organization in 1990 [see chart]. Beginning with a non-opioid drug for mild pain, it matches the patient’s reported pain intensity with the potency of analgesic to be prescribed. It recommends opioid therapy starting in patients with moderate to severe pain; however, Richard Payne, MD, and other physicians strongly agreed that some type of pain should be treated very aggressively at the outset, jumping to a higher level up the Ladder. 
Morphine is still considered the “gold standard” by which other analgesics are measured. Full mu-receptor agonists such as morphine, hydromorphone, fentanyl, and methadone do not have ceiling effects to their analgesic activity and are useful for severe chronic pain.  Since tolerance for opiates does not automatically develop, when patients need increased dosages it may mean the underlying disease has spread or worsened, or more positively that the patient’s activity level has increased as analgesia has provided relief. 
Analgesic effects are reversed with mixed antagonist-agonist opioids, so they are not recommended for patients with chronic pain, and especially not if they are being treated with full agonist therapy (or on methadone maintenance). 
At all levels of the Analgesic Ladder, adjuvant therapy is particularly useful in patients with chronic pain, since those medications may enhance opioid analgesia. Antidepressants, anticonvulsants, corticosteroids, and psycho-stimulants are used.  However, patients undergoing addiction treatment may already be taking one or more of those medications for associated disorders (e.g., depression), so care is needed to avoid potential adverse interactions when prescribing multiple medications.
Methadone & Pain
A research poster presented at the PMCD Conference by Peggy Compton, RN, PhD, and Walter Ling, MD, of Los Angeles noted that methadone patients appear to have a greater sensitivity to pain, regardless of maintenance dose level, and may require more aggressive analgesia interventions.  This would imply higher analgesia doses at more frequent intervals.
Accordingly, Herman Joseph told A.T. Forum, “A patient on higher-dose methadone may be blocked against the euphoric effects of morphine-based analgesics, but they still need sufficient doses of pain-killer. There is no fear of overdose due to the cross-tolerance effects engendered by methadone. Whatever the patient’s methadone dose, sufficient analgesia should be administered to relieve pain.”
Daniel P. Alford, MD, speaking at the annual meeting of the Society of General Medicine, observed that methadone patients often get inadequate doses of narcotic analgesics due to mistaken perceptions that MMT itself provides pain relief and more narcotics may induce relapse. He affirmed that there is no evidence suggesting that this is the case, and, similar to the above findings, he noted that, due to cross-tolerance, methadone patients actually need higher, more frequent dosages of common analgesics than other patients. 
Herman Joseph further noted, “Methadone patients do not experience an increase in drug craving when given opiate analgesics, and they should be titrated off of them just as with opiate-naïve patients once the situation is resolved. The real issue and challenge facing us is getting physicians to prescribe pain medications in sufficient dose and frequency, without the misconception that methadone acts as an analgesic. The drug tolerance issue can be confusing to all medical professionals, possibly even more so for physicians who already use methadone in some patients as an analgesic.”
It is common for former substance-dependent persons to be fearful of losing control and thus refusing any analgesia. However, MMT patients should be assured that the blockade effect of an adequate methadone dose will impede any euphoric effects of analgesics, which serve only to relieve pain. Patients on lower methadone doses can be advised of a partial blockade and that they will feel very little euphoria, if any, from the opioid pain medication. In either case, patients should be reassured that their methadone maintenance dose will not necessarily be increased. 
Still, patients’ fears should not be dismissed casually, since practical experience indicates that for a variety of reasons potent analgesia has resulted in cases of relapse. Reassurances by medical staff need to be supported by close supervision and follow-up with patients, possibly including relapse prevention counseling.
The FDA and DEA indicate that as long as patient charts are properly updated, doctors can prescribe whatever they want. Yet, many physicians fear government control and intervention if pain meds are aggressively prescribed.
Such fears have been termed “opiophobia.” Ronald Buzzeo, RPh, commenting at the PMCD Conference, attributed this to the fear and stigma associated with addiction and controlled substances. Many physicians still avoid prescribing controlled substances altogether or prescribe less tightly controlled alternative drugs that are less potent. 
A fairly recent Public Policy Statement by the American Association of Addiction Medicine acknowledges that “Physicians are obligated to relieve pain and suffering in their patients. … [and] opioids are often required as a component of effective pain management.” 
And, while recognizing that some patients may seek such medications for purposes other than pain e.g., diversion for profit, recreational abuse, or maintenance of an addiction ASAM states: “The physician who is never duped by such patients may be denying appropriate relief to patients with significant pain all too often. It must be recognized that physicians who are willing to provide compassionate, ongoing medical care to challenging, psychologically stressed patients may more often be faced with deception than physicians who decline to treat this difficult population.” 
1. Public Policy Statement on the Rights and Responsibilities of Physicians in the Use of Opioids for the Treatment of Pain. ASAM News. July/August/September 1997;12(4).
2. Pain Management and Chemical Dependency: Evolving Connections. Final program and presentation summaries from second conference. New York City, NY; January 15-17, 1998.
3. Krick SE. Pain Management in Patients with Cancer. Pharmacy Times. February 1998:91-100.
4. MDs too often fail to give adequate analgesic doses. Oncology News Intl. December 1997.
5. Compton P, Ling W. Pain tolerance of opioid maintained subjects. In Pain Management and Chemical Dependency: Evolving Connections. Final program and presentation summaries from second conference. New York City, NY; January 15-17, 1998.
6. Nidecker A. Methadone-maintained patients may need opioids for pain. Internal Med News. July 15, 1997.
7. Payte JT, Khuri E, Joseph H, Woods J. Methadone patients and the treatment of pain. CDRWG Monograph. December 1994; 2.
Overpowering the Perils of Pain
1. MMT patients experience normal pain and thus need appropriate analgesia just like any other persons with acute or chronic pain.
2. Methadone patients may need analgesics (including opiates) more frequently and in larger doses.
3. Blockade effects of adequate methadone dose protect the patient from euphoric effects, drug craving, and/or respiratory depression due to large doses of analgesics.
4. The regular methadone maintenance dose should be continued while adequate short-acting opiates are prescribed.
5. Prior detoxification from methadone is counterproductive and can negatively affect the health of the patient.
6. Patients’ fears of relapse into prior chemical dependency should be acknowledged and appropriate supervision, follow-up, and relapse prevention support provided.
From the Editor
Words… Foes of Reality
Novelist Joseph Conrad once wrote, “Words, as is well known, are the great foes of reality.”
In the second issue of Journal of Maintenance in the Addictions [see Where to Get Info, p.4 ], Joyce Woods, president of NAMA (National Alliance of Methadone Advocates), similarly observes how words can distort reality. Referencing NIAAA Director Enoch Gordis, she states: “The word addiction itself leads to ambiguous connotations. In one sense it is associated with alterations of mood, compulsive use and criminal behavior. In another sense, it is the strict biological phenomenon of physical dependence, tolerance and withdrawal. In the public’s mind both intertwine semantically to conceptualize a nebulous state defined or labeled addiction.”
JMA editor Tom Payte, MD, expressed his concern over how words also obfuscate the field of methadone maintenance treatment. For example, at a time when there is a need to counter arguments that methadone is just a replacement for heroin, “the treatment modality is increasingly referred to as ‘opioid replacement therapy’ or ‘opioid substitution treatment,'” he writes.
The messages of Payte and Woods became quite poignant as we researched for this edition of A.T. Forum the separate topics of pain management and alcohol dependence among MMT patients. Stigma raised its ugly head as we found that many “addicts” are still denied adequate analgesia, while “alcoholics” are sometimes required to detox from methadone prior to treatment for their drinking disorders.
Actually, the terms “addiction” and “alcoholism” were long ago abandoned by the American Psychiatric Association in their Diagnostic and Statistical Manual of Mental Disorders substance (or alcohol) abuse and the more serious substance (or alcohol) dependence are preferred. Dependence includes physiological symptoms of tolerance and withdrawal, and behavioral symptoms such as impaired control over substance use, chronicity, and potential for relapse. Abuse is a less severe, residual category for diagnosing those who do not meet all the criteria for dependence, but who continue drug/alcohol use despite substance-related physical, social, psychological, economic, legal, or occupational problems, or in dangerous situations such as while driving.
The fourth and most recent edition in 1994 (DSM-IV) further refined the definitions and also highlighted the fact that symptoms of certain disorders, such as anxiety or depression, could be related to an individual’s aberrant use of alcohol or other drugs.
Payte has hopes that JMA can play a role in “bringing about a coherent standard nomenclature for all of us that does not involve language that contributes to stigma and public misunderstanding and misperceptions about maintenance treatment.” We certainly wish him success in that endeavor.
After all, as Rudyard Kipling once said, “Words are the most powerful drug used by mankind.”
Methadone Survey – Last Call
In our last edition [Winter 1998], we issued a call to readers to help us update our survey of nearly five years ago concerning methadone dosing practices of clinics around the U.S., and hopefully also include international data. If you haven’t already done so, PLEASE RESPOND. Here are the questions about your clinic’s operation:
1. The Highest typical daily methadone dose is _____ mg/d.
2. The Lowest typical daily methadone dose is _____ mg/d.
3. The Average daily methadone dose is _____ mg/d
4. We operate on a ___ for profit ___ non-profit basis (check one).
Be certain to include the city/state and country of your clinic.
There are several ways for you to reply: A. Provide your answers on the postage-free feedback card in this issue; B. Write or fax us [see info below]; or C. Visit our Web site to respond via e-mail . As always, your written comments will help us better discuss the results in our next issue.
- Stewart B. Leavitt, PhD, Editor
- Addiction Treatment Forum
- 1750 East Golf Rd., Suite 320
- Schaumburg, IL 60173
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- Internet: http://www.atforum.com