Stacy E. Seikel, MD PA

Author: Stacy E. Seikel, M.D.

ABSTRACT: Methadone, a full mu-opioid agonist, is the recommended treatment for opioid addiction during pregnancy. Many medical providers are confused about its use and some perpetuate the stigmatization of this very important treatment for pregnant women who are addicted to opioids. In this article, methadone and buprenorphine will be presented as safe and effective treatments for the pregnant addicted patient. Clinical tools such as the Prescription Drug Monitoring Program will be discussed and its utilization reviewed. Also, the use of Point of Care (POC) drug screens will be presented in the context of the primary care physician’s office setting.

I remember the first day of my “methadone clinic rotation” over ten years ago. Having left the field of anesthesiology, I had a good fund of knowledge for the use of opiates in treating pain. The thought of using an opiate to treat opiate addiction, just seemed wrong. I was familiar with “abstinent based recovery.” That’s easy. You get off drugs and you do whatever it takes to stay off drugs, right? “Medication Assisted Recovery” was a new concept for me. I was excited about my new job in a large publicly-funded substance abuse treatment agency. I had worked in detox, worked with substance abusing adolescents in the Department of Juvenile Justice programs, and worked in a men’s residential drug treatment program. Now I was working in the Methadone Clinic, and in my naïve, somewhat arrogant mindset, I thought I would find people just replacing one drug for another. Was I wrong about that. One of my first patients was a single mother of a six year-old girl, who was twenty weeks pregnant. This patient walked her daughter to the bus stop to see her off to school every morning. She then caught public transportation with three bus changes to get the Methadone Clinic. (The new politically correct term is now Opiate Treatment Program (OTP). This patient would get her daily dose of methadone at the clinic and then attend either group or individual therapy sessions. She would then catch another bus to her job cleaning houses, and be back in time to greet her daughter at the bus stop after school. She walked her home, helped with homework, fixed dinner, bathed her daughter, and got her to bed. She would then do her assignments from the counseling group, call her sponsor in Narcotics Anonymous, say her prayers, and go to bed. She got up the next morning and did the same thing again. She was one of the most grateful and joyful people I had ever met. Eighteen months earlier, she was injecting heroin and living on the street. What did I know about working hard for one’s recovery? These patients were teaching me about recovery every day.

But what about methadone treatment during pregnancy? I remember during this time sarcastically saying to the medical director, “So we are going to expose these developing fetuses to methadone for nine months? Surely we can come up with something better than that!” Again, I had a lot to learn. I learned that methadone was the gold standard of treatment for the opiate addicted pregnant patient.¹ It stopped craving, was typically dosed once per day, did not create euphoria, and it blocked the effects of short acting opiates due to its high affinity for the mu receptor. This was backed by over fifty years of solid clinical research. Well, that sounded pretty good for the mom, but what about the baby? Drugs are bad for babies, right? Well, as it turns out, methadone has been used and studied in pregnant women and their babies since the 1950’s. We have over fifty years experience showing that pregnant women with opiate dependence/addiction have much better fetal outcome than mothers who taper off opiates during pregnancy.² The reason for this is that the relapse rate is so high, and with the relapse, typically comes polysubstance use. So it seemed to me, at that point in my career, that methadone in pregnancy was the lesser of two evils. A person could go on methadone maintenance, learn recovery and parenting skills, and have a full term, normal weight, healthy infant. Alternatively, she could taper off the opiates, have a ninety percent chance of relapsing, and expose the fetus to a plethora or illicit drugs. When a fetus is in and out of withdrawal throughout pregnancy, it cannot grow and develop normally because it is in distress. When a baby is on a stable dose of methadone in utero, it can grow and develop normally because it is not in distress.³ This full-term, normal weight, otherwise healthy newborn will be physically dependent on opiates.⁴ They are not addicted to opiates. Addiction is characterized by use despite harm, cravings, and pre-occupation. Babies don’t have that; they have physical dependence. Now we have the opiate withdrawal to treat, known as Neonatal Abstinence Syndrome (NAS). This can be treated by early effective intervention, sometimes requiring IV opiates, sometimes not.⁵ I began to see how that would be better than exposing the fetus throughout pregnancy drugs.

So let’s look at the science behind this totally counter-intuitive treatment in the pregnant opiate addict. First of all, what is this disease of addiction? Is it physical dependence, lack of willpower, or a brain disease? According to the American Society of Addiction Medicine, addiction is “a primary chronic neurobiologic disease, with genetic, psychosocial, and environment factors influencing the development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving.” One can remember these criteria as the “Four C’s.”

The use of methadone or buprenorphine for the treatment of opiate addiction is called Opioid Agonist Therapy.⁶ In pregnancy, studies are unclear regarding the relationship between the dose of methadone and the severity of NAS. However, studies are very clear that most patients (pregnant or non-pregnant) relapse if taken off methadone before one year of methadone is completed.⁷ Sublingual buprenorphine was FDA approved in 2004 for use in opiate addiction. It can be obtained in a private physician’s office, not only at an OTP. Buprenorphine is being used successfully in pregnancy for opiate addicted patients.⁸ A recent publication in the New England Journal of Medicine compared newborn Neonatal Abstinence Syndrome in methadone or buprenorphine maintained pregnant women.⁵ The outcomes showed less severe Neonatal Abstinence Syndrome and shorter hospital stays in the babies born to the buprenorphine maintained mothers. Both drugs are designated “Category C” by the FDA. However, Methadone is approved for use in pregnancy by the National Institute of Health consensus panel. This approval is due to our fifty years of successful experience in its use in pregnancy. Methadone remains the gold standard for opiate replacement therapy in the opiate addicted pregnant patient.

Every pregnant woman with opiate addiction comes to me wanting to “detox” and get off “everything.” It takes support and education with the patient and family for them to understand that they are doing the right thing for the baby by going on methadone. They must understand the difference between untreated withdrawal (intrauterine) and treatable withdrawal in the neonate. The patient needs to be constantly be reassured that she is putting her infant first and doing the right thing. A team approach of obstetricians, pediatricians, neonatologists, nurses, addictionologist, and primary care providers all giving the patient the same message, that she is doing the right thing by going on methadone, is invaluable.⁹ It will not be difficult for a patient to find someone who will say that their babies are addicted and they are harming their unborn child. These statements are not only inaccurate, but they also are harmful. I have many pregnant patients who are stable in their recovery, active in counseling, and engaged in twelve step recovery who are living a lifestyle that will be healthy and supportive for the newborn. Sometimes these stable successful patients will request to taper while pregnant. When I inquire as to why they are requesting a taper, typically it is due to pressure and guilt from a family member or sometimes even a misinformed medical professional. It is not difficult to induce guilt in these women; they are remorseful and concerned about the well-being of their babies. It is difficult to assess the impact of polysubstance use in early pregnancy. However, we know of limited to no long-term negative sequelae on babies born to mothers who are on stable doses of methadone, engaged in psychosocial services, and in a stable living environment.⁷

As I worked with pregnant women in the Opiate Treatment Program, I came to understand that addiction is a brain disease affecting 10-15% of the general population.⁹ More importantly, I saw that treatment works. I felt humbled to see this amazing transformation of a woman whose brain was being run by a limbic system in overdrive, to one with intact executive function and a prefrontal cortex that could override a thought of using. By studying Nora Volkow’s work at the National Institution of Drug Addiction (NIDA), I saw evidence that the limbic system had markedly increased activity on PET images.¹⁰ The prefrontal cortex in these patients with active addictive disorders, had diminished cellular activity.¹¹ In neuroimaging, this is called “hypofrontality.”¹² Scientists could predict relapse in cocaine addicts by “how dark,” or the degree of hypofrontality, in these patients.¹⁰ Now it made sense. This was a brain disease, not a moral failing. When this information was coupled with Dr. Kreek’s work on the effects of short acting opiates on the mu receptor¹³, it all came together for me. When the mu receptor is chronically activated by short acting opiates over a period of time, it results in altered gene expression. Once there is new gene expression, the playing field had changed. With new genes being expressed, new metabolic pathways are activated from new enzymes, and the brain had been changed¹ most probably permanently.⁹ In Narcotics Anonymous, there are sayings “once an addict, always an addict” and “you can’t change a pickle back into a cucumber.” That now made sense to me. With this information, I understood now why methadone was necessary in early recovery, in order for my patients to learn new coping skills, relapse prevention skills, parenting skills, and the ability to ask for help through an extensive support network. This support network started with her counselor and peers in the OTP, but eventually grew to include women in recovery in community-based twelve step programs.

So how prevalent are addictive disorders in pregnant women? It appears that the prevalence is about the same as the general population (i.e. 12-25%). There appears to be no difference in socioeconomic status and no difference in the patient being seen in a public clinic versus a private practice.⁹

Screening pregnant women for substance abuse has become a controversial topic. Opponents are concerned that marginal populations will be targeted and punished instead of getting treatment.¹⁴ This is a legitimate concern with which I agree. I believe that all women should have a drug screen on their first prenatal visit. Physicians need to use that data to engage the patient into treatment services if needed. A punitive, judgmental attitude will scare the patient away. Often they will continue their drug use and not continue their prenatal care. There are many questionnaire-based screens that are designed specifically for women. Personally, I believe the best screen is a drug screen. Point of Care (POC) drug screens provide results in 3-5 minutes, on site.¹⁵ These tests are inexpensive; a 12 panel test is about $5.00, practical and easy to use. When that is coupled with a patient query in Florida’s new Prescription Drug Monitoring Program (PDMP), the playing field is leveled between the physician and the patient who may have a substance use disorder. These patient queries are called Patient Advisory Reports (PAR) and can be obtained in less than a minute. Physicians can get a username and password by going to www.E-FORCSE.com. Once credentials have been obtained, go to www.hidinc.com/flpdmp to run a patient query. It only makes sense to know what controlled substances a patient may be taking. Physicians need to remember that the “spirit of the law” is not to incarcerate every person with a substance use disorder. I use this resource as a clinical tool. My office staff obtains a Patient Advisory Report (PAR) the day before a patient is scheduled to come in and clips the report to the chart. I look for inconsistencies between what the patient is telling me and what the PAR is indicating. I respectfully point out to the patient that it appears the patient may have a substance use disorder. I discuss addiction as a brain disease, that is responsive to treatment. I then reinforce that I know this pregnant woman wants to be a good mother and does not want to put her unborn child at risk. Pregnant women are the most motivated patient population that I treat.

My hope is to diminish the stigmatization of methadone and buprenorphine of Opiate Treatment Programs. In pregnant patients, methadone is the gold standard of treatment. It stops craving, allowing the patient to fully engage in the recovery process. I have heard people say “Oh, she’s just not ready. She’ll stop when it’s bad enough.” That is simply not true. I do not know one patient in active addiction who truly wants to continue being a prisoner to this disease. They are hopeless and afraid, and often convinced that treatment does not work. The brains of patients who have abused drugs and alcohol often have been altered significantly. Some of these patients need medication in order to engage in treatment and to stabilize. Some will be able to successfully undergo a medically supervised taper after delivery, and some will need to be on medication long term. Methadone is not an evil drug. It is a highly effective medication for the treatment of opiate addiction in pregnancy. I know, because I see it working every day.

Author: Stacy E. Seikel, M.D.

The letter Sunday, December 6, 2009, titled “Methadone warnings might save lives”, was heartbreaking. The letter was from the parent of a teenager who died from apparent methadone medical mismanagement and was an attempt to clear up some misconceptions about methadone. I would like to respond to the request for a follow-up article because methadone is a medication that is riddled with misconceptions and stigma.

As stated in the letter, methadone is used both for pain management as well as the treatment of opiate addiction. Opiates are a class of drugs which includes medication such as oxycodone, morphine, hydrocodone, methadone and heroin. Addiction is a bio-psycho-social disease manifested by loss of control over drug use, use despite harm, and cravings. Addiction is not the same as “physical dependence.” Physical dependence occurs in any person who takes opiates consistently for more than a few weeks, and is manifested by a characteristic withdrawal syndrome when the medication is stopped abruptly. Someone can be addicted, but not have physical dependence and vice versa.

Methadone clinics (also known as Opiate Treatment Programs or OTPs) use methadone to treat opiate addiction. I understand that it seems counterintuitive to treat drug addiction with a drug. I thought the exact same thing before I started working at an OTP. As a physician specializing in both Addiction Medicine and Pain Management, I thought I would go in there and show them what recovery was really about. I assumed that the clinic patients were people in active addiction, who had found a legal way to get drugs. To my surprise, what I found were clients who were doing the hard work of recovery, just like the clients in “abstinent based recovery.” These clients who were in a “medication assisted” recovery process were not only abiding by all of the strict state and federal regulations that govern OTPs, but they were flourishing in recovery. These clients were attending individual therapy, group therapy and 12 step meetings in the community. Many were recovering in all aspects of their lives, and helping the new comer to achieve the same. Just as in “abstinence based recovery,” some clients in “medication assisted recovery” do not stabilize. Despite our best efforts, many people may continue to be active in their addictive process. It is frustrating for families, friends, and most of all for the client.

Methadone, when prescribed for pain management, is prescribed by physicians in their office. They do not operate under the strict regulations of an OTP. Methadone for relief of pain should be dosed about every eight hours. Methadone in an OTP, where it is used to relieve the signs and symptoms of withdrawal, only needs to be dosed once a day and this is usually done under direct observation at the clinic. Methadone is a very potent opioid analgesic (pain killer). It should only be used for pain in patients who have developed tolerance to opiates. It is very easy for an “opiate naive” patient, (a person without tolerance to opiates), to overdose on methadone. This is the result of respiratory depression which is dose dependent meaning that the higher the dose, the more likely it is for a person to stop breathing. Also, when methadone or any opiate is combined with other sedatives, such as Xanax, Valium, Klonopin or alcohol, there is an increased risk for respiratory depression and death. Physicians prescribing methadone need to be aware of the potential lethal combination of opiates and benzodiazepines (Valium, Xanax, and Klonopin).

Another characteristic of methadone that makes it so dangerous when not prescribed or taken appropriately is its long duration of action (i.e., half life). Methadone levels build up in the blood for about five days even while taking the same dose due to its long half-life of 24 hours. This means a person may be prescribed ten milligrams, three times a day and feel fine the first day or two. As the blood level continues to get higher even while taking the same dose, the person may become overmedicated. In a worst case scenario, they may stop breathing and die from an accidental overdose. This is particularly easy to do if the patient is also taking benzodiazepines, barbiturates or alcohol.

Whether a physician is prescribing methadone in an OTP or in a pain management practice, it is imperative to “start low and go slow.” Patients need to be educated regarding the signs of opiate toxicity and they need to be monitored closely.

My hope is to diminish the stigmatization of methadone and of Opiate Treatment Programs. Medication Assisted Treatment is not the first choice when a person is initially attempting to recover from addiction. However, in many patients, their brains never stop craving long enough to fully engage in the recovery process. I have heard people say “Oh, he’s just not ready. He’ll stop when it’s bad enough.” That is simply not true. I do not know one patient in active addiction who truly wants to continue being a prisoner to this disease. They are hopeless and afraid, and often convinced that treatment does not work. The brains of patients who have abused drugs and alcohol often have been altered significantly. These patients need medication in order to engage in treatment and to stabilize. Some will be able to successfully undergo a medically supervised taper and some will need to be on medication long term.

Methadone is not an evil drug. Methadone is an effective medication for chronic pain. It is relatively inexpensive and it is safe when prescribed by a knowledgeable physician and taken as prescribed. Methadone, when coupled with psycho-social support, is also a highly effective medication for the treatment of opiate addiction. I know, because I see it working every day.

Stacy Seikel, MD
Medical Director
The Center For Drug-Free Living, Inc.

Pain & Addiction Specialist
Hanley Pain and Rehab

By: David A. Fiellin, M.D.

By: NIDA International Program

Buprenorphine combined with naloxone (Suboxone) and buprenorphine alone (Subutex) are both safe and effective at reducing opiate use and craving when administered in an office-based setting.

A new report from the Buprenorphine/Naloxone Collaborative Study Group, led by researchers at the National Institute on Drug Abuse (NIDA), is the largest treatment trial of its kind. Funded by NIDA, which developed buprenorphine in collaboration with Reckitt-Benckiser Pharmaceuticals, the double-blind, placebo-controlled clinical trial involved 326 opiate-addicted patients at eight U.S. sites. The study was reported in the September 4 New England Journal of Medicine.

Patients taking combined buprenorphine and naloxone were three times more likely than patients taking placebo to screen negative for opiate use, and those taking buprenorphine alone were 3.6 times more likely to screen negative for opiate use. The results were so positive that the trial was terminated early because the institutional review board that approved the study no longer deemed it ethical to treat participants with placebo.

After four weeks of double-blind study, all patients were offered the opportunity to continue in an open-label phase for an additional 48 weeks with either buprenorphine alone or the combination. The trial, conducted in from late 1996 through 1997, became a pivotal study in the Food and Drug Administration’s approval of buprenorphine for office-based treatment of opiate addiction.

“Buprenorphine represents a major step forward in the treatment of opiate addiction,” said Nora Volkow, M.D., director of NIDA, in announcing the study’s publication. “It allows physicians to treat patients for this disease in the same manner that other people are treated for such other chronic illnesses as diabetes or high blood pressure.

“Office-based buprenorphine increases the availability of therapy by offering patients greater flexibility in treatment scheduling and integration with the mainstream public for their health services.”

Buprenorphine, chemically related to morphine, is a ?-opiate receptor agonist and a ?-opiate receptor antagonist that has been used in intravenous form in many countries (including the United States) for decades to treat moderate to severe pain. NIDA’s decade-long development of the medication into a sublingual formulation allows the drug to be absorbed into the bloodstream without having to go through the liver’s first-pass metabolism. While the drug has a potential for abuse—much like methadone and the soon-to-be-discontinued levomethadyl acetate (see page 36)—combining buprenorphine with naloxone significantly reduces this potential.

Naloxone is thought to block the effects of opiates by competing directly for binding with the same receptors. This limits the effects of the opiate, including buprenorphine.

Office-based treatment with buprenorphine was authorized by the Drug Treatment Act of 2000, which allows Schedule III, IV, and V narcotics that are approved for addiction treatment to be administered for either medically supervised tapering (detoxification) or long-term maintenance therapy. On October 8, 2002, the FDA approved buprenorphine alone and in combination with naloxone (both Schedule III medications) for that use.

Physicians who wish to prescribe buprenorphine must take an eight-hour training course (APA provides an online training course on its Web site) and apply to the Substance Abuse and Mental Health Services Administration (SAMHSA) to be certified.

In an editorial accompanying the study, H. Westley Clark, M.D., J.D., M.P.H., director of SAMHSA’s Center for Substance Abuse Treatment, noted that “as of July 11, 2003, [SAMHSA] had received only 1,981 [applications for certification]. Many more physicians need to provide office-based treatment if the promise offered by the availability of buprenorphine is to be achieved.”

An abstract of the study is posted on the Web at http://content.nejm.org/cgi/content/abstract/349/10/949. More information on buprenorphine training through APA is posted at www.psych.org by logging into the online CME section where APA member number and password are required.