AT Forum Volume 23, #1 Winter 2013 Newsletter

OTPs Can Now Dispense Buprenorphine Take-Homes with No Waiting Periods

As of January 7, 2013, opioid treatment programs (OTPs) can now dispense buprenorphine take-homes, with no predetermined waiting period for stable patients. The Substance Abuse and Mental Health Services Administration (SAMHSA) at last issued its final rule giving OTPs the welcome flexibility this past November, and the rule was published in the Federal Register December 6, 2012. Fears of diversion were probably the driving force behind the delay in the final rule; the proposed rule was issued in June 2009.

Because Schedule III substances—like buprenorphine—have a lower potential for abuse compared to Schedule II substances—like methadone—there is justification for the less-restrictive rules on dispensing buprenorphine, according to SAMHSA.

Of course, states can have stricter rules. Some require OTPs to be open 7 days a week, and the idea of buprenorphine take-homes isn’t even on their radar screens. Still, the final rule is a very important first step for OTPs and their patients.

Most OTP physicians (80 percent) have already completed the DATA training and obtained the required waivers, according to SAMHSA. OTPs will not have a cap on how many patients they can treat with either buprenorphine or methadone. However, for take-homes, OTPs will still be “required to assess and document each patient’s responsibility and stability to handle opioid drug products, including buprenorphine products,” SAMHSA said in the final rule.

At this important juncture in the history of OTPs, accompanying articles in this issue take a look back at the development of buprenorphine and methadone for treating patients with opioid use disorders, and the differences between the two medications. We also report thoughts from leaders in the field as to what the new rule is likely to mean to OTPs and their patients.

Buprenorphine vs. Methadone

Buprenorphine and methadone, both being opioids, activate the opioid (mu) receptors on nerve cells. And both drugs have long half-lifes, meaning that they’re long-acting medications. The half-life can vary from 24 to 60 hours for buprenorphine, and from 8 to 59 hours for methadone. (The half-life is the amount of time a drug stays in the body before its concentration in the plasma drops by half. A drug’s half-life can vary from patient to patient.)

The long half-lifes of buprenorphine and methadone account for their usefulness in treating opioid dependence. Simply put, these drugs lack the peaks and troughs that are associated with short-term opioids, like heroin—swings in drug plasma levels that can cause overdose and withdrawal symptoms.

But there are key differences between buprenorphine and methadone.

Full Agonist vs. Partial Agonist

Buprenorphine is a partial agonist; methadone, like heroin, is a full agonist. It is by their actions on opioid receptors that opioids achieve their analgesic (pain-killing) as well as their addictive effects.

Methadone, as a full mu opioid agonist, continues to produce effects on the receptors until either all receptors are fully activated, or the maximum effect is reached.

Buprenorphine, as a partial agonist, does not activate mu receptors to the same extent as methadone. Its effects increase until they reach a plateau. At that level, opioid-addicted patients can discontinue opioid use without experiencing withdrawal. Buprenorphine reaches its ceiling effect at a moderate dose, which means that its effects do not increase after that point, even with increases in dosage.

Like all opioids, buprenorphine can cause respiratory depression and euphoria, but its maximal effects are less than those of full agonists. The benefits of this from an overdose perspective constitute the safety profile of buprenorphine—a lower risk of abuse, addiction, and side effects than with full agonists.

For people who are not addicted to or dependent on opioids, the effects of partial (buprenorphine) and full (methadone) agonists are indistinguishable. However, at a certain point, the increasing effects of partial agonists reach maximum levels. For this reason, people who are dependent on high doses of opioids are better suited to treatment with a full agonist, such as methadone.

Buprenorphine, like methadone, has a serious potential for drug-drug interactions. It must be used cautiously with other medications, in particular benzodiazepines, other sedatives, opioid antagonists like naltrexone, and opioid agonists.




Partial agonist Full agonist Full agonist
Long half-life (24 to 60 hours) Long half-life (8 to 59 hours) Short half-life
Ceiling effect; good safety profile No ceiling effect (useful in patients dependent on high doses of opioids) No ceiling effect

Formulations of Buprenorphine

In October 2002, the Food and Drug Administration (FDA) approved the buprenorphine monotherapy product, Subutex, and a buprenorphine/naloxone combination product, Suboxone, for treating opioid addiction.

Subutex is no longer sold in this country. It has been replaced by generic buprenorphine. Suboxone, a sublingual tablet (designed to dissolve under the tongue), comes in two dosage forms. Suboxone film was approved by the FDA in 2010. The sublingual film dissolves faster than the tablet, and is individually wrapped in unit-dose, child-resistant pouches. According to the manufacturer, Reckitt Benckiser, Suboxone film is clinically interchangeable with the tablet.

Last fall, Reckitt Benckiser voluntarily removed its Suboxone tablets from the market, citing a few pediatric overdoses. But it protected its hold on the Suboxone market by retaining the film formulation. The patent on the tablets had long expired; the patent on the film runs until 2023. Patients, of course, had to be switched to the film, unless their physicians wanted to switch them to generic buprenorphine. At the same time that Reckitt pulled the tablets, it filed a Citizen’s Petition with the FDA, calling on all buprenorphine products to be sold in childproof packaging.

The effect of these moves by Reckitt on the buprenorphine marketplace are not clear, said Nicholas Reuter, MPH, who was senior public health analyst with SAMHSA’s Center for Substance Abuse Treatment (CSAT) when this story was written (he retired on January 31, 2013). “Submitting a Citizen’s Petition doesn’t mean the FDA has to accept it,” he said. In addition, in November 2012 the FDA accepted Orexo’s New Drug Application for Zubsolv, a buprenorphine-naloxone combination. Zubsolv could well be the first generic competition to Suboxone. And on December 17, 2012, Titan licensed Probuphine, its buprenorphine implant, to Braeburn Pharmaceutical for exclusive commercialization in the U.S. and Canada. “The buprenorphine marketplace is looking at different formulations,” noted Mr. Reuter. “There could be a generic competitor [for Suboxone] tomorrow.”

Making the Decision: Methadone vs. Buprenorphine

Aside from the dosage issue, there is no “cookie-cutter” approach for deciding what patient gets buprenorphine and what patient gets methadone. Philip L. Herschman, PhD, chief clinical officer of CRC Health Group, pointed out that different patients react differently to different medications. “Some feel better on buprenorphine, some feel better on methadone,” he said. CRC has been using generic buprenorphine in its OTPs on the same basis as methadone. The extent to which CRC will be able to give buprenorphine take-homes will depend in large part on state regulations—just because the federal government has approved the plan doesn’t mean states will.

“Buprenorphine is great, but it’s not for everybody,” said Walter Ginter, CMA, project director of the Medication Assisted Recovery Support (MARS) project. He doesn’t think the final rule is going to make a big difference for most patients. He noted that few patients go to methadone maintenance as their first course of treatment.

In fact, Mr. Ginter can speak as an expert on subjective effects in a personal way: he has been maintained on both medications—buprenorphine during its development in the 1990s, when he was a study subject, and then methadone. He has been on a high dose of methadone for years, and says “I don’t think I’m clouded out.” Indeed, he is one of the most energetic and articulate advocates in the field. It comes down to a matter of personal preference, he said. “With methadone, you’re never sick and you’re never high, but you do get the serum peaking four hours after the dose,” he said. “I think Suboxone is too much the same, with no ups or downs.”

Still, there are OTPs that do switch patients from methadone to buprenorphine, titrating very carefully downward for patients on doses of 80 milligrams or more of methadone before switching to buprenorphine, said Mark Parrino. MPA, president of the American Association for the Treatment of Opioid Dependence (AATOD). In general, if a patient has been using opioids for a longer period, or has a higher tolerance, methadone would be more appropriate. The reason is that buprenorphine’s ceiling limits those higher-dose equivalents.

Publishers Note: Nicholas Reuter, MPH joined Reckitt Benckiser in February 2013 as a Treatment Manager.

History of Buprenorphine

 Buprenorphine has been in active use for 10 years as a treatment medication for opioid addiction.

As explained by Nicholas Reuter, MPH, senior public health analyst with SAMHSA’s Center for Substance Abuse Treatment (CSAT), the development of buprenorphine was preceded by the development and approval by the Food and Drug Administration (FDA) of levo-alpha-acetyl-methadol (LAAM). The government supported the development of LAAM, but the medication “couldn’t generate enough income from patient use to be sustainable,” he said.

“At the time, there was a lot of discussion about the treatment gap,” he told AT Forum. There were at least 2 to 3 million people who needed treatment for opioid addiction, and only 150,000 or fewer could get into Opioid Treatment Programs (OTPs). “The thinking was that we needed to develop an office-based model,” said Mr. Reuter.

Buprenorphine had been approved for addiction treatment in other countries, Mr. Reuter said, and the molecule is interesting because it is a partial agonist, which gives it a ceiling effect. This means that the risk of overdose is attenuated. “Taken in increasing amounts, it causes dysphoria [anxiety, depression, unease],” noted Mr. Reuter.

People on Capitol Hill were working to see how buprenorphine could be developed as an office-based treatment for opioid addiction, and this led to the development of DATA 2000, said Mr. Reuter. “It was set up as an experiment.” Safeguards were built into the law, so that if treating patients in the physician’s office with narcotic drugs did not turn out to be a good idea, the law could be rescinded. “We were required to do a formal analysis.”

The “experiment” worked, and in 2002 the FDA approved buprenorphine for the treatment of opioid addiction.

Why Not More OTPs?

Why didn’t SAMHSA just increase methadone slots in OTPs, if there was a need for more treatment? First of all, it’s not that easy to increase the number of OTPs, said Mr. Reuter, noting that almost everyplace a program tries to open up, there is a NIMBY battle from the local community. But perhaps more important, there were concerns about methadone overdoses. It turned out that the overdoses were mainly related to pain prescribing, but that was not known at the time. That’s because the increase in pain prescribing coincided with the rule allowing more flexible methadone take-home doses.

But SAMHSA was in a difficult position, nevertheless. “Here you have people saying methadone is a dangerous drug, too many people are dying from it, and we have to look at how it’s used,” said Mr. Reuter. “Methadone mortality was such a significant concern. We would hear it every day.”

While there has been an increase in the number of OTPs in the past decade, there is still a treatment gap, said Mr. Reuter. There were 900 OTPs ten years ago, and now there are 1,260. The number of patients treated in OTPs has gone from 170,000 In 1998 to about 300,000.

Instead of expanding some office-based models for methadone, the government decided to look at buprenorphine—in large part because of problems with methadone mortality, which peaked in 2001, said Mr. Reuter.

Buprenorphine in Practice

Something similar has happened with buprenorphine’s early years—in spite of all of the agency collaboration. “What’s interesting is that as physicians got more experience in treating opioid addiction, they realized that there is a high relapse rate, and maintaining the patient is better than withdrawing the patient,” said Mr. Parrino. This doesn’t mean that every patient will need to be on medication for life.

But by increasing access to buprenorphine, DATA 2000 did not necessarily provide access to counseling and other comprehensive treatment services, said Mr. Parrino. “As far as we know, many patients did not receive counseling in addition to the medication prescribed, did not receive routine toxicology tests to guide clinical decision making, and appeared to divert buprenorphine take-home medication,” he told AT Forum. “Without question, treatment access was increased significantly because patients who never would have sought treatment in the OTP, or simply felt more comfortable receiving such care in a physician office setting, did get access to treatment. But what kind of treatment did they receive?”

Buprenorphine Prescribing Trends

It’s easy to find the number of physicians who are certified through the DATA waiver process to prescribe buprenorphine, but much more difficult to find out how many of them are actually prescribing, or how many patients they have, or whether they are providing counseling or drug testing.

According to the Drug Enforcement Administration’s ARCOS data, over 190 million dosage units of buprenorphine were distributed to pharmacies in 2010, said Mr. Reuter. That’s almost five times the 40 million distributed in 2006. Only 1.1 million dosage units were distributed to OTPs during 2010. Almost 800,000 individuals got prescriptions for buprenorphine from office-based physicians in 2010—five times the 140,000 estimated in 2006.

SAMHSA measures the number of prescribing physicians by how many submit applications to get certified to prescribe buprenorphine. Currently, that’s about 23,000, according to Mr. Reuter. But that doesn’t mean that they are all prescribing—far from it. In fact, the number of physicians prescribing buprenorphine has gone down; fewer physicians are prescribing to more patients, and there is a clear need for more access to buprenorphine.

In 2005, there were 22,000 physicians certified to prescribe buprenorphine under DATA 2000. Of these, almost 5,200 requested to treat up to 100 patients, according to the final rule. In 2009, when the DEA stepped up its investigations of buprenorphine-prescribing physicians, to make sure they were adhering to 100-patient caps, some physicians objected, and surrendered their certificates. Mr. Reuter noted that some of these doctors (about 2,000) had obtained the certification but not gotten any patients, and didn’t want to be bothered with the inspections.

As of September 2012, about 3.9 million patients had been treated with Suboxone, said Tim Baxter, MD, global clinical director of Reckitt Benckiser, which makes the Suboxone brand of buprenorphine.  Of the 23,000 physicians who are waivered to prescribe buprenorphine, 12,000 have actually prescribed it—“many have written only one prescription,” said Dr. Baxter. In fact, there aren’t enough physicians prescribing it. “Initially the number of prescribers went up, and then it flattened out,” he said. Many active prescribers are now fully booked. “With the 100-patient limit, it’s harder for patients to find a prescriber.”

Buprenorphine Diversion

Abuse and diversion of buprenorphine are a concern to us and the FDA, said Mr. Reuter. The 2010 DAWN national data showed an increase in buprenorphine reports in the emergency department.

There are concerns about increases in buprenorphine abuse and diversion, which has paralleled the prescribing increase in the buprenorphine mono formulation, the one without naloxone. The naloxone is what prevents people from being able to get high from melting down and injecting the medication.

One problem is that the mono formulation has been available in generic versions for three years. Generic versions are less expensive than Suboxone, and prescribing of mono buprenorphine has increased steadily.

According to the final rule, HHS “is not aware of compelling evidence to support the assertion that more OTPs than office-based physicians will dispense mono buprenorphine.” But controls already in place regarding OTPs—much more intense controls than those regarding office-based physicians—“will mitigate diversion issues in OTPs with either buprenorphine formulation,” the final rule states. In addition, “the risk for buprenorphine diversion from buprenorphine dispensed by OTPs in accordance with this final rule will be less than the risk of diversion associated with office-based settings.”

If an OTP patient gets a 30-day supply of methadone, or, under the new rule, buprenorphine, that patient is “still subject to drug-testing requirements, still subject to counseling, and still has a treatment plan,” said Mr. Reuter. “On the other end of the spectrum are the buprenorphine prescribers who could prescribe a 30-day supply of Suboxone or buprenorphine, with no requirements for drug testing or counseling,” he said. “That may explain why there is an escalating abuse and diversion of buprenorphine.”

Buprenorphine Not a Miracle Cure

Treatment with buprenorphine is effective, said Mr. Reuter. Medication-assisted treatment has expanded, even in parts of the country where it wasn’t available, such  as Wyoming and North Dakota. Those states don’t permit OTPs. “But the success has to be looked at in terms of the real world, in which people relapse,” he said. “It’s not a miracle cure, and I never thought it would be. To my mind, it’s expanded treatment capacity, but it’s not a cure. And now we see increasing abuse and diversion.”

Mr. Parrino thinks the reason buprenorphine has been successful is that it is not “stigmatized,” the way methadone is. Interestingly, the earliest prescribers of buprenorphine were using it primarily as a withdrawal agent, rather than a maintenance agent, he said. Many of these patients undoubtedly relapsed; as a huge NIDA clinical trial showed, more than 9 out of 10 patients who were tapered off buprenorphine, relapsed.

See comment from Robert Newman, MD in comment section. 


Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. DHHS Publication No. (SMA) 04-3939. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004.

Promise of Health Care Reform for Opioid Treatment Programs Dimmed by State Discrimination

Health care reform will bring increased access to opioid treatment programs (OTPs), but not as great an increase as the federal government keeps saying it will be. The impediment is the states—specifically, the anti-methadone states, which many are in one way or another. Either they won’t let Medicaid pay for methadone maintenance, or they won’t force private insurers to cover it, or both.

Medicaid expansion, a cornerstone of the Affordable Care Act (ACA), won’t mean anything if the state involved doesn’t allow Medicaid to pay for treatment in an OTP, Mark Parrino, MPA, president of the American Association for the Treatment of Opioid Dependence (AATOD) told AT Forum. “For example, Georgia is a large state with many OTPs, but the state does not reimburse methadone treatment,” he said.

The other cornerstone of the ACA—exchanges, where individuals and small businesses can purchase affordable insurance—is also a state-by-state matter. California chose as its “benchmark” plan—the one that defines what benefits will be included in the exchange—a plan that doesn’t reimburse for methadone maintenance at all.

Of course, the federal Center for Medicare and Medicaid Services (CMS) has to approve the plans, for both Medicaid and exchanges. AATOD encourages CMS and the Substance Abuse and Mental Health Services Administration (SAMHSA) to include methadone, buprenorphine, and naltrexone for the treatment of opioid dependence as covered, Mr. Parrino said. “That is a critical issue of health care reform.” Since there are only three medications approved to treat opioid addiction, these medications should be part of the essential health benefits package, he said.

John O’Brien, the architect of the substance abuse treatment provisions of the ACA, is at the federal Department of Health and Human Services. He met with the AATOD board December 7, 2012. Mr. O’Brien also met with the AATOD board in Chicago in October 2010, and at that time recommended that states move to have Medicaid reimbursement for methadone maintenance, in order to be prepared for health care reform.

But in states that embrace methadone maintenance, and have a generous plan for Medicaid expansion and a generous benchmark package, there will be increases in patients—although not a “massive influx,” said Philip L. Herschman, PhD, chief clinical officer of CRC Health Group. He said that unlike residential programs, which have fixed numbers of beds, OTPs always have the capacity to expand. “It’s a matter of hiring the right number of counselors and nurses and other staff when you add patients,” Dr. Herschman told AT Forum. “You have to have enough capacity at the window to maintain decent wait times,” he said. “I don’t think there’s unlimited capacity, but there is some capacity in the system.”

But in some states, there are caps on the number of patients a clinic can have, regardless of the staffing, said Dr. Herschman, citing Washington State.

“There is no mandate for Medicaid to cover methadone maintenance,” agreed Dr. Herschman. “I don’t expect any immediate change in which states cover methadone maintenance.  But in those states that already have methadone maintenance, we will see an increase in the number of patients.”

And it’s still not clear whether the exchanges, in which people will choose between different private insurance plans, will cover methadone maintenance. “That’s where the rubber meets the road,” said Dr. Herschman. “Methadone maintenance is not covered now in the vast majority of private plans. That leads one to believe that it won’t automatically be covered.”

 The irony is that one year of treatment in an OTP with methadone is less expensive  than one year of Vivitrol alone or one year of Suboxone film alone— and the treatment in the OTP includes a lot more than giving methadone. “OTPs provide a tremendous service,” said Dr. Herschman. Counseling, not just medication, is included, and treatment is comprehensive.

 Another facet of the ACA—the health home, in which patients receive all medical care in one place—is something that a few OTPs are interested in—mainly ones that are affiliated with hospitals. But in general, it will be “very difficult for an OTP to be a health home,” said Dr. Herschman. Health homes will primarily be multi-specialty physician practices, and some will be mental health homes. “We’ve tried over the years to expand an OTP into a true outpatient substance abuse treatment program, offering all kinds of treatment, including drug-free,” said Dr. Herschman. “If you can expand, you have a chance of being that kind of mental health home,” he said, although CRC had only “limited success.” But making an OTP into a full medical home with primary care and other health services—that is not likely to happen except in rare cases, said Dr.Herschman.

 HHS, CMS, and SAMHSA did not respond to repeated requests for interviews on the topic of health care reform and OTPs.

Chronic Pain in Opioid Treatment Program Patients Typically Untreated

Many patients in opioid treatment programs (OTPs) are likely to have chronic pain, but in many, that pain will not be adequately treated, in part because there are so many problems balancing the methadone they are given for opioid dependence with the types of medications needed to treat pain.

“Most physicians in an OTP have experience treating addiction and pain, I can guarantee that,” said Nicholas Reuter, MPH, senior public health analyst with the Center for Substance Abuse Treatment (CSAT) at the federal Substance Abuse and Mental Health Services Administration (SAMHSA). “I go in and inspect the programs, and I can see patients who obviously have some chronic pain issues. They’re not hard to identify—they have canes, walkers, and scars.”

But OTPs cannot be pain management clinics because of regulations, said Randy Seewald, MD, medical director of the methadone maintenance treatment program at Beth Israel Medical Center in New York City.  “If a patient comes to us and says, ‘I just want methadone once a day for pain,’ we can’t admit them,” said Dr. Seewald, who has a fellowship in pain management. Sometimes patients may say this because they don’t want to admit that they are addicted.

Methadone needs to be given multiple times each day for pain relief. And the federal regulations allow OTPs to dose only once a day, which is adequate to prevent withdrawal.

At Beth Israel, the first OTP in the country, many patients are older, noted Dr. Seewald. “In general as people age, they are more likely to develop chronic pain,” she said, adding that many Beth Israel patients have had significant illnesses, including HIV and hepatitis C. She defines chronic pain as pain lasting 6 months or more.

Study: Epidemiology of Pain in MMT Programs

“We know this is a vulnerable population of chronic pain patients,” said Lara K. Dhingra, PhD, Co-chief of the Research Division in the Department of Pain Medicine and Palliative Care at Beth Israel. “Patients who are on methadone for treatment of their addictive disorder may still require treatment for their chronic pain, and at present there aren’t any guidelines for protocols we should be following with respect to the medication regimen,” said Dr. Dhingra, who works with Dr. Seewald. “The majority of patients are likely to not have their pain treated.”

Dr. Dhingra is the lead author of “Epidemiology of pain among outpatients in methadone maintenance treatment programs,” part of a larger study funded by the National Institute on Drug Abuse (R01DA020781, R01DA020841), published in the August 27 issue of Drug and Alcohol Dependence. Her study (Dr. Seewald and Russell K. Portenoy, MD, chairman of the Department of Pain Medicine and Palliative Care, are among the co-authors) was based on sites in New York and San Francisco in which all patients had hepatitis C. Of the 489 patients in the study, 237 (48.5 percent) had clinically significant pain.

The patients treated their pain with prescribed opioids (38.8 percent of patients), non-opioids (48.9 percent) and self-management approaches, including prayer (33.8 percent), vitamins (29.5 percent), and distraction (12.7 percent). (Some patients used more than one approach.)

The same steps that are followed for people who are not opioid dependent should be followed for OTP patients with chronic pain, said Dr. Seewald. This means diagnosing and trying to treat the cause if possible, starting with non-drug therapies and nonopioid drugs, and considering opioids only if an assessment indicates that these drugs are likely to be safe and effective, and taken in a responsible way over time. In this population, opioids often are viewed as the last resort, but for many OTP patients who have hepatitis C, acetaminophen, with its liver effects, would not be appropriate, and NSAIDs have a high risk of gastrointestinal bleeding, she said.

The primary care provider (PCP) is generally in charge of pain management, said Dr. Seewald. But she noted that the OTP sees the patients much more frequently than either the pain specialist or the PCP, and the OTP is required by the Joint Commission to assess pain at every visit.

Methadone for Pain

Interestingly, methadone can be a great medication for pain in general, because it does not produce the euphoria or rush of other opioids in patients who may be predisposed to this effect, said Dr. Seewald. “Methadone is challenging to use for pain, however, and doctors who do not have experience in using it this way should obtain help before doing so.” 

Although Dr. Seewald did a fellowship in pain management—precisely because so many OTP patients have pain—she does not treat patients for pain alone, even in her private practice. “I’m also a pain specialist, but if I have someone with pain and addiction, I will work with another pain specialist,” she said. “You don’t want to be the only one involved.”

 Need for Training on Opioids and Pain

“The federal regulations don’t say anything about pain treatment,” said Mr. Reuter. “They’re really tailored toward treating dependence.” But OTPs are ideal, in many ways, for dealing with patients who need opioids. With all of the training given to OTP physicians about the pharmacology of methadone treatment, said Mr. Reuter, these physicians would be likely to have more knowledge about opioids and their risks than average physicians. “Methadone is one of the most complicated opioids there are,” he said.

Primary care physicians need to know more about medication-assisted treatment of addiction, but it works both ways—OTPs need to know more about pain, said Dr. Seewald. “I worked in drug treatment with methadone patients for 20 years before I took my pain fellowship. We were never trained to treat pain.”

Drug Addiction: It’s Different—and Riskier—for Women

When it comes to drug addiction, gender does make a difference.

Women start using substances and become addicted differently from men. Their addiction progresses faster, they find it harder to quit, they recover differently from men, and they relapse for different reasons.

These gender differences have a substantial impact on treatment for substance abuse. But when women’s specific needs are understood and addressed from the outset, better treatment engagement and successful outcomes often follow.

Women and Addiction: The Biopsychosociocultural Framework

The Substance Abuse and Mental Health Administration TIP 51, Substance Abuse Treatment: Addressing the Specific Needs of Women, proposes approaching substance abuse treatment for women from the perspective of “the biopsychosociocultural framework.”

Differences between women and men in genetics, physiology, anatomy, and sociocultural expectations and experiences lay the foundation for women’s unique health concerns related to substance-use disorders (SUDs). The biopsychosociocultural framework encompasses the impact of gender and culture and the contexts of a woman’s life, including her social and economic environment, and her relationships with family and support systems.

Risk Factors for Substance Use in Women

Some factors are associated more strongly with initiation of illicit drug use in women than with progression to abuse. They include risk-taking (as a personality trait), depression, obsessiveness, anxiety, and difficulty controlling behavior (as indicated by temper tantrums or tearfulness).

Genetics and environment both play a role in some risk factors. Parents who abuse substances may pass along a genetic susceptibility. They may also fail to adequately protect their children from abuse by others, and may be of little help to them emotionally. And they may unintentionally pass along the message that it’s okay to use substances to cope with problems.

Among other risk factors:

  • Divorce, never having been married, and widowhood (the incidence of SUDs in married women is only 4%)
  • Sexual or physical abuse or domestic violence in childhood or adulthood
  • A history of having adult responsibilities as a child: caring for younger children, performing household duties, emotionally supporting their parents
  • Unemployment or underemployment; low income; low education level
  • A partner who abuses alcohol or drugs (some women continue using substances in order to maintain the relationship, a situation that also occurs in some same-sex relationships)
  • Sexual orientation: lesbians have higher rates of SUDs than heterosexual women; younger lesbians and bisexual women are most likely to abuse prescription drugs

Protective Factors

Factors that help protect a woman against substance use, abuse, and dependence include a good marriage, a supportive partner, parental warmth during her childhood, religious affiliation and beliefs, and deep personal devotion.

Research Results: Characteristics of Women with OUDs

Women face a higher risk of co-occurring mental and physical disorders. A UCLA study examined gender differences in 578 men and women with opioid-use disorders (OUDs), drawn from the National Epidemiologic Survey on Alcohol and Related Conditions. The study found that “women were about twice as likely as men to have either a mood or anxiety disorder.” Women were also “more likely to have paranoid disorder, and men, more likely to have antisocial personality disorder.” Another study, the National Survey on Drug Use and Health, found higher rates of “serious psychological distress” and “cigarette use” related to non-medical use of prescription opioids among women, but not among men. In contrast, “serious psychological distress” was a significant predictor of abuse/dependence for both sexes.

Other studies have found that women are much more likely than men to have co-occurring mental disorders, often three or more, including anxiety disorders, major depression, eating disorders, and post-traumatic stress disorder (PTSD). Typically, PTSD follows trauma, sexual abuse, or violence—events that unfortunately are all too common in women with OUD. Physical disorders in women include gynecological infections, high blood pressure, amenorrhea (absence of menstrual periods) and pneumonia.

In a symposium report, Florence Haseltine, PhD, MD, noted that women tend to take illicit drugs to relieve stress; men, to get a high; women, for self-medication; men, as an adventure.

She added that women with OUDs are more likely to

  • Self-medicate, especially using drugs to manage negative moods
  • Need help for emotional problems, and at a younger age
  • Have attempted suicide

Others have observed that, in addition, women with OUDs tend to use more prescription drugs (and use prescription drugs that can be abused), obtain prescription opioids free from family or friends (men are more likely to buy them), and have partners who use illicit drugs.

Relationships and family history are key factors in women’s—but not men’s—initiation and continued illicit use of opioids and other substances. Women are more likely than men to have a family background of dysfunction and alcohol dependency, and to be brought into and maintained in drug use by a partner or family member. It almost seems that when women start to abuse substances, they already have three strikes against them.

Women are more likely to borrow needles and equipment from the person they inject drugs with. They’re also likely to inject immediately after that person—putting themselves at added risk of HIV and hepatitis infections. Intravenous drug use accounts for up to half the cases of HIV infection among women in the U.S., twice as many as sexual transmission.

But, importantly, women can temporarily change their pattern of substance use to meet caregiver responsibilities involving the family, such as pregnancy.

Looking Back When In Methadone Maintenance Treatment

In gender-specific focus groups in a methadone maintenance clinic at UCLA, comments from participants older than 50 years revealed clear differences between men and women in their views of their previous life in addiction. Women talked about the impact on their families, and their regrets about “. . . not being the mother I should have been.” And their remorse: “I almost lost my family.”  Men typically expressed surprise at still being alive, and previous fears about incarceration.


If a woman’s menstrual periods stop when she is using opioids, she may assume at first that the early signs of pregnancy are symptoms of withdrawal or underdosing. This often delays her pregnancy diagnosis and prenatal care.

But, as TIP 51 points out, “Women are socialized to assume more caregiver roles and to focus attention on others.” Indeed, once a woman is told she is pregnant, she typically casts aside her vulnerability and regains her traditional role of caregiver. She is likely to accept medical care for herself and her unborn child, and to stop or substantially curtail her use of illicit drugs, alcohol, and cigarettes, throughout her pregnancy.

*     *     *

This article is the first in a series on the special challenges that make coping with addiction especially difficult for women. Future topics include the barriers women face in seeking and accepting treatment, and the best approaches to treatment for women in medication-assisted treatment programs. Programs need to address the special needs of women by offering auxiliary or wraparound services, or both—such as child care and prenatal services, and workshops on woman-focused topics.


Center for Substance Abuse Treatment. Substance Abuse Treatment: Addressing the Specific Needs of Women. Treatment Improvement Protocol (TIP) Series 51. HHS Publication No. (SMA) 09-4426. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2009.

Becker JB, Hu M. Sex differences in drug use. Frontiers in Endocrinology. 2008;29:36-47.

Haseltine FP. Symposium Report: Gender differences in addiction and recovery. J Womens Health Gend Based Med. 2000;9(6).

Hamilton AB, Grella CE. Gender differences among older heroin users. J Women Aging. 2009;21(2):111-124.

Grella CE, Karno MP, Warda US, et al. Gender and comorbidity among individuals with opioid use disorders in the NESARC study. Addict Behav. 2009;34(6-7):498-504.

Grella CE, Lovinger K. Gender differences in physical and mental health outcomes among an aging cohort of individuals with a history of heroin dependence. Addict Behav. 2012;37(3):306-312.

Subramaniam GA. Clinical characteristics of treatment-seeking prescription opioid versus heroin using adolescents with opioid use disorder. Drug Alcohol Depend. 2009;101(1-2):13-19.

Back SE, Payne RL, Simpson AN, Brady KT. Gender and prescription opioids: Findings from the National Survey on Drug Use and Health. Addict Behav. 2010;35(11)1001-1007.

Admissions for Combined Benzodiazepine and Narcotic Pain Reliever Abuse Rise Sharply

In ten short years, substance abuse treatment admissions for combined benzodiazepine and narcotic pain reliever abuse jumped a startling 569.7 percent—from 5,032 in 2000 to 33,701 in 2010—while all other admissions dropped 9.6 percent.

These figures come from the Treatment Episode Data Set (TEDS) Report issued December 13 by the Substance Abuse and Mental Health Services Administration (SAMHSA). The report notes that benzodiazepines, used to treat anxiety and drug and alcohol withdrawal symptoms, are commonly used— licitly and illicitly—to boost the effects of narcotic pain relievers, such as oxycodone.

The “Combination” Group: A Treatment-Resistant Population

TEDS describes the characteristics of people who abuse benzodiazepines and narcotic pain relievers—we’ll call them the “combination” group—compared to the “other” admissions, those who did not abuse drugs of either type.  People who co-abuse the two drugs are a “high-need, treatment-resistant population.” They report more severe withdrawal symptoms and higher treatment attrition rates than people withdrawing from narcotic pain medications alone. This is no surprise, as benzodiazepine withdrawal is notoriously difficult—similar to alcohol and barbiturate withdrawal.

Compared to the “other” group, the “combination” group was

  • Mostly non-Hispanic white, with a low percentage of Hispanic and non-Hispanic black
  • More likely to be from the South
  • Evenly divided by sex (70% of the “other” group was male)
  • More likely to report a co-occurring psychiatric disorder
  • Concentrated in the age group 18-34 years (Chart 1)
  • Most often self-referred to treatment rather than referred by the criminal justice system (Chart 2)
  • Less likely to be receiving regular outpatient treatment
  • More likely to report daily use of any substance during the month before admission

There was no difference between the groups in education or employment status.

Implications for Treatment Programs

According to the report, daily use before admission points to “behavioral patterns that may be difficult to change.” Programs need to be prepared for the severe withdrawal effects from both drugs, “particularly since benzodiazepines compound the withdrawal effects of narcotic pain relievers. Providing medical and supportive services to mitigate the severe withdrawal effects may be critical to avoid treatment attrition and relapse.”

The report notes that the high rate of mental health disorders in the combination admissions group—perhaps partly due to using benzodiazepines for self-medication— may give programs a “unique opportunity to facilitate access to both substance abuse treatment and mental health services for people who co-abuse these drugs.”

A current review article summarizing data from about 200 articles on opioid and benzodiazepine combination use agrees with the self-medication possibility, but adds that the data suggest that the benzodiazepine use is primarily recreational. Co-users report seeking benzodiazepines to enhance “opioid intoxication or ‘high,’” and use doses exceeding therapeutic range. The review encourages further investigation and more cautious prescribing practices.

Chart I:  Age Distribution of Benzodiazepine and Narcotic Pain Reliever Combination Admissions and Other Admissions*: 2010

Chart 2: Sources of Referral to Treatment among Benzodiazepine and Narcotic Pain Reliever Combination Admissions and Other Admissions*: 2010

Full TEDS report:

Review article: Jones JD, Mogali S, Comer SD. Polydrug abuse: a review of opioid and benzodiazepine combination use. Drug Alcohol Depend. 2012; Sep 1; 125(1-2):8-18. doi: 10.1016/j.drugalcdep.2012.07.004. Epub 2012 Aug 2

MMT Patients Need Physical Activity; Brief Interventions Could Help

Physical activity is so important for patients in methadone maintenance treatment (MMT). They’re already at increased risk of physical and mental health disorders, including chronic pain and sleep problems. Lack of enough physical activity carries additional risks: cardiovascular disease, various psychiatric disorders, high blood pressure, diabetes, osteoporosis, obesity, and colon cancer.

Given the importance of physical activity to their patients, how can MMT programs help?

A study in the Journal of Substance Abuse Treatment (in press) offers some suggestions. The study assessed the levels of physical activity in 305 MMT patients, cited patients’ perceptions of the benefits of and barriers to exercise, and provided recommendations.

Study Group Characteristics

Participants were recruited between December 2008 and May 2011 at nine MMT sites in New England. All were taking part in a smoking cessation intervention trial, and had been enrolled in MMT for at least four weeks.

Additional characteristics of the group:

  • Average age: 40 years
  • 50% men
  • 243 (80%) non-Hispanic white
  • 113 obese; 103 overweight; 18 refused to be weighed
  • Cigarette use: at least 10 per day (inclusion criterion); average, 19.7
  • Average methadone dose: 109 mg/day

Almost 45 percent considered themselves in fair or poor physical health.

Physical Activity Guidelines

The American Heart Association recommends a healthy adult have at least 30 minutes of moderate-intensity aerobic physical activity five days a week, or at least 20 minutes of vigorous activity three days a week.

Study Results

Only 38 percent of participants met or exceeded recommended guidelines, and almost 25 percent reported no physical activity. In contrast, about 49 percent of adults in the U.S. meet guidelines, and almost 14 percent are inactive (less than 10 minutes of activity of moderate intensity per week).

In general, study participants highly endorsed (rated favorably) the benefits of exercise. More than 75 percent credited exercise with giving a sense of accomplishment, improving health, increasing energy level, feeling stronger, improving cardiovascular fitness, becoming physically fit, increasing confidence to stay clean and sober, and maintaining or losing weight in order to look better. Interestingly, those who met activity guidelines were significantly more likely than the others to report relapse prevention and reduced anxiety as benefits.

Motivation: The Key for MMT Patients

The most frequently perceived barrier to exercise was lack of motivation (103 participants). This is consistent with findings from previous studies in substance users. The authors cite an earier study showing that, “encouragingly, motivation to exercise was the best predictor of physical activity.” Among other barriers cited were not having enough energy, having an injury or disability, and health problems.

Noting that brief interventions or counseling sessions have helped increase physical activity in a variety of populations, the authors suggest this approach for MMT patients. Measures could include “brief, counselor administered physical activity or exercise intervention” based on adaptations of the widely used five A’s for smoking cessation intervention—ask, advise, assess, assist, arrange—to provide “a standardized framework for a clinic based brief intervention.” They add that the potential benefits in mental health and relapse prevention, highly endorsed by participants, should be covered during the “advise” part of the exercise.

“Another potentially cost-effective intervention,” according to the authors, “could involve peer led exercise promotion groups run through methadone clinic programs.” Moreover, it would be useful to have a brief discussion of exercise and physical activity during monthly counseling sessions or doctors’ visits, the authors said. “Developing efficacious and low-cost physical activity adjuncts to this population at high risk for lifestyle-induced medical conditions may have important benefits for health and drug treatment outcomes.”

*     *     *

Caviness CM, Bird JL, Anderson BJ, et al. Minimum recommended physical activity, and perceived barriers and benefits of exercise in methadone maintained persons. J Subst Abuse Treat. 2012.

Link to the five As of smoking cessation:



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