Breaking the Habit
When a woman is a heroin addict, one discovery may persuade her to get off drugs-that she's pregnant. After decades of study here, a new maintenance drug is making it easier to quit.
By Lavinia Edmunds
Lauri Klein's heroin addiction couldn't have begun more innocently. Five years ago, when she was 30, her doctor prescribed Percoset to relieve her pain after knee surgery. Klein liked the serene feeling the medication gave her and started increasing her dosage. When 60 pills a day no longer satisfied, she tried heroin. Within months, she was hooked, spending the grocery money, overcharging her credit cards and ultimately begging on the street to support her $100-a-day habit. By the end of a couple of years, Klein had traded in her life as a suburban mother with two children for a garage with no heat or electricity that she shared with four other drug abusers. All she cared about was her next fix. And then she discovered she was pregnant. It was that realization that brought her last fall to the clinic at CAP-the Center for Addiction and Pregnancy-at the Johns Hopkins Bayview Medical Center.
Klein related her story as she sat cross-legged on a bed in a hospital room wearing a black, rhinestone-studded designer T-shirt and sweat pants. Her hollowed eyes and cheeks gave her a fragile look. She said she had tried to get over her addiction by taking methadone, the standard drug treatment for heroin. Now she had enrolled in a study at CAP comparing methadone and buprenorphine, a promising new heroin substitute. Buprenorphine had been reported to have a milder withdrawal than methadone, doctors told her. It might be easier to quit. More important, it could have less impact on her infant after birth. "I never realized how serious my addiction was," Klein admitted nervously, as she sat awaiting her first dose of buprenorphine. "I just want to feel normal."
Heroin is what's known as an opiate: It derives its euphoria-inducing properties from the opium in the poppy plant. When ingested or injected, opiates rush through the bloodstream to the brain where they bind to the mu receptors that control sensations of pleasure and the relief of pain. The rush-and-crash cycle heroin abusers experience is torturous. Right after they inject the drug, they feel a quick, warm euphoria. That's often followed by a period of "nodding" or drowsiness. Then, within hours, the collapse into withdrawal hits-drug sickness, as it is known on the street. The tremors, nausea and irrational frenzy that characterize this state are relieved only by another dose.
To try to detoxify heroin abusers, scientists typically substitute a longer-acting opioid. Until now, methadone, developed as a synthetic painkiller by the Germans during World War II, has turned out to work best. A once-a-day dose can ward off symptoms of withdrawal, it's affordable and it acts more like a sedative than a stimulant. But methadone itself is highly addictive, so only regulated clinics can administer the syrupy liquid. And while there's no denying that those clinics move drug abusers off the streets, communities often prefer not to have such a facility in their midst. Other medications developed to treat this patient population, however, present different problems. The latest, LAAM (levomethadyl acetate hydrochloride), approved by the FDA in 1993, has been associated with cardiac problems and had its use limited.
Enter buprenorphine. For the more than 800,000 dependent heroin-users in this nation, this is their newest hope for quick withdrawal and a clean life. If heroin turns the light on full blast, buprenorphine uses the dimmer switch. Commonly taken as a pain reliever by cancer patients, the drug only partially activates the mu receptors and creates only a flicker of a high sensation. It is milder even than methadone and carries little risk of overdose. It appears also to work on a second set of receptors called "kappa." Less is known about the kappa receptors, but they appear to block rather than stimulate effects of increased doses. And buprenorphine lingers on the mu receptors for up to 48 hours in comparison with shorter-acting heroin or methadone.
For someone like Lauri Klein, that gives this new detoxifier a practical advantage. If she uses buprenorphine as her maintenance drug, she will only need to find a ride to the Bayview clinic three times a week, not once a day as she's had to with methadone. Buprenorphine has another appeal, too: Any physician who is board-certified in addictive medicine, or who has passed a special eight-hour course and gained certification to prescribe buprenorphine, may administer the drug in an office setting. For drug-users who shied away from entering a high-visibility methadone clinic, this privacy feature has been a big draw. It symbolizes a major change toward the treatment of drug abusers: at last, they are being offered the same consideration as patients with other chronic illnesses.
Lauri Klein prepared herself mentally for her switch to buprenorphine. She spent time thinking about how good it would be to be drug-free again, she tinted her hair red to symbolize her new beginning, and finally in the 48 hours before her first dose, under the watchful eyes of the Bayview doctors, she made the transition off methadone. To facilitate this process, she took a dose of morphine, a shorter-acting opiate. Many users find this step excruciating, and because it's never clear how a body will react to the exchange, the Bayview team monitored Klein carefully. They photographed her eyes to make certain her pupils were properly dilated, tested her urine, measured her sweat glands and hair follicles and checked every vital sign. Klein's physical health, they determined, was good. Mentally she was motivated to get off drugs. She would be a fine candidate for buprenorphine.
And so, early on a Friday morning at the beginning of December, a nurse laid two buprenorphine pills, about the size of Tic Tacs, under Lauri Klein's tongue. Grimacing briefly at the fake peach flavor, she held them there for five minutes. Buprenorphine is more effective taken sublingually like this, because it goes directly into the bloodstream without first being metabolized by the liver. Over the next few days, nurses on the Bayview unit would track Klein's condition and report everything to Donald Jasinski and Rolley (Ed) Johnson, the key investigators on this clinical trial.
Donald Jasinski could be called the father of buprenorphine. Trained as a physician at the University of Illinois, Jasinski opted to go into pharmacological research when he realized he didn't have the hands to do surgery. In the mid-1960s, he took a job through the U.S. Public Health Service at the Addiction Research Center in Kentucky. Located on a farm in the rolling bluegrass country outside of Lexington, the facility had been established shortly after World War II and was staffed by some 25 scientists. It was the first national laboratory set up to deal with narcotics and their effects. For subjects, the researchers studied prisoners at an adjacent federal penitentiary for heroin abusers who came to the farm for detoxification, treatment and remedial instruction.
Every time a new opiate came on the market as a painkiller the scientists would test it as a treatment for warding off withdrawal symptoms from heroin. The prisoners would show up at what was called "the shooting gallery" and a cart would go round with doses. In the early days, they would be injected with morphine and codeine, but those drugs were so short-acting the convicts would be in withdrawal again in no time. The cart would have to roll around two or three times a day. By 1948, methadone had been introduced, and immediately it was clear that this was a longer-acting medication. The carts wheeled around only once a day. But even as methadone was being promoted, the scientists could see its abuse potential.
It was in these surroundings in the early 1970s that Jasinski first recognized the tremendous potential of buprenorphine. "Bu-pren-or-phine," he says, elongating the syllables. "It sounded like a song."
"We were looking for 'the bee without the sting,' and this was the closest we'd come,"adds Johnson, who adopted Jasinski as his mentor at the Kentucky farm almost 30 years ago and has collaborated with him ever since (until earlier this year, when Johnson took a year's leave of absence to become a vice president at Reckert Benckiser Inc., the Richmond, Va., company that will market buprenorphine).
In 1976, the prison's research unit closed, and all at once Jasinski and Johnson found themselves without research subjects for their buprenorphine studies. Jasinski, who had become the federal center's director, wanted to relocate to Baltimore City Hospitals. That would put them close to both Washington and the National Institutes of Health, as well as Baltimore's large population of drug abusers, who could provide a ready source of volunteers. An added benefit would be the chance to collaborate with Johns Hopkins researchers who were studying opiate receptors and addictive behaviors.
The national center opened in Baltimore in 1979 (five years before Baltimore City Hospitals closed and its campus was taken over by Hopkins). By then, Jasinski had published his first report showing that buprenorphine remained active in the body as long as methadone and could offer several additional benefits. Methadone, however, had become the gold standard for treating opiate addiction, so there was no pressure to approve another maintenance medication. And questions still abounded about buprenorphine's safety and how it would be regulated.
Jasinski and Johnson soldiered on. Using hundreds of volunteers primarily recruited from outpatient clinics at Bayview, they would demonstrate again and again that buprenorphine could be taken with less frequency than methadone and with a diminished likelihood of becoming addicted to the maintenance drug. Scientists around the country would realize the merit of the Bayview studies, but it would take 10 more years for the FDA to approve buprenorphine. During that period, the program Jasinski headed would become the Intramural Research Program of the National Institute on Drug Abuse (NIDA). "Drug development," Jasinski says matter-of-factly, "takes a long time."
Lauri Klein felt calm an hour after taking her first dose of buprenorphine. The drug's slight euphoric effect filled her with warm thoughts of re-uniting with her family and becoming a good parent again. She cradled a school picture of her smiling 4-year-old daughter. She talked happily of re-establishing a loving relationship with her 11-year-old son who had been living with relatives in Pennsylvania.
But within 24 hours, Klein began to throw up the "vile yellow" that she associated with her worst withdrawal symptoms. Panic rushed over her. She had left her family in ruins, she lamented. How would she ever make up the lost time to her son? Facing her boyfriend, a recovered drug abuser himself, was even more daunting. Her heart raced so wildly she feared it would stop. "On heroin," she said, "you feel good, your emotions are shelved." Now, she wasn't prepared to confront the feelings her drugged stupor had hidden. She made her decision: she hated methadone's addictive qualities, but she had to go back on it.
Johnson puzzled over Klein's reaction. "I wish I could develop an algorithm," he said, "and describe by age, race, socioeconomic level or previous health history who is going to do best on buprenorphine." The transition from methadone is a problem, he admitted. It is yet to be fine-tuned, and methadone is believed by many to be more addictive than heroin. Later, he postulated that Klein's failure on buprenorphine may have occurred because the drug had unmasked certain previously suppressed emotions.
Despite such failures, Jasinski has no doubts about buprenorphine's capabilities as a rapid detoxification agent. As a testimonial, he cites the drug's success in the emergency department at The Johns Hopkins Hospital, where addiction is a complicating factor in an estimated 80 percent of admissions.
Through a special FDA ruling, psychiatrist Alan Romanoski, who works closely with heroin-addicted inpatients, has been able to use tapered doses of buprenorphine to stabilize drug users who suffer from life-threatening diseases like AIDS or hepatitis C. Romanoski refers to buprenorphine as "almost a miracle drug" and predicts it will have a major impact on the treatment of addiction.
"It opens up huge possibilities," he says, because addicts don't have to go out everyday to get it as they do with methadone. They also can taper off buprenorphine much more easily than methadone. Most of the addicts Romanoski has treated with buprenorphine, in fact, have made a smooth transition off heroin, making it easier here for physicians to concentrate on their life-threatening medical problems.
Tonya Brown was one of those patients. Addicted to heroine, Brown showed up in the ED early last winter in anguish from a pelvic infection. But managing pain in someone who's drug addicted is no simple matter. Addicts build up such a tolerance to strong narcotics that they need powerful doses of medication to gain relief. Brown (this is not her real name) received a course of the heavy-hitting pain medication oxycontin.
Afterward, to detoxify her, she was placed on tapered doses of buprenorphine over five days. This gave her some mild nausea, but also first clarity of mind she'd known since she began using drugs four years before. On her fifth and last day of buprenorphine, Brown proclaimed proudly that she was clean. Later, sitting at a table in the psychiatric unit, awaiting the beginning of her counseling session, she appeared resolute, almost prim, in her camel sweater and slacks. She's planning, she says, to study nursing.
Still, Romanoski urges caution when it comes to viewing buprenorphine as a quick panacea. Addicts can be lulled "into a false sense of security," he warns. Many leave after the brief detox and relapse in days or months. Case histories, in fact, suggest that relapse is likely unless an addict stays drug-free for five years. For heroin addiction, 15 years is a better benchmark. Romanoski likens the problem to overeating. "If you want to lose weight," he says, "taking diet pills will work for awhile. But it takes changing your eating habits to keep it off."
By December of last year, as Lauri Klein entered the last trimester of her pregnancy, she was back on methadone. Every day, she rode the bus to the CAP clinic for her dose and for prenatal care and intensive counseling. She gained weight, filling out the hollows in her cheeks. And she gradually began coping with some of the psychological issues that had surfaced during her panic attack. For Klein and the 100 or so other pregnant drug abusers in this program, CAP offers a safe haven. It provides newcomers a seven-day residential detox program with shelter and food and overnight beds, and it dispenses top-notch medical and emotional care to all the women. One Friday, CAP awarded Klein a certificate to celebrate another week clean. "It's 9 weeks now since I quit heroin," Klein announced on that winter morning. "Some days I count the minutes. I still wake up wanting drugs."
Very early one morning at the beginning of March, Klein's baby was born, a 6 pound 15 ounce little girl. She named her Kiya. Compared with other infants born to women in CAP, who come into the world dependent on drugs, Kiya was in good shape. She didn't suffer from dysfunction of the nervous and gastrointestinal systems, and she didn't need "drops" of morphine for withdrawal. Still, Kiya did exhibit tremors and have difficulty sucking. Observing these sure signs of drug withdrawal in her tiny, perfectly formed baby filled Klein with dismay and guilt.
Hendree Jones, the psychologist who is CAP's research director, is studying these drug-dependent women to pinpoint the differences in how methadone and buprenorphine affect their newborns. Jones exudes the energy of the bright young comer who knows which questions to ask and how to find solutions. She's found that women on buprenorphine like it and report minimal levels of heroin craving (Klein was the exception). More importantly, their babies seem to suffer markedly fewer withdrawal symptoms. The study should yield more information about these differences. The stakes are high for these women. Without significant recovery, a hardened drug-user can be forced to give up her baby to social services.
Sometimes Lauri Klein regrets not having stuck to buprenorphine. In her present stabilized condition, she ponders that she might have withstood the panic attack and today be free of drugs instead of taking methadone. That, however, is speculation. One thing Klein knows for sure: "I got treatment because of this baby, and I have stayed in treatment for this baby. I call her an angel of God."