April 1, 2005 - Wired Magazine (US) Buprenorphine: The Bitter Pill By Douglas McGray

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Buprenorphine could end heroin addiction, curb disease, and cut crime. But bureaucrats, doctors, and much of the treatment industry are just saying no. A case study in why the best technology doesn't always win.

At 28, Joe has become something of an expert at heroin detox - he's tried it nine times. Between programs, he's attempted to quit on his own. Once, when the cravings got the best of him, he tried to knock himself out by hitting his head against a brick wall. So late last year, when Joe checked himself into a New York outpost of Phoenix House, the country's largest residential rehab program, he knew exactly what to expect: the plastic cups of methadone to wear down his dependence, the sedated days and sleepless nights, the chill of the toilet seat, the sickening sight of food. But then a doctor handed him a medication he'd never heard of. Something called buprenorphine - or simply, bupe. No way, Joe thought. No way this little orange pill is going to do the job.

That first day at Phoenix House, Joe remembers, his last heroin high was wearing off. He felt the familiar beads of sweat. Nausea began to creep to his throat. Perfect conditions, his doctor said; bupe works only when patients are in withdrawal. So Joe curled back his tongue, placed the little hexagonal tablet underneath, and waited. He felt it slowly soften to a gritty paste and disappear. It still amazes him how quickly it worked. He didn't feel high, didn't feel withdrawal symptoms, didn't even feel medicated; he just felt better. "It took away the pain," he says. "It even took away the craving. I had my strength back, and I was eating sooner than I ever had in detox. I got clarity when I took that first pill." The details of his addiction - kicked out of high school, stripped of a college basketball scholarship, and ultimately sent upstate to prison - already seem like stories from someone else's life.

Bupe won approval as an addiction treatment in late 2002. Sold by British firm Reckitt Benckiser and prescribed under the brand name Suboxone, bupe is a synthetic opiate that pushes the same buttons as heroin or painkillers like Vicodin, Percocet, or OxyContin, only without the high or any other significant side effects. It frees recovering addicts from cravings and crashes, allowing them to focus on counseling, work, and relationships. "It is the first real innovation in treatment in 40 years," says Phoenix House medical director Terry Horton.

Before bupe, there was mainly methadone, an amber syrup that offers similar relief from opiate cravings but is highly habit-forming. By law, methadone must be dispensed at special clinics and, for most patients, only in single daily doses. Widely prescribed beginning in the 1970s, methadone was medical science's first real attack on addiction, and study after study showed it prevented relapses and deaths by overdose. But public opinion swelled against it. Neighborhood groups battled methadone clinics, where patients congregate daily for their meds. Politicians charged that junkies were merely swapping one habit for another. Methadone has been controversial among addicts, too. Some rejected it for producing a powerful sedative effect that makes it difficult for a recovering addict to perform job duties. Others took methadone illegally as a cheap tranquilizer. "People get a methadone habit because it feels like what you were taking before," says Solinda, a former Wall Street office manager, heroin addict, and occasional methadone abuser who also went through bupe detox at Phoenix House.

Patients on bupe do become physically dependent on the pill - as do people taking medication for most chronic conditions. Suboxone, though, has no strong side effects. Nor can users get high by taking a larger dose - in other words, no inching up from dependence to addiction. Bupe is also safer than methadone - which, like any strong opiate, suppresses breathing if too high a dose is taken - and easier to taper off. And instead of visiting a treatment center every morning or quitting cold turkey, addicts can get a bupe prescription from their regular doctor. This offers real appeal to addicts, particularly white-collar ones, who cringe at the stigma of methadone lines. "You're just taking medication," Solinda says. "You don't feel sick. You don't feel high. It makes you feel stronger as a person."

For all these reasons, doctors and mental health professionals expected bupe to take off quickly. But that has not been the case. While Reckitt Benckiser won't disclose sales data, Shaun Thaxter, vice president of pharmaceutical marketing, says that 5,000 doctors are now prescribing buprenorphine. However, according to two prominent bupe researchers, sources inside the company late last year said only half that number is prescribing either Suboxone or Subutex, a form of pure bupe often used at hospitals for detox. And Herbert Kleber, director of the substance abuse division at Columbia Medical School, says the company told him it had recorded only about 1,500 prescribing doctors nationwide last summer.

Reckitt Benckiser estimates that since bupe was introduced, 100,000 patients in the US have used it, whether in the form of a single dose during detox or in ongoing treatment. But Yale scientist David Fiellin, a longtime bupe researcher, says that medical privacy laws make it impossible for the company to accurately count the number of patients taking the drug. "They can't know," he says. A more reliable indicator is the number of prescriptions filled by pharmacies, which are required to report their data to state health agencies. In New York City, home to an estimated 200,000 heroin addicts and perhaps two to three times that many prescription opiate addicts, some 34,000 people were on methadone maintenance throughout 2004, while only about 1,000 people filled a bupe prescription last year. "It's depressingly few," says Lloyd Sederer, New York City's deputy executive commissioner for health and mental hygiene.

So why has bupe's progress been so sluggish when it's clearly a superior innovation? There are several reasons. The general practitioners who were meant to write most of the prescriptions have proved ambivalent, at best, about treating addicts. Lawmakers have bungled regulations; at one point, there was even a federal law barring methadone clinics from dispensing bupe, despite their experience and reach within addiction circles. Meanwhile, Reckitt Benckiser has been conservative in marketing the new drug.

It's all enough to drive Sederer crazy. Reducing the number of active addicts in the city would help check the spread of HIV and other diseases that hang out on dirty needles. It would lessen the number of deaths by overdose. It would cut crime; 20 percent of all convicted felons in New York test positive for opiates. It might even save money. The National Institute on Drug Abuse estimates that every $1 spent on drug treatment erases $7 in social costs ranging from unpaid ER bills to prison overhead.

But Sederer remains hopeful. He and Andrew Kolodny, a city health department psychiatrist, have launched a campaign to place at least 60,000 New Yorkers on bupe maintenance by 2010 - nearly double the number on methadone. They are turning city staffers into part-time drug reps to push bupe to health workers and patients at needle exchanges, methadone and HIV clinics, residential treatment centers, hospital wards, even prisons. They figure that if the bupe brand surges in these settings, then the harder-to-reach patients like white-collar professionals will hear about it, either when they make the occasional foray from their middle-class world to buy drugs, or when the city's inroads on addiction make headlines. Then these patients will ask their doctors for prescriptions, which in turn will make the medical community more comfortable with treating addiction as an illness.

"We're doing all the work for the drug company," Sederer says laughing. "Here you have a couple of psychiatrists launching a marketing campaign!"

Andrew Kolodny looks uncomfortable at the head of a long conference table in the city's Department of Health and Mental Hygiene, where staffers are filing in for a final briefing on the bupe campaign. Soft-spoken, with a shy demeanor and a disarming smile, Kolodny, 36, joined the health department a couple of years ago while doing a fellowship at Columbia Medical School for doctors interested in clinic or government work. Tomorrow, the city's marketing literature, written by health department staff, will arrive from the printer. "Hopefully, by the time we're done today, everyone will feel comfortable delivering this information," Kolodny begins encouragingly.

It's cram time. Kolodny reminds his colleagues of the drug's advantages. He stresses that bupe in the form of Suboxone is safe and almost impossible to abuse, a huge selling point at many of the clinics they will visit. Suboxone has a second active ingredient in the mix, he explains, an anti-overdose drug called naloxone. It does nothing if you take bupe as directed. But if you sniff bupe or inject it or otherwise try to pack enough into your bloodstream to get high, the naloxone acts like a chemical booby trap, erasing the effects of any opiate, bupe included, and bringing on sweaty, nauseating withdrawal. "That's the last time you'll do it," Kolodny says dryly. The length of treatment varies, with some doctors preferring a short detox and others believing addiction is best treated as a chronic condition - like depression or diabetes - with ongoing medication.

"Any questions?" he asks. One employee is still confused about why Reckitt Benckiser needs help marketing its drug. If anything, pharmaceutical firms promote their products too well, turning millions of otherwise sensible Americans into Googling hypochondriacs, and doctors into vending machines.

"They are not a pharmaceutical company," Kolodny replies. "They make Lysol."

"Woolite, also," adds another employee. "And French's mustard," Kolodny says, smiling a bit. The room breaks up laughing. "How did they come up with this?" another staffer asks. "Were they injecting Woolite?"

"I hope they're not making all this stuff in the same lab," a guy in the back mutters.

Reckitt Benckiser, "the world's number one in household cleaning," according to company literature, stumbled upon the compound in the 1970s. A few years later, scientists at Kentucky's Addiction Research Center discovered that buprenorphine reduced opiate craving. It bound tightly to the brain's opiate receptors - nerve endings designed to catch the body's pain-easing, pleasure-pumping endorphins - so that even a low dose blocks the effects of heroin or anything else a relapsing addict might take.

In the early 1990s, when bupe began its slow path toward FDA approval, it faced more obstacles than the average drug. Until the early 20th century, you could order just about any narcotic you wanted from the Sears, Roebuck & Co. catalog: morphine, heroin, opium. But in 1914, Congress passed the Harrison Narcotic Act, barring doctors from prescribing opiates to known addicts. Congress amended the act in 1966 to permit methadone as an addiction treatment and again in 2000, to allow doctors to prescribe bupe. But it tacked on strict conditions in 2000, partly in response to methadone's troubled history.

First synthesized in the 1940s by German scientists and scooped up after the war by pharmaceutical giant Eli Lilly, methadone attracted attention in the addiction community in the 1960s. That's when a husband and wife team, doctors Marie Nyswander and Vincent Dole of Rockefeller University, found that with a daily dose of methadone and some counseling, opiate addicts had a much better chance of staying clean. Public health officials heralded the discovery as a revolution. To get methadone to the masses, Congress created a class of tightly regulated health clinics to treat nothing but addiction and barred them from issuing any prescription but daily single doses of methadone.

Some 40,000 New Yorkers were signed up by the mid-1970s. But the public success fizzled as NIMBY neighbors protested the location of clinics, illicit methadone hit the street, and critics slammed maintenance programs as nothing more than legalized addiction paid for by the government. "Methadone is stigmatized, destroyed," says Edwin Salsitz, a leading methadone expert based at New York's Beth Israel hospital and a regular instructor in buprenorphine licensing classes. "It's a medical tragedy."

Meanwhile, methadone regulations effectively ostracized addiction treatment from the medical mainstream. Most med schools leave it off the curriculum for all but psychiatry students, who get a mere four weeks of exposure. When young doctors train at big-city hospitals, most of their encounters with addicts are hard cases showing up in the ER in the middle of the night. "The top attendings make fun of them," Salsitz says.

An opportunity to bring addiction treatment back into the mainstream appeared when lawmakers amended the Harrison Act in 2000 to enable bupe to come to market. It made a step in that direction by allowing general practitioners to prescribe the new drug. Yet it barred methadone clinics from prescribing the pill at all. This set the stage for some treatment centers to view private-practice physicians as rivals. Yale's David Fiellin, who attended several early training courses, recalls clinic workers standing up to share horror stories about hardcore addicts and suggesting that family physicians, if they prescribed the new drug, could expect the same in their waiting rooms.

After bupe had been on the market a year, the law was amended to permit methadone clinics to prescribe it, but only under the same rules used for methadone (one dose per visit), which erases one of bupe's major advantages - - that you don't have to schlep to a clinic every day. Meanwhile, many methadone providers have remained openly skeptical of the new med, fearing that it will further stigmatize methadone, or siphon off their most stable patients. The government reimburses methadone programs for the number of patients they oversee, not for the specific services they provide, so the payment for a stable patient who takes a dose and goes to work subsidizes treatment for more fragile clients with multiple addictions, mental illness, housing and unemployment issues, and more.

The regulatory problems didn't stop there. Influenced by tales of unscrupulous methadone clinics taking on huge case-loads for the reimbursement cash, Congress barred doctors from maintaining more than 30 bupe patients at a time. And in a monumental blunder, the law classified giant HMOs like Kaiser Permanente, as well as hospitals, as single providers, with the same 30-patient cap that Kolodny has in the solo practice he maintains on evenings and weekends. Four years later, the law remains unchanged. One clear sign of the law's unintended consequences: The world-renowned Addiction Institute of New York (better recognized by its old name, Smithers) doesn't mention bupe in its advertising because with a 30-patient limit, it fears it would have to turn people away.

Meanwhile, even private-practice physicians open-minded enough to seek bupe training find that it reinforces old stereotypes. "The courses are a disaster," says Columbia's Herbert Kleber, who has a contract from the federal Center for Substance Abuse Treatment to redesign the curriculum. The classes rely on scenarios instead of letting doctors interact with live patients - who tend not to be the monsters that many doctors imagine, Kleber says. The message that comes across? "Addicts are a difficult group to deal with. They'll rob your office blind and steal your nurse's purse," Kleber says, frowning. "You're a general practitioner: Tell me if you're going to prescribe."

The result is that bupe faces an uphill battle to find its way into doctors' offices.

Kolodny steers a big government sedan through the busy streets of Queens, past a billboard that promises, somewhat disturbingly, The World's Boldest Corrections Officers, then over the bridge to Rikers Island, where he'll talk about bupe to a group of prison docs and nurses. "Best-case scenario, everyone hears my speech and thinks this is an amazing treatment," he says. "But they may not want to be innovators. They may be content in what they're doing." What they're doing is maintaining inmates on methadone, trying to tame their addictions before they return to the street. Kolodny hopes that with the enticement of meds donated by Reckitt Benckiser - seed drugs - the prison will agree to put some inmates on bupe instead. Then, when they check out, they can tell their neighbors about it and increase the pressure on local doctors to write prescriptions.

A security escort leads Kolodny through two guard stations and a razor-wire fence that stands between roughly 17,000 inmates and a postcard view of the Manhattan skyline. He hands Kolodny a visitor ID - "Lose this and I'll fucking kill you," he instructs - and asks what brings him to Rikers. "You're talking about replacing methadone?" he says, skeptically, before Kolodny corrects him. "We're pretty anal about change here," the guard warns. "We don't like change."

A group of 25 doctors and nurses is already waiting when Kolodny arrives at the prison's health offices. He surveys the collection of bored, tired faces staring back at him, shuffles his notes, and begins. "With any new medication with significant advantages, you'd see ads on TV, like you do with Zoloft, you'd see ads in journals, docs would start prescribing it," Kolodny says. That obviously hasn't happened with bupe.

The doctors ask about side effects. Good news there. They ask whether it shows up on a drug screen (methadone does, so many people who might face a urine test at work avoid it). Nope, Kolodny says, a bupe patient's urine tests negative - more good news. They ask about the potential for black-market dealing; inmates learn to hold their methadone in their throat, spit it back up, and sell the spit. That's pretty much impossible, Kolodny says, to nods of approval. Will inmates be able to keep receiving bupe after they leave prison? Some, but not all, Kolodny says. That's because of the nearly 300 doctors in New York licensed to prescribe bupe, only a handful will accept Medicaid, even though it covers the treatment. Any more - well, the city is working on it.

As he leaves through the tall, steel gates, Kolodny breaks into a smile. "I didn't think people would greet us this warmly," he says, genuinely surprised. "I don't know if I'd go so far as to say we achieved buy-in, but it was a start."

On the drive back to his office downtown, Kolodny's Treo rings twice, just minutes apart. Two more people looking for bupe treatment at his private practice. "That's weird," he laughs. Or, maybe, an encouraging sign.

Douglas McGray wrote about microcars in issue 12.10.

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