THE BITTER PILL

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.