Learn more about buprenorphine and its use in the treatment of addiction
Photos from day one and two of the series
A summary of notable abuses in three nations
The history of the use of buprenorphine in treating addiction
Interviews with addicts, a pharmaceutical company executive and the city health commissioner
Dr. Jean-Pierre Aubert considers himself not only a general practitioner but a dealer of sorts.
From his second-floor office up a winding staircase in an apartment building near the Sacre-Coeur Basilica, the doctor prescribes a drug called buprenorphine to 200 patients as a way to treat opiate addiction.
He is not an addiction expert. He does not screen patients to ensure that they, in fact, are opiate-dependent and need treatment. He concedes that some of them might misuse the medicine, including by injection. And he acknowledges that some of the pills he prescribes might end up the stuff of street sales.
Getting addicts in the door is what matters. Even patients who initially show up seeking the drug to get a fix, he said, might progress into proper treatment.
"I'm a legal dealer," he said. "But being a legal dealer, I can help them with many, many other health issues."
Aubert, along with 20,000 other doctors prescribing the medication in France, embodies the revolutionary approach the country adopted 11 years ago in its fight against drug use and the public health problems that accompany it. The French system encourages physicians unfamiliar with addiction to prescribe buprenorphine and trusts patients to use it properly.
In many ways, the plan has worked. The medication, which dampens the craving for opiates, has helped to drive down overdose deaths and contain the spread of HIV/AIDS among injectors. Schering-Plough, the company that sells it in France, terms it a "tremendous success story."
But the French experience also has a down side, one the United States largely overlooked when it followed a similar path by giving private doctors authority to prescribe buprenorphine to addicts.
Buprenorphine, available in France in a formulation called Subutex, has proved addictive for many and has been widely abused. Pills that addicts legally take home are being sold illegally, just like heroin.
Similar problems have begun to emerge in the United States. Street sales are increasing, leading to growing abuse of the drug, a Sun investigation found. American addicts are also injecting buprenorphine, even though U.S. officials took the precaution of approving a form of the drug, Suboxone, with a chemical intended to deter injection. It is the only difference between the two formulations.
With the longest experience in using buprenorphine to treat addiction, France provides the clearest picture of the implications of making such a powerful opiate widely available.
Buprenorphine has become an entry drug for people who haven't used opiates before, a re-entry drug for former addicts, and a factor in more than 100 deaths since 1996 when taken in combination with other substances, according to researchers and public health authorities.
The drug has created a quandary that no one seemed to anticipate: how to get patients off it. Many stay in treatment for years, including some who want to quit, prompting criticism that substitution therapy doesn't address the underlying problem of opiate dependence.
Buprenorphine has been widely sold on the streets of France, and well beyond. A report by the French Monitoring Center for Drugs and Drug Addiction found that a fifth to a quarter of all buprenorphine sold was being illegally diverted. Pills originating in France are being smuggled to places as far-flung as the nation of Georgia and the Indian Ocean island of Mauritius.
"It's overprescribed, and it's too easily prescribed, without any control," said Dr. Agnes Lafforgue, who helps recovering addicts at a treatment and assistance center in Toulouse, a university city in southwest France.
She questions treating longtime heroin injectors with Subutex, for fear they will inject it, too, and worries about its addictive qualities. She said she has "practically never" successfully weaned a patient off it, despite having done so many times with methadone.
"It's a scandal the way Subutex has been introduced in France," she said.
Aubert and other doctors concede it is easy for a patient to get multiple buprenorphine prescriptions from multiple doctors, and sell the pills. Yet he maintains that such sales don't make the treatment program a failure, as it connects addicts with the health care system and provides them what he considers a safer drug. The government shares that view.
Good medicine involves a sometimes precarious balance for which there is no textbook guide. With every course of treatment they prescribe, physicians have to weigh potential benefits against the possibility of harm. The introduction of buprenorphine treatment in France - and elsewhere - raised that issue: how to properly balance widespread access to the drug, getting as many addicts as possible into treatment, with adequate control.
Health officials in France introduced Subutex a year after methadone, less to try to cure the country's estimated 150,000 addicts than to reduce the associated dangers of intravenous drug use - principally, the spread of HIV. At the time, up to 40 percent of addicts using needles were thought to be infected.
Officials believed it would be impossible to stem HIV by treating addicts with methadone alone; as in the United States, methadone was administered initially under tight supervision only at specialized centers. There were hardly enough of the centers. And methadone carried a much higher risk of fatal overdose.
In giving general physicians the right to prescribe buprenorphine from their offices, the government did not require training or certification and placed no limit on the number of patients doctors could treat. The United States, by contrast, requires minimal training - eight hours - and limits a doctor's buprenorphine practice to 100 patients.
In France, no central registry tracked prescriptions, and tablets were dispensed in take-home doses like antibiotics or antihistamines.
By the late 1990s, 65,000 French patients were taking Subutex. By 2005, the number had climbed to 90,000, nine times more than the total taking methadone, according to researchers. Schering-Plough estimates that 85,000 people are being treated now.
"We needed to urgently treat heroin addicts," said Nathalie Arens-Richard of the French Health Products Safety Agency, which, like the U.S. Food and Drug Administration, monitors the safety and misuse of medicines. "We didn't know what the problems with the treatment were going to be."
Over the years, concerns over misuse and the high costs for the government led to adjustments in how Subutex is dispensed. In 1999, France tightened the take-home limit. In 2004, the government further clamped down to counter a black market trade that France was, in effect, subsidizing. Subutex had become one of the top drugs paid for by the government.
Although the 2004 change prevented patients from submitting multiple prescriptions for reimbursement, they still could fill multiple prescriptions as long as they paid for the drug themselves. Critics suggested the government had acted not because of health or social costs but rather budget concerns.
Last year, the French health ministry rejected a proposal to reclassify the drug in a way that would result in tougher penalties for peddling it.
Michel Mallaret, president of the National Commission on Narcotics and Psychotropic Substances, recognizes the trafficking problem but sees benefits in keeping the drug widely available.
"We have to be very cautious if we have more control," he said. "The great risk is to see AIDS increase again, or injection, or overdose."
French officials have also discussed using Suboxone, which the European Union approved for marketing in 2006. But the government has been weighing whether that makes sense, given the possible higher cost of Suboxone and doubts about the effectiveness of its injection deterrent.
Pierre Chappard is typical of Subutex users who prefer to inject it. The former heroin addict has been receiving the drug by prescription for 10 years and is dependent on it. Twice he tried to quit but, for now at least, has given up on giving it up.
Four times a day, the one-time high school math teacher shoots up the drug and feels a pleasant rush. Chappard, 35, first used Subutex the year it was introduced, crushing it and mixing it in an injectable solution. It didn't give him the same flash as heroin, but it sufficed. Best of all, it was legal. You could get it from a regular doctor, and France's health care system would pay the cost.
Chappard is among the many addicts who say they can't, or won't, give up the ritual of injection. "The people who have injected heroin, we won't go to a Subutex pill," he said. "To just stop injecting and start taking a pill, it's too difficult."
But he admits to a motive beyond that: "You're injecting because you want more effect. The Subutex gives me a little bit of high, but I'm normal."
He still shoots heroin a few times a year but said he doesn't share needles. He filters his Subutex to remove large particles that could make injection dangerous.
"The biggest advantage of substitution treatment is it allows me to avoid AIDS, prisons and hepatitis," said Chappard, who works for Self-Help for Drug Users (ASUD), an association of current and former drug users that lobbies for such treatment.
"Instead of going to see a dealer, I go to see a doctor."
For some, Subutex use has had unintended effects. Injectors who were not as careful as Chappard developed abscesses, infections, swollen limbs and blocked veins. Eric Schneider, national president of ASUD and a former heroin injector, said he witnessed this aspect of Subutex abuse almost as soon as the drug became available.
"The lucky ones only lost maybe a couple of fingers, the unlucky ones lost a leg or an arm," said Schneider, co-director of a drop-in center for addicts in Marseille.
He had anticipated that drug users would inject Subutex, in part because France had experienced a problem with the injection of Temgesic, a low-dose form of buprenorphine also sold by Schering-Plough as an analgesic.
"Nobody could tell me that people would be observant and take it as prescribed, knowing it was as easy to inject as Temgesic," Schneider said. "Injectors will inject, that's why they're injectors. So if we put something on the market that's injectable, we shouldn't be surprised that they do."
The French monitoring center reported in 2004 on Subutex trends. Because of its widespread availability, Subutex was serving as a first opiate for some drug users and a re-entry opiate for some who had previously injected heroin. The report found it to be highly addictive and hard to stop. And it was increasingly being used in dangerous combinations with alcohol, benzodiazepines (such as tranquilizers) and even cocaine.
Subutex was implicated "as a contributing or causal factor" in 136 deaths in France from 1996 to 2000, in combination with benzodiazepines, alcohol or other substances, according to a 2004 article in the American Journal on Addictions. From 2001 to 2005, Subutex was implicated in combination with other substances in 31 deaths, according to government and police reports.
Researchers say that in the early years of buprenorphine prescribing, there was not widespread awareness of the danger of prescribing it with other drugs.
Serge Escots, a family therapist and addiction specialist in Toulouse, did some of the research on the unintended hazards of Subutex use.
"We could see it," he said. But, "If I talked about it, [Subutex proponents] said, 'You're wrong, you're anti-substitution, you're against public health, you want to see AIDS all over the street.'
"You couldn't talk about it. We weren't invited to talk about it. We were only invited to say good things about it," he said.
Subutex's staunchest supporters in and out of government embrace the public health philosophy known as harm reduction. It acknowledges that some addicts can't or won't quit their habits, and emphasizes ways to minimize the dangers.
Buprenorphine has played a major role in addiction treatment that has saved 3,500 lives, experts say. Opiate overdose deaths have declined 79 percent since the drug was introduced, and the HIV infection rate among injection drug users has fallen sharply - from 40 percent in 1996 to 20 percent in 2003.
"The difficulty, the problem, of Subutex is [that] on one side, it has helped enormously," said Xavier Thirion, a buprenorphine proponent who tracks trends for a Marseille-based center on drug dependency research. "On the other hand, we found the misuse. Every policy has advantages and disadvantages. All of public health policy is about balance."
Schering-Plough has aggressively promoted the drug in France, funding the work of harm reduction groups. Company officials say they are aware of the trafficking and misuse. By their estimate, 25 percent of patients use buprenorphine "non-medically," a figure that includes illegal sales and inappropriate practices such as injection and drug sharing. They term that "a small number" and say the benefits of treatment outweigh the risks especially given the level of opiate addiction.
"By all accounts, what you have is a tremendous success story of the benefits of increasing access to therapy - making it available through general practitioners - and the tremendous benefits to the public health of the community," said Leslie Amass of Schering-Plough's Global Medical Affairs Department.
But many general practitioners - who write the vast majority of buprenorphine prescriptions - lack experience in addiction treatment. While some belong to voluntary networks that sponsor occasional education sessions and include specialists trained in addiction medicine, most GPs do not.
According to doctors and addiction experts, some physicians have mistakenly prescribed buprenorphine as a treatment for marijuana use, potentially creating new Subutex addicts. Others have prescribed it in dangerous combinations with sleeping pills and tranquilizers.
Dr. Alain Morel, a psychiatrist at Le Trait d'Union, a drug treatment center in the Parisian suburb of Boulogne, thinks general physicians should be trained, certified and permanently "attached" to a drug clinic to prescribe buprenorphine. Many, he said, "don't do any follow-up, so it's up to the patient to use - or misuse - the drug."
Some countries put more trust in patients than others, and it shows in their different take-home policies. Doctors could prescribe 28 days worth of pills at the outset of the French program. Although abuses led the government to tighten the take-home recommendation to a week's worth of pills, doctors are allowed to prescribe more.
The United States has a fairly permissive take-home policy, letting doctors prescribe at least a month's supply, among the largest anywhere. By contrast, in Germany unsupervised dosing is not the norm. There, some patients are permitted a week's worth of take-home doses but only after showing compliance for six months.
Finland allows up to eight days of take-home doses once a patient has become stabilized. After Finns were found to be traveling to Latvia or Estonia to obtain Subutex, those Baltic countries introduced new restrictions. Estonia, for example, allows one to two weeks' worth, depending on a patient's dose.
In France, illegal sales persist despite law enforcement efforts. Over the past year, police have arrested 30 people in a Subutex ring, including a Tunisian man who had nearly 40 prescriptions for the drug. They were from the same doctor, about half filled out in the name of a single patient, said Commissioner Roland Desquesnes of the Brigade des Stupefiants, the anti-drug unit. The physician, who was among those arrested, had sold them for $30 to $45 apiece.
France is also an international hub of Subutex trafficking, a source of the drug in Finland, Georgia and the Czech Republic, according to officials in France and in several countries.
"I think that some percentage of [France's] Subutex comes straight to our country," said Khatuna Todadze, director of a methadone maintenance program at the Georgian Institute of Addiction. "Our problem depends on their system. It's too liberal. Maybe it's good for their patients, but it must be more controlled."
Authorities in Mauritius say they have traced large amounts of illegal Subutex to France, such as the 50,000 tablets brought to the island in May by a French steward for Air France.
It is a profitable trade. In France, an 8-milligram Subutex tablet costs the equivalent of $4 to $8. In Finland, it goes for at least $50. In Georgia, where experts say it has surpassed heroin in popularity, it sells for $100 or more per pill.
"It's more lucrative than heroin," said Desquesnes. "People are very interested in dealing it, and in France, it's very easy to get."
Schering-Plough, the distributor, has come under fire from critics who say it has done little to discourage abuse and illegal diversion of a drug that makes money. The company says that its employees take security seriously, and that "we control the product when it's in our hands."
The company has suggested ways to reduce trafficking, including "reinforcing surveillance" and training doctors better, according to Arens-Richard of the French Health Products Safety Agency.
"Schering-Plough is actually training a lot of doctors," she said, "but it hasn't reduced the misuse of the drug."
Lafforgue, the general practitioner from Toulouse, doesn't see buprenorphine as a solution to opiate addiction.
"We've made drug users addicted to Subutex because it calmed them down," she said. "We've cleaned up the country, but we haven't solved the problem of drug abuse."