How Safe Is America's Hottest Heroin Addiction Treatment?
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How Safe Is America's Hottest Heroin Addiction Treatment?

Vivitrol is all the rage amid a brutal opioid epidemic. But it may also make it almost impossible to feel pleasure—and raise the risk of fatal overdose after relapse.

Claire* felt she had no choice. Pressured by her parents and counselors, the then college student signed a contract agreeing to take anti-opioid medication for six months—or face losing her home and contact with her family. She had struggled to kick heroin and prescription pain medication for years.

"I've had depression before," Claire recalled of the side effects she experienced from the new drug. "But this was just ongoing, constant… It made me extremely depressed, disillusioned, and uninterested in things I used to love.


"I didn't even eat—there was no enjoyment in it," she added. "I didn't talk to people; I didn't enjoy company… I was a zombie: I got up, went to class, came home, and went to sleep."

Or tried to—Claire lived in Chicago near a noisy L train, so she's not sure whether her insomnia was related to the medication, Vivitrol.

Now 24, Claire said that before she took the stuff, playing music was her greatest joy. "Afterward, I just wasn't interested, and it's my favorite thing to do."

More disturbingly, at least one friend who signed a similar contract with their parents fatally overdosed not long after the medication wore off, Claire said.

Watch this short look at how one person beat the deadly opioid fentanyl:

Vivitrol is the brand name for the long-acting form of the drug naltrexone. Delivered via monthly injection, it completely blocks the high from heroin and other opioids like OxyContin. Leaving aside its steep price—upward of $1,000 per dose—it sounds like the perfect weapon against addiction in a country where opioid deaths are spiraling out of control. In fact, Tom Price, President Donald Trump's health secretary, hyped Vivitrol at the expense of more established treatments after visiting the drug manufacturer's factory in Ohio this spring.

But Vivitrol has also been the subject of recent exposes by the New York Times, ProPublica, and NPR, each featuring different examples of hardball tactics employed by that manufacturer, Alkermes. In some cases, the reports found, the company targeted prisons, jails, and drug courts, which can legally coerce patients to take the drug as part of an alternative to incarceration. In others, Alkermes pressed legislators to pass preferential laws by stoking stigma against cheaper, proven competitors.


Yet problems stemming from the risky nature of this addiction medication itself—particularly for those pressured to take it—have so far gone largely unexplored.

In an emailed statement, a spokesperson for Alkermes wrote, "No patient should ever be 'coerced' to use any medication," and that the company "has advocated for access to ALL available treatments… The patient that is right for Vivitrol may very well be different than a patient who may take the path of maintenance therapy. Whatever the choice, it is our goal to help more patients reach recovery."

Likewise, it's worth emphasizing from the jump that during an overdose epidemic, I believe patients should have access to all FDA-approved options—Vivitrol included. But the fact is that the majority of prisons and jails and many of America's drug courts ban alternatives—some even describe themselves as a "Vivitrol court." Meanwhile, tough-love pressure tactics like those employed by Claire's parents and counselors are not uncommon. Sales of Vivitrol have risen 33 percent since last year, and while in 2012, just 15 American drug-treatment programs specialized in treatment with the drug, now some 450 do so. Vivitrol ads cover an entire esplanade in Grand Central Station in New York City and dot the New Jersey Turnpike .

No one knows how it's really affecting people like Claire.

Five mostly small and industry-funded clinical trials have found Vivitrol to be effective in treating opioid problems—at least for those who choose to stick with it. The problem is that many do not: In a trial in which participants had been released from jail or sentenced to supervision, had a goal of abstinence, had not had a recent overdose requiring hospitalization, and could receive up to $820 if they took all six shots, only 61 percent of participants did so. In a real-world study of 1,900 more typical patients treated for opioid addiction, alcoholism or both, 39 percent accepted only one shot and just 14 percent took five or more. (The drug is approved for treating both alcoholism and opioid addiction, but is less controversial for alcohol because overdosing on booze is relatively rare.)


Side effects like Claire's may drive some of this dropout. As acknowledged on its label, Vivitrol can cause depression and suicidal thoughts and may increase overdose death risk when people stop treatment. The drug's label also reports two completed suicides of patients who received Vivitrol during clinical trials—and that 10 percent of patients reported depression, compared to 5 percent on placebo.

The reason for these problems cut to the core of the drug's pharmacology. Opioid medications aren't the only chemicals Vivitrol can impact—its active ingredient may also block the brain's natural opioids, endorphins, and enkephalins. Consequently, it has the potential to reduce normal pleasures like those from food, exercise, music, and perhaps most important, the "warmth" of feeling connected to others.

The human brain's opioid system is believed to have evolved to make socializing enticing, promoting survival. In concert with hormones like oxytocin, brain opioids allow relationships to relieve stress—helping parents calm children, lovers soothe each other, and friends offer solace. This may be why trauma survivors are at high risk of opioid addiction: These drugs offer a sense of being loved and safe that they often can't get elsewhere.

In fact, when scientists want to learn whether a brain function is opioid-driven, they typically give participants naltrexone. If the drug mutes or eliminates pleasure associated with the experience in question, this suggests that the function involves opioid activation. In numerous studies, naltrexone has been found to reduce pleasure from food, exercise, socializing—and, yes, music.


"We have shown in our laboratory that you develop a relative endorphin deficiency during long-term heroin or other short-acting opiate administration," said Mary Jeanne Kreek, professor of neurobiology at Rockefeller University in New York. She was one of the original developers of methadone treatment and is recognized as a leader in opioid neuroscience.

Kreek explained that methadone and buprenorphine—the only two treatments proven to cut the death rate among people with opioid addiction by half or more —work by relieving this deficit. Studies have even found that stable methadone patients have a more normal stress response than people who recover via abstinence.

Naltrexone, however, has a very different effect on the brain. "You're completely blocking the limited, deficient amount of endorphins present, so [patients are] getting less than they might have if they weren't on naltrexone, and they feel horrible," Kreek said.

In Claire's case, once she connected her distress to Vivitrol, she sought help. But instead of stopping the medication, her doctor added to it, she said. "I probably tried eight different antidepressants. It didn't work, and it was miserable going on and off."

Unsurprisingly, Claire relapsed immediately after her contract with her parents lapsed. Which brings us to another pharmacological concern: When someone stops opioids—for any reason—tolerance is lost within days, and with it, protection from overdose. After leaving prison, for example, overdose death risk has historically been multiplied by a factor of ten. (Indeed, maintaining tolerance is part of why staying on methadone or buprenorphine cuts the death rate, even when people keep taking other drugs as well.)


Since naltrexone completely blocks opioid receptors, theoretically, risk could be even higher after cessation: It could produce the antithesis of tolerance, known as sensitization. But Adam Bisaga, a professor of psychiatry at Columbia who has conducted some research funded by Alkermes, told me in an interview that while there is evidence this occurs in rodents, the same results aren't seen in humans.

Research from Australia on the oral version of the drug, however, suggests the risk to humans could be real. One study compared 1,200 patients who took oral naltrexone or synthetic opioids such as methadone or buprenorphine. Members of the naltrexone group were, on average, eight times more likely to overdose following treatment cessation. Another Australian study of more than 14,000 patients found that the death rate following oral naltrexone cessation was nearly quadrupled, compared to that for methadone.

Proponents argue that Vivitrol is safer than oral naltrexone, because its effects last longer and don't rely on patients choosing to take a pill every day. They say the shot keeps patients protected from overdose because it wears off gradually, which isn't the case with the pills. As Bisaga put it, "In a recent randomized study, no overdoses were reported in patients who were treated with [Vivitrol], compared with seven overdoses during [non medication talk therapy] treatment as usual."


But there's also less data out there on Vivitrol compared to methadone and buprenorphine. There have been just five trials for the drug's impact on opioid addiction—compared to hundreds on buprenorphine and methadone. Vivitrol was FDA approved for opioid treatment, based on a single trial, conducted in Russia, where other medications are illegal. No comparative studies have been done.

"The data is mixed," offered Walter Ling, professor of psychiatry at the University of California, Los Angeles, on the question of whether Vivitrol increases overdose risk above and beyond that of abstinence. "We don't know for sure." He added that even if it doesn't produce sensitization, the elevation of risk is still dangerous.

Fortunately, Claire did not overdose during her relapse. "I went back to using daily," she told me. "I was probably really lucky… I know people who have OD'd right afterwards."

In fact, while researching this story, I heard from at least half a dozen people in the field who reported such deaths and gathered accounts of several other apparent instances in the media of OD following Vivitrol treatment, including cases where insurance issues cut people off from desired care.

Unfortunately, unless researchers specifically track these deaths, increased risk is unlikely to be detected. To find it, death investigators would have to ask survivors or seek prescription records to determine if the victim had recently stopped using Vivitrol. Coroners don't typically test for it—and it might not be detectable even if they did.


"That's what's so scary about people being forced to take it. The risk of overdose is so great, it's terrifying." —Kat, 31

The problem is especially acute since the drug is already widely used in the criminal justice system, where it's preferred in part for the simple reason that it cannot be used to get high. Ling, who was involved in the early development of naltrexone, told me, "Law enforcement loves the idea and that hasn't changed." Methadone and buprenorphine are often seen as coddling people with addiction, while naltrexone not only shuts down drug pleasures, but potentially others as well. That seems like a feature, not a bug, in a system designed to punish evildoers.

All of this is far from suggesting that the drug is useless. Self-motivated patients say Vivitrol can really help. Kat, who lives in Charlotte, North Carolina, was homeless when she started Vivitrol, recalling, "I was desperate for any kind of help and super-excited to get on it."

Now 31, Kat had started taking heroin at 13—and said that being on Vivitrol was "the first time I ever got more than three months off of opioids." In contrast to Claire, Kat said the drug lifted her depression, and research suggests this is true for some others who manage to stay on it, too. Odd as it seems, such opposing responses are common in psychiatry: drugs like Prozac, for example, can both cause depression in some and relieve it for others.


After nearly a year of recovery, though, Kat missed her shot and relapsed. "I didn't realize how much it helped with craving until I was without it in a situation where people were using," she recalled. Her parents pushed her to try again. But when pressured, her experience was less positive. "I got [the shot] but I was still out on the streets and didn't have any support. I was using the next day, trying to break through it." Her first attempts failed—so she added cocaine, which is not blocked by naltrexone.

She also jacked up her dose. "I was using in tremendous amounts," Kat told me. "My friends were concerned."

To protect herself, she didn't inject while alone—but part of her also didn't care what happened. "That's what's so scary about people being forced to take it," she said. "The risk of overdose is so great, it's terrifying." Kat is now on buprenorphine, but eventually wants to switch back to Vivitrol. "I think it's a really great tool, but if [people don't have support] or if it's coerced, it's useless or dangerous," she said.

Sam Tarplin, a 28-year-old college student and videographer in Massachusetts, had a similar experience. He switched to shooting and smoking cocaine when he found opioids didn't get him high anymore after going on Vivitrol. "I had messed with it a little bit before, but once that was only real option, that's what I went with," he said. Like Kat, he thinks the medication can be useful—but works best if people are committed to abstinence. Tarplin now has been off drugs for four years, he told me.

Despite her bad experience, Claire feels much the same way. "People need to know the truth and the risks," associated with all of the medications, she said. With help from buprenorphine, Claire now has two years in recovery—and is back to playing jazz and funk.

In the face of an unprecedentedly deadly epidemic, multiple options for recovery are essential. What helps one person recover might be useless or even harmful for someone else. But informed consent is essential, too: No one should be pressured into taking a treatment with such potentially dangerous side effects.

*Some last names have been withheld to protect the privacy of people in recovery.

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