Fighting drugs with drugs

Often misconstrued and exorbitantly priced, Vivitrol stands at the forefront of the pharmacological effort to fight drugs with drugs. Assessing its effectiveness means sifting through competing claims from the manufacturer, patients, clinicians and the generally accepted model of recovery itself.

Standing in a small restroom in a building across the parking lot from the Boulder County Jail, Robert, a robust man in his fifties, lowers his jeans a few inches in the back so that a nurse practitioner can access the meat of his right buttock. “Little pinch,” she advises, but she doesn’t really have to; Robert has been through this process several times already, usually with this same provider. And while he doubts the drug’s direct effects on his system, it’s getting him other things he values: a place to stay at the local homeless shelter, a weekly therapy group to attend and food.

Vivitrol, manufactured by Ireland-based Alkermes Pharmaceuticals, is a once-a-month injectable form of the opioid-receptor antagonist naltrexone that was approved by the U.S. Food and Drug Administration in 2006 for the treatment of alcohol abuse. It seems odd that not until four years later was this opioid-blocker approved to treat opioid addiction as well, but oddities are hardly unusual where the business of pushing pharmaceuticals meets the business and science of practicing medicine.

The cost of a shot of Vivitrol varies across the country and depends on who is administering it, but is in the ballpark of $1,000. With the Affordable Care Act’s provisions becoming reality in January 2014, and with Colorado embracing the attendant Medicaid expansion, a significant number of low-income and homeless Coloradans with long-standing substance-abuse problems acquired health insurance that would pay for the shot.

Throughout a 15-year-long, society-searing rise in opioid addiction nationwide, Vivitrol’s use among clinicians for both alcohol and opioids has continued to spread despite a decade of statistically equivocal results — and no real promise of landslide effects to start with. A 2013 article in The Fix pointed out that despite fewer than 1 in 10 heavy drinkers who received Vivitrol in a 2005 clinical trial remaining abstinent from alcohol throughout the six-month trial, and perhaps 1 in 5 people seeing any benefit from the drug, the FDA okayed a label promoting Vivitrol as an abstinence-enhancer, thereby seemingly touting unproven beneficial effects and largely ignoring proven ones such as basic harm reduction (more on this below).

A 2015 article in the Washington Post noted that some 40 jails across the U.S. had begun using Vivitrol on opioid-addicted inmates, with positive results. Of course, it was unclear how well these results would translate to post-release sobriety, especially absent other forms of treatment such as therapy and recovery meetings. Then, in June 2017, the New York Times ran a story suggesting that Alkermes, the U.S. headquarters of which is outside Boston, is capitalizing on the opioid crisis and the company’s “shrewd use of political connections” to boost Vivitrol sales and use “despite scant science to prove the drug’s efficacy.” (The irony of a drug company perhaps profiting unethically from another’s unethical product, in this case OxyContin, is presumably self-evident.)

Weeks later, the investigative news website ProPublica, echoing elements of the Times’ reporting, noted that Vivitrol’s booming sales were owed in large part to Alkermes’ skirting of typical sales channels; it had, for example, staged clinical trials in Russia and evaded the obstacle of skeptical physicians by focusing its marketing efforts on drug courts, where recipients exert less freedom in certain medical decisions — a kind way of saying that for many of them, it’s Vivitrol or jail. This alliance with the justice system has helped push the number of people getting Vivitrol nationwide to about 30,000 a month; in the first quarter of 2017, sales of the drug totaled $58 million, a 33 percent increase over 2016.

Meanwhile, some Vivitrol users swear by it. Michelle Goranson of Lyons abused alcohol for more than 20 years before her family cajoled her into detox in October 2014. After starting Vivitrol within the week, she stayed on it for 16 months, and is now almost three years clean. Goranson admits that she is a rarity; as far as she knows, no one else in her original cohort of Vivitrol recipients — all of whom are expected to attend a weekly Vivitrol meeting at the detox, which also provides their shots along with pizza and calzones from Black Jack’s — is still sober. She now keeps an oral form of naltrexone on hand for what she calls “risky situations.”

People inhabiting the world of substance-abuse treatment and recovery seem divided into those who have never heard of Vivitrol (a shrinking group) and those who have strong opinions about it. Those in the latter category have conflicting views about it, shaped, in some cases, at least as much by their expectations as by their experiences.

Vivitrol comes to Boulder County

Fred Michel, M.D. is a psychiatrist by training and the medical director of Mental Health Partners (MHP), the nonprofit that provides mental-health and substance-abuse treatment to residents of Boulder and Broomfield counties. MHP is an ambitious organization, having added the Ryan Wellness Center on Alpine Avenue and a 24/7 walk-in crisis center since the end of 2014. At the beginning of 2015, MHP took over the administration of the detox from the Addiction Recovery Center (ARC). Talk to people who have gotten therapy or services from MHP providers, and you’ll almost certainly hear praise for the outfit’s efforts.

MHP now administers about 50 doses of Vivitrol a month, according to Ann Noonan, director of MHP’s Substance Use Disorder Center of Excellence and formerly the director of ARC. Most of the clients are Medicaid recipients who are recruited to the Vivitrol program — and often to Medicaid itself — because of repeatedly landing in detox for alcohol intoxication. The typical length of treatment through MHP, she says, is six to nine months.

According to Noonan, Todd Dorfman, an emergency medicine physician at Boulder Community Health, had grown frustrated over the number of emergency admissions for alcohol intoxication involving a comparatively small number of people, some of whom were landing in the hospital dozens of times a year. Dorfman did some research and uncovered Vivitrol, and advanced the idea of using it to those in charge of ARC, including Noonan. Thus Boulder scrambled aboard the Vivitrol train relatively early in its journey around the country’s mental-health delivery system.

Today, detox workers dispense literature on Vivitrol to clients identified as likely to be chronic alcohol abusers, such as those who end up in the detox repeatedly. Along with these handouts, clients receive the assurance that Vivitrol may ease or even eradicate alcohol cravings. Once a client agrees, and has Medicaid, the path to the shot is straightforward, and may take less than a week, although most people who leave the detox before getting the shot never return for their maiden dose.

Statistical Sophistry?

Whatever its real effectiveness, Vivitrol cannot be written off as pure smoke and mirrors. “Randomized clinical trial data shows that [Vivitrol] reduces heavy drinking days, which is a positive outcome in alcohol treatment. Less heavy drinking in homeless, alcohol-dependent persons would be great and probably save a lot of money,” says Joshua Lee, M.D., an addiction specialist at New York University School of Medicine. “That is a very difficult population to treat, in which we don’t see a great deal of abstinence, no matter the treatment approach.”

Michel from MHP echoes Lee’s observations. “We have much anecdotal success with Vivitrol around alcohol craving reduction and decreased tendency to drink as heavily,” he says. “A harm reduction hypothesis is in play for both scenarios.”

But these endorsements by responsible doctors stop notably short of what those in Vivitrol’s parent company would clearly prefer people to think. Alkermes is no different from other drug companies in both wanting to profit from its investment and making strategic use of numbers to maximize Vivitrol’s apparent effectiveness, and it is not difficult to play games with the data to present a rosier-than-reality picture without lying outright.

For example, from the results of the same clinical trial in 2005 that led to Vivitrol’s approval for alcohol deterrence, from which The Fix drew its aforementioned conclusions: “Neither the rate of National Institute on Alcohol Abuse and Alcoholism risky drinking nor the rate of any drinking was significantly lower with either dose of long-acting naltrexone.” Translation: In this study, Vivitrol didn’t foster abstinence from drinking, and when problem drinkers on Vivitrol drank, they drank as recklessly, by NIAAA criteria, as they would have without the shot.

On its website, Alkermes notes that people who had already stopped drinking for a week before getting their first Vivitrol injection were more likely to subsequently stay abstinent, drink less and have fewer days of drinking than people who started Vivitrol with no cessation of drinking — especially compared to those who went on to receive the placebo.

This, however, may merely reflect the effects of a higher overall commitment to sobriety. And the results of study at the University of Pennsylvania reported in 2013 revealed that over an eight-week period, 10.3 percent of people on Vivitrol (4 of 39) reported days of abstinence from drinking, compared to 17.1 percent who were on a placebo. That’s a statistically significant difference — in precisely the wrong direction.

So how did a drug that generally fails to promote abstinence, but may put a dent in the amount of booze drinkers consume at a time, achieve a reputation as a savior in some treatment circles?

Lost in Translation

Part of the reason for the controversy of Vivitrol is that it was never supposed to be any more a panacea than it has proven to be, and is not embraced as a quantum leap in addiction treatment by those in the know. Someone coming up with a drug capable of eliminating cravings for mood-altering, physically addictive substances is about as likely at this stage of medical science as someone producing a pill that can prevent all forms of cancer. But this doesn’t mean that useful treatments for addiction and cancer don’t exist. Putting the brakes on magical claims is, then, not only helpful but necessary; it’s the only way that humbler, still helpful ones can be better appreciated.

“One of the mistakes we’ve made,” says Noonan, who has worked in the addiction field since the 1980s, “is saying that you’re either a cucumber or a pickle.” That is, people have been slotted into basic on-off categories when it comes to substance use: either they’re alcoholics or they’re not.

As a counterexample, Noonan notes the archetypal daily drinker who never misses a day of work or gets in any trouble despite knocking back a six-pack a night. After years of this, such a drinker may have avoided psychosocial problems, but is likely to have suffered organ damage thanks to his or her sheer lifetime exposure to ethanol. Such people might be ideal candidates for a drug that helps them drink less, even if it doesn’t lead them to stop altogether.

Apart from the court system, Vivitrol’s burgeoning success relies largely on garden-variety ignorance much of it within the anti-substance-abuse trenches. Unlike career health professionals such as Michel and Noonan, most everyday professional shepherds of recovery, including those who staff the Boulder detox, lack the critical background to even detect, much less oppose, misleading claims in the lengthy provider information packets that drug companies publish, and are generally not aware of what is actually contained in the studies on which this information is based.

By the same token, most people who land in the detox do not have the wherewithal or the desire to explore their own skepticism about Vivitrol. But one man who, in his words, “Gave the stuff a fair shake for four months” a year ago was asked by an MHP employee not to discuss what he had read about Vivitrol on the internet with detox clients while he attended open-to-the-public recovery meetings at the facility.

The reason? He might discourage people from getting the shot. This same employee, however, reportedly could not describe Vivitrol’s clinical mechanism of action or provide even circumstantial evidence that it actually worked. “They do give clients the stuff [i.e., Vivitrol brochures],” says the man, who now says that therapy and steady employment have helped keep him sober for five months. “But no one bothers to read it and no one understands that language.”

Yet for all MHP’s laudable enthusiasm for getting people on Vivitrol, it is extraordinarily difficult to objectively assess how the program is serving individuals or the community. Even when people have a stable living environment and a phone, it can be hard to keep in touch with them to see how they’re faring. If people getting the shot simply stop showing up at the weekly Vivitrol meeting at the detox, the leaders of those groups have little recourse but to hope for the best while assuming the worst.

What it all means

So how has a very expensive drug that may be marginally effective gained a reputation as a veritable savior in some treatment circles? It is clearly not because medical professionals don’t know what they’re talking about, or, in the case of MHP, not because they lack a strong motivation to help people in every possible way.

Aggressive, shotgun-style, opportunistic marketing and the drug manufacturer’s careful cultivation of an erroneous perception seem to be a big part of the mix. Alkermes has never claimed that people won’t want to drink if they take Vivitrol. But they are keenly aware that this is how a lot of non-clinical professionals in the substance-abuse-treatment sector understand and present the medication, and the company is unlikely to change a strategy that has gained it enormous and ever-rising profits.

Critically, however, to judge Vivitrol’s efficacy requires a close and honest look at the very definition of success. The categorical, ongoing avoidance of alcohol and other drugs is vital to most self-described addicts, and represents the stated ideal for most. But when people fail to achieve abstinence the first time they try, or the second, or the 10th, they often give up. This is understandable; for decades, the only real measure of truly kicking a drinking problem has been kicking it completely, because the primary voice of recovery has been 12-step groups such as Alcoholics Anonymous.

Twelve-step meetings are abstinence-centric, as they surely should be. But when people relapse and drink, A.A.’s offering them a “white chip,” meant in the best of faith, effectively sends them back to the zero point on the game board of recovery, whether they relapsed after 30 days of sobriety or 30 years. A lot of people, from addicts to judges to medical professionals, are therefore conditioned to view sobriety as an all-or-none phenomenon, and to dismiss statistically meaningful but imperfect assets such as Vivitrol as worthless. As Michel, Noonan and Lee emphasize, some effect is better than no effect. And as expensive as a shot of Vivitrol is, so are a lot of other formal treatments — probably most of them. The $1,000 price tag of Vivitrol may not even buy a single day in inpatient treatment, which is not covered by Medicaid.

It is true as well that with a problem that routinely shatters lives and ends them outright, as does substance abuse, it is worth investing a good amount of money and labor to produce some effect, even if that effect does not appear profound or reduce to a neat column of data. Noonan says that as soon as Dorfman’s Vivitrol suggestion was implemented, “We saw amazing results” in terms of how often familiar names were being seen in the ER for acute intoxication. Even if most of them didn’t sober up outright, they were perhaps drinking less, and as a result, placing themselves in less danger of freezing to death and keeping themselves further from mortal harm.

If there is one thing everyone seems to agree on, it is that almost no one with a serious and long-standing substance abuse disorder is likely to achieve lasting sobriety through a single intervention. Some blend of individual and group counseling, sobriety meetings, medication and other psychosocial support modalities is almost always in the equation.

Goranson from Lyons, who struggles with a mood disorder but maintains an unrelenting proactive stance in seeking the right medication, says: “Vivitrol is not the wonder shot. It is not going to work unless you do everything that goes along with being sober.” She says that her success on the medication was not in fact predicated on the idea that it was a wonder drug. “It gave me the chance to not take the first drink,” she says. “But it’s not the reason, by itself, that I am sober now.” Asked what she would tell a prospective Vivitrol client, she says, “I would tell them it’s an aid, not a solution. It’s a tool, one of many.”

Some chronic drinkers, notes Noonan, are not ideal candidates for insight-oriented psychotherapy because of the neurological damage from years of drinking. For these types, Vivitrol might be the one of the last lines of defense against lethal drinking. And in the end, MHP is interested not in how much Vivitrol bolsters its bottom line, but in saving as many lives as available means and funding allow.

SIDEBAR: What naltrexone does

Naltrexone is a competitive inhibitor of opioid drugs, binding to the same receptors as heroin, morphine and other prescription painkillers (narcotics) without activating them. (Think of the pharmacological equivalent of sticking chewing gum in a lock; you won’t get past the door, but neither will anyone who has a key.)

Oral naltrexone has been in circulation since 1984. Vivitrol was conceived as an alternative to the oral form for a simple reason: it would obviate patient compliance issues. For one thing, because it is administered in a clinical setting, the prescribing agency has a record of who received doses and when. Also, people can simply not take (or vomit up) pills that need be taken at least once daily to ensure a therapeutic blood level, or take them for a while but slack off; almost everyone has been medication-noncompliant at some point. But once a bolus of naltrexone has been shot into your butt muscle, it will gradually find its way into your bloodstream over the ensuing days and weeks, and if you wish to evict it, there’s nothing you can do besides wait for your body to metabolize the dose.

The potential of such drugs to limit opioid abuse is obvious; in theory, people won’t shoot up or drink if they don’t believe they will feel any positive effects. But the potential drawbacks are just as clear. Natural opioids (endorphins) also activate the affected receptors, producing a natural painkilling effect as well as some of the euphoria associated with pleasurable activities such as exercise and sex. Correspondingly, the reason Vivitrol is offered to alcohol abusers as well as opioid addicts is that alcohol may exert some of its pleasure-inducing effect through direct and indirect effects on opioid receptors, at least in some people. But no one wants to think that he’s possibly living his days without the ability to fully enjoy perfectly licit pleasures, too.