Addiction experts protested loudly when the Food and Drug Administration approved a powerful new opioid painkiller last month, saying that it would set off a wave of abuse much as OxyContin did when it first appeared.
An F.D.A. panel had earlier voted, 11 to 2, against approval of the drug, Zohydro, in part because unlike current versions of OxyContin, it is not made in a formulation designed to deter abuse.
Now a new issue is being raised about Zohydro. The drug will be manufactured by the same company, Alkermes, that makes a popular medication called Vivitrol, used to treat patients addicted to painkillers or alcohol.
In addition, the company provides financial support to a leading professional group that represents substance abuse experts, the American Society of Addiction Medicine.
Hmm. Let’s see,
they profit from a drug that will produce addiction;
they profit from a drug to treat addiction;
they manage to get their drug approved over a very lop-sided FDA panel objections;
they fund the American Society of Addiction Medicine (ASAM);
they funded the publication of a portion of the ASAM Patient Placement Criteria, which is the dominant framework for treatment placement decisions;
another of ASAM’s sponsors makes billions off of a medication with “near universal relapse” when they try to taper patients off it (It’s worth noting that the feds have also invested heavily in promoting Suboxone.);
The number of people who had used heroin in the previous year increased between 2007 and 2012, from 373,000 to 669,000. Meanwhile, federal data from 2011 finds that nearly 80 percent of people who had used heroin in the past year had also previously abused prescription painkillers classified as opioids.
“Using an intent-to-treat analysis, the researchers found that topiramate was more efficacious than placebo at increasing the participants’ weekly proportion of cocaine nonuse days and in increasing the likelihood that participants would have cocaine-free weeks,” the university said Friday in a statement.
Similarly, Johnson’s team found a significant association between topiramate and both a decrease in craving for the drug and an improvement in the subjects’ overall level of functioning in comparison to a placebo.
Here are a few things you should know.
What does “more efficacious than placebo” mean? It means that the number of days subjects did not use cocaine increased to 13.3% or 8.9%. (Depending on how you calculate it.) So, subjects still used cocaine 86.7% or 91.1% of days.
The lead researcher left his last post after losing a whistleblower lawsuit. One of his projects had been accused improperly charging the federal government for time spent on a study. He also attacked the character of the whistleblower.
Are legalization advocates troubled by this? I’m asking sincerely.
Same thing with K2 and Spice. They were banned in Michigan earlier this year, without protest.
At what point does the conversation turn to the issue of eliminating restrictions on access to prescription drugs? If recreational use of pot or heroin (I recognize that a lot of pot legalization advocates do not advocate legalizing all drugs.) are legalized and regulated, why not fentanyl and vicodin? What principles or values should guide these decisions?
Motherlode notes a trend in e-cigarettes and is concerned:
I was standing outside our neighborhood ice cream shop one recent evening when I noticed a plume of smoke rise above a gaggle of teenagers waiting in line ahead of me.
“Wow,” I thought, “that takes some serious chutzpah.” These kids were smoking in public without the fear of getting caught.
A few minutes later, I realized that it wasn’t actually smoke coming out of their mouths; it was vapor, being inhaled and exhaled from battery-operated electronic cigarettes.
E-cigs are devices that vaporize an addictive nicotine-laced liquid solution into an aerosol mist that simulates the act of tobacco smoking. Also known as “personal vaporizers” and “electronic nicotine delivery systems,” e-cigs are sold in trendy shops and are increasingly turning up in bars, clubs, workplaces and other spots where traditional tobacco cigarettes have long been outlawed.
As a mother, I find this terribly distressing.
I’ve spent years telling my children that smoking can kill you. And thanks to decades of sensible public health policies — including laws banning cigarette advertising and smoking in public places — as well as brutally graphic antismoking marketing campaigns, my 15- and 21-year-old kids have grown up in a culture in which puffing on cigarettes is stigmatized. Last year, cigarette smoking among teens fell to a record low.
Now, it seems, all that progress is about to vaporize. “Smoking,” at least in the form of vaping, is becoming cool again. This week, the Centers for Disease Control reported that 1.8 million middle- and high-school students said they had tried e-cigarettes in 2012 — double the number from the previous year.
The FDA’s desire to have enough authority to require e-cigarette sellers to manufacture them properly and label them accurately, to limit marketing aimed at minors, and to be able to force the removal of unsafe product from the market, seems quite reasonable. What’s not reasonable, and what is likely to be bad, on balance, for health, is the idea that anything that delivers nicotine vapor should have the same rules applied to it as an actual cigarette.
At the same time, he acknowledges the unknowable:
None of this is simple or straightforward. I can imagine myself, five years from now, bitterly regretting not having spotted the e-cigarette menace before it got out of control. But regulations can do harm as well as good, and what I’m not hearing right now is much willingness to think carefully and proceed with caution. The principle of aggregate harm minimization, net of benefits (and nicotine does have benefits, including at least a temporary cognitive boost) still seems to me the right approach, for nicotine no less than for cannabis or cocaine. Unless and until someone can point to demonstrated and serious risks, rather than speculative ones, e-cigarettes ought to be thought of mostly as a part of the solution rather than as a part of the problem.
What does Kleiman mean by part of the solution? A recent study found that e-cigarettes outperformed traditional nicotine replacement for smokers trying to quit:
the New Zealand government funded a head-to-head comparison study. Chris Bullen and his colleagues at the National Institute for Health Innovation in Auckland gave e-cigarettes to 289 smokers who were trying to quit. A separate group of 295 people were given nicotine patches, while 73 received dummy nicotine-free e-cigarettes.
Six months later, the team asked participants if their attempts to quit had been a success. Those who had used the nicotine e-cigarettes had the highest success rate: 7.3 per cent had managed to stay away from tobacco. Of the nicotine patch users, 5.8 per cent had quit. And of those taking the placebo around 4 per cent were successful.
“The quitting rates were about 25 per cent better than patches for the e-cigarettes, but statistically we’re more confident with saying that they were comparable, rather than superior,” says Bullen.
I’m a little late on posting this one, but it still seems worth sharing.
Reckitt Benckiser has decided to pull Suboxone tablets from the market. Why? It’s an evidence-based decision and an expression of their desire to be a good corporate citizen and their concern for children.
Late last month, Reckitt Benckiser created a stir by unexpectedly announcing that its Suboxone tablet for treating opioid dependence will be withdrawn from the US market sometime over the next six months. The reason? The drugmaker, which is based in the UK and actually best known for household cleaning products, expressed concern that children could be accidentally harmed by easy access to tablets that are marketed in bottles.
In making its case, Reckitt cited specially commissioned data showing “consistently and significantly higher rates of accidental unsupervised pediatric exposure” with Suboxone tablets than with Suboxone Film, a newer version of its drug that dissolves under the tongue and can only be accessed by tearing open individual blister packaging. Specifically, the rates for Suboxone tablets were roughly eight times greater (read here).
What’s the big business picture?
To generic drug makers, some physicians and Wall Street analysts, however, the moves amounted to a transparent one-two punch designed to delay lower-cost generic tablets from reaching the market. The patent on Suboxone tablets, in fact, expired two years ago, while patent on Suboxone Film expires in 2022, according to the Reckitt spokesman. “If Reckitt is so concerned about safety,” says one industry source, who asked not to be named, “then why not take the tablets off the market right away? Their tablets are still on the market without blister packing, which they themselves say is unsafe.”
Meanwhile, Reckitt has gradually raised the price of Suboxone Tablets in order to switch patients. The current wholesale average cost (WAC) for a bottle of 30 Suboxone Tablets is $161.70 for the 2 mg dose and $289.80 for the 8 mg dose, according to the Reckitt spokesman. In July, however, the same bottle of the 2 mg dose cost $140.00 and the 8 mg WAC was $252.00, industry sources say. Meanwhile, Suboxone film pricing has held steady: WAC pricing for a carton of 30 Suboxone Film strips remains $117.85 for the 2 mg dose and $211.15 for the 8 mg dose.
More recently, sales of Suboxone tablets fell 19 percent between August 2011 and August 2012, to $658.5 million, according to IMS Health, while sales of Suboxone film doubled to more than $764 million during the same period. “They are (removing the tablets) because generics are expected in 2013 on the tablet,” says Sanford Bernstein analyst Ronny Gal. “The critical question is whether their argument that film is always safer for children will convince FDA not to approve any oral solid generic.”
For these reasons, the back-to-back announcements have been met with outrage. “They have known for years that a generic tablet could destroy their golden calf — and Suboxone is Reckitt Benckiser, from an earnings standpoint. If they do not destroy the tablet, it destroys them,” Jeff Junig, a psychiatrist at the University of Wisconsin Oshkosh Student Health Service and an assistant clinical professor of Psychiatry at the Medical College of Wisconsin, wrote in a letter to Alcoholism & Drug Abuse Weekly.
“I’m sure I sound… paranoid? Cynical?,” wrote Junig, who also authors a blog about Suboxone. “But it is so frustrating when you see marketing trump science. This will discourage generics from making buprenorphine, which will keep the price high, which will cause deaths. Shame on them.”
This study did not find a significant main effect of modafinil on the rate or duration of cocaine use among cocaine-dependent patients.
Now they decide to polish the turd:
Although these results are disappointing, we did find that modafinil-treated patients had nonsignificantly higher odds of attaining abstinence across all of the study time points, and those treated with 400 mg/day had significantly greater odds of attaining abstinence (p = .04) at the end of their 8-week medication trial (Visit 24). There was also a significant difference (p = .02) in the OR for abstinence at the final follow-up visit, suggesting the possibility that modafinil facilitated delayed clinical improvement that was not captured by our 8-week study design.
It is important to note that all of the patients in this study tested positive for cocaine at baseline. It is well established that patients who test positive for cocaine at study start have extremely poor clinical outcomes when compared with those who are able to produce a cocaine-negative urine sample ( [Ahmadi et al., 2009],[Kampman et al., 2001], [Patkar et al., 2002] and [Poling et al., 2007]). The reason for this finding is unclear, but it probably stems from greater addiction severity, less motivation for recovery, or both of these clinical features.
There will be evidence, dammit!
Despite our negative study, we believe it is premature to dismiss modafinil as a potential treatment for cocaine dependence.
Abstract: This paper raises the question about whether the data on the medications we call antidepressants justify the label of antidepressant. The authors argue that a true antidepressant should be clearly superior to placebo, should offer a risk/benefit balance that exceeds that of alternative treatments, should not increase suicidality, should not increase anxiety and agitation, should not interfere with sexual functioning, and should not increase depression chronicity. Unfortunately, these medications appear to fall short on all of these dimensions. Many of the “side effects” of these medications have larger effect sizes than the antidepressant effect size. To call these medications antidepressants may make sense from a marketing standpoint but may be misleading from a scientific perspective. Consumers deserve a label that more accurately reflects the data on the largest effects and helps them understand the range of effects from these medications. In other words, it may make just as much sense to call these medications antiaphrodisiacs as antidepressants because the negative effects on libido and sexual functioning are so common. It can be argued that a misleading label may interfere with our commitment to informed consent. Therefore, it may be time to stop calling these medications antidepressants.
From the conclusion:
If we do not call these medications antidepressants, what are some alternative labels that may better fit the existing data? The effect sizes for many of the “side effects” are larger than the antidepressant effect sizes. Using labels like antiaphrodisiac medications, agitation enhancers, insomnia inducers, suicidality inducers, mania stimulators, or gas busters obviously would not offer the same marketing appeal. Though tongue in cheek, we consider these possible labels to be more accurate than the commonly used label of “antidepressant.” It could be argued that the outcomes with the largest effect sizes should be offered as the primary label for a medication.
These guys are pretty sarcastic. And, their sarcasm is unlikely to be a conversation starter, but I suspect that there is more of this backlash to come.
It brings to mind a comment from a recent episode of On Being[emphasis mine]:
…individuals are hopelessly biased, they cannot perceive the truth by themselves.
Science is not just an individual activity. We expect our scientists, we exhort them, to be as objective as they can and a good scientist tries to do so very earnestly, but still fails. So therefore, there must be a social process that causes science to work to be a truth-discovering process.
This thing about scientific truth-discovery being a social process puts it’s finger on something very important. It’s one of the things that so frustrating about hearing people tout evidence-based policies.
Consider the arguments for naloxone distribution. I’ve honestly got no quarrel with it, I just believe that it’s a woefully inadequate response. Of course it’s true that it’s an evidence based policy. I’m sure it saves lives. My problem is that advocates draw a straight line from this truth to universal implementation, AND anyone who balks is anti-science. The problem is that these advocates don’t ask what else we know to be true. For example, treatment also reduces overdose deaths. We fail to discuss what else improves this measure (overdose deaths), we also fail to discuss what other measures are important. If we have that conversation, then we can discuss why it sh0uld or shouldn’t jump to the top of the list without accusing others of being anti-science.
This social aspect of truth-discovery is too often too exclusive. Of course, we can not and should not give equal standing to every goofball with a pet theory, but the points in the antidepressant paper above and the recent GSK scandal demonstrate that the current custodians of evidence are all too capable of leading us into policies based on something other than truth while scolding anyone who questions their evidence.
UPDATE: Just to clarify two things.
First, we’re not anti-medication, but we do believe that their benefits are overstated, the adverse effects are understated, that other methods are just as effective or more effective (And, provide additional benefits.) and that they too often constitutes risk management rather than real treatment.
Second, I see naloxone as first aid. I have no interest in interfering with access to first aid of any kind to anyone with any kind of physical crisis. However, first aid should be FIRSTaid (Not last aid or only aid.), and meaningful treatment for the real problem should follow. I tend to bristle because these calls for naloxone programs never seem to include calls for access to treatment of adequate quality, intensity and duration following the overdose.
The details are simultaneously exactly what you’d expect and shocking.
And some people wonder why we’re reluctant to embrace the latest and greatest pharmacological fad. Keep all of this in mind next time someone suggests that medicalizing addiction treatment will improve professionalism, ethics and reliance on scientific evidence.
Glaxo also used sham advisory boards and speakers at lavish resorts to promote depression drug Wellbutrin as an option for weight loss and a remedy for sexual dysfunction and substance addiction, according to the government. Customers were urged to use higher-than-approved dosages, the government said.
GSK paid millions to doctors to promote the drug off-label during meetings sometimes held at swanky resorts, the government said. The company relied on pharmaceutical sales reps, “sham advisory boards,” and continuing medical education programs that appeared independent but were not.
The company went to extreme lengths to promote the drugs, such as distributing a misleading medical journal article and providing doctors with meals and spa treatments that amounted to illegal kickbacks, prosecutors said.
“GSK’s sales force bribed physicians to prescribe GSK products using every imaginable form of high priced entertainment, from Hawaiian vacations to paying doctors millions of dollars to go on speaking tours to a European pheasant hunt to tickets to Madonna concerts, and this is just to name a few,” said Carmin M. Ortiz, U.S.attorney in Massachusetts.
Crimes and civil violations like those in the GlaxoSmithKline case have been widespread in the pharmaceutical industry and have produced a series of case with hefty fines. One reason some have said the industry regards the fines as simply a cost of doing business is because aggressively promoting drugs to doctors for uses not officially approved — including inducing other doctors to praise the drugs to colleagues at meetings — has quickly turned numerous drugs from mediocre sellers into blockbusters, with more than $1 billion in annual sales.
Stories have noted that Pfizer agreed to a $2.3 billion settlement in 2009. Also, Johnson & Johnson settled with Arkansas for $1.2 billion for several violations, including:
…for not disclosing the risks of the antipsychotic Risperdal.
GSK allegedly participated in the publishing of medical journal articles that stated paroxetine was effective in patients under 18, when, in fact, the data showed that the opposite was true. At the same time, the company withheld study data in from two other studies in which Paxil also failed to demonstrate efficacy in treating depression in patients under 18, according to a press release from the Justice Department.
Keith Humphreys offers a brief history of the “treatment” and some lessons:
…when the next wonder drug for addiction comes along (and it will), we must not yield to our powerful collective desire to believe before we have hard evidence of effectiveness from disinterested, respected sources. The simpler, faster and more miraculous-seeming the cure, the greater should be our skepticism.
There is a worrisome vulnerability in the US FDA’s new drug approval process. As was the case with another would-be ‘miracle cure’—ultra-rapid opiate-detoxification—a manufacturer was able to market an untested treatment protocol to addicted patients because the components of the treatment protocol had been previously FDA-approved for the treatment of other disorders.
Independent scientific research on addiction is essential for public health and safety.