Better Safe than Sorry in Addiction Research

In an era when politicians pledge allegiance to a "drug-free" world and Big Pharma seeks new markets for new products, addiction research is a tricky business. A study published this week in The Lancet [subscription required] found that people abstained from using heroin and other opioids when taking a once-monthly, injectable form of the medication naltrexone. Disturbing, however, was the decision of study sponsors to offer nothing more than a placebo and counseling to some trial participants, and not to report what happened to the many who dropped out of the trial.

Researchers also didn't detail whether follow-up was done to monitor for post-treatment opioid overdose among participants. As I and other co-authors argued in a commentary linked to the Lancet article, the U.S. Food and Drug Administration, which approved the efficacy of the medicine for opioid users based on this one trial in Russia, should have demanded more data and higher ethical standards before giving marketers the green light.

While use of injectable naltrexone in opioid dependence is new, the FDA’s own Adverse Event Reporting System has recorded 51 fatal reports associated with injectable naltrexone since it was approved for alcoholism dependence—a magnitude of unlabeled adverse events that in the past has triggered black-box warnings for other drugs. Further, a review of 13 trials on opioid substitution treatment options in Australia found that patients on oral naltrexone were three times more likely to experience heroin overdose than those on opioid-agonist medications, such as methadone and buprenorphine. When a patient had stopped taking naltrexone, the risk of overdose rose eightfold.

In light of such evidence, the FDA must explain why it required just one study before declaring this medication safe to use.

Also left unanswered is how the study’s authors deemed it ethical to expose some trial participants to placebo. In 1964, the World Medical Association issued guidelines for ethical research known as the Helsinki Declaration. One of the declaration's key principles holds that use of a placebo in clinical trials is unjustified when there is a demonstrated standard of treatment.

In the case of addiction to heroin and other opioids, earlier studies have shown the effectiveness of the medicines methadone and buprenorphine, and demonstrated the perils of making clinical trial participants go without. Inexplicably, investigators chose to conduct the trial in Russia, where authorities outlaw use of methadone or buprenorphine. Taking Russian data and using it to seek marketing approval in the U.S. represents a particularly insidious and ethically questionable “bait and switch.”

Injectable naltrexone is now being marketed to heroin addicts at as much as a whopping $1,100 per month. One hopes that the rush to market does not mean that desperate patients end up paying an even steeper, fatal price.

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Since when is US/FDA using data gathered only in one country,in this case Russia,to base its criteria allowing any medication (drug) to be sold on the market. The injectable form of any substitute for weaning morhine/heroine addiction is more than questionable without any 'hygienic' oversight (clean needles,cleansing skin,allergic reaction without the help of a phlebothomist(?)) and the excessive cost of naltrexone should initiate injunctive action. NALLINE was a trademark for NALORPHINE -a semisynthetic congener of morphine;used as narcotic antagonist. I do not know which company produced said medicine,but I know,that under the previous administration (GWB) US tried to interfere per Wikileaks in other countries enacting laws for cheaper medications with retalitory action in esse being the drug companies in-chief enforcer wannabe; luckily that effort failed, and saved the country a lot of euros .I also read that FDA is allowing orphan drugs to be speed-approved by giant drug companies without any cost for R&D and trials. It is imperative to educate any drug addiction patients with known treatment benefits and the perils of switching to naltrexone with the possibility of od'ing and by the exorbitant price causing some to fall off the wagon(and possibly the law-dealing).WMA- act in the best interest of the patients now.

When Rapid detox onto naltrexone was seen as "The Cure" many patients I knew did rush into this treatment. Yes some died, but many relapsed into Amphetamine use and one patient was charged with a serious crime and others still led chaotic lives and many returned to gaol. Many families have paid large amounts of money and hence the patients still continue to feel like failures because of the negative opinions of pharmacotherapy treatment.

This is outrageous! I hope this issue gets further attention. Is it just one company that now markets naltrexone and thus profits from this?

I have long been concerned about the ethics of many clinical trials relating to addiction see Lancet. 2003 Feb 22;361(9358):662-8 for example or is 20mg of methadone really better than a placebo? (JAMA. 1992 May 27;267(20):2750-5.A controlled trial of buprenorphine treatment for opioid dependence.)
But basing FDA approval on such a study is truly egregious.
I am so glad that the commentary is in Lancet.

We gave money to our governments as taxes, let's don't use that money for worse please

My brother was recruited for an experimental methadone detox program. He was given a placebo, and while he thought it was helping him kick his heroin addiction, it did absolutely nothing for him. He ended up back on the street addicted to even more drugs. He is just now finally getting the help he needs at a rehab center. I truly hope one day no one will have to go through any of this.

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