What can we learn from the failure of yet another ‘miracle cure’ for addiction?

Authors


The first long-term double-blind study of PROMETA has demonstrated that this putative miracle cure for methamphetamine addiction is ineffective. Given the vulnerability of addicted people and their desperation for a cure, effective governmental regulation and a shared spirit of skepticism about ‘wonder drugs’ should always be maintained.

In this issue of Addiction, Ling and colleagues' [1] rigorous clinical trial concludes that the much-ballyhooed PROMETA™ protocol is ineffective as a treatment for methamphetamine dependence. Patients receiving the protocol did no better than those on placebo, regardless of whether the outcome was self-reported methamphetamine use, urinanalysis confirmed use or self-reported craving. The story of this ‘miracle cure’ will, in some ways, be familiar to students of the history of addiction treatment [2], yet warrants analysis because of what it might teach us about the addiction treatment and research enterprise.

Like most of the putatively simple cures for addiction that have risen rapidly to prominence through history [2], PROMETA™ burst onto the public scene during an epidemic, namely the rapid growth of methamphetamine addiction in the western United States in the early 2000s. Treatment professionals, politicians and most of all methamphetamine-addicted people and their families were understandably desperate for a cure. In this environment, a former junk bond trader with no medical background raised US$150 million in capital to market a combination of three medications (gabapentin, flumazenil and hydroxyzine) as a treatment for methamphetamine addiction [3]. Normally, introducing a new medication requires approval by the US Food and Drug Administration (FDA), including tests of product safety and an efficacy trial such as that conducted by Ling and colleagues [1]. A loophole in this regulatory system is that a combination of previously approved medications can be marketed without review as a new treatment protocol, despite the fact that none of the individual medications had any evidence nor were originally approved as a treatment for the condition the new protocol targets. The manufacturer of PROMETA™ was therefore able to immediately market and sell a new ‘addiction treatment protocol’ with no federal review or clinical trial evidence.

Grateful testimonials from individuals who said that PROMETA™ had cured them of methamphetamine addiction ‘overnight’ soon appeared in major media outlets [3]. A drug court-based treatment agency in Pierce County, Washington then reported astounding results from a pilot study: 98% abstinence confirmed by random urine tests [4]. County and state officials bestowed an US$900 000 grant to expand the PROMETA™ program. Meanwhile, a small, open-label single-group study in Texas by Urschel and colleagues [5] reported positive preliminary results on PROMETA™ (although the study's methods were sharply critiqued [6]), and some well-known clinicians around the country endorsed the treatment's value [7]. All these developments were touted by the manufacturer in a massive marketing campaign, bringing further media attention and interest from potential patients. Patients and their families cobbled together the US$12 000–15 000 required to purchase the wonder drug, which was made available in franchised for-profit treatment centers. Amid this boomlet of enthusiasm, those who wanted to wait for rigorous research [8] before embracing the miracle cure were largely swept aside as fuddy-duddies who were denying life-saving care to seriously ill people.

A subsequent audit of the Pierce County program put the first needle into the bubble by uncovering that PROMETA™'s effectiveness had been ‘greatly exaggerated’[9]. The incredible 98% rate of clean urines had been calculated only after excluding patients who did not show up for required tests or had dropped out of the treatment program entirely. Equally damaging was the revelation that the Pierce County treatment program manager, and some of the county and state officials who had helped arrange the US$900 000 in funding, were stockholders in PROMETA™'s manufacturer [10]. This was the start of a pattern: sometimes through commendable disclosure by the people concerned [7] and sometimes through investigative journalism, it became evident that a large proportion of the pro-PROMETA™ voices in the addiction field had a significant financial stake in the product's success1. As the reputation of the treatment became tarnished, its manufacturer's fortunes declined. The most recent corporate report [11] of the formerly US150-million-dollar company projected that it would run out of cash by September 2011. Shares of its once-valuable stock are currently trading at the price of 1 penny (i.e. 1% of 1 US$).

THREE LESSONS FROM THE RISE AND FALL OF PROMETA™

  • 1The wish for a simple, quick cure for addiction is understandably widespread among addicted people, their families, politicians and professionals in the addiction field. Many serious, good-hearted people will be shocked at Ling's [1] negative results because they believed sincerely that PROMETA™ was a miracle cure for methamphetamine addiction.
  • From this latest disappointment, we should absorb the following lesson: 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.

  • 2There 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 [8]—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. It seems very unlikely that the typical addicted patient understands that ‘all components of this treatment protocol have been FDA-approved’ does not necessarily imply that the treatment protocol itself has any evidence of being an effective treatment for addiction. Off-label use of medications is well-established in medical practice and has significant value in many cases, but a balance must be struck with the risk this creates for evasion of the normal safety and efficacy checks by creators of new treatment protocols. The FDA should convene a high-level study group to develop proposals to better trade off these two concerns, using the experience of PROMETA™ as one of its subjects for analysis.
  • 3Independent scientific research on addiction is essential for public health and safety. We have a huge advantage at this historical moment which was not available to people in prior eras who could not determine whether ‘Dr. Keeley's Double Chloride of Gold Injections’, ‘Dr. Revaly's Guaranteed Remedy for the Tobacco Habit’ and ‘Dr. Meeker's Addiction Antidote’ were effective [2]: a well-developed addiction treatment research enterprise. Those who devote themselves to this calling should point with pride to Ling et al.'s work as an example of how high-quality science can inform suffering people about what will help them and what will not; and those who set public research budgets need look no further for an example of return on investment. Society needs more than anecdotes, testimonials and marketing materials to decide which interventions should be allowed a place in our health-care system; treatment research is how to get it.

Authors' note

Dr Humphreys' work on this paper was supported by a US Department of Veterans Affairs Senior Research Career Scientist award. The content of this paper do not necessarily reflect official positions of the Department of Veterans Affairs.

Declarations of interest

None.

Footnotes

  • 1

    Whether financial conflicts of interest clouded any particular individual's judgment about PROMETA™'s effectiveness is not something I presume to know. Certainly, an individual can have a financial stake in a proprietary addiction treatment and at the same time believe sincerely that it will benefit patients. My sole point here is that PROMETA™'s standing with addiction professionals and the public was eroded by the unusually high prevalence of potential financial conflicts of interests among its advocates, particularly when such conflict of interests came to light through investigation by others rather than being disclosed voluntarily by the individuals concerned.