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What can we learn from the failure of yet another
miracle cure for addiction?add_3652 237..239
The first long-term double-blind study of PROMETA
has demonstrated that this putative miracle cure formethamphetamine 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] rigor-
ous 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 methamphet-amine 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 allmethamphetamine-addicted people and their families
were understandably desperatefor a cure. In this environ-
ment, a former junk bond trader with no medical back-
ground raised US$150 million in capital to market a
combination of three medications (gabapentin, flumaze-
nil and hydroxyzine) as a treatment for methamphet-
amine 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 pro-
tocol, despite the fact that none of the individual medica-
tions 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 studys methods were sharply critiqued[6]), and some well-known clinicians around the country
endorsed the treatments value [7]. All these develop-
ments were toutedby themanufacturer in a massive mar-
keting campaign, bringing further media attention and
interest from potential patients. Patients and their fami-
lies cobbled together the US$12 00015 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
PROMETAs effectiveness had been g reatly exagger-
ated [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 outof thetreat-
ment program entirely. Equally damaging was the revela-
tion that the Pierce County treatment program manager,
andsome of thecounty andstate officials who hadhelped
arrange the US$900 000 in funding, were stockholders
in PROMETAs manufacturer [10]. This was thestart of
a pattern: sometimes through commendable disclosure
by the people concerned [7] and sometimes through
investigative journalism, it became evident that a large
proportion of the pro-PROMETA voices in the addiction
field had a significant financial stake in the products
success1. As the reputation of the treatment became
1Whether financial conflicts of interest clouded any particular individuals judgment about PROMETAs effectiveness is not some-
thing I presumeto know. Certainly, an individual can havea financial stake in a proprietary addiction treatment and at the same time
believe sincerely that it will benefit patients. My sole point here is that PROMETAs standing with addiction professionals and the
publicwas erodedby the unusuallyhigh prevalence of potential financial conflictsof interests among itsadvocates,particularlywhen
such conflict of interests came to light through investigation by others rather than being disclosed voluntarily by the individuals
concerned.
EDITORIAL doi:10.1111/j.1360-0443.2011.03652.x
Published 2012. This article is a U.S. Government work and is in the public domain in the USA. Addiction, 107, 237239
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tarnished, its manufacturers fortunes declined.The most
recent corporate report [11] of the formerly US150-
million-dollar company projected that it would run out
of cash by September 2011. Shares of its once-valuable
stock arecurrently trading at the price of 1 penny (i.e. 1%
of 1 US$).
THREE LESSONS FROM THE RISE AND
FALL OF PROMETA
1 Thewish fora simple, quick cure foraddiction is under-
standably widespread among addicted people, their
families, politicians and professionals in the addic-
tion field. Many serious, good-hearted people will be
shocked at Lings [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 foraddiction 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, res-
pected sources. The simpler, faster and more miraculous-
seeming the cure, the greater should be our skepticism.
2 There is a worrisome vulnerability in the US FDAs
new drug approval process. As was the case with
another would-be miracle cureultra-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 thetreatment 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 proposalsto better trade off these two concerns, using the
experience of PROMETA as one of its subjects for
analysis.
3 Independent 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 deter-
mine whether Dr. Keeleys Double Chloride of Gold
Injections, Dr. Revalys Guaranteed Remedy for the
Tobacco Habit and Dr. Meekers Addiction Antidote
were effective [2]: a well-developed addiction treat-
ment research enterprise. Those who devote them-
selves to this calling should point with pride to
Linget 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.
Keywords Clinical trials, drug addiction, metham-
phetamine, PROMETA protocol, treatment.
KEI TH HUMPHREYS
Veterans Affairs and Stanford University Medical Centers,
795 Willow Road, Menlo Park, Palo Alto, CA 94025, USA.
E-mail: [email protected]
References
1. Ling W., Shoptaw S., Hillhouse M., Bholat M. A., Charuvas-
tra C., Heinzerling K.et al. Double-blind placebo-controlled
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