Double‐blind placebo‐controlled evaluation of the PROMETA™ protocol for methamphetamine dependence

Abstract

Aims To evaluate the efficacy and safety of the PROMETA™ Protocol for treating methamphetamine dependence. Design A double-blind, placebo-controlled 108-day study with random assignment to one of two study conditions: active medication with flumazenil (2 mg infusions on days 1, 2, 3, 22, 23), gabapentin (1200 mg to day 40) and hydroxazine (50 mg to day 10) versus placebo medication (with active hydroxazine only). Setting Three substance abuse treatment clinics: two in-patient, one out-patient. Participants Treatment-seeking, methamphetamine-dependent adults (n = 120). Measurements Primary outcome was percentage of urine samples testing negative for methamphetamine during the trial. Findings No statistically significant between-group differences were detected in urine drug test results, craving, treatment retention or adverse events. Conclusions The PROMETA protocol, consisting of flumazenil, gabapentin and hydroxyzine, appears to be no more effective than placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving.

Methamphetamine-Related Disorders

“…Nor did a further RCT (15) show any efficacy of combined pharmacotherapy with flumazenil, gabapentin, and hydroxyzine, which did, however, cause more frequent serious side effects, such as epileptic seizures. This type of treatment should not be given.…”

Methamphetamine Addiction: A Review of the Literature

“…It appears to be no more than a placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving [99].…”

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

“…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.…”

“…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 success 1 . As the reputation of the treatment became 1 Whether financial conflicts of interest clouded any particular individual's judgment about PROMETA™'s effectiveness is not something I presume to know.…”

“…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.…”