Riluzole for treatment of men with methamphetamine dependence: A randomized, double-blind, placebo-controlled clinical trial

Abstract

Background: Riluzole is a glutamate regulator and effective in treatment of neuropsychiatric conditions. Aims: We assessed riluzole for treatment of methamphetamine dependence. Methods: In this randomized, double-blind, placebo-controlled clinical trial, male outpatients with methamphetamine dependence who were 18–65 years old received either 50 mg riluzole (n=34) or placebo (n=54) twice daily for 12 weeks. Patients were excluded in case of comorbid serious medical conditions or neurologic disorders, comorbid psychiatric disorders other than methamphetamine dependence requiring specific treatment interventions, simultaneous positive urine test result for substances of abuse other than methamphetamine, smoking >3 days per week, simultaneous consumption of medications which are contraindicated or have interaction with riluzole. Results: Concerning primary outcomes, the cumulative mean number of attended weekly visits was higher in the riluzole arm compared with the placebo arm approaching a statistically significant difference (riluzole, median (range)=13.00 (2.00–13.00); placebo=4.00 (2.00–13.00); Mann-Whitney U=505.00, p-value=0.073), and the weekly measured rate of positive methamphetamine urine test results was significantly lower in the riluzole arm by the end of the study (riluzole=1 (5.00%), placebo=9 (45.00%), p-value=0.004). Patients in the riluzole arm experienced significantly greater improvement on all the craving, withdrawal, and depression measures regarding mean score changes from baseline to endpoint. No significant difference was detected between the two arms in terms of incidence of adverse events. Conclusion: Future randomized clinical trials are needed to investigate proper dosing strategy in a more inclusive sample.

Pharmacological Treatment of Methamphetamine/Amphetamine Dependence: A Systematic Review

“…Of the 4065 participants reported on in the reviewed studies, 2858 (70.3%) were male. Nine of the 43 studies (21%) enrolled only males [24,29,30,34,46,52,55,57,58], however not all of these were by design. One study [45] did not report the sample by those randomised, only by completers (in a non-intention-to-treat analysis) and so the total randomised figure of men versus women was not able to be determined based on randomisation (authors did not respond to a request for further data).…”

“…Females were underrepresented in the data, being only 29.7% of the total participants. This comprises both studies that only enrolled males (nine studies, 21%) [24,29,30,34,46,52,55,57,58] and those enrolling both males and females but with higher male enrolments. Thirty-four (79.1%) of the studies we reviewed excluded participants with depression or psychotic disorders, or those taking an antidepressant or antipsychotic medication.…”

“…Ten studies (23.3%) were funded by pharmaceutical companies, or the study drug(s) were provided by a pharmaceutical company, or a mix of funding and drugs were provided by a pharmaceutical company [29,31,45,46,48,49,56,59,61,65]. Four studies (9.3%) did not state their funding source [43,52,53,62], and one study (2.3%) received no funding [34].…”

“…Glutamatergic agents have been assessed, as either riluzole [34], N-acetyl cysteine (NAC) [53], or a combination of NAC and naltrexone [37]. A recent trial of Iranian men found that riluzole (50 mg po OD) was associated with higher rates of retention in treatment and abstinence at Week 12, as well as overall improvements in a range of secondary outcomes [34]. Efficacy for NAC is conflicted, however.…”

“…One study of 86 men examining the benzothiazole riluzole demonstrated positive results [34], with participants randomised to riluzole more likely to be retained in treatment and provide MA-negative UDS than those randomised to placebo. However, the study excluded participants who smoked cigarettes > 3 days per week.…”