Pexacerfont as a CRF1 antagonist for the treatment of withdrawal symptoms in men with heroin/methamphetamine dependence

Abstract

We assessed the efficacy of pexacerfont, a CRF1 antagonist, for the treatment of withdrawal symptoms. In this randomized, double-blind, placebo-controlled clinical trial, male patients with amphetamine or opioid dependence, on the basis of the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR), in the age range 18-55 years, received either pexacerfont or placebo (300, 200, and 100 mg/day in the first, second, and third week, respectively). No antidepressants, behavioral interventions, or substitution therapy were administered. Candidates were excluded if they had DSM-IV-TR axis I or II disorders (other than depressive/anxiety disorders). The primary outcomes were difference in the distribution of positive urine test results for heroin and methamphetamine at the end of the trial, and the mean difference in the change in the Visual Analog Scale (VAS) score for craving from the baseline to the endpoint between the two groups. No significant difference was detected for urine test results, but a significant difference was observed for craving scores. Also, significant time×treatment interactions were found for all the scales including VAS craving, VAS temptation severity, frequency of temptation, Clinical Opiate Withdrawal Scale, Amphetamine Withdrawal Questionnaire, Beck Anxiety Inventory, and Beck Depression Inventory II. Our findings favor pexacerfont as a potential treatment for withdrawal from drug dependence; however, further comprehensive studies are warranted.

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).…”

“…Thirty of the 43 studies (69.8%) included participants dependent on MA only [24-30, 32-35, 38-41, 44, 45, 47-50, 53-55, 57, 59-62, 65]; four (9.3%) were on MA/ AMPH [31,37,51,64]; four (9.3%) were on AMPH only [42,43,46,56]; three (7.0%) were on amphetamine-type stimulants (ATS) and opioids [52,58,63] and two (4.7%) were on MA/cocaine [36,66].…”

“…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].…”

“…We reviewed pexacerfont in one study, a 3-week trial of 51 Iranian men within residential treatment camps where treatment is not normally provided [52]. Dosing was tapered from 300 mg po OD for the first week, to 200 mg po OD in Week 2 and 100 mg po OD in Week 3.…”