Very low dose naltrexone addition in opioid detoxification: a randomized, controlled trial

Abstract

Although current treatments for opioid detoxification are not always effective, medical detoxification remains a required step before long-term interventions. The use of opioid antagonist medications to improve detoxification has produced inconsistent results. Very low dose naltrexone (VLNTX) was recently found to reduce opioid tolerance and dependence in animal and clinical studies. We decided to evaluate safety and efficacy of VLNTX adjunct to methadone in reducing withdrawal during detoxification. In a multi-center, double-blind, randomized study at community treatment programs, where most detoxifications are performed, 174 opioid-dependent subjects received NTX 0.125 mg, 0.250 mg or placebo daily for 6 days, together with methadone in tapering doses. VLNTX-treated individuals reported attenuated withdrawal symptoms [F = 7.24 (2,170); P = 0.001] and reduced craving [F = 3.73 (2,107); P = 0.03]. Treatment effects were more pronounced at discharge and were not accompanied by a significantly higher retention rate. There were no group differences in use of adjuvant medications and no treatment-related adverse events. Further studies should explore the use of VLNTX, combined with full and partial opioid agonist medications, in detoxification and long-term treatment of opioid dependence.

Figure 1

Flow chart of clinical trial participants.

Figure 2

Subjective opioid withdrawal scores (SOWS) in 174 opioid-dependent inpatients undergoing 6-day methadone detoxification. VLNTX treatment was associated with significantly reduced withdrawal [repeated measures ANOVA, change of scores, F = 7.24 (2,170); P = 0.001] and a significant time × treatment interaction [F = 5.64 (10, 200); P = 0.001; day 6 Tukey’s test = 0.001]. Withdrawal reduction was still significant after controlling for recent alcohol use [F = 5.39 (1,171); P = 0.006]. VLNTX, very low dose naltrexone.

Figure 3

Objective opioid withdrawal scores (OOWS) in 174 opioid-dependent inpatients undergoing 6-day methadone detoxification. VLNTX treatment was associated with significantly reduced withdrawal [repeated measures ANCOVA, F = 13.28 (2,170); P = 0.001] and a significant time × treatment interaction [F = 7.12 (10, 202); P = 0.001; day 6 Tukey’s test = 0.001]. Withdrawal reduction became non-significant after controlling for recent alcohol use [F = 1.44 (2, 155); P = 0.14].VLNTX, very low dose naltrexone.

Figure 4

Time until discontinuation from treatment in 174 opioid-dependent inpatients undergoing 6-day methadone detoxification. Kaplan–Meier survival analysis: χ² [Breslow] = 2.93, d.f. = 2, P = 0.23.