Addiction Treatment in Russia: Oral vs. Naltrexone Implant

The usual treatment of heroin addiction in Russia involves detoxification and 2-4 weeks of
rehabilitation with referral to outpatient follow-up. Though most patients complete inpatient
treatment, few keep follow-up appointments and relapse rates are high. More effective
therapies are needed, especially in view of the epidemic of heroin addiction that has
resulted in the spread of HIV and other infectious diseases. A recently-completed study of 52
patients randomized to oral naltrexone (ON) or oral naltrexone placebo (ONP) has shown
efficacy in preventing relapse and reducing HIV risk but dropout was a problem with only 44%
of ON patients proven to have not relapsed by 6 months (as compared to 16% of ONP patients).
A larger study of 280 patients randomized to ON or ONP replicated these results and found
some indication that adding an selective serotonin reuptake inhibitor (SSRI) to naltrexone
may improve its efficacy in women, probably because they tend to have higher levels of
psychiatric symptoms than men.

We think that retention and outcome can be improved by using a longer acting naltrexone
preparation, and in this study we propose to compare ON with a depot naltrexone implant (DNI)
that is manufactured and approved for use in Russia, and provides opioid blockade for 8-10
weeks. We will use a placebo-controlled, double-blind/double-dummy design since a
placebo-controlled trial is required by the Russian equivalent of our FDA as a condition for
testing a pharmacotherapy. Participants will be male and female heroin addicts who have been
detoxified in addiction treatment hospitals or outpatient settings in St. Petersburg and have
a family member willing and able to supervise medication adherence and facilitate follow-up.
After giving informed consent and confirming the absence of physiologic dependence, 306
patients will be randomly assigned to a 6-month treatment in one of three groups of 102 each:
oral naltrexone (ON) + depot naltrexone implant placebo (DNIP); oral naltrexone placebo (ONP)
+ depot naltrexone implant (DNI); or ONP + DNIP. All patients will receive biweekly clinical
management/adherence enhancement counseling. Assessments will be done at baseline, at each
biweekly appointment during the 6-months of medication treatment, and at 3 and 6 months
following the end of study medication. Primary outcome will be the relapse free proportion at
months 1-6; secondary outcomes will be time to dropout, opioid positive urines, HIV risk, use
of alcohol and other drugs, psychiatric symptoms, and other measures of overall adjustment.
We hypothesize that outcomes will be better with DNI than ON, and that each will be more
effective than placebo.

Inclusion Criteria:

- Current opioid dependence

- Recently completed opioid detoxification

Exclusion Criteria:

- Serious medical or psychiatric condition requiring immediate hospitalization or that
would make participation in the study hazardous

- Planning to leave the study area within the 12 months following study entry

- Imminent incarceration

- Pregnancy