Improving Treatment Outcomes for Prescription Opioid Dependence

Opioid dependence is a serious public health problem, particularly with the dramatic rise in
prescription opioid abuse, but long-term opioid agonist maintenance with methadone or
buprenorphine (BUP) may not be optimal for many prescription opioid abusers. Yet current
opioid detoxification strategies are limited by high relapse rates and/or lack of efficacy in
relieving subjective symptoms. In addition, antagonist maintenance with naltrexone (NTX),
which may be an optimal longer-term strategy for this population, requires prior opioid
detoxification and has been associated with relatively poor outcomes in heroin abusers. This
application takes a novel, broad approach to address the problem of prescription opioid
dependence by determining the 1) utility of adjunct gabapentin (GBP) during outpatient BUP
detoxification to improve initial outcomes and 2) feasibility of transitioning prescription
opioid -dependent patients to depot NTX following detoxification, which may improve
longer-term outcomes. GBP, an N-type calcium channel blocker with low abuse potential,
potentiates opioid analgesia, decreases both postoperative morphine consumption and
movement-related pain, and reverses tolerance to the antinociceptive effects of morphine. GBP
is also well tolerated and effective in reducing craving and illicit opioid use in pilot
detoxification trials. The efficacy and tolerability of adjunct GBP during BUP-assisted
detoxification and the feasibility of subsequent transition to depot NTX therapy in
prescription opioid -dependent participants will be assessed. This 12-week, randomized,
placebo-controlled clinical trial will determine the potential utility of adjunct GBP in 150
prescription opioid -dependent individuals undergoing outpatient BUP detoxification and
whether transition to short-term depot NTX therapy is feasible. Our three specific aims are
to determine (1) the efficacy and tolerability of GBP to reduce craving and illicit use of
opioids in prescription opioid-dependent individuals undergoing outpatient BUP
detoxification; (2) acceptability and feasibility of transition to, and short-term
maintenance on, depot NTX following detoxification; and (3) prognosticators of completion of
the BUP taper, successful induction onto depot NTX, symptomatology, and longer-term outcomes.
Currently, the only FDA-approved medications for the treatment of opioid withdrawal are the
opioid agonists methadone and BUP, both of which have abuse liability, and NTX, which can
produce low levels of withdrawal-like symptoms, especially early in treatment. Findings, if
positive, will support further development of GBP as an adjunct medication as well as provide
an integrated, seamless approach to outpatient prescription opioid-dependence treatment.
Ultimately, this work could impact the addiction field by providing both procedural and
pharmacological tools for treating prescription opioid dependence that significantly improve
outpatient detoxification outcomes and markedly enhance access and transition to NTX therapy.
This would shift clinical practice, establishing an effective adjunct regimen for BUP
detoxification and an integrated approach for transition to NTX therapy. GBP may also be
clinically useful for other situations where opioid withdrawal is a concern.

Inclusion Criteria:

1. be between the ages of 18-65

2. be available to attend clinic 6 days a week for approximately 30-60 minutes per day
during the first 4 3 weeks

3. fulfill Diagnostic Statistical Manual-V criteria for moderate to severe opioid
dependence. These criteria will be ascertained in the following manner: the physician
will determine whether the individual is appropriate based on several clinical
assessments that are routinely employed by methadone program physicians, including
history and severity of opioid use, presence of track marks, prior treatment history,
self-reported and/or observed signs and symptoms of opioid withdrawal. If any
individual's degree of opioid dependence is questionable, that person will be excluded
from further consideration as a participant.

4. submit a urine sample negative for benzodiazepines or barbiturates prior to starting
the study.

Exclusion Criteria:

1. report having had a severe adverse reaction to study medications

2. have an unstable medical condition or stable medical condition that would interact
with study medications or participation, including a current chronic pain or other
medical condition that requires ongoing opioid agonist treatment (determined by
physician assessment)

3. have a major psychiatric disorder (psychosis, schizophrenia, bipolar)

4. have major depression or anxiety disorder requiring psychoactive medication (as
determined by physician)

5. physiological dependence on alcohol or drugs other than opioids, tobacco or marijuana
(as determined by physician assessment)

6. are pregnant, plan to become pregnant or have inadequate birth control, if relevant

7. report ongoing use of over-the-counter or prescription drug (including Maalox) that
would have major interaction with study drugs

8. have any of the following: liver function tests >3 times normal, blood urea nitrogen
and Creatinine outside normal range; electrocardiogram abnormalities including but not
limited to: bradycardia (<50 bpm); prolonged QT interval corrected for heart rate
(>450 msec); Wolff-Parkinson White syndrome; wide complex tachycardia; 2nd degree,
Mobitz type II heart block; 3rd degree heart block; left or right bundle branch block;
pre-existing severe gastrointestinal narrowing (pathologic or iatrogenic).

Individuals with anxiety or depression will not be excluded unless they are taking
prescription medication for their disorder under a physician's care or findings during
screening indicate a need for immediate treatment determined by the study physician and/or
the Columbia-Suicide Severity Rating Scale.