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Predictors of buprenorphine-naloxone dosing in a 12-week treatment trial for opioid-dependent youth:
Secondary analyses from a NIDA Clinical Trials Network Study
RD Weissa,b, A Chakrabartia,b, GE Woodyc, ML Griffina,b, G Subramaniam d, DR Dodda
a
Division of Alcohol & Drug Abuse, McLean Hospital, Belmont, MA
b Department of Psychiatry, Harvard Medical School, Boston, MA
c Department of Psychiatry, University of Pennsylvania and Treatment Research Institute, Philadelphia, PA
d Department of Psychiatry, Johns Hopkins University, Baltimore, MD
Abstract
Results
Methods
Results
Fig 2. Percentage of patients
with opioid-positive urines over time
as a function of pain at baseline
100%
Extreme Pain
% opioid-positive urines
Aims: The present investigation examines baseline patient characteristics to predict dosing of buprenorphine–naloxone, a promising treatment for opioid addiction in youths.
Background
Currently, methadone and the partial opioid agonist buprenorphine are the most widely used FDA-approved pharmacotherapies for opioid dependence. Buprenorphine,
combined with naloxone in a 4:1 ratio to lower its abuse potential, has been effective for detoxification and maintenance treatment. Research suggests that dosing levels in
opioid dependence treatment are associated with patient-related factors: race, psychiatric symptoms, gender, and, potentially, chronic pain.
Methods
This study of 69 opioid-dependent youths is a secondary analysis of data collected during a National Institute on Drug Abuse (NIDA) Clinical Trials Network study. Outpatients
aged 15–21 were randomized to a 12-week buprenorphine–naloxone dosing condition (including 4 weeks of taper). Baseline measures examined to predict dosing included
sociodemographic characteristics, substance use, and clinical characteristics.
Results
Most (75.4%) reported having either “some” (n = 40, 58.0%) or “extreme” (n = 12, 17.4%) pain on enrollment. Reports of level of pain were similar for heroin users and for
prescription opioid users. Average daily dose of buprenorphine–naloxone (19.7 mg) received by patients reporting “extreme” pain at baseline was significantly higher than the
dose received by patients reporting “some” pain (15.0 mg) and those without pain (12.8 mg) (fig. 1). In the adjusted analysis, only severity of pain and withdrawal significantly
predicted dose (table 1). Withdrawal significantly predicted dose because this study used withdrawal symptomatology (among other factors) to titrate the dosing. During the
dosing period, level of baseline pain made no significant differences in illicit opioid use outcomes, as measured by urinalysis at weeks 4, 8, and 12 (fig. 2). Neither pain at
baseline nor dosing was significantly correlated with withdrawal (as measured by the Short Opiate Withdrawal Scale), with baseline frequency of heroin or opioid use, or with
years of heroin or opioid use.
Conclusion
These data suggest that the presence of pain predicts buprenorphine–naloxone dose levels in opioid-dependent youth, and that patients with pain have comparable opioid use
outcomes to those without pain, but require higher buprenorphine–naloxone doses.
Some Pain
80%
No Pain
(n =8-9)
(n=29-32)
(n=9-14)
60%
40%
20%
0%
Week 4
Week 8
Table 1. Prediction model for maximum daily dose of
buprenorphine-naloxone in a 12-week treatment condition
Dosing Methods
•52% high school graduates
•74% white
•57% male
•86% daily cigarette smokers
•61% reported heroin as their main problem; 39% reported prescription opioids
20
19.7
15
•72% completed the full 12-week treatment (n = 50)
0.11
0.14
0.11
0.01
-0.07
Clinical Symptoms
Pain (degree)*
Withdrawal (severity)*
0.33
0.32
12.8
10
* p = .01
5
Conclusions
0
• The presence of pain at intake predicts higher buprenorphine–
naloxone dose levels in opioid-dependent youth (fig. 1).
for fewer than 10 days
•Injection was the preferred route of administration for 55% of heroin users vs. 7% of prescription opioid users
Opioid type
Alcohol (days)
Cannabis (days)
Cocaine (days)
Nicotine (days)
15
participants in the 30 days preceding enrollment
•56% of those who used cannabis in the 30 days prior to enrollment used it for 10 days or more
Substance Use
25
•Alcohol (48%), cannabis (62%) and cocaine (39%) were the most common other substances used by
•79% of those who used alcohol and 89% of those who used cocaine in the 30 days prior to enrollment used it
Gender
Race
Age
Education (Years)
Baseline Predictors
by pain severity
Mean dose in mg.
Sample (N=69)
Sociodemographic
Maximum Daily Dose
Standardized beta
0.05
-0.18
0.18
-0.17
Fig 1. Average daily dose of buprenorphine
Patients were told to abstain from opioids for >6 hours and to be in mild or moderate withdrawal before their
first dose, which was 2 mg buprenorphine/0.5 mg naloxone. A second dose of 2-6 mg of buprenorphine was
administered when appropriate, based upon withdrawal, signs and symptoms of sedation or other medicationrelated adverse events. Dosing adjustments were made following observation on days 2 and 3 and based on
medication response (substance use including urine toxicology results), withdrawal, and medication-related
adverse events with a maximum of 24 mg per day. Reports of pain were not used for dose adjustments.
Week 12
Extreme Pain*
Some pain
No pain
*Doses higher in patients with extreme pain vs. all others (p = .01)
•The presence of pain does not predict poorer addiction
treatment outcomes in opioid-dependent youth (fig. 2).