Naltrexone and buprenorphine combination in the treatment of opioid dependence
Gilberto Gerra1*,
A. Fantoma1,
A. Zaimovic2
1 National Department on Drug Policy, Rome, Italy
2 Addiction Research Centre, Ser.T., AUSL, Parma, Italy
* To whom correspondence should be addressed.
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Abstract |
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Naltrexone treatment has demonstrated some advantages for special populations of
heroin addicted individuals, but patients' compliance seems to be very poor, with a low
adherence and low retention rate. Kappa-opioid system overdrive seems to contribute to
opioid protracted abstinence syndrome, with dysphoria and psychosomatic symptoms during
naltrexone treatment. The objective of this observational study was to determine the
effectiveness of a functional k antagonist in improving naltrexone treatment outcome. A
partial mu agonist/kappa antagonist (buprenorphine) and a mu antagonist (naltrexone)
were combined during a 12 weeks protocol, theoretically leaving k antagonism as the
major medication effect. Sixty patients were submitted to outpatient rapid
detoxification utilizing buprenorphine and opioid antagonists. Starting on the fifth
day, 30 patients (group A) received naltrexone alone. Alternatively, 30 patients (group
B) received naltrexone (50 mg oral dose) plus buprenorphine (4 mg sublingual) for the 12
weeks of the observational study. The endpoints of the study were: retention in
treatment, negative urinalyses, changes in psychological symptoms (Symptom Checklist-90
Revised: SCL-90) and craving scores (visual analysis scale (VAS)). Thirty-four subjects
(56.67%) completed the 12 weeks study. Twenty-one patients (35.0%) had all urine samples
negative for opiates and cocaine. nine subjects (15.0%) had urine samples negative for
cocaine and opiates for the last 4 weeks of the study. five subjects (8.3%) continued to
use cocaine during the 12 weeks of the study. No significant change in pupillary
diameter after buprenorphine administration was evidenced during clinical observations
from baseline across the weekly measurements. Retention rates in group A (naltrexone)
and group B (naltrexone + buprenorphine) at week 12 were respectively 40% (12 patients)
and 73.33% (22 patients), with a significant difference in favour of group B (p
= 0.018). Patients treated with naltrexone in combination with buprenorphine (B
patients) showed a significantly lower rate of positive urines for morphine (4.45%) and
cocaine metabolites (9.09%) than those treated with naltrexone alone (A) (25%, morphine;
33.33% cocaine) (p < 0.05; p < 0.05). Irritability,
depression, tiredness, psychosomatic symptoms and craving scores decreased significantly
less in Group A patients than in group B patients. The dysfunction of opioid system with
kappa receptors hyper-activation provoked by heroin exposure, probably underlying
dysphoric and psychosomatic symptoms during naltrexone treatment, seems to be
counteracted, at least in part, by buprenorphine. The combination of buprenorphine and
naltrexone may significantly improve the outcome of opioid antagonists treatment in
terms of retention, negative urinalyses, and reduced dysphoria, mood symptoms and craving.
Key Words:
naltrexone, buprenorphine, heroin, craving, opioid dependence, opioid receptors
