"Office-Based Treatment of Opiate Addiction" is a great example of a paper on addiction. The above article describes the results of a study conducted on persons addicted to opiates, particularly ‘ heroin’ which is the vernacular name of di-acetyl morphine, one of the popular addictive substances among many used by drug addicts. The study was conducted as a multicenter trial in which volunteering participants within the age group of 18-59 years, and who met the diagnostic criteria of opiate dependence as described in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) were subjected to therapeutic intervention with the administration of a combination of buprenorphine and naloxone, used as a sublingual dosage form in 4:1 ratio in an office-based setting (Fudala et al, 2003).
The use of this combination is a standard form of substitution pharmacotherapy for opiate addiction in order to assist chronic addicts to stay away from the more noxious illegal drug. The primary drug used, Buprenorphine is a partial μ -opiate– receptor agonist and a κ -opiate– receptor antagonist used traditionally for relieving severe pain in some countries, thereby posing the risk of potential abuse but its combination with naloxone, an opiate antagonist nullifies this potential.
Standard exclusion criteria were employed while selecting participants in this year-long study and only qualifying candidates who signed informed consent were selected. The study was conducted after due approval of appropriate regulatory authorities with provision to terminate if certain criteria were not satisfied during its course. The actual procedure involved two phases. In the first phase, a 4-week, double-blind, placebo-controlled efficacy trial was conducted while in the second phase the qualifying participants were subjected to an open-label safety phase lasting 48 weeks for persons who had participated in the efficacy trial and 52 weeks for others who had not participated.
The trial was conducted as a double-blind study conducted eight sites within the United States. Participants were randomly assigned to daily treatment with either buprenorphine at a dose rate of 16 mg in combination with naloxone at a dose rate of 4 mg, buprenorphine alone at the dose rate of 16 mg, or a placebo (no drug). The medication was administered in the respective clinical setting on weekends while taking home dosage was provided on Fridays for weekend use.
One hour of individualized counseling was provided to each patient along with general counseling to make the patients aware of the risks associated with HIV infection. Outcome measures included the percentage of opiate-negative urine samples and self-reported incidents of cravings by the participants. Urine samples collected on Mondays, Wednesdays, and Fridays were subjected to analysis for the presence of morphine, codeine, and other corresponding metabolites as well as for the presence of other substances of abuse. The participants’ craving was assessed using a 100-mm visual analog scale with 0 representing ‘ no craving’ and 100 representing ‘ intense craving’ (Fudala et al, 2003).
Overall status was rated three times a week using a similar 100-mm visual analog scale where 0 represented ‘ much worse, ’ 50 ‘ no change’ and 100 ‘ much better (Fudala et al, 2003). In addition, other tests such as electrocardiography and common laboratory tests of health evaluation were conducted. For statistical analysis, the combined therapy group was compared with the placebo group with the group receiving buprenorphine alone serving as a control.
An alpha level of significance with value 0.05 was considered significant in the two-sided tests. The used statistical tools included the Kruskal– Wallis test, the Cochran– Mantel– Haenszel test, and a two-factor ANOVA (analysis of variance) for other variables. Fisher’ s exact test was used to compare adverse effects between groups. Opiate-craving scores and subject, as well as clinician-rated impressions of overall status, were analyzed by ANOVA. Although the authorities recommended termination of the double-blind trial due to better efficacy of the drug combination and buprenorphine alone as compared to placebo 243 (82%) of the participants completed the trial in the open phase and received medication for 90% of the days of the trial.
Analysis of data measured from the global-impression rating scale revealed that the participants belonging to the combination therapy group and the buprenorphine-only group improved significantly in terms of overall health as compared to the placebo group as evaluated by own rating scales of the participants. The clinicians rating for the overall health of the participants though initially not consistent with their personal ratings, showed similar improvements in figures of better overall health ratings collected later.
Other drugs besides opiates detected in the urine samples from all three groups included cocaine, benzodiazepines, amphetamines, barbiturates, and methadone. Combination therapy, as well as buprenorphine-only therapy, was well tolerated with only a few reports of adverse effects such as suicide ideation and inpatient detoxification. However, eighty-one serious adverse events were reported in the open-label study which included high hepatic enzyme levels which were later found to be not associated with drug use. The authors concluded that their novel approach of administration of the sublingual-tablet formulation of buprenorphine and naloxone in combination in the office setting was a success during the double-blind trial as well as the open phase stage.
This mode of administration ensured compliance in addition to being more efficacious and safe. Inclusion of naloxone serves the additional advantage of reducing abuse potential of buprenorphine which cannot be used through parenteral route by potential abusers. Moreover, the multiple outcome measures employed in this study yielded consistent results with a high percentage of negative urine samples which prove the advantages of using this approach. Conclusion The authors have meticulously carried out the study for evaluating the advantages of employing the sublingual route for the administration of opiate substitutes for pharmacotherapy in identified addicts in the office setting.
Comprehensive modes of observation, thorough and frequent laboratory tests and opinion of the participants and clinicians obtained independently have proven the safety and efficacy of this mode of drug administration which has been substantiated with a selection of appropriate statistical tools which provided accurate data for arriving at the inference. Moreover, the authors’ contention of popularizing this mode of pharmacotherapy in addicts is correct as it overrides the risk of potential abuse by addicts, as the combination cannot be administered parenterally.
The study has been conducted following all necessary ethical and administrative protocols with instant compliance with the administrative directives as well as active counseling and monitory support to the participants. The subjects’ health parameters were appropriately subjected to screening at required intervals to identify any adverse events associated with the administration of the drugs. Such adverse events were, fortunately, few and were addressed instantly with appropriate therapeutic interventions. There are negligible shortcomings in this study but a vital factor has been missed i. e.
compliance by persons with a severe addiction to multiple drugs of abuse, which needs to be investigated further.
Fudala, P.J., Bridge, T. P., Herbert, S. et al (2003). Office-Based Treatment of Opiate Addiction
with a Sublingual-Tablet Formulation of Buprenorphine and Naloxone, N. Engl. J. Med.,
Vol. 349, Pgs.949-958.