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PII‐78
Author(s) -
Belendiuk K. A.,
Preston K. L.,
Schmittner J.,
Schroeder J. R.,
Epstein D. H.,
Voskanian S. J.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.203
Subject(s) - medicine , methadone , adverse effect , randomized controlled trial , attendance , heroin , methadone maintenance , ceiling effect , opioid , clinical trial , anesthesia , pharmacology , drug , alternative medicine , receptor , pathology , economics , economic growth
BACKGROUND/AIMS Clinical trials in opioid‐dependent patients sometimes limit the maximum dose of methadone to reduce variability in the intervention being studied. This raises the possibility of compensatory heroin use, perhaps leading to an increased likelihood of adverse events (AEs). We systematically evaluated this possibility. METHODS Design ‐ randomized controlled trial. Setting ‐ outpatient methadone‐maintenance clinic. Participants − 252 treatment‐seeking opioid‐dependent patients. Intervention − 25‐week methadone‐maintenance trial with random, double‐blind assignment to 70 mg/day or 100 mg/day. AEs were assessed weekly by nurses. Incidence‐density ratios (IDRs) were calculated for each group and compared using a normal approximation to the binomial. RESULTS Participants reported 717 AEs in 6601 person‐weeks of attendance. Events per person‐week were 0.10 in the 70 mg group and 0.11 in the 100 mg group. This corresponded to an IDR of 1.08, p = .31. Separate analyses for individual study phases (baseline, randomized dose increase, and detox) similarly showed no difference in likelihood of AEs across dose groups. CONCLUSIONS At the doses studied, a dose ceiling did not increase overall risk of AEs. This does not imply that dose ceilings are clinically ideal, but suggests that they can be used when scientifically necessary without raising the ethical concern addressed here. Clinical Pharmacology & Therapeutics (2005) 79 , P56–P56; doi: 10.1016/j.clpt.2005.12.203