Benzodiazepine and opioid dependence. Clinical and meta-analytical studies

Sammanfattning: The thesis contains 4 papers, two clinical studies and two meta-analyses.

In the BZD taper study (Paper I) 21 BZD dependent (DSM-IV) patients were included for a 10-day inpatient detoxification. The average defined daily dose (DDD) was 4.7 doses. Withdrawal symptoms were not more pronounced compared to more extended detoxification procedures reported in literature. Five patients, all with concomitant codeine dependence and a more pronounced BZD tolerance, dropped out after 2-3 days.

In the dependence rate study (Paper II) the frequency of prescribed drug dependence among 130 alcohol dependent patients in open care, 23 long-term institutionalized alcoholics, and 120 healthy controls were analysed. Alcoholics were more often dependent on total prescribed drugs, BZD and zopiclone than healthy controls 17% versus 2%, 15% versus 1%, and 5% versus 0%. Institutionalized alcoholics had higher rates than outpatient alcoholics. 1/5 of the BZD dependent and 1/3 of the opioid dependent patients reported high tolerance, DDD > 4.0 of each drug.

Common for the third and forth paper was the meta-analytical technique. In the methadone paper 8 RCT were included with 1,511 patients. In the naltrexone study 15 RCT were included with 990 patients.

In the methadone review (Paper III) retention in treatment was higher (d=0.90), and opioid abuse and criminality was lower (d=0.61) and (d=0.35) respectively compared to controlled conditions. Type of study design (gradual detoxification, placebo or untreated controls) could explain some of the heterogeneity found.

In the naltrexone review (Paper IV) naltrexone was significantly better than controlled conditions in reducing the number of opioid positive urines (d=0.44). If the retention level in the experimental group increased above a certain level naltrexone was also significantly better than the controls for difference in retention (d=0.31), craving (d=1.50), re-arrest (d=0.63), and success (d=0.43). Contingency management increased retention rate and naltrexone use resulting in a reduced number of opioid positive urines.