A pilot trial of the alpha-1 adrenergic antagonist, prazosin, for alcohol dependence.

BACKGROUND: Current medications for alcohol dependence (AD) show only modest efficacy. None target brain noradrenergic pathways. Theory and preclinical evidence suggest that noradrenergic circuits may be involved in alcohol reinforcement and relapse. We therefore tested the alpha-1 adrenergic receptor antagonist, prazosin, as a pharmacotherapy for AD. METHODS: We randomized 24 participants with AD but without posttraumatic stress disorder to receive either prazosin or placebo in a 6-week, double-blind pilot study. Medication was titrated to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS by the end of week 2. Participants received 5 medical management treatment sessions. Participants were reminded 3 times each day via a text pager to take medications and to call a telephone monitoring system once daily to provide self-reports of alcohol consumption and craving, the primary outcome measures. Results were analyzed using mixed linear regression adjusted for drinking days per week at baseline and week number. RESULTS: Twenty of the 24 (83%) subjects completed. Among the completers, the prazosin group reported fewer drinking days per week than the placebo group during the final 3 weeks of the study. Since only 1 woman was randomized to placebo and only three women completed the trial, the following results focus on the 17 male completers. The prazosin group reported fewer drinking days per week and fewer drinks per week during the final 3 weeks of the study; average total number of drinking days for the placebo group 5.7 (SEM 1.9) versus 0.9 (SEM 0.5) for the prazosin group, and average total number of drinks 20.8 (SEM 6.5) for the placebo group versus 2.6 (SEM 1.3) for the prazosin group. Rates of adverse events were equivalent across conditions. CONCLUSIONS: Prazosin holds promise as a pharmacologic treatment for AD and deserves further evaluation in a larger controlled trial.

An open-label pilot study of risperidone in the treatment of methamphetamine dependence.

Psychopharmacological treatments for methamphetamine (MA) dependence have questionable efficacy. Open-label risperidone was evaluated in veterans seeking MA dependence treatment. Participants (N = 11) received four weeks of risperidone. They provided weekly self-reports of substance use, urine drug screens, and adverse effects. Neuropsychological assessments and psychiatric symptomatology (Brief Symptom Inventory; BSI) were measured at baseline and follow-up. The eight completers had an average risperidone dose of 3.6 mg/day and decreased days of MA use during the trial from a mean of 13.0 (SD = 6.5) in the 30 days prior to starting risperidone to a mean of 0.125 (SD = 0.4; t = 5.7, p = .001), When measured over time, fine motor function (Grooved Peg Board Dominant Hand) was the only neuropsychological domain to improve significantly. No other domain changed significantly from baseline to follow-up among study completers. BSI data were converted to demographically corrected T-scores utilizing appropriate normative data (mean = 50, SD = 10). BSI somatization T-scores declined from a mean of 59.0 (SD = 8.4) to 51.8 (SD = 8.3; t = 2.7, p <.05), and positive symptom distress declined from a mean of 52.8 (SD =8.0) to 41.7 (SD = 8.6; t= 3.0, p <.05). Risperidone was well tolerated and associated with decreased MA use.

Implications of chronic methamphetamine use: a literature review.

Methamphetamine (MA) abuse is increasing to epidemic proportions, both nationally and globally. Chronic MA use has been linked to significant impairments in different arenas of neuropsychological function. To better understand this issue, a computerized literature search (PubMed, 1964-2004) was used to collect research studies examining the neurobiological and neuropsychiatric consequences of chronic MA use. Availability of MA has markedly increased in the United States due to recent technological improvements in both mass production and clandestine synthesis, leading to significant public health, legal, and environmental problems. MA intoxication has been associated with significant psychiatric and medical comorbidity. Research in animal models and human subjects reveals complicated mechanisms of neurotoxicity by which chronic MA use affects catecholamine neurotransmission. This pathology may underlie the characteristic cognitive deficits that plague chronic MA users, who experience impairments in memory and learning, psychomotor speed, and information processing. These impairments have the potential to compromise, in turn, the ability of MA abusers to engage in, and benefit from, psychosocially based chemical-dependency treatment. Development of pharmacological interventions to improve these cognitive impairments in this population may significantly improve the degree to which they may be able to participate in treatment. Atypical antipsychotics may have some promise in this regard.

Prognosis for the recovery of surgeons from chemical dependency: a 5-year outcome study.

HYPOTHESIS: Rates of relapse, monitoring contract completion, and return to medical practice may differ between surgeons and nonsurgeons being monitored for diagnosed substance use disorders. DESIGN: Retrospective 5-year longitudinal cohort study. SETTING: A sample of 16 state physician health programs in the United States. PARTICIPANTS: Nine hundred four physicians who underwent treatment for a substance use disorder and were consecutively admitted to 1 of 16 state physician health programs between September 1, 1995, and September 1, 2001. The study analyzed a subset of data comparing 144 surgeons with 636 nonsurgeons. MAIN OUTCOME MEASURES: Rates of continued drug and alcohol misuse (relapse), monitoring contract completion, and return to medical practice at 5 years. RESULTS: Surgeons were significantly more likely than nonsurgeons to enroll in a physician health program because of alcohol-related problems (odds ratio, 1.9; 95% CI, 1.3-2.7; P = .001) and were less likely to enroll because of opioid use (odds ratio, 0.5; 95% CI, 0.3-0.8, P = .002). Surgeons were neither more nor less likely than nonsurgeons to have a positive drug test result, complete or fail to complete the monitoring contract, or extend the monitoring period beyond the original 5 years specified in their agreements. Fewer surgeons than nonsurgeons were licensed and practicing medicine at the conclusion of the monitoring period, although this difference was not statistically significant. CONCLUSIONS: Surgeons in this study had positive outcomes similar to those of nonsurgeons. However, further research is necessary to conclude whether surgeons are less likely than their nonsurgeon peers to successfully return to medical practice following chemical dependency treatment.

Open trial of injectable risperidone for methamphetamine dependence.

We tested acceptability and tolerability of long-acting injectable risperidone for methamphetamine (MA) dependence in an open trial with the hypothesis that participants would reduce MA use. Participants were also evaluated for changes in neurocognitive function and psychiatric symptomology. Participants with MA dependence (n = 34) entered a 7-day open-label run-in with oral risperidone. Participants who tolerated oral risperidone (n = 22) were begun on long-acting injectable risperidone 25 mg intramuscular medication with subsequent injections q 2 weeks to a total of 4 injections. Participants remained on oral risperidone during the first 3 weeks after initial injection. Participants were offered 8 weekly individual sessions of relapse prevention counseling. At baseline, participants reported using MA an average of 4.1 days per week (SD = 1.9). Estimated mean days of MA use per week while on injections was 1.0 (95% confidence interval = 0.6-1.4), with days of use decreasing significantly from baseline through week 8 (ß = -0.27; 95% confidence interval: - 0.38--0.16; P < 0.001). Mean week 6 risperidone + 9-OH risperidone plasma levels for participants abstinent from MA from weeks 5 to 8 (n = 7, 63.6%) were 18.8 ng/mL (SD = 6.6) compared with 12.3 (SD = 4.0) for those not abstinent (n = 4; P = 0.075). No serious adverse events occurred. Verbal memory improved at week 4 compared with baseline (P < 0.05). Participation in this trial of injectable risperidone was associated with reductions in MA use as well as some positive benefits on verbal memory. However, these results are limited by the use of an open trial design with a high dropout rate. Risperidone deserves further study in controlled trials as a pharmacotherapy for MA dependence.