P. J. Geerlings

Acamprosate and Prevention of Relapse in Alcoholics

Acamprosate is registered in the Benelux for the treatment of alcohol dependence. In a randomised, placebo-controlled, double-blind study in 262 subjects from 22 treatment centres in the Benelux count

Pharmacokinetics of methadone and its primary metabolite in 20 opiate addicts

In a closed metabolic ward the pharmacokinetics of methadone and its primary metabolite (EDDP) were studied in 20 long-term opiate addicts. After administration of the daily oral dose of methadone HCl (mean 60 mg, range 10–225 mg) blood samples were taken and analysed, using a newly developed high-performance liquid chromatography (HPLC) method. The steady-state plasma concentrations of the 20 subjects varied from 65–630 ng·ml−1 and from 5 to 55 ng·ml−1, whereas the peak concentrations were 124–1255 ng·ml−1 and 10 – 301 ng·ml−1 for methadone and EDDP, respectively. The calculated ratios between the area under the curve (AUC(0–24 h)) for methadone and the AUC(0–24 h) for EDDP varied from 5.9 to 44.6, indicating interindividual differences in metabolic activity. In 19 out of 20 subjects the pharmacokinetics of methadone are best described using a two-compartment model. The mean body clearance was 1.64 ml·min−1·kg−1, whereas the mean elimination rate constant (β) and plasma half-life (t1/2β) were 0.026·h−1 (range 0.013–0.053·h−1) and 31.2 h (range 13–53 h), respectively. Differences of gender were also found. A poor correlation was found between the methadone dose and the steady-state level. A much better correlation was found between the normalized steady-state level and the body clearance.

Predictors of acamprosate efficacy: results from a pooled analysis of seven European trials including 1485 alcohol-dependent patients

RationaleAcamprosate is a proven effective intervention in the treatment of alcohol dependence. However, acamprosate prevents lapses or relapses only in a minority of patients. An important question, therefore, is whether there is a specific subgroup of patients who respond particularly well to acamprosate.ObjectivesTo identify predictors of acamprosate efficacy. Based upon the available evidence and hypotheses about the mechanisms underlying acamprosate’s effects on drinking behavior, the following variables were considered to be potential positive predictors: high physiological dependence at baseline, negative family history of alcoholism, late age-of-onset, serious anxiety symptomatology at baseline, severe craving at baseline, and female gender.MethodPotential predictors of acamprosate’s efficacy were analyzed in a pooled analysis of data from seven randomized placebo-controlled trials involving a total of 1485 patients with alcohol dependence. Outcome is measured in terms of cumulative abstinence duration (CAD), continuous abstinence (ABST), and time to first relapse (TFR).ResultsCAD and ABST were predicted by baseline measures of craving and anxiety, as well as by study and treatment condition. Acamprosate efficacy was not differentially associated with any of the predictor variables. Importantly, the hypotheses were rejected despite the large sample size and sufficient statistical power.CommentThe most straight-forward clinical implication of this study is that acamprosate can be considered as a potentially effective pharmacotherapy for all patients with alcohol dependence. The effect size of acamprosate alone is, however, moderate. Some evidence indicates that the combination of acamprosate with naltrexone or disulfiram leads to substantially better outcomes.

Prevalence of psychopathology in drug-addicted Dutch

In Dutch samples of treated heroin addicts, high prevalences of a heterogeneous psychiatric co-morbidity can be found with regard to Diagnostic and Statistical Manual (third edition) (DSM-III) classifications, Zung Depression Inventory, and sum scores of a 90-item Symptom Checklist (SCL-90). A high-threshold (N = 87) and a low-threshold (N = 116) program are compared with regard to psychopathology and severity of psychopathology. A consecutive admissions design was used. More than 50% of the respondents suffered from a lifetime DSM-III Axis I disorder (70% with antisocial personality disorder included), and 40% were still suffering from one of the disorders in the year preceding the interview. Schizophrenia was diagnosed five times as much as in normal population samples (5%). The most frequently diagnosed disorders were recurrent major depression, phobic disorders, alcohol abuse and dependence, dysthymic disorder, and antisocial personality disorder. The prevalences of DSM-III disorders, the total number of symptoms, and the score on the Zung Depression Inventory and 90-item Symptom Checklist were all significantly higher in treatment-seeking drug addicts entering the high-threshold program. Within each program, three clinically meaningful subgroups can be distinguished: one group with DSM-III Axis I lifetime or current psychopathology and/or antisocial personality disorder, one with antisocial personality disorder only, and one with neither DSM-III psychopathology nor antisocial personality disorder. Possibly, self-selection results in patients with more serious conditions entering more treatment-oriented facilities. Odds ratios show that schizophrenia and mood disorders and especially associated on a lifetime and current basis.

Farmaca in de behandeling van verslavingen (deel 2)

Alcohol- en drugsverslaving behoren tot de meest voorkomende psychiatrische stoornissen en zijn verantwoordelijk voor veel menselijk leed, een aanzienlijke sterfte en veel maatschappelijke overlast. Over het voorkomen van verslavingsproblemen bij psychiatrische patienten is nog weinig bekend, maar bij een aanzienlijk aantal patienten spelen ze een belangrijke rol. De laatste jaren is duidelijker geworden welke interventies effectief zijn.Farmacologische behandelmethoden (farmacotherapie) nemen bij de groep effectieve interventies een steeds prominentere plaats in. In dit overzicht komen de doelstellingen daarvan en specifieke farmacologische interventies voor specifieke verslavingen aan de orde. Achtereenvolgens bespreken we alcohol en heroine. In het volgende nummer wordt aandacht geschonken aan cocaine en het belang van psychosociale begeleiding.