Searching for responders to acamprosate and naltrexone in alcoholism treatment: rationale and design of the PREDICT study.

Background: Alcoholism represents a major public health issue and treating alcohol dependent patients remains an imminent challenge. Evidence based psychotherapies and pharmacotherapies are available. However, when administered to heterogeneous populations of patients effect sizes are only modest. We present the rationale and design of a double-blind randomized trial comparing acamprosate, naltrexone, and placebo. Additionally we subtype patients on the basis of biological and psychometric measures and explore their treatment response to both acamprosate and naltrexone. According to our initial hypothesis, the "relief drinker/craver" is an endophenotype associated with glutamatergic dysfunction who responds to acamprosate. The "reward drinker/craver" is mainly associated with alterations in the dopaminergic and opioidergic system and responds to naltrexone.

Methods: The study is planned for 430 patients (2:2:1 for both drugs and placebo) over 12 weeks of medication. All receive manualized counselling to improve compliance (Medical Management) which is extended to 6 months. Subtyping is primarily done using the acoustic startle reflex, functional magnetic resonance imaging, positron emission tomography (in a subset of patients), and the Inventory of Drinking Situations. Relapsers will be re-randomized into a second study where additional psychotherapy (Cognitive Behavioral Intervention) is used in a stepped care approach. Genotyping and additional analyses such as health economy are being done as well. The study follows the assessment methods, treatments, and medications used in the U.S. based COMBINE study, which will allow for a direct comparison between this U.S. study trial and a study performed in Europe.