Effects of long-term treatment with modafinil on relapse and impulse control in alcohol dependence.

There is growing evidence that cognitive deficits play an important role in the development, course and relapse of substance abuse disorders. In particular, functions that involve control over one’s own behavior (impulsivity), and over behavior when confronted with motivationally relevant drug cues (craving) are related to relapse in recent studies. Because pharmacological manipulations of cognitive deficits are rare and relapses after treatment are the rule rather than the exception, we will present a randomized, double-blind, placebo-controlled trial with modafinil, a known cognitive enhancer and wake-promoting agent. Hundred alcohol dependent patients will be randomized to a single morning dose of modafinil (300mg/d), or matching placebo, for 10 weeks. Both neurocognitive tests (on impulsivity and overall cognitive functioning) and self-report questionnaires will be administered before, during and after treatment. Patients will be followed up 6 months after treatment, to measure relapse rate. Primary outcome variables are test performance, craving ratings and relapse. It is expected that modafinil improves cognitive functioning, increases time to first relapse and reduces relapse rates and relapse severity. In addition, DNA samples will be taken to investigate different polymorphisms associated with addiction and impulsivity. It is expected that participants with different genotypes will be affected differently by modafinil.

It is expected that modafinil improves cognitive functioning in abstinent alcohol dependent patients, increases time to first relapse and reduces relapse rates and relapse severity. In addition, it is expected that participants with different genotypes will be affected differently by modafinil.

Both neurocognitive and self-report questionnaires will be administered:

1. Before treatment (= baseline measurement);

2. During treatment (after at least one week of a fixed dose of medication/placebo);

3. After treatment (= after 10 weeks of treatment AND testing at least one week after cessation of medication/placebo).



Follow-up: 3 and 6 months after cessation of treatment with modafinil.

MODAFINIL GROUP:

1. 300mg/day;

2. Single dose;

3. Oral administration;

4. (3 x 1 tablet of 100mg/day) during 10 weeks.

Adminstration scheme:

1. Day 1-5 : 100mg/day;

2. Day 6-10: 200mg/day;

3. Day 11-70: 300mg/day.



CONTROL GROUP:

1. Placebo tablets, containing lactose (3 x 1 tablet);

2. Comparable administration and administration scheme as the modafinil group.