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On the treatment of the alcoholic organic brain syndrome with an alpha-adrenergic agonist modafinil

Saletu B; Saletu M; Grunberger J; Frey R; Zatschek I; Mader R

Department of Psychiatry, 
University of Vienna, Austria.
Prog Neuropsychopharmacol Biol Psychiatry, 14(2):195-214 1990


1. In a double-blind study forty abstinent hospitalized male patients with an alcoholic organic brain syndrome (OBS) were treated for 6 weeks with either 200 mg modafinil or placebo.

2. Modafinil (CRL 40476) is a putative central alpha-1 adrenergic agonist.  It's pharmacological profile is quite different from that of amphetamine, which can be seen by the lack of peripheral sympathomimetic effects.  The vigilance promoting effect of modafinil has been shown previously in pharmaco-EEG and psychometric studies as well as in clinical studies involving treatment of daytime sleepiness in idiopathic hypersomniacs and narcoleptics.

3. The present clinical investigations demonstrated that the spontaneous restitution of the alcoholic OBS was significantly augmented and accelerated by modafinil.

4. Psychometric tests did not show significant intergroup differences.  Modafinil- and placebo-treated patients improved continuously over the 6-week period.

5. Psychophysiological and autonomous nervous system parameters were affected neither by placebo nor by modafinil.

6. Neurophysiological investigations by means of quantitative pharmaco-EEG showed partly inconsistent findings. However, superimposed dosages of modafinil (on the top of 6 weeks chronic administration) induced a decrease of slow activity and an increase of alpha activity suggesting an improvement of vigilance after the daily drug intake. 

7. Considering the beneficial effects of modafinil in abstinent chronic alcoholic patients, it may be said that activation and improvement of adaptive behaviour by an alpha-adrenergic agonist could be regarded as a therapeutic principle in the treatment of the OBS, eventually due to noradrenergic deficits.

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