Symptoms of anxiety and depression are common in a large proportion of alcohol-abusing/dependent individuals during alcohol detoxification. The aim of this study was to examine the impact of a combined psychotherapeutic-psychopharmacological (either with mirtazapine or venlafaxine) treatment of these symptoms during the early withdrawal phase of alcohol compared to a group treated only with psychotherapy. A total of 60 alcohol-dependent/abusing subjects randomly assigned to three groups (psychotherapy, psychotherapy plus mirtazapine, psychotherapy plus venlafaxine) were studied. Assessment of psychopathology and global functioning throughout a 4-5-week detoxification period was done by the Hamilton Anxiety Rating Scale (HARS), the Hamilton Depression Rating Scale (HDRS), and the Global Assessment Scale (GAS). At baseline, high scores of anxiety and depression were recorded (HARS: controls: 33.1+/-7.8, mirtazapine: 33.2+/-12.6, venlafaxine: 36.6+/-5.4; HDRS: controls: 39.5+/-7.4, mirtazapine: 37.9+/-7.8, venlafaxine: 41.9+/-4.5). A marked improvement (p<0.000) was evidenced in all groups by the end of the detoxification period. However, patients on mirtazapine improved significantly more compared to the other two groups (HARS: controls: 9.6+/-7.6, mirtazapine: 4.3+/-4.4*, venlafaxine: 7.2+/-4.1, *p=0.011; HDRS: controls: 8.6+/-7.9, mirtazapine: 3.8+/-3.2*, venlafaxine: 8.2+/-3.5, *p=0.017; GAS: controls: 79.5+/-9.4, mirtazapine: 87.5+/-5.5**, venlafaxine: 83.0+/-8.0, **p=0.006). It is concluded that addition of mirtazapine, but not venlafaxine, to a standard psychotherapy-oriented alcohol detoxification treatment may facilitate the detoxification process by minimizing psychological discomfort. Consequently, it may prove to be a facilitator for the long-term abstinence from alcohol.