Adjunctive aripiprazole therapy with escitalopram in patients with co-morbid major depressive disorder and alcohol dependence: clinical and neuroimaging evidence

Abstract

The effective treatment of depression has been reported to reduce the severity of alcohol use, potentially reflecting improvements in common brain reward circuits. We hypothesized that augmentation therapy of escitalopram with aripiprazole would improve depressive symptoms as well as reduce craving for alcohol and cue-induced brain activity in patients with co-morbid alcohol dependence and major depressive disorder, compared with treatment with escitalopram alone. Thirty-five subjects with major depressive disorder and alcohol dependence were recruited and randomly assigned into 17 aripiprazole + escitalopram and 18 escitalopram only groups. At baseline and following six weeks of treatment, symptoms of depression, craving for alcohol and brain activity were evaluated. During the six week treatment period, Beck Depression Inventory and clinical global index-severity (CGI-S) scores decreased in both the aripiprazole + escitalopram and escitalopram only groups. In addition, following the treatment period, the Korean alcohol urge questionnaire scores in the aripiprazole + escitalopram group were reduced from 23.3±8.4 to 14.3±4.9, compared with those of the escitalopram group of from 21.6±8.4 to 19.3±7.1 (F=13.1, p<0.01). The activity within the anterior cingulate was increased in response to the presentation of alcohol drinking scenes following treatment in the aripiprazole + escitalopram group. The change of brain activity within the left anterior cingulate gyrus in all patients with co-morbid alcohol dependence and major depressive disorder was negatively correlated with the change in craving for alcohol. These findings suggest that the effects of aripiprazole on anterior cingulate cortex might mediate the successful treatment of alcohol dependence in patients with major depressive disorder.

Figure 1

Consort diagram of recruitment. BDI: Beck Depression Inventory scale score; d/t: due to

Figure 2

The design of the fMRI block paradigm.

Figure 3

The changes in BDI scores, AUQ-K scores and beta values during six weeks. (a) The changes in Beck Depression Inventory (BDI) scores between the aripiprazole (APZ) + escitalopram and escitalopram only groups, repeated measures ANOVA, F=2.3, p=0.13. (b) The changes in Korean alcohol urge questionnaire (AUQ-K) scores between the aripiprazole + escitalopram and escitalopram only groups, repeated measures ANOVA, F=4.9, p=0.03. (c) The changes in beta values of left anterior cingulate gyrus between the aripiprazole + escitalopram and escitalopram only groups, repeated measures ANOVA, F=6.3, p=0.02.

Figure 4

Brain areas in response to alcohol drinking scene stimuli.