Clinical studies that have evaluated serotonergic medications to reduce alc
ohol consumption have yielded conflicting results. These studies primarily
treated patients with alcohol dependence, excluding those with a current de
pressive disorder, in an effort to differentiate any medication effects dir
ectly on drinking from those on mood. Yet despite the exclusion of current
depression, a group of alcohol-dependent patients who are not depressed can
be highly heterogeneous. For example, this subgroup can include those with
a Lifetime depressive disorder. If these patients were more sensitive to s
erotonergic medications than patients without a Lifetime depressive disorde
r, medication effects in a subgroup of patients who were not depressed coul
d be obscured. Thus, the purpose of this study was to examine the efficacy
of sertraline for treating alcohol dependence in patient groups that were d
ifferentiated by the presence or absence of Lifetime depression. This study
examined the effectiveness of sertraline (200 mg/day) or placebo for 14 we
eks in 100 alcohol-dependent subjects with (N = 53) or without (N = 47) a l
ifetime diagnosis of comorbid depression. Sertraline treatment seemed to pr
ovide an advantage in reducing drinking in alcohol-dependent patients witho
ut lifetime depression, illustrated best with a measure of drinking frequen
cy during treatment. However, sertraline was no better than placebo in pati
ents with a diagnosis of lifetime comorbid depression, and current depressi
on did not change the results. Treatment with selective serotonin reuptake
inhibitors may be useful in alcohol-dependent patients who are not depresse
d. Subtyping those with alcohol dependence on the basis of the absence vers
us the presence of a Lifetime depressive disorder may help to resolve confl
icting findings in the literature on the treatment of alcohol dependence wi
th serotonergic medications.