Objective: The authors assessed the frequency of atypical depression i
n depressed outpatients and compared clinical and biological features
of patients with atypical and nonatypical depression. Method: Depresse
d outpatients (N=114) were diagnosed with the Schedule for Affective D
isorders and Schizophrenia (SADS) according to Research Diagnostic Cri
teria. Patients were assessed for presence or absence of atypical depr
ession with the Atypical Depressive Disorder Scale. Atypical depressio
n was defined as the presence of mood reactivity during the depressive
episode, along with at least one of four associated features: hyperso
mnia, hyperphagia, leaden paralysis, and rejection sensitivity. All pa
tients completed the SCL-90 and were rated with the Hamilton Depressio
n Rating Scale, extracted from the SADS. To assess biological function
ing, the authors examined cortisol response to 75 mg of desipramine, a
relatively selective norepinephrine reuptake inhibitor. Results: Twen
ty-nine percent of patients met criteria for atypical depression. Pati
ents with atypical depression were significantly more likely to be fem
ale. Patients with atypical and nonatypical depression did not differ
on SCL-90 subscale scores. Although extracted Hamilton depression scal
e scores were significantly higher for patients with nonatypical depre
ssion, the difference was not clinically significant. Patients with at
ypical depression exhibited a significantly different cortisol respons
e to desipramine injection than patients with nonatypical depression,
which suggested that nonatypical depression may be associated with a m
ore impaired norepinephrine system. Conclusions: In view of data in th
is study, as well as earlier studies, atypical depression has a unique
symptom profile, may be widely prevalent, has a distinct treatment re
sponse, and may indicate a less impaired biological system than nonaty
pical depression. Since this is the first report to evaluate the frequ
ency of atypical depression as well as the norepinephrine system in at
ypical depression, this study needs to be replicated Nonetheless, the
data support the inclusion of atypical depression as a subtype of the
depressive disorders an DSM-IV.