The milder spectrum of depressive disorders is one of the most common clinical conditions seen in medical or psychiatric settings. Milder depressive syndromes often do not reach the threshold of a defined mood disorder. DSM III-R criteria are unable to specify affective disorders satisfactorily. Several attempts have been made to operationalize milder depressive syndromes that do not fall within the DSM III-R categories of major depression or dysthymia (D). Most diagnostic criteria are based on the presence of a minimal number of symptoms out of a larger list during a minimal period of time. Quantitative modification of the duration criteria led to the definition of Recurrent Brief Depression. A decrease in the minimal number of symptoms needed for the diagnosis of depression is frequently and improperly named subsyndromal depression or minor depression. Minor depressions lasting at least 2 years receive the diagnosis of D while the others that of Depression not Otherwise Specified (NOS).Dysthymia is an old nosological concept that refers to protracted or fluctuating low-grade affective states which in other classifications were categorized as neurotic or characterological depression. One of the defining features of this illness, its low-grade chronicity, probably contributes most to the problem of undertreatment and misdiagnosis. In recent years evidence has suggested that a significant proportion of patients with D may respond to treatment with antidepressant meditations. Open studies of follow-up long-term treatment suggest that the prophylaxis of symptom recurrence also exists. Many of patients with Depression NOS reach scores of 13 or more on the Hamilton Rating Scale for Depression (HRSD) which is severe enough to justify a therapy trial with antidepressants.The aim of the current study was to assess the efficacy of the various classes of antidepressants (tricyclics, TCAs; selective serotonin reuptake inhibitors, SSRIs; amisulpride) in the treatment of mild and moderate depression.Subjects were recruited among patients presenting for new evaluations at the Psychiatric Clinic, University of Turin, from January 1993 to December 1994. They were 18-65 years old, were physically healthy, met DSM III-R criteria for current mood disorder, had a 21-item HRSD score [lt ]10 and agreed to take part in an acute treatment study involving antidepressant medications. Diagnostically, the most important distinction was to exclude subjects with current major depression. Of the 313 subjects (males/females:107206 ) included in the study, 105 met criteria for D and 208 for Depression NOS. Patients were treated with either SSRIs (50%), TCAs (16%), amisulpride (14%) or with other antidepressants (20%). Subjects completed at least 6 weeks of treatment were considered for outcome analysis (n = 212; 75 D and 137 Depression NOS). Sixty per cent of the patients either with D or with Depression NOS responded to treatment. Response was defined as 1) 50% or greater decrease in HDRS from baseline and 2) a score of [ldquo ]much improved[rdquo ] or [ldquo ]very much improved[rdquo ] on item 2 of the Clinical Global Impression (CGI). In our naturalistic study the different antidepressant medications presented similar efficacy. SSRIs and amisulpride presented better tolerability than TCAs. Our findings suggest that many patients with minor depression show an initial response to antidepressant treatment. Because D is a chronic disorder and requires a long-term treatment, it is important to known whether this disorder responds to newer antidepressants reported to be safer and with relatively few side effects over time.