Amisulpride (50 mg o.d.) was compared with sertraline (50-100 mg o.d.) for 12 weeks in a double-blind, parallel-group study in 313 outpatients with dysthymia (DSM-IV +/- episode of major depression). Full response rate [> or = 50% decrease in Hamilton Depression Rating Scale (HAMD) total score] was higher with amisulpride after 4 weeks (63% versus 50%, P < 0.02) and 8 weeks (82% versus 69%, P < 0.009). Time to initial improvement (> or = 25% decrease in HAMD total score) and to > or = 50% HAMD decrease were significantly shorter with amisulpride (P < 0.0033 and P < 0.0080, respectively). A faster response was also present in the subgroup of patients with pure dysthymia. The improvement in HAMD, Montgomery and Asberg Depression Rating Scale and Social and Occupational Assessment Scale total scores, as well as Clinical Global Impression improvement, was significantly greater with amisulpride after 4 weeks. Both drugs were equally effective at week 12. The tolerability of both drugs was satisfactory. Amisulpride is significantly more effective than sertraline during the first weeks of treatment in dysthymia.