Depressed in-patients respond differently to imipramine and mirtazapine

Tricyclic antidepressants and more recent antidepressants are generally con sidered to have equivalent efficacy in the treatment of depression. After a previous report of a marked difference in the response to mirtazapine comp ared to imipramine, we report here an analysis of different symptom cluster s. One hundred seven consecutive in-patients with major depression (Diagnos tic and Statistical Manual III-R, DSM-III-R) and a Hamilton Rating Scale fo r Depression (HRS-D) score of 18 points or more were randomly;assigned to d ouble-blind treatment. Two and four weeks after predefined blood levels had been obtained, the severity of depression was assessed using the HRS-D. Th e mean dosages used were 235 mg/day of imipramine and 77 mg/day of mirtazap ine, the latter being in excess of the 15-45 mg/day range currently advised . Total HRS-D scores and seven symptom clusters were analyzed in the 85 pat ients (79%) who were not receiving any co-medication. Imipramine was more e ffective against the clusters related to core symptoms of depression: "depr ession and guilt", "retardation", and "melancholia", respectively. Mirtazap ine showed a biphasic response with regard to the clusters "sleep" and "anx iety/agitation", respectively, which consisted of a mark:ed response after two weeks of predefined blood level, but with a waning of this effect at fo ur weeks. Imipramine produced a more gradual response on these clusters, wh ich was more pronounced at four weeks than with mirtazapine. Two aspects of the present study could be related to this finding: blood level control re sulted in optimal treatment with imipramine but not mirtazapine, and - most importantly - the patients were not receiving any anxiolytic or hypnotic c o-medication. These findings suggest that mirtazapine may have anxiolytic a nd sedative properties and fewer antidepressant properties than imipramine in severely depressed in-patients.