Tricyclic antidepressants and more recent
antidepressants are generally considered to have equivalent efficacy in the treatment of depression. After a previous report of a marked difference in the response to
mirtazapine compared to
imipramine, we report here an analysis of different
symptom clusters. One hundred seven consecutive in-patients with major depression (Diagnostic and Statistical Manual III-R, DSM-III-R) and a Hamilton Rating Scale for Depression (HRS-D) score of 18 points or more were randomly assigned to double-blind treatment. Two and four weeks after predefined blood levels had been obtained, the severity of depression was assessed using the HRS-D. The mean dosages used were 235 mg/day of
imipramine and 77 mg/day of
mirtazapine, 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 patients (79%) who were not receiving any co-medication.
Imipramine was more effective against the clusters related to core symptoms of depression: "depression and guilt", "retardation", and "
melancholia", respectively.
Mirtazapine showed a biphasic response with regard to the clusters "sleep" and "anxiety/agitation", respectively, which consisted of a marked response after two weeks of predefined blood level, but with a waning of this effect at four weeks.
Imipramine produced a more gradual response on these clusters, which was more pronounced at four weeks than with
mirtazapine. Two aspects of the present study could be related to this finding: blood level control resulted in optimal treatment with
imipramine but not
mirtazapine, and - most importantly - the patients were not receiving any
anxiolytic or
hypnotic co-medication. These findings suggest that
mirtazapine may have
anxiolytic and
sedative properties and fewer
antidepressant properties than
imipramine in severely depressed in-patients.