2-Hydroxydesipramine and desipramine plasma levels: how are they related to antidepressant response?
Thirty-six outpatients aged 20 to 51 with RDC primary major depressive disorder (MDD) completed a 5-week trial of desipramine following a week of single-blind placebo. Five had a past history of hypomanic disorder. For all but one patient, daily dosage at bedtime was constant for the final 4 weeks, with a mean (S.D.) of 168.1 (46.5) mg. Plasma samples drawn at the three final weekly visits were assayed by high-performance liquid chromatography for 2-hydroxydesipramine (2-OH-DMI) and desipramine. Mean (S.D.) plasma levels were 59.8 (30.0) ng/ml for 2-OH-DMI and 142.9 (138.6) ng/ml for desipramine. Thirteen patients (36%) had a final 17-item Hamilton depression rating < and = 6 and were classified as responders. According to receiver operating characteristics analysis, patients with plasma 2-OH-DMI levels > and = 58 and < 92 ng/ml had a greater likelihood of responding than those with lower or higher levels (p = 0.005, Fisher's exact test), while patients with plasma desipramine levels > and = 64 ng/ml were more likely to respond than those with lower levels (p = 0.032, Fisher's exact test). Results using an alternate response criterion were similar. These findings suggest that in desipramine-treated outpatients with primary MDD the relationship between therapeutic response and plasma levels is curvilinear for 2-OH-DMI and linear for desipramine.
Stern
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Department of Psychiatry, Ohio State University, Columbus 43210-1228, USA.
Cooper
T B
TB
Nelson
L D
LD
Johnson
M H
MH
Suckow
R F
RF
D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000097:blood* / Q000627:therapeutic use; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D003891:Desipramine / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales
D000929:Antidepressive Agents, Tricyclic; D003891:Desipramine; C028653:2-hydroxydesipramine