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 we ek of single-blind placebo. Five had a past history of hypomanic disor der. 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 samp les drawn at the three final weekly visits were assayed by high-perfor mance liquid chromatography for 2-hydroxydesipramine (2-OH-DMI) and de sipramine. Mean (S.D.) plasma levels were 59.8 (30.0) ng/ml for 2-OH-D MI and 142.9 (138.6) ng/ml for desipramine. Thirteen patients (36%) ha d a final 17-item Hamilton depression rating less than or equal to 6 a nd were classified as responders. According to receiver operating char acteristics analysis, patients with plasma 2-OH-DMI levels greater tha n or equal to 58 and < 92 ng/ml had a greater likelihood of responding than those with lower or higher levels (p = 0.005, Fisher's exact tes t), while patients with plasma desipramine levels greater than or equa l to 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-tr eated outpatients with primary MDD the relationship between therapeuti c response and plasma levels is curvilinear for 2-OH-DMI and linear fo r desipramine.