Antidepressant activity of 2-hydroxydesipramine.
We describe the relationship of 2-hydroxydesipramine (OH-DMI) plasma levels and response in a prospective DMI study in which dosage was rapidly adjusted to achieve a relatively uniform DMI plasma level. In prior studies, OH-DMI plasma levels were not related to response, but in these fixed-dose protocols the effects of OH-DMI are easily obscured by the higher concentrations of the parent drug. We hypothesized that in this study a contribution of OH-DMI to response might become apparent because DMI levels were relatively constant. Inpatients with nonpsychotic, unipolar DSM-III major depression who remained depressed (Hamilton score greater than 18) after 1 week of hospitalization without medication received a 4-week DMI trial. Twenty-four-hour drug plasma levels were used to adjust dose to reach a target DMI steady-state plasma level. Twenty-seven patients completed the trial. On every measure of response, total drug levels (DMI + OH-DMI) were more strongly correlated with outcome than were DMI levels alone. With multiple regression, both DMI and OH-DMI levels were independently and significantly associated with response. These findings suggest that OH-DMI has antidepressant activity.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510.
J C
JC
Nelson
C
C
Mazure
P I
PI
Jatlow
D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy*; D003891:Desipramine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors
D000929:Antidepressive Agents, Tricyclic; D003891:Desipramine; C028653:2-hydroxydesipramine