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Antidepressant activity of 2‐hydroxydesipramine
Author(s) -
Nelson J Craig,
Mazure Carolyn,
Jatlow Pater I
Publication year - 1988
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1988.151
Subject(s) - antidepressant , clinical pharmacology , plasma concentration , depression (economics) , drug , plasma levels , medicine , prospective cohort study , pharmacology , endocrinology , hippocampus , economics , macroeconomics
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 > 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. Clinical Pharmacology and Therapeutics (1988) 44 , 283–288; doi: 10.1038/clpt.1988.151