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Antidepressant activity of 2‐hydroxydesipramine

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 > 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Pharmacology & Therapeutics Wiley

Antidepressant activity of 2‐hydroxydesipramine

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References (29)

Publisher
Wiley
Copyright
© 1988 American Society for Clinical Pharmacology and Therapeutics
ISSN
0009-9236
eISSN
1532-6535
DOI
10.1038/clpt.1988.151
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Clinical Pharmacology & Therapeutics – Wiley

Published: Sep 1, 1988

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