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Evidence exists that oversecretion of cortisol may be responsible for the clinical
manifestations and serotonergic abnormality, in depressive illness. Using the cortisol
synthesis inhibitor ketoconazole, we investigated the effects of directly lowering
cortisol on the symptoms and the response of prolactin (PRL) to d-fenfluramine in
eight patients suffering from major depression. Prolactin responses to d-fenfluramine
were measured, and patients were treated with 400–600 mg of ketoconazole for 4 weeks,
after which they were retested.
Five patients treated with ketoconazole recovered from their depression, while the
other three had decreases in their Hamilton Depression Rating Scale (HAMD) scores
of ≤ 50% and were deemed partial responders. Posttreatment prolactin responses to
d-fenfluramine were higher than pretreatment values.
Ketoconazole normalizes the blunted prolactin responses to d-fenfluramine and may
be an effective method by which to treat depression. This implies that hypercortisolemia
may be responsible for the clinical features and serotonergic subsensitivity observed
in depression.
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Article info
Publication history
Received in revised form:
April 28,
1994
Received:
December 15,
1993
Identification
Copyright
© 1995 Society of Biological Psychiatry. Published by Elsevier Inc.
