Mifepristone Plasma Level and Glucocorticoid Receptor Antagonism Associated With Response in Patients With Psychotic Depression
| Autor: | Ned H. Kalin, Alan F. Schatzberg, Thaddeus Block, Joseph K. Belanoff, Georgios Petrides, Harvey Kushner |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male medicine.medical_specialty Hydrocortisone Original Contributions mifepristone Psychotic depression cortisol Pharmacology Placebo law.invention Young Adult 03 medical and health sciences Receptors Glucocorticoid 0302 clinical medicine Adrenocorticotropic Hormone Double-Blind Method Randomized controlled trial law Internal medicine Brief Psychiatric Rating Scale Humans Medicine Pharmacology (medical) plasma level Depressive Disorder Major glucocorticoid receptor antagonism business.industry HPA axis Hamilton Rating Scale for Depression Mifepristone Middle Aged medicine.disease Interim analysis Antidepressive Agents 030227 psychiatry Psychiatry and Mental health Treatment Outcome psychotic depression ComputingMethodologies_DOCUMENTANDTEXTPROCESSING Major depressive disorder Female business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Clinical Psychopharmacology |
| ISSN: | 1533-712X 0271-0749 |
| DOI: | 10.1097/jcp.0000000000000744 |
| Popis: | Supplemental digital content is available in the text. Background Psychotic depression has no Food and Drug Administration–approved treatment. Patients demonstrate significant dysregulation of the hypothalamic-pituitary-adrenal axis providing a biologically targeted treatment opportunity. The purpose of this study was to explore the clinical and biological effects of short-duration (7-day) glucocorticoid receptor antagonism with mifepristone and the role of mifepristone plasma levels in patients with psychotic depression. Methods This double-blind, randomized study took place at 34 US clinical research centers and included patients with a diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, major depressive disorder, severe, with psychotic features. Patients underwent daily, observed, in-clinic administration of oral study drug (mifepristone 1200 mg or placebo) for days 1 to 7 of the 56-day trial, followed by treatment with a single Food and Drug Administration–approved antidepressant on days 8 to 56. The following scales were administered on days 0, 7, 14, 28, 42, and 56: Brief Psychiatric Rating Scale (BPRS), BPRS Positive Symptom Subscale, Hamilton Rating Scale for Depression, and Columbia-Suicide Severity Rating Scale. The primary end point was a categorical analysis evaluating the proportion of patients with 50% or greater reduction from baseline in BPRS Positive Symptom Subscale score on both days 7 and 56, demonstrating early and durable response. Cortisol and adrenocorticotropic hormone were measured on days 0, 7, 28, and 56. Mifepristone plasma levels were assessed on days 0 and 7. Results An interim analysis indicated that the primary efficacy end point was unlikely to be met, and the study was stopped early with 292 of the planned 450 patients enrolled. Although the primary end point was not met, in a secondary prespecified analysis, patients who attained a mifepristone plasma level of 1637 ng/mL or greater (defined a priori and termed the high plasma level; 66.7% of patients) demonstrated statistically significant reductions in psychotic symptoms compared with patients who received placebo starting on day 28. This group also showed nonsignificant, numeric superiority on Hamilton Rating Scale for Depression improvement. No significant improvements were observed in the low-mifepristone group ( |
| Databáze: | OpenAIRE |
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