Abstract
Background: The relationship between plasma concentrations of psychiatric medications and their efficacy is rarely evaluated or relied upon in clinical practice. While it is generally accepted in clinical settings that patients respond to varying doses of medication, few studies have formally tested whether plasma concentrations of psychiatric medicine predict patients’ responses. We hypothesized that the amount of mifepristone detected in the plasma after dosing for 7 days would correlate with reduction of psychotic symptoms in patients with psychotic depression. This hypothesis was generated from the exploratory analysis phase of an early clinical trial. In that trial, a statistically significant linear correlation was observed between change in psychotic symptoms and mifepristone plasma concentrations observed at day 7.
Method: Secondary analyses were conducted using data from three multicenter randomized clinical trials. For each of the three trials, hypothesis testing was conducted to test whether patients assigned to mifepristone whose plasma concentrations were above pre-specified concentration values would exhibit significantly greater reduction in psychotic symptoms than patients assigned to placebo.
Results: In all studies, there was a statistically significant linear correlation between plasma concentration and change in psychotic symptoms. In two of the three clinical trials, the response rate of patients with mifepristone plasma concentrations above 1660 ng/ml was significantly greater than the placebo response rate. Results are presented for the three studies separately and for the combined data.
Discussion: Although correlations between plasma correlations and clinical response are not often observed in psychiatric medications, there is evidence that trough mifepristone plasma concentrations are associated with clinical improvement.
Study identification numbers clinicaltrials.gov: NCT00130676 (Study 07), NCT00146523 (Study 09), NCT00128479 (Study 06).
Keywords: Plasma concentration, Psychotic depression, Mifepristone, Cortisol, Glucocorticoids, HPA axis.
5