Medication Enhanced Rapid Therapy

Overview

The purpose of this research study is to determine whether taking a one-time dose of a combination of putatively learning-enhancing medications can improve treatment response to a brief learning-based psychotherapy for public speaking anxiety. The two medications are (1) d-cycloserine (DCS), a medication that is an agonist (facilitator) of the NMDA glutamatergic receptor and has been shown in previous studies to facilitate some kinds of learning and memory; and (2) mifepristone, a medication that blocks cortisol, and in preclinical (animal) studies has been shown to reverse certain kinds of stress-related learning impairment or negative learning. Specifically, the investigators goal is to determine if DCS and mifepristone taken together augment the learning that occurs during a brief psychotherapy session---a public speaking exposure exercise. Evidence for this learning effect would be a finding that participants have reduced anxiety at subsequent public speaking exposures.

The study has a total of 4 visits, and the medications are given as a one-time dose at only one visit (the second visit). 1. During the first visit, a trained clinical interviewer will provide informed consent and conduct a structured clinical interview. Participants will be included if they are adult males diagnosed with social anxiety disorder and express a fear of public speaking, as well as approximately 10 healthy control participants. Eligible participants will be asked to complete self-report ratings of social anxiety and psychological symptoms and a standard interview about anxiety symptoms. The experimenter will conduct neuropsychological tests used to measure the participant's cognitive functioning. 2. At the second visit the participant will be administered a one-time only dosage of both medications. The participant will be asked to prepare a speech within a short period of time, this is an example of exposure therapy. In exposure therapy, people are exposed to a situation they fear, such as public speaking, in a safe and controlled environment. Often when people do exposure therapy, they find that the situations they have been afraid of are not actually as scary as they seem. The exposure exercise in this study will consist of giving a speech while being video-recorded. Before the exposure exercise, participants will be provided with 250mg DCS and up to 1200mg of mifepristone. Participants will rate their anxiety level and negative and positive affect before and after the speech, as well as during the speech. The experimenter will again conduct neuropsychological tests used to measure the participant's cognitive functioning. 3. (3) \& (4) During the next two visits, participants will complete a second and third public speaking exposure exercise identical to the first, with the exception that they will NOT receive medication. Participants will complete a similar battery of symptom measures and anxiety ratings. The investigators will look at a change in anxiety ratings and symptomatology between exposure session 1, exposure session 2, and exposure session 3.