WASHINGTON – The use of D-cycloserine has promise as a way to augment the beneficial effects of virtual reality therapy of posttraumatic stress disorder, results of two recently published studies show. The results were discussed during a symposium at the annual convention of the American Psychological Association.
In one study of Iraq and Afghanistan veterans, the use of D-cycloserine (DCS) did not provide an advantage overall, compared with alprazolam or placebo. However, DCS was associated with favorable effects on cortisol and startle reactivity, compared with the other two groups, said one of the authors, Tanja Jovanovic, Ph.D. In another trial, a small proof-of concept study, the PTSD remission rate 6 months after treatment was almost 70% among those treated with a combination of virtual reality (VR) therapy and DCS, compared with 17% among those treated with VR therapy and placebo.
DCS, an NMDA (N-methyl-D-aspartate)-receptor partial agonist approved as an antibacterial by the Food and Drug Administration, has been found to enhance exposure therapy for conditions that include social anxiety and acrophobia in previous studies. NMDA also has been found to facilitate extinction learning in animal studies, said Dr. Jovanovic director of the neurophysiology laboratory at the Grady Trauma Project at Emory University, Atlanta.
In the study, 156 veterans of the Iraq and Afghanistan wars were randomized to treatment with DCS (50 mg), alprazolam (0.25 mg), or placebo plus five sessions of virtual reality exposure therapy (after an introductory VR session). Assessments of patients – which included evaluation of PTSD symptoms, psychophysiologic responses, and cortisol reactivity – were performed before treatment and 3, 6, and 12 months after treatment. Monitoring included placing electrodes under the eye to measure the contraction of the eye blink muscle and skin conductance testing during exposure to the VR scenes (two convoy explosion scenes and a city scene), said Dr. Jovanovic, one of the authors of the study, which was published in June (Am. J. Psychiatry 2014;171:640-8).
After five series of VR treatment, PTSD symptoms significantly decreased in all three groups after treatment, based on changes on the Clinician-Administered PTSD Scale (CAPS) score, but the greatest degree of reduction in symptoms at 12 months was observed in the DCS group, she said. Those treated with DCS "showed the biggest decline and actually maintained those gains at 6 months, which we did not see with the other groups."
In addition, those treated with DCS had a reduction in cortisol and startle reactivity that was greater than the changes observed in the two other groups. The magnitude of startle reactivity at baseline was related to the change in the CAPS score 6 months later, "so those gains they are maintaining at 6 months are predicted by their initial response to the virtual reality session pretreatment ... the more reactive, the better they got," Dr. Jovanovic reported.
The same also was true for skin conductance findings: The more reactive they were at baseline in this measure, the more improved the patients were at follow-up, but this association was only evident in the DCS-treated patients, Dr. Jovanovic said.
Measurements of cortisol levels before exposure to the VR scenes, immediately afterward, and 15 minutes afterward determined that cortisol reactivity was attenuated with treatment. Cortisol reactivity significantly dropped in all three groups, from before treatment to the 6-month follow-up but was the lowest in the DCS-treated patients. In the alprazolam-treated group, the higher the cortisol reactivity was before treatment, the worse the outcomes were with treatment, the reverse of what was seen with other psychophysiological measures, she added.
During the same symposium on the use of VR in the treatment of PTSD, JoAnn Difede, Ph.D., professor of psychiatry, Cornell University, New York, described the use of DCS "as a cognitive enhancer" for treatment of people with PTSD related to the World Trade Center attacks in 2001. "We see this as very promising," she said.
In one double-blind, proof-of-concept study, 25 people with PTSD were randomized to DCS (100 mg) or placebo administered 90 minutes before weekly sessions of VR therapy, timed so that plasma concentrations would peak during the session. In the placebo group, 3 dropped out, but none of the 13 patients in the DCS group dropped out (Neuropsychopharmacology 2014; 39:1052-8).
Six months after treatment, 9 of the 13 patients (69%) in the DCS group were in remission, compared with 2 of the 12 (17%) on placebo plus VR exposure. Remission was defined as a CAPS total score of 20 or less, and minimal or no impairment in social, occupational, and other important areas of function, as judged by an independent blinded assessor.