In treatment-resistant depression, repeated ketamine infusions showed greater antidepressant effects than the active placebo midazolam after five doses, but when compared head-to-head against a single ketamine infusion added to midazolam over two weeks, the difference was not statistically significant. Fifty-four participants completed all six infusions. The primary outcome, change in depression severity measured by the Montgomery-Åsberg Depression Rating Scale at 24 hours after the last infusion, did not differ significantly between the six-ketamine group and the single-ketamine group. Remission and response rates favored six ketamine after the fourth and fifth infusions, respectively, compared to midazolam before the single ketamine.
Meditation-based therapies such as mindfulness-based stress reduction and Transcendental Meditation can reduce PTSD symptoms in veterans. In 72 veterans with PTSD, those with the 5HTTLPR LALA high expression genotype of the serotonin transporter gene who had experienced early life trauma showed greater symptom improvement. Additionally, changes in DNA methylation at nine specific sites in the FKBP5 gene from before to after treatment were linked to greater symptom improvement, with an odds ratio of 2.8. These findings suggest that genetic and epigenetic markers in the SLC6A4 and FKBP5 genes may be important for understanding treatment mechanisms and predicting symptom improvement.
Transcendental Meditation (TM), a mantra-based technique, appears to be an acceptable and effective treatment for veterans with posttraumatic stress disorder (PTSD). In a pilot study of 29 veterans (20.7% female), eight weeks of TM instruction led to reductions in PTSD symptoms, experiential avoidance, and depressive and somatic symptoms, along with increases in mindfulness and quality of life. These gains were maintained or improved at a two-month follow-up. Electroencephalography (EEG) showed increased low-frequency (1-7 Hz) spectral power during meditation states at posttreatment and follow-up, indicating TM-specific changes in brain state. The findings warrant further study of TM's outcomes and beneficial brain changes.
Veterans with PTSD who responded to Mindfulness Based Stress Reduction (MBSR) showed decreased methylation in a specific region of the FKBP5 gene after treatment, while non-responders showed increased methylation. The change occurred in a glucocorticoid response element, suggesting meditation may affect stress-related molecular pathways. No baseline methylation differences were found between responders and non-responders. These preliminary results from 22 veterans indicate FKBP5 DNA methylation could be a biomarker for MBSR treatment response in PTSD, but validation in larger studies is needed.