Neuromodulation for Treatment-Refractory PTSD
Early Clinical Experience
The authors have initiated the first ever clinical trial (NCT02091843) evaluating use of DBS for PTSD and are now recruiting patients. Enrollment is limited to 6 combat veterans with disabling PTSD that has not responded to pharmacotherapy and psychotherapy. This VA-funded single-site study, being conducted at the VA Greater Los Angeles Healthcare System (VAGLAHS), was approved by the VAGLAHS Institutional Review Board and the FDA. The authors have published the 2-year trial’s protocol, which includes an active-versus-sham stimulation phase; continuous electroencephalogram monitoring; baseline and posttreatment 18FDG (fluorodeoxyglucose) PET performed during a resting state vs during investigator-guided exposure to trauma reminders; and extensive psychological and neuropsychological assessments.33 The literature includes only 1 case report on amygdala DBS.34 The authors of that report used DBS of the basolateral nucleus of the amygdala to treat a teenaged boy with severe autism and found that the therapy was safe.
As of this writing, the authors have recruited and implanted 1 patient and reported on his clinical results (including baseline PET) over the first 8 months of stimulation35 and on the electrophysiologic findings over the first year.36 After experiencing extremely severe combat PTSD refractory to pharmacotherapy and psychotherapy treatments for more than 20 years, the patient treated with DBS is now experiencing substantial symptom relief, and his CAPS score (primary outcome measure) has improved by about 40%. He has tolerated continuous stimulation without any serious DBS-related AEs for up to 16 months. Notably, he has not had a single severe combat nightmare in a year—in stark contrast to nightly combat nightmares during the 20-year period leading to the trial. Furthermore, he has not been having any episodes of severe dissociation, which had been a common disabling problem before the trial. He has taken a second trip out of the country, improved his relationships with family, and made strides (albeit limited) in pursuing additional social interactions.
Avoidance remains a major problem. He recently left his job after 7 years, because he prefers a more nature-oriented rather than people-oriented environment. In addition, his interest in intensive psychotherapy has increased, and he has been considering options for spending more time working on his therapy.
Over 15 months of treatment, the patient’s CAPS total and subscale scores have decreased—his symptoms have improved (Table).21 He has had rapid and substantial reductions in recurrence and hyperarousal symptoms but slower improvement in avoidance. Improvements in emotional reactivity would be expected to occur before any change in behavior (eg, avoidance). Patients likely must first recognize changes in emotional reactivity to events before they can engage in a cognitive process to modify learned behavioral responses to those events.
After about 9 months of treatment, all of the study patient’s symptoms were somewhat stabilized, and the authors began making gradual stimulation adjustments to the latest parameters—3.5 V, 60 µs, and 160 Hz for the right electrode and 1.5 V, 60 µs, and 160 Hz for the left electrode—using the contacts in the basolateral nucleus of the amygdala, per postoperative neuroimaging.3
After 15 to 18 months, when improvement peaked at 48% symptom reduction from baseline, the patient experienced psychiatric decompensation (depression, suicide gesture) not attributable to changes in stimulation settings and not associated with exacerbation of PTSD symptoms. Treatment team members and independent psychiatric consultants attributed the decompensation to the patient’s difficulty in changing a long-standing avoidant behavior routine, owing to severe recurrence and hyperarousal symptoms in the past. His persistent inability to overcome avoidance and isolation, despite core PTSD symptom improvement, had left him feeling worthless.
The patient remains in the study but also is participating in other medication and psychotherapy trials and is making a career change. Periodic decompensations may be part of the treatment course as patients reach a more complex and volatile phase of improvement that requires more intensive cognitive reprocessing. If this proves to be the case with other patients enrolling in the study, intensive psychotherapy that addresses cognitive and emotional PTSD symptoms may be needed once there is improvement in intrusive and hyperarousal symptoms.
