Deep Brain Stimulation for PTSD
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: VA Greater Los Angeles Healthcare System
Must not be taking: Anticoagulants, Psychotropic herbs
Disqualifiers: Suicide attempt, Psychosis, Bipolar, Alcohol use, others
No Placebo Group
Trial Summary
What is the purpose of this trial?Posttraumatic stress disorder (PTSD) affects approximately 30 % of American veterans returning from Iraq and Afghanistan. Although the current therapy is effective, a percentage of patients will fail to improve and will develop chronic treatment-resistant PTSD. Patients suffering from PTSD experience intense suffering, lack of productivity and a higher risk of suicide. Unfortunately, combat PTSD has a tendency to be resistant to current treatments.
The central goal of this project is to develop a new therapeutic strategy involving the placement of intracranial electrodes to treat the symptoms of PTSD. The project is based on recent evidence showing abnormal activity in a specific brain region of PTSD patients, thought to be responsible for the core symptoms of PTSD.
Will I have to stop taking my current medications?
Participants must be stable on their current psychotropic medications for 2 months before the trial and cannot increase dosages or add new medications for the first 6 months, unless medically necessary.
What data supports the effectiveness of the treatment Deep Brain Stimulation for PTSD?
Deep Brain Stimulation (DBS) has shown promise in treating conditions like movement disorders, depression, and obsessive-compulsive disorder. In a rat model of PTSD, DBS of the basolateral amygdala was validated, and limited human data suggest it may be safe and effective. Additionally, in one case, DBS in the amygdala was associated with pleasant memories and improved sleep patterns, indicating potential benefits for PTSD.
12345How is the treatment of deep brain stimulation for PTSD different from other treatments?
Deep brain stimulation (DBS) for PTSD is unique because it targets the basolateral nucleus of the amygdala, a brain area involved in emotion regulation and memory of negative events, using electrical signals to reduce its activity. This approach is different from traditional PTSD treatments, as it directly modulates brain circuits rather than relying on medications or talk therapy.
23678Eligibility Criteria
This trial is for male veterans aged 25-70 with chronic, treatment-resistant PTSD from combat. They must have a stable medical condition and psychotropic medication use, cohabitate with someone who can report on their symptoms, and have tried multiple treatments without success. Excluded are those with certain implants, recent suicide attempts or substance abuse issues, significant cognitive impairments or other major psychiatric disorders.Inclusion Criteria
Able to give informed consent in accordance with institutional policies and participate in the 2-year follow-up, involving assessments and stimulator adjustments
Confirmation of PTSD as the primary psychiatric diagnosis by the study psychiatrist via clinical interview and CAPS
I have tried specific medications for at least 3 months.
+15 more
Exclusion Criteria
Current pursuit of new or increased disability compensation for PTSD
Patients suffering from a condition associated with a significant cognitive impairment
Significant abnormality on preoperative structural brain MRI
+18 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Surgery
Placement of intracranial electrodes for deep brain stimulation
1 week
Post-operative Recovery
Participants recover from surgery before starting stimulation
4 weeks
DBS Treatment
Deep brain stimulation of the amygdala BLn starting at 30 days post-operatively
30 days
DBS Treatment
Deep brain stimulation of the amygdala BLn starting at 90 days post-operatively
90 days
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 weeks
Participant Groups
The study tests Deep Brain Stimulation (DBS) of the Basolateral Nucleus of the Amygdala using Medtronic Activa PC DBS to alleviate PTSD symptoms. Participants will undergo electrode implantation in the brain and receive follow-up assessments and stimulator adjustments over two years.
2Treatment groups
Experimental Treatment
Group I: DBS of the Amygdala-90 daysExperimental Treatment2 Interventions
Deep brain stimulation of the amygdala BLn starting at 90 days post-operatively.
Group II: DBS of the Amygdala-30 daysExperimental Treatment2 Interventions
Deep brain stimulation of the amygdala BLn starting at 30 days post-operatively.
DBS of the Basolateral Nucleus of the Amygdala is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Deep Brain Stimulation for:
- Parkinson's disease
- Essential tremor
- Obsessive-compulsive disorder
- Clinical trials for PTSD (not FDA-approved)
🇪🇺 Approved in European Union as Deep Brain Stimulation for:
- Parkinson's disease
- Essential tremor
- Obsessive-compulsive disorder
- Clinical trials for various psychiatric conditions including PTSD (not EU-approved for PTSD)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
VA Greater Los Angeles Healthcare SystemLos Angeles, CA
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Who Is Running the Clinical Trial?
VA Greater Los Angeles Healthcare SystemLead Sponsor
References
Anterior thalamic deep brain stimulation in epilepsy and persistent psychiatric side effects following discontinuation. [2020]We report a case of a patient with drug-resistant epilepsy treated with deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS). The patient developed psychiatric side effects (PSEs), namely irritability, hostility, aggressiveness, and paranoia, after implantation and stimulation initiation. The stimulation was discontinued and the PSEs were mitigated, but the patient did not return to her pre-implantation state, as documented by repeated psychiatric reports and hospitalizations. To our knowledge, this is the first report of a patient who developed long-term PSEs that did not disappear after stimulation discontinuation. We suppose that ANT-DBS caused a persistent perturbation of the thalamic neuronal networks that are responsible for long-term PSEs.
Deep brain stimulation of the basolateral amygdala for treatment-refractory combat post-traumatic stress disorder (PTSD): study protocol for a pilot randomized controlled trial with blinded, staggered onset of stimulation. [2023]Combat post-traumatic stress disorder (PTSD) involves significant suffering, impairments in social and occupational functioning, substance use and medical comorbidity, and increased mortality from suicide and other causes. Many veterans continue to suffer despite current treatments. Deep brain stimulation (DBS) has shown promise in refractory movement disorders, depression and obsessive-compulsive disorder, with deep brain targets chosen by integration of clinical and neuroimaging literature. The basolateral amygdala (BLn) is an optimal target for high-frequency DBS in PTSD based on neurocircuitry findings from a variety of perspectives. DBS of the BLn was validated in a rat model of PTSD by our group, and limited data from humans support the potential safety and effectiveness of BLn DBS.
Deep Brain Stimulation of the Basolateral Amygdala: Targeting Technique and Electrodiagnostic Findings. [2020]The amygdala plays a critical role in emotion regulation. It could prove to be an effective neuromodulation target in the treatment of psychiatric conditions characterized by failure of extinction. We aim to describe our targeting technique, and intra-operative and post-operative electrodiagnostic findings associated with the placement of deep brain stimulation (DBS) electrodes in the amygdala. We used a transfrontal approach to implant DBS electrodes in the basolateral nucleus of the amygdala (BLn) of a patient suffering from severe post-traumatic stress disorder. We used microelectrode recording (MER) and awake intra-operative neurostimulation to assist with the placement. Post-operatively, the patient underwent monthly surveillance electroencephalograms (EEG). MER predicted the trajectory of the electrode through the amygdala. The right BLn showed a higher spike frequency than the left BLn. Intra-operative neurostimulation of the BLn elicited pleasant memories. The monthly EEG showed the presence of more sleep patterns over time with DBS. BLn DBS electrodes can be placed using a transfrontal approach. MER can predict the trajectory of the electrode in the amygdala and it may reflect the BLn neuronal activity underlying post-traumatic stress disorder PTSD. The EEG findings may underscore the reduction in anxiety.
[The effect of stimulation of the amygdala basolateral nuclei on the neuron activity of Deiters vestibular nuclei in rabbits]. [2016]A modulating character of the amygdala basolateral nuclei effect upon the vestibular sensory system was determined in rabbits [correction of rats]. A mechanism of the descending effect of the amygdaloid complex on the activity of the Deiters nucleus neurons, is discussed.
[THE BASOLATERAL NUCLEUS IN THE SYSTEM OF REPRODUCTIVE CENTERS OF THE AMYGDALA]. [2015]In this review contains the systematized data available in modern literature, which characterize the basolateral nucleus of the amygdala as one of the sexual dimorphism zones (SDZ) and its relationship with other reproductive centers of the amygdala. The basolateral nucleus, as the structure of the phylogenetically new part of the amygdala--receives the major amount of the pheromone and olfactory information through phylogenetically old--corticomedial division of the amygdala. Integrating it with the sensory signals of different modality, coming from the thalamus and cortical formations, the basolateral nucleus, together with the SDZ of corticomedial division, participates in the organization of sexual behavior and regulation of gonadotropin secretion. Sexual dimorphism of the basolateral nucleus, which is involved in the functional system of emotion formation and memory mechanisms, determines sex-dependent features of their behavioral manifestations, especially in stress reactions.
Deep Brain Stimulation for Post-Traumatic Stress Disorder: A Review of the Experimental and Clinical Literature. [2022]Up to 30% of patients with post-traumatic stress disorder (PTSD), especially combat veterans, remain refractory to conventional treatment. For them, deep brain stimulation (DBS) has been suggested. Here, we review the literature on animal models of PTSD in which DBS has been used to treat PTSD-type behavior, and we review and discuss patient reports of DBS for PTSD.
Preferential recruitment of the basolateral amygdala during memory encoding of negative scenes in posttraumatic stress disorder. [2019]The vast majority of functional neuroimaging studies in posttraumatic stress disorder (PTSD) have examined the amygdala as a unitary structure. However, an emerging body of studies indicates that separable functions are subserved by discrete amygdala subregions. The basolateral subdivision (BLA), as compared with the centromedial amygdala (CMA), plays a unique role in learning and memory-based processes for threatening events, and alterations to the BLA have been implicated in the pathogenesis of PTSD. We assessed whether PTSD is associated with differential involvement of the BLA versus the CMA during successful encoding of emotionally charged events.
Deep brain stimulation of the amygdala alleviates post-traumatic stress disorder symptoms in a rat model. [2022]Post-traumatic stress disorder (PTSD) is an anxiety disorder triggered by a life-threatening event causing intense fear. Recently, functional neuroimaging studies have suggested that amygdala hyperactivity is responsible for the symptoms of PTSD. Deep brain stimulation (DBS) can functionally reduce the activity of a cerebral target by delivering an electrical signal through an electrode. We tested whether DBS of the amygdala could be used to treat PTSD symptoms. Rats traumatized by inescapable shocks, in the presence of an unfamiliar object, develop the tendency to bury the object when re-exposed to it several days later. This behavior mimics the symptoms of PTSD. 10 Sprague-Dawley rats underwent the placement of an electrode in the right basolateral nucleus of the amygdala (BLn). The rats were then subjected to a session of inescapable shocks while being exposed to a conspicuous object (a ball). Five rats received DBS treatment while the other 5 rats did not. After 7 days of treatment, the rats were re-exposed to the ball and the time spent burying it under the bedding was recorded. Rats treated with BLn DBS spent on average 13 times less time burying the ball than the sham control rats. The treated rats also spent 18 times more time exploring the ball than the sham control rats. In conclusion, the behavior of treated rats in this PTSD model was nearly normalized. We argue that these results have direct implications for patients suffering from treatment-resistant PTSD by offering a new therapeutic strategy.