Deep Brain Stimulation for PTSD

Overseen By Ralph Koek, MD

Age: 18+

Sex: Male

Trial Phase: Academic

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 All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

6 Participants Needed

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. ^{1 2 3 4 5}

How 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. ^{2 3 6 7 8}

Eligibility 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.

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

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

Treatment Details

Interventions

• DBS of the Basolateral Nucleus of the Amygdala
• Medtronic Activa PC DBS of the Basolateral Nucleus of the Amygdala

Trial Overview 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.

Participant Groups

Group I: DBS of the Amygdala-90 days Experimental Treatment 2 Interventions

Deep brain stimulation of the amygdala BLn starting at 90 days post-operatively.

Group II: DBS of the Amygdala-30 days Experimental Treatment 2 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)

Who Is Running the Clinical Trial?

VA Greater Los Angeles Healthcare System

Lead Sponsor

Trials

53

Recruited

8,700+

Findings from Research

A patient with drug-resistant epilepsy experienced significant psychiatric side effects, including irritability and paranoia, after receiving deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS).

Even after stopping the stimulation, the psychiatric side effects persisted long-term, suggesting that ANT-DBS may cause lasting changes in thalamic neuronal networks responsible for these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anterior thalamic deep brain stimulation in epilepsy and persistent psychiatric side effects following discontinuation. Doležalová, I., Kunst, J., Kojan, M., et al.[2020]

This study outlines a Phase I pilot trial investigating the safety and efficacy of deep brain stimulation (DBS) targeting the basolateral amygdala in six combat veterans with severe, treatment-resistant PTSD, with a primary goal of achieving a 30% reduction in PTSD symptoms as measured by the Clinician Administered PTSD Scale (CAPS).

The trial design includes rigorous safety monitoring and assessments of psychiatric and neurological symptoms, aiming to gather valuable data that could inform future studies on DBS for PTSD in both veterans and non-veterans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Koek, RJ., Langevin, JP., Krahl, SE., et al.[2023]

Deep brain stimulation (DBS) electrodes can be effectively implanted in the basolateral nucleus of the amygdala using a transfrontal approach, which may help treat severe post-traumatic stress disorder (PTSD).

Intra-operative neurostimulation elicited pleasant memories, and post-operative EEG monitoring showed improved sleep patterns, suggesting that DBS may reduce anxiety and enhance emotional regulation in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation of the Basolateral Amygdala: Targeting Technique and Electrodiagnostic Findings. Langevin, JP., Chen, JW., Koek, RJ., et al.[2020]

The study investigated how the amygdala's basolateral nuclei influence the vestibular sensory system in rabbits, suggesting a modulatory role.

It discusses the mechanism by which the amygdala affects the activity of neurons in the Deiters nucleus, which is important for balance and spatial orientation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of stimulation of the amygdala basolateral nuclei on the neuron activity of Deiters vestibular nuclei in rabbits]. Minasian, SM., Baklavadzhian, OG., Adamian, TsI., et al.[2016]

The basolateral nucleus of the amygdala is identified as a key area exhibiting sexual dimorphism, influencing sexual behavior and the regulation of reproductive hormone secretion.

This nucleus integrates sensory information and plays a significant role in emotional responses and memory, which may lead to different behavioral reactions to stress between sexes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[THE BASOLATERAL NUCLEUS IN THE SYSTEM OF REPRODUCTIVE CENTERS OF THE AMYGDALA]. Akhmadeyev, AV., Galiyeva, LF., Kalimullina, LB.[2015]

Deep brain stimulation (DBS) has been explored as a treatment for PTSD, particularly in combat veterans, with promising results observed in animal models targeting specific brain areas like the medial prefrontal cortex and amygdala.

In clinical reports involving 3 patients, all showed varying degrees of improvement after receiving DBS, indicating potential efficacy, but the treatment remains investigational due to ethical concerns and challenges in recruitment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Post-Traumatic Stress Disorder: A Review of the Experimental and Clinical Literature. Meeres, J., Hariz, M.[2022]

In individuals with PTSD, there is greater activation of the basolateral amygdala (BLA) compared to the centromedial amygdala (CMA) during the successful encoding of negative emotional scenes, indicating a specific role of the BLA in processing threatening information.

This increased BLA activation during memory tasks was found to independently predict PTSD status, suggesting that targeting this subregion could be important for understanding and potentially treating PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential recruitment of the basolateral amygdala during memory encoding of negative scenes in posttraumatic stress disorder. Patel, R., Girard, TA., Pukay-Martin, N., et al.[2019]

Deep brain stimulation (DBS) of the amygdala significantly reduced PTSD-like behaviors in rats, as evidenced by treated rats spending 13 times less time burying a stress-inducing object compared to control rats.

The treated rats also showed a marked increase in exploratory behavior, spending 18 times more time interacting with the object, suggesting that DBS may effectively normalize PTSD symptoms and offers a promising new treatment strategy for patients with treatment-resistant PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the amygdala alleviates post-traumatic stress disorder symptoms in a rat model. Langevin, JP., De Salles, AA., Kosoyan, HP., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Anterior thalamic deep brain stimulation in epilepsy and persistent psychiatric side effects following discontinuation. [2020]

2. England pubmed.ncbi.nlm.nih.gov

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]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation of the Basolateral Amygdala: Targeting Technique and Electrodiagnostic Findings. [2020]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The effect of stimulation of the amygdala basolateral nuclei on the neuron activity of Deiters vestibular nuclei in rabbits]. [2016]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[THE BASOLATERAL NUCLEUS IN THE SYSTEM OF REPRODUCTIVE CENTERS OF THE AMYGDALA]. [2015]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Post-Traumatic Stress Disorder: A Review of the Experimental and Clinical Literature. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Preferential recruitment of the basolateral amygdala during memory encoding of negative scenes in posttraumatic stress disorder. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the amygdala alleviates post-traumatic stress disorder symptoms in a rat model. [2022]