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 stimulationReportar como inadecuado




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Trials

, 15:356

First Online: 10 September 2014Received: 23 May 2014Accepted: 21 August 2014DOI: 10.1186-1745-6215-15-356

Cite this article as: Koek, R.J., Langevin, JP., Krahl, S.E. et al. Trials 2014 15: 356. doi:10.1186-1745-6215-15-356

Abstract

BackgroundCombat 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.

Methods-DesignWe describe the protocol design for a first-ever Phase I pilot study of bilateral BLn high-frequency DBS for six severely ill, functionally impaired combat veterans with PTSD refractory to conventional treatments. After implantation, patients are monitored for a month with stimulators off. An electroencephalographic EEG telemetry session will test safety of stimulation before randomization to staggered-onset, double-blind sham versus active stimulation for two months. Thereafter, patients will undergo an open-label stimulation for a total of 24 months. Primary efficacy outcome is a 30% decrease in the Clinician Administered PTSD Scale CAPS total score. Safety outcomes include extensive assessments of psychiatric and neurologic symptoms, psychosocial function, amygdala-specific and general neuropsychological functions, and EEG changes. The protocol requires the veteran to have a cohabiting significant other who is willing to assist in monitoring safety and effect on social functioning. At baseline and after approximately one year of stimulation, trauma script-provoked FDG PET metabolic changes in limbic circuitry will also be evaluated.

DiscussionWhile the rationale for studying DBS for PTSD is ethically and scientifically justified, the importance of the amygdaloid complex and its connections for a myriad of emotional, perceptual, behavioral, and vegetative functions requires a complex trial design in terms of outcome measures. Knowledge generated from this pilot trial can be used to design future studies to determine the potential of DBS to benefit both veterans and nonveterans suffering from treatment-refractory PTSD.

Trial registrationPCC121657, 19 March 2014.

KeywordsStress disorders Post-traumatic Veteran’s health Deep brain stimulation Amygdala Positron emission tomography Electroencephalograms Caregivers Controlled clinical trial Neuropsychiatry AbbreviationsADIPSAmygdala DBS in PTSD Scale

AEadverse effect

SAEserious AE

ALICanterior limb of internal capsule

BLnbasolateral nucleus

BOLDblood oxygen level dependent

CAPSClinician Administered PTSD Scale

CESCombat Exposure Scale

CGI-IClinical Global Impression of Improvement

CGI-SClinical Global Impression of Severity

CPTcognitive processing therapy

CSconditioned stimulus

C-SSRSColumbia-Suicide Severity Rating Scale

DBSdeep brain stimulation

DSMDiagnostic and Statistical Manual of Mental Disorders

DSMBData Safety Monitoring Board

DTSDavidson Trauma Scale

ECGelectrocardiogram

ECTelectroconvulsive therapy

EEGelectroencephalogram

EMDReye movement desensitization and reprocessing therapy

FDAUS Food and Drug Administration

FDGfluorodeoxyglucose

fMRIfunctional magnetic resonance imaging

GAFGlobal Assessment of Functioning

GLAVeterans Administration, Greater Los Angeles Healthcare System

GPiGlobus Pallidum Interna

HAM-AHamilton Anxiety Rating Scale

HDEhumanitarian device exemption

IDEinvestigational device exemption

IRBInstitutional Review Board

ISTSSInternational Society for Traumatic Stress Studies

LFIPSLife Function in PTSD Scale

MADRSMontgomery Asberg Depression Rating Scale

MINIMINI International Neuropsychiatric Interview

mPFCmedical prefrontal cortex

mTBImild traumatic brain injury

NCPTSDNational Center for PTSD

NIMHNational Institute of Mental Health

OCDobsessive-compulsive disorder

OIF-OEFOperation Iraqi Freedom-Operation Enduring Freedom

PADRECCParkinson’s and Related Disorders Research, Education and Clinical Center

PEprolonged exposure therapy

PETpositron emission computed tomography

PTSDpost-traumatic stress disorder

RCTrandomized controlled trial

SANTEstimulation of anterior nucleus of thalamus for epilepsy

SF-36vVeterans Quality of Life Assessment

SPECTsingle photon emission computed tomography

SPMstatistical parametric mapping

SSRIserotonin selective reuptake inhibitor

TBItraumatic brain injury

UCLAUniversity of California at Los Angeles

UCSunconditioned stimulus

VAVeterans Affairs

VAROVA Research Office

VHISVietnam Head Injury Study

vmPFCventromedial prefrontal cortex

WICWelfare and Institutions Code

YMRSYoung Mania Rating Scale.

Electronic supplementary materialThe online version of this article doi:10.1186-1745-6215-15-356 contains supplementary material, which is available to authorized users.

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Autor: Ralph J Koek - Jean-Philippe Langevin - Scott E Krahl - Hovsep J Kosoyan - Holly N Schwartz - James WY Chen - Rebecca 

Fuente: https://link.springer.com/







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