psychopharmacologic treatments for traumatic disorders · u cns = central nervous system ... of the...
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Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
09-09-2017
LauraGLeahy,DrNP,APRN,[email protected] APNA-NJChapterFallConference20171
Neurobiology & Psychopharmacologic Treatments for Traumatic Disorders
LAURA G LEAHY, DRNP, APRN, PMH-CNS/FNP, CARNP-AP, FAANPPSYCHIATRIC & ADDICTIONS ADVANCED PRACTICE NURSE
MASTER CLINICIAN IN PSYCHOPHARMACOLOGY
AmericanPsychiatricNursesAssociation-NJChapterFallConference- September9,2017
Objectives
u Bytheendofthissection,Participantswillbeableto:u Identify&describethebrainstructuresrelatedtotrauma&PTSD
u DescribetheneurochemistryrelatedtoPTSD&traumasymptomprescribing
u Discuss3psychopharmacologicalagentsusedtotreatsymptomsoftrauma
Faculty Disclosures
u Thispresenterhasnoconflictsofinterestorcommercialsupporttodisclose.
u Discussionofoff-labelmedicationuseswilloccurinthispresentation.
u PresentermayreceiveroyaltiesforpublicationoftextthroughtheAmericanPsychiatricAssociation
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
09-09-2017
LauraGLeahy,DrNP,APRN,[email protected] APNA-NJChapterFallConference20172
Faculty Contact
� Laura G Leahy, DrNP, APRN, PMH-CNS/FNP, CARN-AP, FAANP� APNSolutions, LLC� 123 Egg Harbor Road� Suite 703, Sewell, NJ 08080� Phone/text: 856.556.0860� Fax: 844.276.7656� Email: [email protected]� Website: www.APNSolutions.com
Important Abbreviations
u PTSD=PostTraumaticStressDisorderu SUD=SubstanceUseDisordersu HPA=Hypothalamic-Pituitary-AdrenalAxisu CNS=CentralNervousSystemu CRH=Corticotropin-releasingHormoneu ACTH=AdrenalCorticotropinHormoneu 5HT=Serotoninu NE=Norepinephrineu DA=Dopamine
PhotoscourtesyofWilOkken,Mosul,Iraq2017
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
09-09-2017
LauraGLeahy,DrNP,APRN,[email protected] APNA-NJChapterFallConference20173
ThomasEakinsdepictssubjectGeorgeReynolds’battlescars&hintsatdeeperwoundsofthesoul.
‘TheVeteran’(1885)
PTSD Mnemonic—TRAUMA
uTraumaticEventuRe-experienceuAvoidanceuUnabletoFunctionuMonthorMoreofSymptomsuArousalIncreased
Caplan&Stern(2008).Mnemonicsinamnutshell.CurrentPsychiatry7(10):27-33
©LGLeahy2014allrightsreservedCurrNeuropharmacol.Dec2010;8(4):335–358.
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
09-09-2017
LauraGLeahy,DrNP,APRN,[email protected] APNA-NJChapterFallConference20174
“Toooftenonlythe20%abovethesurfaceis
diagnosed&treated;theother80%remainshidden.”
--WilliamShryer,LCSW
Major Symptom Clusters in Trauma
uIntrusionSymptomsuMemories/flashbacks/dreamsuPhysiologicalreactions
uAvoidanceSymptomsuIsolativebehaviors,napping
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
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LauraGLeahy,DrNP,APRN,[email protected] APNA-NJChapterFallConference20175
uNegativeCognitions&MoodSymptomsuDissociativeamnesiauNegativebeliefsaboutoneself,others,world
uPersistentnegativeemotionalstate
uAlterationsinArousal&ReactivitySymptomsuIrritable/angrybehavior&outburstsuReckless/self-destructivebehavioruSleepdisturbance,hypervigilance,poorconcentration
LGLeahy © 2017
Trauma’sImpactontheSoul
SOUL
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
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LongitudinalProgressionofPTSD:PointsforClinicalIntervention
Reed,Gore&Engel(2011).EpidemiologyinClinicalManualforManagementofPTSD.APPI.
Am J Psychiatry 2010;167:648-662.
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
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LauraGLeahy,DrNP,APRN,[email protected] APNA-NJChapterFallConference20177
Developmentally Sensitive Criterion
uPTSD in Children 6 Years & YoungeruExperienced, witnessed, learneduIntrusive Memories
uRecurrent Distressing DreamsuDissociative Reactions/Flashbacks
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©LGLeahy2014allrightsreserved
CurrNeuropharmacol.Dec2010;8(4):335–358.
Lanius,Vermetten,Loewenstein,etal(2010).EmotionModulationinPTSD.AmJPsychiatry(167):p640-647.
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©LGLeahy2014allrightsreserved
CurrNeuropharmacol.Dec2010;8(4):335–358.
©LGLeahy2014allrightsreserved
THREAT
ArousalContinuum
Dissociative Continuum
1) Norepinephrine(locuscoeruleus)
2)Dopamine(nigrostriatal/mesolimbic)
3)GABA4)Serotonin
1) OpioidReceptors2) Serotonin3) Dopamine(mesolimbic/mesocortical)
Impact of Neurotransmitters & Hormones in PTSD
Neurotransmitters & Hormones
Impact in PTSD
Corticotropin Releasing Hormone
Increased Activates release of cortisol
Cortisol Mixed Stress, Reduced Immunity, chronic elevation may reduce sensitivity to
danger/threat & exhaust the HPA axis DHEA Increased Reduced immune response
Norepinephrine Increased Anxiety, insomnia, nightmares, stress, worry
Serotonin 1A Decreased Depression, avoidance
Dopamine Increased Psychosis, flashbacks, arousal
Testosterone Decreased Fatigue, anhedonia, avoidance
Neuropeptide Y Decreased Anxiety, arousal, stress©LGLeahy2014allrightsreserved CurrNeuropharmacol.Dec2010;8(4):335–358.
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
09-09-2017
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Role of Serotonergic System
Drugabuse.gov
Serotonin & PTSD
u Mood&Anxietyu Memory&Agingu CircadianRhythmsu Eating&Satietyu GI&BowelIssues
u MigraineHeadachesu PrematureEjaculationu Painu SubstanceAbuseu Vasoconstriction&
Vasodilation
Role of Noradrenergic System
http://drsaulmarcus.com/mentalillness/neurotransmittertesting.html
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Role of Dopaminergic System
http://quizlet.com/4038817/b8w2-neurobiology-of-addiction-and-reward
http://kellygough.com/gallery17.html
PTSD Comorbidities by Population
Comorbid Disorder PopulationMajor Depressive Disorder General & Women
Other Anxiety Disorders General & Women
Alcohol Use & Abuse Disorders Combat Veterans, Rescue Workers, Accident & Assault Survivors & Men
Other Drug Use & Abuse Disorders Combat Veterans, Accident & Assault Survivors & Men
Somatization Disorder Childhood Abuse Survivors & Women
Bipolar Disorder Socioeconomically Disadvantaged & Chronically Ill (disorder is preexisting)
North,Suris&Adewuyi(2011).PsychiatricConditionsinClinicalManualforManagementofPTSD.APPI
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uOver50%men&about30%womenETOHuAbout35%men&27%womenDrugsuMayreduceabilitytodiscriminatebetweensafety&dangerà high-riskbehaviors&increasedriskforfurthertraumaexposure
Relationship of PTSD & SUDs
u PTSD Arousal Symptoms
u Difficult falling/staying asleep
u Irritability & Angry Outburstsu Difficulty Concentratingu Hypervigilanceu Exaggerated Startle
Responseu Flashbacks
u CNS Depressant Withdrawal Symptomsu Insomniau Psychomotor Agitationu Anxietyu Autonomic Hyperactivityu Increased Hand Tremoru Transient Hallucinationsu Nausea/Vomitingu Seizures
©LGLeahy2014allrightsreserved
They promised that Dreams can come True.
But forgot to mention that Nightmares are Dreams too.
OSCAR WILDEIRISH WRITER (1854-1900)
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
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PTSD Mneumonic—DREAMS
u DisinterestinUsualActivitiesu Re-experienceu EventPrecedingSymptomsu Avoidance
u MonthorMoreofSymptomsu SympatheticArousalCaplan&Stern(2008).Mnemonicsinamnutshell.CurrentPsychiatry7(10):27-33
©LGLeahy2014allrightsreserved
https://pixabay.com/en/military-soldiers-sleeping-rest-668988/
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
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Comparing Sleep
PTSDu Chronicityimpairsobjectivityu SignificantDisruptionu REMsleepbrokenu Elevatedadrenaline2°
Norepinephrineu Memoriesstored&attached
emotionsremain
NORMALu Fairlyobjectivereportingu Restful&Refreshingu REMsleeprestorativeu Norepinephrine/adrenaline-freeenvironment
uMemoriesprocessed&triggersremoved
©LGLeahy2014allrightsreserved
PTSD Sleep Cycle
Bedtime• Racing thoughts• Rx dependent• Restless Legs
• Time Monitoring• Worry & Stress
Nightime• Nightmares
• Insomnia• Lost/Broken Sleep
• Motor Activity• Sleep Breathing
D/Os
Wake Up• Un-refreshed
• Lethargic• No Motivation
• Inertia• Low Energy
Daytime• Sleepiness
• Desire to Nap• Impairment• Poor Coping• Avoidance
R.BruceLydiard,Ph.D.,M.D.;MarkH.Hamner,M.D.FOCUS2009;7:176-183.
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Lab & Diagnostic Tests
Test Clinical Indications
T3, T4, TSH Restlessness, insomnia, autonomic hyperactivityT3 & T4 have been elevated in patient with PTSDTSH typically unaffected in PTSD alone
Drug Screen High incidence of comorbidity in PTSD
Head CT or MRI Comorbid head trauma, amnesia or cognitive deficits
Neuropsychiatric Testing
Head trauma, memory difficulties & cognitive decline
Polysomnography(Sleep Studies)
Symptoms predating trauma, symptoms of 1° sleep disorder (eg: OSA, Idiopathic Hypersomnolence, Restless Leg Syndrome &/or Periodic Limb Movement Disorder
Khouzam,HR(2013).PTSD:Makingthediagnosis.Consultant.2013;53(8):578-580
Allimagesinpublicdomain
Psychopharmacogenetics&PTSD
“Over 25% of ALL common medications have genetic
information that can be tested and used to personalize
medical treatment”
--Frueh and Colleagues, 2008
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
09-09-2017
LauraGLeahy,DrNP,APRN,[email protected] APNA-NJChapterFallConference201716
Selective Serotonin Reuptake Inhibitors
u Regulate mood, anxiety, depressive symptoms, sleep & appetite
u Reduce hyperarousal & avoidanceu Sertraline (Zoloft)
uFDA approved, Most evidenceu Paroxetine (Paxil)
uFDA approvedu Fluoxetine (Prozac)
uOff-LabelImageinpublicdomain
Tricyclic Antidepressants (Imipramine)
uNot 1st line 2° side effects (cardiac arrhythmias)
uGlobal improvementuPrevented PTSD in
Pediatric Burn Patients
http://www.nursinged.com/about.html
Buspirone (BuSpar)
�Usedadjunctivelytotreathyperarousalsymptoms
� ActsonSerotonin&maydecreaseanxiety
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
09-09-2017
LauraGLeahy,DrNP,APRN,[email protected] APNA-NJChapterFallConference201717
Other Antidepressants
u Venlafaxine (Effexor)u At lower doses acts as 5HT reuptake
inhibitoru At higher doses also NE reuptake
inhibitoru Mirtazapine (Remeron)
u Treatment of insomnia in PTSDu Trazodone (Desyrel)
u Treatment of insomnia in PTSD, little evidenceImage:https://beyondmeds.com/2014/04/27/antidepressant-drugs/
©LGLeahy2014allrightsreserved
Older Medications for PTSD
Prazosin (Minipress)uReduces nightmares & improves sleepuBlocks noradrenergic stimulation of α-1 receptoruDecreases sensitivity to adrenaline
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
09-09-2017
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� Blocksadrenaline(epinephrine)onorganssuchastheheart,sweatglands&muscles
� Propranolol(Inderal),Guanfacine(Tenex)
NursingEducationConsultants(2007)
Mood Stabilizers
u BlockGlutamateorPotentiateGABAorBothu Carbamazepine(Tegretol)
uInducesitownmetabolism&mayincreasemetabolismofotherdrugs(eg:oralcontraceptives)
uDivalproex(Depakote)
uTargetdosageis10x’spatient’sweightinpounds
uMonitorforhepatotoxicity&thrombocytopenia
uGabapentin(Neurontin)uAnticonvulsantthatexertsanxiolytic,antinociceptiveandsleep-promotingeffects
uWorksonCalciumchannelsà decreasedreleaseofNE,5HT,Glutamate&SubstanceP
uEnhancesslow-wavesleep,reducesarousal&increasestotalsleeptime
uNormalizesGABAinamygdala
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
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Lamotrigine(Lamictal)Mayreducearousal&reactivityRequiresSLOWtitration2° riskofSteven’sJohnsonSyndrome
Topiramate(Topamax)MayreducenightmaresinPTSDMonitorforglaucoma,sedation,cognitivedulling
Atypical Antipsychotics
uNOTrecommendedasMonotherapyuInhibitDopamine&BlockReuptakeofSerotonin
Risperidone(Risperdal)contraindicatedforuseasanadjunctiveagentduePotentialsideeffectsexceedbenefits
InsufficientevidencetorecommendanyasadjunctivetreatmentsMaybehelpfulwithco-morbidpsychosis
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
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Benzodiazepines & PTSD
u ActdirectlyonGABAreceptorsu Calmscentralnervoussystem,butlittleimpactoncore
PTSDsymptomsu Potentialfordisinhibition&addiction
u Lorazepam(Ativan)u Clonazepam(Klonopin)u Alprazolam(Xanax)
The Benzodiazepine Controversy
http://www.psychiatrictimes.com/articles/religion-benzodiazepines
Drugs in the Pipeline for PTSD
uD-cycloserine(DCS)uPartialAgonistofGlutamatergicN-methyl-D-aspartate(NDMA)receptor
uUsedinpanicdisordertoenhanceeffectsofexposuretherapy
Neurobiology&PsychopharmacologicalTreatmentsforTraumaDisorders
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Memantine(Namenda)Protectsagainstglutamatergicdestructionofneurons
NeuropeptidesInterveneatHPAaxisoronGlucocorticoidreceptorstomodulateeffectsofstressSubstanceP&NeuropeptideY
“While medicine can help control some of the symptoms,
psychotherapy is still the gold standard.”
--Dr. Gregory WeissDurham VA Medical Center & DUKE University
PTSDTreatmentResources
Images:screenshotsofappbuttonsLGLeahy 2017
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http://www.nimh.nih.gov/health/publications/anxiety-disorders/nimhanxiety.pdf
http://www.nimh.nih.gov/health/publications/mental-health-medications/nimh-mental-health-medications.pdf
http://www.nimh.nih.gov/health/publications/post-traumatic-stress-disorder-ptsd/nimh_ptsd_booklet.pdf
NIMHFREEPUBLICATIONS
“PTSD is a whole-body tragedy, an integral human event of enormous proportions with
massive repercussions.”
--Susan Pease Banitt
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