Psychopharmacologic Treatments for Traumatic Disorders · u CNS = Central Nervous System ... of the soul. ‘The Veteran’ (1885) PTSD Mnemonic—TRAUMA uTraumatic Event ... u REM

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


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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


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ThomasEakinsdepictssubjectGeorgeReynolds’battlescars&hintsatdeeperwoundsofthesoul.

‘TheVeteran’(1885)

PTSD Mnemonic—TRAUMA

uTraumaticEventuRe-experienceuAvoidanceuUnabletoFunctionuMonthorMoreofSymptomsuArousalIncreased

Caplan&Stern(2008).Mnemonicsinamnutshell.CurrentPsychiatry7(10):27-33

©LGLeahy2014allrightsreservedCurrNeuropharmacol.Dec2010;8(4):335–358.


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“Toooftenonlythe20%abovethesurfaceis

diagnosed&treated;theother80%remainshidden.”

--WilliamShryer,LCSW

Major Symptom Clusters in Trauma

uIntrusionSymptomsuMemories/flashbacks/dreamsuPhysiologicalreactions

uAvoidanceSymptomsuIsolativebehaviors,napping


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uNegativeCognitions&MoodSymptomsuDissociativeamnesiauNegativebeliefsaboutoneself,others,world

uPersistentnegativeemotionalstate

uAlterationsinArousal&ReactivitySymptomsuIrritable/angrybehavior&outburstsuReckless/self-destructivebehavioruSleepdisturbance,hypervigilance,poorconcentration

LGLeahy © 2017

Trauma’sImpactontheSoul

SOUL


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©LGLeahy2014allrightsreserved

LongitudinalProgressionofPTSD:PointsforClinicalIntervention

Reed,Gore&Engel(2011).EpidemiologyinClinicalManualforManagementofPTSD.APPI.

Am J Psychiatry 2010;167:648-662.


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Developmentally Sensitive Criterion

uPTSD in Children 6 Years & YoungeruExperienced, witnessed, learneduIntrusive Memories

uRecurrent Distressing DreamsuDissociative Reactions/Flashbacks


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CurrNeuropharmacol.Dec2010;8(4):335–358.

Lanius,Vermetten,Loewenstein,etal(2010).EmotionModulationinPTSD.AmJPsychiatry(167):p640-647.


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CurrNeuropharmacol.Dec2010;8(4):335–358.


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.


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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


They promised that Dreams can come True.

But forgot to mention that Nightmares are Dreams too.

OSCAR WILDEIRISH WRITER (1854-1900)


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PTSD Mneumonic—DREAMS

u DisinterestinUsualActivitiesu Re-experienceu EventPrecedingSymptomsu Avoidance

u MonthorMoreofSymptomsu SympatheticArousalCaplan&Stern(2008).Mnemonicsinamnutshell.CurrentPsychiatry7(10):27-33


https://pixabay.com/en/military-soldiers-sleeping-rest-668988/


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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


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


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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


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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/


Older Medications for PTSD

Prazosin (Minipress)uReduces nightmares & improves sleepuBlocks noradrenergic stimulation of α-1 receptoruDecreases sensitivity to adrenaline


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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


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Lamotrigine(Lamictal)Mayreducearousal&reactivityRequiresSLOWtitration2° riskofSteven’sJohnsonSyndrome

Topiramate(Topamax)MayreducenightmaresinPTSDMonitorforglaucoma,sedation,cognitivedulling

Atypical Antipsychotics

uNOTrecommendedasMonotherapyuInhibitDopamine&BlockReuptakeofSerotonin

Risperidone(Risperdal)contraindicatedforuseasanadjunctiveagentduePotentialsideeffectsexceedbenefits

InsufficientevidencetorecommendanyasadjunctivetreatmentsMaybehelpfulwithco-morbidpsychosis


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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


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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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Psychopharmacologic Treatments for Traumatic Disorders · u CNS = Central Nervous System ... of the soul. ‘The Veteran’ (1885) PTSD Mnemonic—TRAUMA uTraumatic Event ... u REM