Update on Update on Pharmacotherapies for PTSDPharmacotherapies for PTSD

Michelle Pent, MD, MPHMichelle Pent, MD, MPH

April 29, 2011April 29, 2011

PresentationPresentation

• Anxiety-spectrum disorder

• DSM-IV criteria– A: Exposure to traumatic event with perceive

threat to life or physical integrity and response of intense fear

– B: Re-experience of the traumatic event– C: Avoidance of stimuli associated with the

trauma– D: Hyperarousal

Target SymptomsTarget Symptoms

• Intrusive ruminations

• Nightmares

• Flashbacks

• Hyperarousal

• Hypervigilance

• Associated irritability, anger, poor focus and concentration, and physiologic distress

NeurochemistryNeurochemistry

• Amygdala

• Central Nervous System– Norepinephrine, Serotonin, Dopamine, GABA

• Peripheral Nervous System– Sympathetic Nervous System– “Fight or flight”

TreatmentTreatment

• Psychotherapy

• Pharmacotherapy

• Most evidence suggests psychotherapy is most effective– CBT– EMDR– DBT where indicated

Complimentary TreatmentsComplimentary Treatments

• Yoga/Meditation

• Acupuncture

• Mindfulness Training

• Relaxation Therapy

PharmacotherapyPharmacotherapy

• Objective is to improve symptoms by minimizing anxiety– Selective Serotonin Reuptake Inhibitors– Other antidepressants– Anxiolytics– Other

Selective Serotonin Reuptake Selective Serotonin Reuptake Inhibitors (SSRIs)Inhibitors (SSRIs)

• Raise serotonin levels in the brain

• Remain standard of care for anxiety disorders

• Linked with– Improvement in baseline level of anxiety– Diminished intrusive ruminations

SSRIsSSRIs

• Fluoxetine (Prozac)

• Sertraline (Zoloft)

• Fluvoxamine (Luvox)

• Paroxetine (Paxil)

• Citalopram (Celexa)

• Escitalopram (Lexapro)

SSRIsSSRIs

• Lag time before efficacy– Usually 4-6 weeks– Adequate trial a minimum of 8 weeks

• Side effects– Nausea, diarrhea– Weight gain– Agitation– Sexual dysfunction

Other AntidepressantsOther Antidepressants

• Selective Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)– Venlafaxine (Effexor)– Duloxetine (Cymbalta)– Desvenlafaxine (Pristiq)

• Tricyclic Antidepressants– Amitryptyline (Elavil)– Doxepin (Sinequan)

AnxiolyticsAnxiolytics

• Benzodiazepines

• Alpha adrenergic antagonists

• Buspirone

• Antihistamines

BenzodiazepinesBenzodiazepines

• Diminish anxiety by enhancing GABA in the central nervous system

• No longitudinal effect on anxiety• Significant tolerance and dependence

– Essentially contraindicated in patients with history of substance abuse

• Intended for short term use• Increasingly considered inappropriate for

long term treatment of anxiety disorders

BenzodiazepinesBenzodiazepines

• Diazepam (Valium)

• Lorazepam (Ativan)

• Alprazolam (Xanax)

• Clonazepam (Klonopin)

• Oxazepam (Serax)

• Chlordiazepoxide (Librium)

• Temazepam (Restoril)

Other AnxiolyticsOther Anxiolytics

• Buspirone (Buspar)– Serotonin agent– May cause headache, nausea

• Antihistamines– Diphenhydramine (Benadryl)– Hydroxyzine (Vistaril)– Side effects include sedation, confusion at

high doses

Other AnxiolyticsOther Anxiolytics

• Alpha adrenergic antagonists– Blood pressure medications– Prazosin (Minipress)– Clonidine (Catapres)– Side effects include dizziness and other

complications of low blood pressure

Other AnxiolyticsOther Anxiolytics

• Gabapentin– Anticonvulsant/Mood Stabilizer– Enhances GABA in central nervous system– Some usefulness for anxiety– Limited addictive potential

Use of AntipsychoticsUse of Antipsychotics

• May be useful as anxiolytics

• Use does not necessarily imply psychosis

• Significant sedation, weight gain, metabolic disturbance

• Most commonly used– Quetiapine (Seroquel)– Olanzapine (Zyprexa)– Ziprasidone (Geodon)

Treating SleepTreating Sleep

SleepSleep

• Review of sleep hygiene is critical

• Complimentary treatments can also be effective

SleepSleep

• Benzodiazepine analogues– Eszopiclone (Lunesta)– Zolpidem (Ambien)– Addictive potential

• Benzodiazepines– Short term use

SleepSleep

• Trazodone (Desyrel)– Often exacerbates nightmares

• Mirtazapine (Remeron)– Associated with weight gain

• Melatonin– Ramelteon (Rozerem)

SleepSleep

• Antihistamines

• Alpha antagonists

• Sedating antipsychotics– Seroquel, Zyprexa

Choosing a Medication?Choosing a Medication?

• Safety

• Tolerability

• Efficacy

• Cost

• Educate patient that symptoms unlikely to improve with medication in the absence of psychotherapy

Questions?Questions?