Update on Pharmacotherapies for PTSD Michelle Pent, MD, MPH April 29, 2011

Presentation 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 Symptoms Intrusive ruminations Nightmares Flashbacks Hyperarousal Hypervigilance Associated irritability, anger, poor focus and concentration, and physiologic distress

Neurochemistry Amygdala Central Nervous System –Norepinephrine, Serotonin, Dopamine, GABA Peripheral Nervous System –Sympathetic Nervous System –“Fight or flight”

Treatment Psychotherapy Pharmacotherapy Most evidence suggests psychotherapy is most effective –CBT –EMDR –DBT where indicated

Complimentary Treatments Yoga/Meditation Acupuncture Mindfulness Training Relaxation Therapy

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

Selective Serotonin Reuptake 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

SSRIs Fluoxetine (Prozac) Sertraline (Zoloft) Fluvoxamine (Luvox) Paroxetine (Paxil) Citalopram (Celexa) Escitalopram (Lexapro)

SSRIs 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 Antidepressants Selective Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) –Venlafaxine (Effexor) –Duloxetine (Cymbalta) –Desvenlafaxine (Pristiq) Tricyclic Antidepressants –Amitryptyline (Elavil) –Doxepin (Sinequan)

Anxiolytics Benzodiazepines Alpha adrenergic antagonists Buspirone Antihistamines

Benzodiazepines 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

Benzodiazepines Diazepam (Valium) Lorazepam (Ativan) Alprazolam (Xanax) Clonazepam (Klonopin) Oxazepam (Serax) Chlordiazepoxide (Librium) Temazepam (Restoril)

Other Anxiolytics Buspirone (Buspar) –Serotonin agent –May cause headache, nausea Antihistamines –Diphenhydramine (Benadryl) –Hydroxyzine (Vistaril) –Side effects include sedation, confusion at high doses

Other Anxiolytics Alpha adrenergic antagonists –Blood pressure medications –Prazosin (Minipress) –Clonidine (Catapres) –Side effects include dizziness and other complications of low blood pressure

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

Use 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 Sleep

Sleep Review of sleep hygiene is critical Complimentary treatments can also be effective

Sleep Benzodiazepine analogues –Eszopiclone (Lunesta) –Zolpidem (Ambien) –Addictive potential Benzodiazepines –Short term use

Sleep Trazodone (Desyrel) –Often exacerbates nightmares Mirtazapine (Remeron) –Associated with weight gain Melatonin –Ramelteon (Rozerem)

Sleep Antihistamines Alpha antagonists Sedating antipsychotics –Seroquel, Zyprexa

Choosing a Medication? Safety Tolerability Efficacy Cost

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

Questions?