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

2. 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

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

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

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

7. Complimentary Treatments Yoga/Meditation Acupuncture Mindfulness Training Relaxation Therapy

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

9. 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

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

11. 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

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

13. Anxiolytics Benzodiazepines Alpha adrenergic antagonists Buspirone Antihistamines

14. 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

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

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

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

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

19. 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)

20. Treating Sleep

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

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

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

24. Sleep Antihistamines Alpha antagonists Sedating antipsychotics –Seroquel, Zyprexa

25. Choosing a Medication? Safety Tolerability Efficacy Cost

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

27. Questions?