PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017 Bruce Capehart, MD General Session PTSD Overview and Psychopharmacology Update September 16, 2017 Bruce Capehart, MD Medical Director, OEF/OIF Program VA Medical Center Durham, NC Disclosures 8 I am employed by the U.S. Department of Veterans Affairs 8 Except where clearly stated, this presentation reflects my opinions and not the VA 8 Off-label use of medication will be discussed 8 If we discuss TBI, I am listed as a co-inventor for a patent application disclosing a novel device for head acceleration and impact measurement, and co-founder and stockholder in a startup company to develop it PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017 Bruce Capehart, MD General Session Objectives 8 Review PTSD epidemiology 8 Distinguish between first line and second line medications in treating PTSD 8 Learn which medications do not have evidence to support use in PTSD PTSD: Changes from DSM-IV to DSM5 /3#,7-03/-2 7-03/- ,423&12 31&22/1 31&22/1 .3142*/. .3142*/. 5/*%#.$& 5/*%#.$& ,3&1&%/(.*3*/. //% 1/42#, 1/42#, &67-03/-2 &$+:21*#% &12*23&.3&(#3*5&-/3*/.2 &,'&2314$3*5&&)#5*/1 PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017 Bruce Capehart, MD General Session PTSD Epidemiology Epidemiology 8 US adult population lifetime prevalence: 6.4 – 6.8% 9 Stable over two studies 5 years apart 9 Point prevalence 4-5% 8 OEF/OIF Veterans lifetime prevalence: 7.3 – 8.6% 9 Expect higher figures with greater combat exposure 8 Military Veterans overall lifetime prevalence: 8% 8 Active-duty DoD prevalence: 2.2% in FY15 9 About one-half of the US population point prevalence 9 Almost certainly under-reported due to concerns about career, security clearance, or peer opinions PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017 Bruce Capehart, MD General Session Epidemiology by Veteran Service Era 8 Vietnam: 9-19% 8 1990-1991 Gulf War: 2-24% 8 OEF/OIF: 5-20% 8 Deployment to a combat zone creates a 1.5 – 3.5x greater risk for developing PTSD The woods are lovely, dark and deep. But I have promises to keep, and miles to go before I sleep. - Robert Frost An infantry soldier serves as a sentinel at The Tomb of the Unknown Soldier, Arlington National Cemetery. May 2014. PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017 Bruce Capehart, MD General Session 20% of US Military Within 5 Hours of Durham Epidemiology for Civilians 8 PTSD risk after… 9 Motor Vehicle Accident: meta-analysis reported point prevalence of 16.5% (8-30%) at 3 months, 14% (7-26%) at 12 months 9 Child admitted to ICU: review reported 10-21% of parents diagnosed with PTSD 9 Breast cancer: prospective study found point prevalence 6 months post-operatively of 11-16% depending upon rating scale 9 NYC residents after 9/11: 16% diagnosed with PTSD after 9 years PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017 Bruce Capehart, MD General Session NC-Specific Civilian Epidemiology 8 Disasters overall show PTSD prevalence around 11%, but mostly disasters linked with fires 8 Hurricanes: a multivariable model of Florida hurricane survivors showed 3.6% prevalence of PTSD with significant risk factors as: 9 Displaced from home >7 days 9 Low social support 9 Significant fear of injury or death 8 Floods: cross-sectional mail survey after floods in the UK showed 28% screening positive for PTSD (not necessarily having the full diagnosis) PTSD Treatment PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017 Bruce Capehart, MD General Session PTSD: Non-Emergent Initial Management 8 Offer trauma-focused psychotherapy 9 If not available or not accepted by the patient, then 8 Offer either medication or other psychotherapy 8 Treat comorbid conditions and problems !"" Pharmacotherapy vs. Psychotherapy 8 One excellent meta-analysis by Watts, et al, from the VA National Center for PTSD 8 Their analysis found large effect sizes (Hedges’ g) of psychotherapy (1.0 – 1.6) compared to more modest effect sizes for medications (0.4 – 0.7) 8 Recommended therapies and Hedges’ g: 9 CPT: 1.69 (1.27 – 2.11) 9 PE: 1.38 (0.9 – 1.86) PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017 Bruce Capehart, MD General Session Stepped care approach Switch SSRI Switch to IMI, Start SSRI or Start SNRI NFZ, or PHZ Start or Add Psychotherapy Anytime! Abbreviations: SSRI – serotonin-specific reuptake inhibitors (paroxetine, sertraline, fluoxetine) SNRI – serotonin-norepinephrine reuptake inhibitors (venlafaxine) IMI – imipramine NFZ – nefazodone PHZ – phenelzine (re-read the psychopharm book chapter first!) Pharmacotherapy for PTSD Sertraline Paroxetine PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017 Bruce Capehart, MD General Session PTSD and Medication: the 2017 Update /./3)&1#0703*/.2 5*%&.$&31&.(3) Sertraline or Paroxetine 31/.( 9 FDA indicated for PTSD; all others are off-label usage !&2 Venlafaxine or Fluoxetine Nefazodone, Phenelzine, Imipramine &#+!&2 Atypicals (except risperidone), Citalopram, &#+ Amitriptyline, Lamotrigine, Topiramate / Divalproex, Tiagabine, Guanfacine, Risperidone, 31/.( benzodiazepines, Ketamine, Hydrocortisone, D- / cycloserine, or cannabis First-Line Choices 31/.( 8 Sertraline, Paroxetine, Fluoxetine, Venlafaxine !&2 9 All are excellent options 9 Other SSRIs and Duloxetine are not first-line recommendations 8 Aim for higher rather than lower daily doses 9 Sertraline 150-200mg 9 Paroxetine 30-40mg 9 Fluoxetine 40-60mg 9 Venlafaxine 150-300mg PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017 Bruce Capehart, MD General Session Key points in using first line agents 8 These medications treat the core symptom clusters of PTSD and not just co-morbid conditions 8 Be sure to provide an adequate trial at an adequate dosage 9 Reduction of anger within two weeks is a positive prognostic sign of good response at 12 weeks 9 Anxiety disorders and PTSD may require up to 12 weeks and dosing closer to the maximum recommended dose for an adequate medication response Second Line Options: Serious Risks to Consider 8 Nefazodone &#+!&2 9 1/300,000 serious hepatotoxicity 9 No sexual side-effects 8 Imipramine &#+!&2 9 100mg per day x 30 days = 3 grams = LETHAL OD RISK! 9 Anticholinergic side effects worse with increasing doses 9 TCAs generally helpful for neuropathic pain 8 Phenelzine &#+!&2 9 If you need to ask, you should re-read the chapter. Orthostasis and drug-drug interactions can be problematic 9 Useful medication but no beer, pepperoni pizza, or OTC cold medications PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017 Bruce Capehart, MD General Session Try to Avoid 8 Unless no other options exist, avoid monotherapy with these medications 9 Some antidepressants (amitriptyline, citalopram) 9 Atypical antipsychotics (except risperidone) &#+ 9 Lamotrigine / 9 Topiramate What to Avoid for PTSD Monotherapy 8 Either lack of efficacy or problematic side-effects recommend against routine use of: 9 Divalproex 9 Tiagabine 9 Guanfacine 9 Risperidone 9 Benzodiazepines 31/.( / 9 Ketamine 9 Hydrocortisone 9 D-cycloserine 9 cannabis PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017 Bruce Capehart, MD General Session The Known Unknowns 8 There is insufficient evidence to recommend for or against monotherapy or augmentation therapy for the treatment of PTSD with: 9 Antidepressants: escitalopram, bupropion, ? desipramine, doxepin, duloxetine, desvenlafaxine, ? fluvoxamine, levomilnacipran, mirtazapine, nortriptyline, ? trazodone, vilazodone, and vortioxetine ? 9 Hypnotics: eszopiclone, zaleplon, and zolpidem 9 Others: buspirone, cyproheptadine, D-serine, and ? hydroxyzine ? PTSD and Medication: the 2017 Update 4(-&.3#3*/.03*/.2 5*%&.$&31&.(3) Topiramate, Baclofen, or Pregabalin &#+ D-cycloserine outside of research protocols / Atypical antipsychotics, benzodiazepines, and 31/.( divalproex / PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017 Bruce Capehart, MD General Session Benzodiazepines in PTSD Benzodiazepines are to be avoided in veterans with PTSD because these medications: 1. Do not treat the underlying PTSD 2. Are potentially habit-forming 3. Interfere with fear extinction, thus making Prolonged Exposure and EMDR sessions pointless 4. Increase the risk of household and motor vehicle accidents PTSD & Benzodiazepines in the VA *3)" *3)/43" #+*.(" Although the percentage (right-axis) of veterans taking benzodiazepines is declining, the absolute numbers continue to increase. Source: Lund et al, 2011. PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017 Bruce Capehart, MD General Session What about Prazosin? 8 For global symptoms of PTSD 9 not recommended 8 For nightmares 9 No recommendation for or against 8 Reason: in a high quality VA multi-site trial (N=304), prazosin failed to separate from placebo in the treatment of both global symptoms of PTSD and nightmares 9 Still unpublished three years after completion $# #% From My Experience 8 For PTSD with either Migraines or Neuropathic Pain, try Nortriptyline + Sertraline 9 Decrease sertraline dose 8 A complete lack of response to venlafaxine could be due to poor metabolism 9 Try desvenlafaxine in this instance 8 Anything for sleep should not be taken more than 5 times per week 9 Trazodone, hydroxyzine, z-drugs, diphenhydramine PTSD Overview and Psychopharmacology Update Saturday, September 16, 2017