1. Benefits of treating impaired sleep in OIF/OEF Veterans with TBI and PTSD Robert L. Ruff, MD, PhD Suzanne S. Ruff, PhD Cleveland Dept of Veterans Affairs Medical Center Cleveland OH 44106

2. To consider how treatment can be adapted to the needs of the OIF/OEF veterans To consider how treatment can be adapted to the needs of the OIF/OEF veterans To consider treating sleep along with PTSD as initial step for veterans with mild TBI associated with exposure to explosions To consider treating sleep along with PTSD as initial step for veterans with mild TBI associated with exposure to explosions ObjectivesObjectives

3. How do you deal with the complex of mTBI, PTSD and impaired sleep? Have to develop a Rx strategy that vets will accept, that may improve their likelihood of responding to other Rx and that enables them to function in society. Have to develop a Rx strategy that vets will accept, that may improve their likelihood of responding to other Rx and that enables them to function in society. We addressed impaired sleep first We addressed impaired sleep first Dr. Murray Raskind found Prazosin to be very effective in improving sleep of veterans with PTSD. Blocks nightmares without disrupting REM or the transition of REM to stage 3 Dr. Murray Raskind found Prazosin to be very effective in improving sleep of veterans with PTSD. Blocks nightmares without disrupting REM or the transition of REM to stage 3

4. Prazosin/Sleep Hygiene Study Study group – 74 OIF/OEF veterans who had neurocognitive deficits and headaches Study group – 74 OIF/OEF veterans who had neurocognitive deficits and headaches All had baseline MOCA and Epworth Sleepiness Scale scores and headache intensity and frequency. All had baseline MOCA and Epworth Sleepiness Scale scores and headache intensity and frequency. All were given sleep hygiene counseling and started on an upward taper of prazosin from 1mg qHS to 7 mg qHS All were given sleep hygiene counseling and started on an upward taper of prazosin from 1mg qHS to 7 mg qHS Assessments – baseline, 9 weeks later, 9 weeks + 6 months later Assessments – baseline, 9 weeks later, 9 weeks + 6 months later

5. Hypotheses 1) OIF/OEF veterans would tolerate prazosin with a low incidence of side effects 2) prazosin combined with sleep hygiene counseling would improve sleep among OIF/OEF veterans with mTBI 3) veterans who took prazosin and received sleep hygiene counseling would have less severe headache pain and fewer headaches.

6. Performance of veterans at baseline and after intervention ESS Scores (0-24) MOCA Score (0-30) Headache Pain Intensity (0-10) Headache Frequency (#/month) Completed Prazosin Baseline (N = 62) After intervention 16.1+ 0.33 6.37+ 0.26 p<0.001 24.1 + 0.26 28.9 + 0.15 p<0.001 7.18 + 0.18 3.58 + 0.13 p<0.001 13.4 + 1.07 4.26 + 0.35 p<0.001 Did not complete Baseline (N=12) After intervention 15.9 + 0.42 12.0 + 0.55 p<0.001 24.7 + 0.53 24.2 + 0.53 p-NS 6.50 + 0.45 6.67 + 0.48 p-NS 7.17 + 0.66 7.42 + 0.72 p-NS Prazosin/Sleep Hygiene Improved Performance

7. Prazosin Compliance – 6 months 64/74 (86%) taking prazosin 64/74 (86%) taking prazosin 26 of the veterans received additional medication for their headaches 26 of the veterans received additional medication for their headaches 22 veterans - changes in the PTSD medication (dosing or drug) 22 veterans - changes in the PTSD medication (dosing or drug)

8. Performance of veterans ESS Scores (0-24) MOCA Score (0-30) Headache Pain Intensity (0-10) Headache Frequency (#/month) Took Prazosin (60) Baseline Baseline End of 9 week End of 9 week End of 6 month End of 6 month 16.2 + 0.20 6.56 + 0.22 4.00 + 0.19 A, B, C 24.0 + 0.24 28.6 + 0.19 28.9 + 0.26 A, B 7.21 + 0.20 3.73 + 0.22 2.48 + 0.21 A, B, C 13.6 + 1.10 4.60 + 0.29 2.26 + 0.29 A, B, C No Prazosin (8) Baseline Baseline End of 9 week End of 9 week End of 6 month End of 6 month 16.0 + 0.44 12.5 + 0.59 10.9 + 0.72 A, B 24.6 + 0.55 24.1 + 0.55 24.1 + 0.55 24.6 + 0.62 6.55 + 0.51 6.75 + 0.50 5.65 + 0.51 7.19 + 0.72 8.19 + 0.79 8.19 + 0.79 6.89 + 0.71 A baseline vs. 9 week - significant at the 0.05 level B baseline vs. 6 months - 0.05 level C 9 week vs. 6 months - 0.05 level

9. Conclusions: Prazosin/Sleep Hygiene Well tolerated Well tolerated Reduced headache frequency and pain intensity and was associated with improved cognitive performance Reduced headache frequency and pain intensity and was associated with improved cognitive performance Improving sleep may be able to break the triad of mTBI-PTSD-Pain (Kerns-P3) Improving sleep may be able to break the triad of mTBI-PTSD-Pain (Kerns-P3) Rod Vanderploeg – impaired sleep may be critical in prolonged post-mTBI symptoms Rod Vanderploeg – impaired sleep may be critical in prolonged post-mTBI symptoms

10. Thank You Robert L. Ruff, MD, PhD Suzanne S. Ruff, PhD Cleveland Dept of Veterans Affairs Medical Center Cleveland OH 44106 robert.ruff1@va.gov suzanne.ruff2@va.gov 216-791-3800 ext 5230 (Robert) 4486 (Suzanne)