Prazosin for the Treatment of Combat Related Nightmares in Military Veterans with PTSD DISCLOSURES. Learning Objectives

Transcription

1 Prazosin for the Treatment of Combat Related Nightmares in Military Veterans with PTSD Jess Calohan, DNP, MN, PMHNP BC Lieutenant Colonel, United States Army Program Chair, Psychiatric Mental Health Nurse Practitioner Program Daniel K. Inouye Graduate School of Nursing Uniformed Services University of the Health Sciences DISCLOSURES The opinions or assertions contained herein are the solely the views of the author and are not to be construed as official or reflecting the views of the Department of the Army or the Department of Defense. Discussion of use of medications include non FDA or off label indications; prescribers are advised to use their own clinical judgment in assessing risks, benefits, adverse effects and treatment alternatives when using medications off label. The speaker has no conflicts of interest to disclose. Learning Objectives Examine the impact of sleep disturbance on level of functioning in military veterans with Post Traumatic Stress Disorder. Describe the standardized titration protocol for Prazosin in treating military veterans with combat related nightmares. Identify standardized tools to evaluate outcomes in military veterans with combat related nightmares receiving treatment with Prazosin. Calohan 1

2 Sleep that knits up the raveled sleeve of care, the death of each day's life, sore labor's bath, balm of hurt minds, great nature's second course, chief nourisher in life's feast. ~William Shakespeare, Macbeth A good laugh and a long sleep are the best cures in the doctor's book. ~Irish Proverb "Some people talk in their sleep. Lecturers talk while other people sleep. ~Albert Camus Combat Related Nightmares Sleep disturbance is a core symptom of PTSD A foundational component that significantly influences functional impairment Reported by 50 70% of Operation Iraqi Freedom and Operation Enduring Freedom (OIF/OEF) combat veterans with PTSD 1 PTSD Hypervigilance Mood Hyperarousal Re experiencing Avoidance Sleep disturbance 1 Lydiard, R. & Hamner, M. (2009). Calohan 2

3 Stress and HPA Axis Hippocampus, Amygdala & HPA axis involved in stress circuits Both may be sensitized in PTSD HPA axis normal response to stress: release of CRF ACTH glucocorticoids negative feedback on CRF stop stress response Resulting neurotransmitter cascade: release of glutamate and norepinephrine fight or flight response GABA attenuates Glutamate and Norepinephrine fight or flight stops Heim C. and Nemeroff, C. (2009). Neurobiological Underpinnings of PTSD Hypothalamic Pituitary Adrenal Axis Negative feedback loop is dysregulated Hypercortisolism (near term) then, Hypocortisolism (chronic) Cortico Releasing Factor over activity in the brain leading to release of norepinephrine from the locus coeruleus Anatomical changes in the brain region that inhibits the HPA axis Neurotransmitters alterations Serotonin Norepinephrine GABA Glutamate Heim C. and Nemeroff, C. (2009). Neurobiological Underpinnings of Combat Related Nightmares Amygdala Hippocampus The locus coeruleus shuts down during normal REM sleep no norepinephrine release. In PTSD, locus coeruleus remains active norepinephrine is released during REM sleep, disrupting REM Calohan 3

4 Prazosin Background One of the few lipid soluble alpha 1 antagonist A non sedating generic that has been used for decades to treat hypertension and BPH Decreases/eliminates the effect of norepinephrine during REM sleep Initially found effective for trauma nightmares in Vietnam veterans 1 reports of improved sleep quality and duration marked decrease in frequency intensity of nightmares well tolerated, improvement is dose related discontinuing medications after improvement associated with return of nightmares potential to reduce co morbid alcohol abuse 1 Raskind M. et al., (2003). Evidence of Prazosin Efficacy for Trauma Nightmares and Global Function In Vietnam veterans, a crossover placebo controlled study (n = 10) 1 and a parallel group placebo controlled study (n = 34) 2 positive improvement in sleep duration and quality, reduction in nightmares In civilians, a crossover study (n = 13) positive and sleep duration 90 minutes longer than with placebo 3 1 Raskind M., et al., (2003). 2 Raskind M., et al., (2007). 3 Taylor F. et al., (2008). Evidence of Prazosin Efficacy for Trauma Nightmares and Global Function In OIF deployed in a combat zone, a prospective study (n = 13) positive improvement in sleep duration and quality, reduction in nightmares and improved overall level of functioning 1 In OIF/OEF combat veterans, a double blind placebo RCT (n = 56, 29 placebo and 27 prazosin) positive improvement in sleep duration and quality, reduction in nightmares and improved overall level of functioning 2 1 Calohan, J. et al., (2010). 2 Raskind. M et al., (2013). Calohan 4

5 Nightmare Reduction Initiative Stigma of seeking help for PTSD 1 Focus on sleep disturbance rather than PTSD Recruit for study participation Engage and coordinate care for Service Members 1 Kim, C. et al., (2009) Prescribing Prazosin Prazosin (Minipress) 1mg 20mg Dose initially at 1mg for two nights to assess for first dose effect. Has been associated with orthostatic hypotension with first dose. Also possibility of reflex tachycardia in the AM upon exertion If pt is tolerates medication and no improvement in nightmares, then increase dose to 2mg HS for four nights. Continue titrating dose upwards by 2mg q 4 days to effect Monitoring: initial orthostatic and ongoing BP monitoring Also can consider low dose during the day (mid AM) 2 6mg to address residual hyperarousal symptoms Outcome Evaluation Tools Clinician Administered Post Traumatic Stress Scale Clinical Global Impression of Change CAPS Sleep Items (B2) Frequency Have you had any problems falling or staying asleep? How often in the past week? When did you first start having problems sleeping? (After the [EVENT]?) 0 Never 1 One a week 2 Two a week 3 Several times a week (3 or 4) 4 Daily or almost every day (5 to 7) Sleep onset problems? N Mid sleep awakening? N Early a.m. awakening? N Total # hrs sleep/night Y Y Y Intensity How much of a problem did you have with your sleep? (How long did it take you to fall asleep? How often did you wake up in the night? Did you often wake up earlier than you wanted to? How many total hours did you sleep each night?) 0 No sleep problems 1 Mild, slightly longer latency, or minimal difficulty staying asleep (up to 30 minutes loss of sleep) 2 Moderate, definite sleep disturbance, clearly longer latency, or clear difficulty staying asleep (30 90 minutes loss of sleep) 3 Severe, much longer latency, or marked difficulty staying asleep (90 min to 3 hrs loss of sleep) 4 Extreme, very long latency, or profound difficulty staying asleep (> 3 hrs loss of sleep) Desired # hrs sleep/night Calohan 5

6 CAPS Nightmare Items (D2) Frequency Have you ever had unpleasant dreams about (EVENT)? Describe a typical dream. (What happens in them?) How often have you had these dreams in the past month? 0 Never 1 One a week 2 Two a week 3 Several times a week (3 or 4) 4 Daily or almost every day (5 to 7) Description/Examples Intensity How much distress or discomfort did these dreams cause you? Did they ever wake you up? [IF YES:] (What happened when you woke up? How long did it take you to get back to sleep?) [LISTEN FOR REPORT OF ANXIOUS AROUSAL, YELLING, ACTING OUT THE NIGHTMARE] (Did your dreams ever affect anyone else? How so?) 0 None 1 Mild, minimal distress, may not have awoken 2 Moderate, awoke in distress but readily returned to sleep (< 30 minutes) 3 Severe, considerable distress, difficulty returning to sleep (> 30 minutes or got up) 4 Extreme, incapacitating distress, did not return to sleep Clinical Global Impression of Change Summary Prazosin is effective for treating combat related nightmares, improving not only sleep, but overall quality of life and functioning Can also be used during the day for residual hypervigilance symptoms Potential secondary effects of reducing ETOH cravings and drinking days in patients with PTSD Easy to use clinician rated assessment and outcome tools CAPS Sleep and Nightmare Items Clinical Global Impression of Change Calohan 6

7 Questions? Jess Calohan, DNP, MN, PMHNP BC Lieutenant Colonel, United States Army Program Chair, Psychiatric Mental Health Nurse Practitioner Program Daniel K. Inouye Graduate School of Nursing Uniformed Services University of the Health Sciences References Calohan, J., Raskind, M., Peskind, E. & Peterson, K., (2010). Prazosin Treatment of Trauma Nightmares Soldiers Deployed in Iraq. Journal of traumatic stress, 23(5), Kim, P., Thomas, J., Wilk, J., Castro, C., & Hoge, C. (2010). Stigma, barriers to care, and use of mental health services among active duty and National Guard soldiers after combat. Psychiatric Services, 61(6), Heim, C. & Nemeroff, C. Neurobiology of posttraumatic stress disorder. CNS Spectrum Jan;14(1 Suppl 1): Levin, R., & Nielsen, T. (2007). Disturbed dreaming, posttraumatic stress disorder, and affect distress: a review and neurocognitive model. Psychological bulletin, 133(3), 482. Lydiard, R. & Hamner, M. (2009). Clinical importance of sleep disturbance as a treatment target in PTSD. FOCUS: The Journal of Lifelong Learning in Psychiatry, 7(2), References (Cont.) Raskind, M., Peterson, K., Williams, T., Hoff, D., Hart, K., Holmes, H., Homas, D., Hill, J., Daniels, C., Calohan, J., & Peskind, E. (2013). A Trial of Prazosin for Combat Trauma PTSD With Nightmares in Active Duty Soldiers Returned From Iraq and Afghanistan. American Journal of Psychiatry, 170(9), Raskind, M., Peskind, E., Kanter, E., Petrie, E., Radant, A., Thompson, C.,... & McFall, M. (2003). Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo controlled study. American Journal of Psychiatry, 160(2), Taylor, F., Martin, P., Thompson, C., Williams, J., Mellman, T., Gross, C.,... & Raskind, M. (2008). Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo controlled study. Biological psychiatry, 63(6), Writer, B., Meyer, E., & Schillerstrom, J. (2014). Prazosin for Military Combat Related PTSD Nightmares: A Critical. Neurosciences, 26, Calohan 7