Combat Posttraumatic Stress Disorder (PTSD), Sleep, Prazosin and Nightmares October 24, 2014 Thomas Demark, MD Kansas City VA Medical Center Honor Annex – PTSD Treatment Program

Objectives To have a better understanding of military/combat related PTSD. Improved ability when treating a patient who has PTSD, Nightmares and Insomnia. Summarizing CSP #563: “Prazosin and Combat Trauma PTSD”

DSM 5 definition of PTSD 1. exposure to traumatic event (combat) 2. persistent re-experiencing (intrusive thoughts/images, nightmares, flashbacks) 3. persistent avoidance (avoidance of triggers, social isolation) 4. persistent hyper-arousal (anxiety, panic attacks, irritability, anger, hypervigalence, paranoia) 5. symptoms > 1 month 6. significant impairment in social or occupational functioning (work, school, relationships, etc)

Civilian: abuse, rape, MVA, injury, divorce, etc (anything traumatic) Combat related PTSD – Post Traumatic Stress Disorder (shell shock, battle fatigue, psychoneurosis, traumatic war neurosis) Severe Anxiety Disorder: hyperarousal of amygdala and (emotional memories and fear), hippocampus and prefrontal region Civilian: abuse, rape, MVA, injury, divorce, etc (anything traumatic) Military Combat: since the times of the Greeks and Romans Non-combat Military Sexual Trauma (MST)

Combat-related PTSD Physical injury and disfigurement (loss of limb/s, loss of eye/s, burns to body/face, loss of genitals) Surrounded by death, watching friends die traumatic deaths: Sole survivor or few survivors after a battle. Observing or participating in atrocities of war Rape, torture, mutilation of bodies, harming of civilians, women, children and/or elderly Taking of life, many lives – killing (“On Killing” D. Grossman)

Treatment for combat PTSD Medication Individual Talk Therapy Group Therapy Couple/ Marital / Family Therapy

PTSD and Insomnia Pts with combat PTSD most often meet criteria for insomnia. Pts generally sleep for 2-4 hours of broken sleep Trouble falling and staying asleep Frequent nightmares and night sweats, 5 or more times per week. Occasional transition from a nightmare into a flashback. Hypervigilence with each waking, will get weapon, check all doors and locks, will secure perimeter. May or may not patrol outside of the home. Many veterans do not get peace of mind until sunrise, thinking I have survived one more night and daytime is safe time. Frequent night missions, this is a time for danger/hyperarousal.

Evaluation of Insomnia 2/2 PTSD Trouble with sleep initiation (falling asleep) Trouble with sleep maintenance (staying asleep) Trouble with both (falling and staying asleep) Presence of nightmares and / or night sweats Any acting out / violence when sleeping Any reports of snoring or stopping of breathing Nightmares are reported by 52% of combat veterans with PTSD diagnosis.

Treatment of Insomnia 2/2 PTSD Trouble with sleep initiation (falling asleep) - zolpidem Trouble with sleep maintenance (staying asleep) - temazepam Trouble with both (falling and staying asleep) – combination therapy Presence of nightmares and / or night sweats – alpha or beta blocker Any acting out / violence when sleeping - atypicals Any reports of snoring or stopping of breathing – sleep study consult

Treatment of Insomnia 2/2 PTSD Good sleep hygeine (get a nightlight for bedroon, do not watch the news, history or military channel before bedtime) MEDICATIONS: Sleep: Diphenhydramine / Benedryl 25-50mg. Hydroxyzine / Vistaril 10-100mg. Trazodone / Deseryl 25-200mg. Zolpidem / Ambien 2.5-10mg at bedtime, up to 20mg Benzodiazepines (alprazolam 0.25-2mg, lorazepam 0.5 to 2mg, diazepam 5- 20mg, temazepam 7.5-30mg, clonazepam 0.5-2mg) SSRI (mirtazipine / remeron 7.5-15mg) Atypicals (seroquel 50-300mg, risperdone 0.25-4mg) Haldol / haloperidol 1-10mg.

Combination Treatment/Polypharmacy Often times combinations of sleep medications, whether used label or off label, in combination with alpha or beta blocker, plus an atypical is what is needed for the patient to get more than 5 hours of sleep. Fluctuations of dosing may be necessary as the condition and insomnia waxes and wanes over time. Vacilating in nature. Increase in severity of insomnia near military holidays: Veterans Day, Labor Day and especially Independence Day (4th of July) – symptoms are triggered by fireworks. Noise made by fireworks resemble small arms fire, rockets, grenades, RPGs, mortars, and IEDs.

Nightmare and Night Sweat suppression Alpha blockers (prazosin) Doses from 1-15mg at bedtime, start with 2-5mg, then titrate upward based on response and tolerability Recent research with prazosin doses up to 20mg total (15mg at bedtime and 5mg in morning) Beta blockers (metoprolol, labetalol, etc) PM dose, titrate up based on tolerability and response Atypicals (quetiapine/seroquel, risperidone, zyprexa) Used for sedation and nightmare suppression, do not help suppress nightsweats.

VA Research Historical Accomplishments 1925 - conducted the first hospital-based medical studies to be formally considered part of VA’s newly established research program. 1928 - Completed studies regarding the mortality of veterans with mental illness. 1941 - Established a research lab at the Northport (NY) VA medical center to conduct clinical and biomedical research in neuropsychiatric disorders. 1958 - Invented the implantable cardiac pacemaker. 1960 - Pioneered the concepts that led to the development of computerized axial tomography (CAT) scans. 1984 - Developed the nicotine patch. 1997 - Identified a gene associated with a major risk for schizophrenia 2003 – Launched the largest-ever clinical trial of psychotherapy to treat posttraumatic stress disorder (PTSD) 2007 – Found that prazosin, an inexpensive generic drug already used by millions of Americans for high blood pressure and prostate problems (BPH), could help improve sleep and lessen trauma nightmares in Veterans with PTSD.

CSP #563: “Prazosin and Combat Trauma PTDS” CSP#563 (PACT) What is CSP? Cooperative Site Program = multi-centered clinical trial. 15 VA sites: Albuquerque, Atlanta, Columbia, Durham, Kansas City, Loma Linda, Long Beach, Madison, Miami, New York Harbor, Palo Alto, Providence, Salisbury, Salt Lake City, Seattle.

Prazosin Prazosin, trade names Minipress, Vasoflex, Pressin and Hypovase, is a sympatholytic drug used to treat high blood pressure, anxiety, PTSD and panic disorder. It is an alpha- adrenergic blocker that is specific for the alpha-1-receptors. These receptors are found on the vascular smooth muscle, where they are responsible for the vasoconstrictive action of noerepinephrine. They are also found throughout the central nervous system. As of 2013, prazosin is off-patent in the USA, and the FDA has approved at least one generic manufacturer.

CSP # 563 (PACT) The dosing strategies of the study were determined by the Chairs during years of research and clinical experience using prazosin to treat nightmares and PTSD. There had appeared to be a considerable range in the optimally effective dose of prazosin: Some patients had marked improvement in nightmares after the first week (low dose of 2mg of prazosin per night), and others required several weeks of titration to a higher dose (15mg at bedtime and 5mg in the morning) to achieve the same effect. The doses were well within the dose ranges of prazosin prescribed for other clinical conditions such as hypertension.

It was a multicentered double blinded placebo controlled study. Patients were combat veterans with combat PTSD ranging from Vietnam, Iraq and Afganistan. This was to determine the efficacy of prazosin vs. placebo in combat Veterans with PTSD. The CAPS (Clinician Administered PTSD scale) was used to rate the severity of nightmares.

Dosing was started at 1mg at bedtime and titrated over a period of 7 to 35 days based on level of nightmares & nightsweats and tolerability. Doses were titrated up to 15mg at bedtime. Doses were titrated up to 5mg in the morning, if nightmare symptoms were still present once a maximum dose of 15mg was reached at bedtime.

Once a patient had achieved his/her optimal dose of medication, he/she will continue on this dose for a total of 26 weeks of treatment. After the week 10 visit (effectiveness phase) safety visits occurred monthly. After the week 10 visit, the study drug could not be further increased, only decreased if there was the development of unacceptable side effects. What was determined from this study?

Results Prazosin was effective for trauma nightmares, sleep quality, global function, CAPS score, and the CAPS hyperarousal symptom cluster. Prazosin was well tolerated, and blood presure changes did not differ between the groups.

Conslusion Prazosin is effective for combat-related PTSD with trauma nightmares and the benefits are clinically meaningful and significant. Substantial residual symptoms suggest that studies combining prazosin with effective pharmacotherapy and effective psychotherapy might demonstrate further benefit.

What if the patient has a re-occurring nightmare that is not responding to medication or if medication for nightmares is contraindicated? Technique called “Dream Restructuring” for a re-occuring nightmare. 1.Write out the nightmare on a single piece of paper, a general description of the nightmare, leave out details 2. Rewrite the nightmare and turn it into a pleasant dream, change the setting and outcome of the nightmare, use vivid details 3. Symbolically and literally destroy the nightmare (burn it, tear it up, bury it, throw darts at it, flush it down the toilet, etc.) 4. Read pleasant dream every night just before bed 5.Over time, the nightmare will change into the rewritten pleasant dream (2 weeks to 2 months, may take longer) Technique may be used with or without medication.

Approach Are you a veteran or in the military? are you a combat veteran? PTSD screen 1. mood disturbance? 2. sleep disturbance? 3. bad dreams or nightmares? 4. problems with anger? * Encourage further evaluation and/or treatment at a local VA Medical Center.

Prevention of combat PTSD, Insomnia and Combat Trauma Nightmares

References Clinicians Manual on PTSD. Yahuda and Davidson CSP# 563: “Prazosin Combat Trauma PTSD” Down Range, to Iraq and Back. Cantrell and Dean DSM 4 and 5 New Yorker Magazine. Dream Restructuring On Combat. Dave Grossman