October 24, 2014Thomas Demark, MD

Kansas City VA Medical CenterHonor Annex – PTSD Treatment Program

Combat Posttraumatic Stress Disorder (PTSD), Sleep, Prazosin

and Nightmares

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 month6. significant impairment in social or

occupational functioning (work, school, relationships, etc)

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)

MilitaryCombat: since the times of the Greeks and RomansNon-combatMilitary 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 sleepTrouble falling and staying asleepFrequent 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 - atypicalsAny 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 tolerabilityRecent 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 bed5.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 screen1. 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

DeanDSM 4 and 5New Yorker Magazine. Dream RestructuringOn Combat. Dave Grossman