War-Zone Related Sleep Disorders Treatment Strategies

War-Zone Related Sleep Disorders Treatment Strategies Barry Krakow, MD Sleep & Human Health Institute Maimonides Sleep Arts & Sciences, Ltd. March 23, 2011

Disclosures Sleep & Human Health Institute Non-profit 501(c)(3)research center Maimonides Sleep Arts & Sciences, Ltd. Private, community-based sleep medical center Websites: sleeptreatment.com sleepdynamictherapy.com nightmaretreatment.com ptsdsleepclinic.com nocturiacures.com soundsleepsoundmind.com sleepingresearch.org

Disclosures Books: Videos: Grants: Insomnia Cures Turning Nightmares Into Dreams Sound Sleep, Sound Mind IRT Training CBT for PAP-NAP Implementation Nasal Breathing & Hygiene Nocturia & SDB Sleep Obesity Series Respironics ( Complex Insomnia ) Consultations: GlaxoSmithKline

Media Perspectives By JAMES DAO, BENEDICT CAREY and DAN FROSCH Published: February 12, 2011 2nd Paragraph: He returned from his second deployment to Iraq complaining of back pain, insomnia, anxiety and nightmares. Doctors diagnosed posttraumatic stress disorder and prescribed powerful cocktails of psychiatric drugs and narcotics.

Media Perspectives 1st Paragraph:.returned from a nine-month tour beset with signs of post-traumatic stress disorder: insomnia, nightmares, constant restlessness. Doctors tried to ease his symptoms using three psychiatric drugs, including a potent anti-psychotic called

Media Perspectives 3 rd Paragraph: Their first line of defense was to prescribe 20 mg of Paxil, 4 mg of Klonopin and 50 mg of Seroquel. These medications helped at first, but later proved ineffective. The doctors responded by continually increasing his dosage until the Seroquel alone reached a whopping 1600 mg per day.

Common Denominators What we know: Most or all died in sleep Polypharmacy Suicides, unintended overdoses, or toxic effects What we do not know: Were they evaluated by a sleep medicine physician? Did they ever receive evidence-based sleep medicine therapies other than medications? Were suspicions ever raised for a physiological sleep disorder?

Recent Research The Journal of Nervous and Mental Disease Volume 198, Number 10, October 2010 Sample size of 137 adult chronic insomniacs 13 year average duration of insomnia 80% never offered another treatment option Average medication efficacy rated fair to poor Average length of drug usage = 3.87 years

History of Mental Disorders

Unexpected Breathing Problems Sleep-Disordered Breathing (SDB) AHI = Apnea Hypopnea Index Normal = < 5 events/hr RDI = Respiratory Disturbance Index Normal = <15 events/hr OSA = Obstructive Sleep Apnea Diagnosis = AHI > 5/hr UARS = Upper Airway Resistance Syndrome Diagnosis = RDI > 15/hr

Recent Research Prim Care Companion J Clin Psychiatry 2010;12(0) Sample 218 adult, chronic insomnia patients Nightly usage of prescription sedating medications Averaged 4.5 years of usage of prescription medication

Prevalence of Sedating Agents

Unexpected Breathing Problems Sleep-Disordered Breathing (SDB) AHI = Apnea Hypopnea Index Normal = < 5 events/hr RDI = Respiratory Disturbance Index Normal = <15 events/hr OSA = Obstructive Sleep Apnea Diagnosis = AHI > 5/hr UARS = Upper Airway Resistance Syndrome Diagnosis = RDI > 15/hr

Sleep Disordered Breathing (SDB) Multidimensional breathing dysrhythmia Apnea (100% reduction, i.e. cessation) Hypopnea (50% reduction) Upper airway resistance (25% reduction): flow limitation flattening of inspiratory or expiratory flow signal Almost invariably with arousal Fluctuating oxygenation w/ or w/o desaturation Chemoreceptor sensitivities response to CO2 fluctuations

SDB Revisited Newer perspective (global or multi-system disease): Central nervous system (depression, strokes, ADHD) Cardiovascular system (MI, arrhythmia, CHF) Endocrine system (diabetes, metabolic syndrome, obesity) Immune system (infections, allergies, sinus conditions) Genito-urinary system (nocturia, impotence, decreased libido) Pathways akin to atherosclerosis/smoking Oxidative stress Pro-inflammatory states Endothelial dysfunction

Normalized Breathing with PAP Therapy

Obstructive Apneas with Oxygen Desaturation

Hypopnea w/asda Arousal

Hypopnea ~50% Airflow Reduction

Flow Limitation with Arousal

Flow Limitation without Snoring

UARS Event w/arousal

Obstructive Apneas with Oxygen Desaturation

Effects of Polypharmacy Respiratory depression in sleep apnea Worsening of breathing event severity Longer oxygen desaturation Deeper oxygen desaturation (hypoxia) Larger buildup of carbon dioxide (respiratory acidosis) All of which leads to cardiac irritability

Cardiac Arrhythmias Effects of respiratory depression Drug poisoning effect on heart Sinus Bradycardia 3 rd degree heart block Ventricular tachycardia Ventricular fibrillation Asystole

Ventricular Tachycardia

Ventricular Fibrillation Marquette Electronics Copyright 1996

Gami, Howard, Olsen, Somers N Engl J Med 2005;352:1206-14.

Gami AS, Somers VK: Sleep disorders and cardiovascular disease. In: Libby P, Bonow RO, Mann DL, Zipes DP, eds. Braunwald s Heart Disease: A Textbook of Cardiovascular Medicine. 8th ed. Philadelphia: Saunders, 2007.

Active Duty Tricare Patients 267 adults seen at Maimonides Sleep Arts & Sciences since January 2008. Eighty-one patients using psychotropic medication: 26 (32%) prescription sedative only 28 (35%) psychotropic med only 27 (33%) prescription sedative & psychotropic med Subset of 13 patients also using opiods for pain

Types of Medications Benzodiazepines Non-Benzo Mood Stabilizers/Antidepressants Clonazepam Zolpidem Trazodone Alprazolam Eszopiclone Sertraline Zaleplon Buproprion Diazepam Fluoxetine Lorazepam Amitriptyline

Complex Patients (N= 81) Sociodemographics Age, mean(sd): 40.4 (9.1) years 20s: 13 (16%) 30s: 23 (28%) 40+: 45 (56%) BMI, mean(sd): 27.8 (5.0) kg/m 2 Gender: 73 (90%) male, 8 (10%)female Ethnicity: 47 (58%) Caucasian 18 (22%) Hispanic 16 (20%) Other

Psychiatric History Anxiety: 59 (73%) Depression: 22 (27%) PTSD: 14 (17%) Claustrophobia: 14 (17%) Panic Attacks: 10 (12%) Dissociative Disorder: 3 (4%) Manic Depression/Bipolar: 2 (3%) Obsessive Compulsive Disorder: 1 (1%)

Subjective Sleep Problems Sleep Complaint Subjective Report Chief Complaint Rank Poor Sleep Quality 75 (93%) 48 (59%) Sleep Breathing 47 (58%) 11 (14%) Insomnia 41 (51%) 15 (19%) Leg Jerks 26 (32%) 4 (5%) Nightmares 20 (25%) 2 (2%) *Pain 28 (35%) -------

Validated Questionnaire Data Insomnia Severity Index, total: 17.5 (4.2) < 15: 21 (26%) > 15: 60 (74%) (Equivalent to Insomnia Disorder) VAS Fatigue 0-6: 15 (19%) 7-10: 66 (81%) (Equivalent to Severe Non-situational Fatigue) VAS Sleepy 0-5: 17 (21%) 6-10: 64 (79%) (Equivalent to Severe Non-situational Sleepiness) Epworth Sleepiness Scale (Scale of Situational Sleepines) Mild: 48 (59%) Moderate: 23 (28%) Severe: 10 (12%)

Polysomnography Data Time in Bed, hrs: 7.0 (0.9) Sleep Onset Latency, min: 11.2 (12.1) Total Sleep Time, hrs: 5.9 (1.1) Sleep Efficiency, %: 84.5 (10.8) Total Awakenings: 27.5 (11.0) Wake After Sleep Onset, min: 49.9 (42.4)

B n B

Sleep Breathing Indices Apnea Hypopnea Index (AHI), events/hr: 19.9 (21.7) Respiratory Disturbance Index (RDI), events/hr: 49.5 (22.4) OSA Diagnosis: Yes 68 (84%) average AHI 25.2 (23.7) events/hr No 13 (16%) average AHI 2.8 (1.3) events/hr UARS Diagnosis: Yes 13 (100%) average RDI 39.0 (14.8) events/hr No 0 (0%)

Research Hypotheses Are soldiers who die in their sleep suffering from undiagnosed sleep apnea? Do medications prescribed for sleep disturbances worsen sleep apnea? Should all soldiers with sleep complaints, particularly poor sleep quality and insomnia, undergo a sleep study prior to the initiation of sedating medication?

Treating PTSD Sleep Disorders Three main treatment pathways used in the PTSD Sleep Clinic: Imagery Rehearsal Therapy (IRT) Cognitive-Behavioral Therapy (CBT) Positive Airway Pressure Therapy (PAP) No CPAP Advanced Devices: ABPAP & ASV Multiple titrations for PTSD patients with OSA/UARS

Nightmare Treatment Imagery Rehearsal Therapy (IRT) Pioneered the development of IRT since 1988 20+ years of research and clinical use Nightmare Treatment & PTSD Sleep Clinic Published peer-review articles: JAMA American Journal of Psychiatriy SLEEP Journal of Clinical Psychiatry Several VAMCs and some sleep centers with BSM programs now using IRT for nightmares

Nightmares: IRT Basics IRT Basis of the Technique Working with nightmare problem while awake Changing the content and images of the bad dreams turning them into new dreams. Using waking imagery to rehearse the new dreams. Results include Marked decrease in nightmares in 2 weeks to 2 months Improvement in insomnia and sleep quality problems PTSD improves as well Long-term followup shows nightmares do not return

Imagery Rehearsal Therapy Level A Nightmare Treatment. Imagery Rehearsal Therapy steps Select a nightmare Preferably not a replay-like dream of a trauma Change the nightmare any way you wish Preferably the patient designs the change Practice the new dream Preferably a few minutes per day

Complex Cognitive Restructuring - 1 Connecting nightmares and sleep Nightmare misery index Original benefits of nightmares What was the purpose the bad dreams? Trauma induced vs habit sustained Nightmares take on a life of their own

Complex Cognitive Restructuring - 2 Nightmares as independent sleep disorder Nightmares as the effect or the cause If independent, what does treatment do? Does anxiety improve, worsen, no change? If independent, what happens to PTSD? Improve, worsen, no change?

Complex Cognitive Restructuring - 3 Nightmare sufferer identity Is the patient attached to nightmares? Linking the imagery system to dreams Can waking imagery affecting dreams? Readiness and capacity to apply IRT Must each nightmare be treated?

Krakow et al 2001, JAMA

Insomnia Treatment Tools Standard Sleep hygiene practices Cognitive-behavioral therapy Sleep restriction Stimulus control Sleep diaries and actigraphy Cognitive restructuring

Insomnia Treatment Tools Advanced Erasing racing thoughts and ruminations Imagery techniques (mind s eye skills) Sleep-related emotional processing Targeting time monitoring behavior Learning to sleep drug-free Tapering off unnecessary or unwanted medications Accessing Treatment Books

Krakow et al 2001, Amer J Psych

Krakow et al 2001, Amer J Psychiatry

Sleep Dynamic Therapy for Cerro Grande Fire Evacuees With Posttraumatic Stress Symptoms: A Preliminary Report Barry J. Krakow, MD; Dominic C. Melendrez, BS, PSG-T; Lisa G. Johnston, MA, MPH; James O. Clark, BS; Erin M. Santana, BA; Teddy D. Warner, PhD; Michael A. Hollifield, MD; Ron Schrader, PhD; Brandy N. Sisley, BA; and Samuel A. Lee, BA. Journal of Clinical Psychiatry August 2002

Sleep Factors after Controlling for Depression Significant findings Duration of sleep complaints (p =.0001) Worse sleep quality (p <.05) Daytime fatigue (p =.02) Prolonged time in bed (p =.07) Lighter sleep (p =.07) Nightmares & disturbing dreams (p =.07)

Summary Bad sleep worsens mental and physical health Bad sleep is treatable Treatment is often non-pharmacological Evidence-based treatment of sleep disorders has clear potential to: Lower suicidal risk Alleviate depression Improve posttraumatic stress Enhance mood and feelings of well-being

Normal Sleep Healing: Piecing Together the Puzzle Normal Breathing Higher Quality Good Dreams Mental NREM Emotional REM

IRT & PTSD Sleep Clinic Training Resources Websites & Contact: (bkrakow@sleeptreatment.com) nightmaretreatment.com ptsdsleepclinic.com Books Krakow & Krakow (2002) Turning Nightmares into Dreams Burgess, Marks, & Gill (2001) Self-Help for Nightmares Davis (2009) Treating Post-Trauma Nightmares Video IRT Training for Sleep and Mental Health Professionals Workshops Albuquerque (April 26-27) or off-site locations IRT Training Introduction to the PTSD Sleep Clinic

Key Principles for Application Positive Airway Pressure Therapy (PAP-T) in PTSD Patients with Sleep Apnea 1. Anxiety patients often suffer expiratory pressure intolerance. 2. Therefore, CPAP therapy (most common PAP-T) typically yields sub-optimal response. 3. PTSD patients respond better to bilevel (BPAP), auto-bpap (ABPAP), or adaptive servoventilation (ASV). 4. Key titration objective: enhance REM sleep consolidation (mean duration of each REM episode)

Normal Hypnogram (One-Night) 5 normal REM periods Horizontal green bars = consolidated REM sleep. Overall average for each of the five REM period is 15 to 20 minutes. Targeted goal for PAP-T user is REM consolidation index of 15 minutes or above.

Pt. K.M. Diagnostic Dec 2007: 96 minutes of REM 22 REM periods = 4.37 REM Consolidation Index (REM-CI) Patient tests positive for a sleep breathing disorder with a high frequency of respiratory events. Note the fragmentation within each attempt at REM, resulting in multiple, short REM periods.

Pt. K.M. 1 st Titration (BPAP) Feb 2008: 80 minutes of REM 17 REM periods = 4.71 REM Consolidation Index (REM-CI) Patient tries BPAP therapy with only modest decrease in breathing events and the emergence of some central apneas (pink marks). Note the persistence of fragmented REM sleep.

Pt. K.M. 2nd Titration (BPAP) Apr 2008: 81 minutes of REM 12 REM periods = 6.75 REM Consolidation Index (REM-CI) BPAP tried again using lower pressures to decrease expiratory pressure intolerance, but same result: persisting breathing events and fragmented REM sleep.

Pt. K.M. 3 rd Titration (ABPAP) July 2008: 104 minutes of REM 11 REM periods = 9.45 REM Consolidation Index (REM-CI) First try at advanced device (ABPAP) shows marked decrease in breathing events and increase in REM sleep consolidation; but, mean REM periods are still shy of targeted goal of 15 mins.

Pt. K.M. 4 th Titration (Split BPAP/ASV) Sept 2009: BPAP 8 minutes of REM 1 REM periods = 8.00 REM Consolidation Index (REM-CI) ASV 61 minutes of REM 3 REM periods = 20.3 REM Consolidation Index (REM-CI) ASV Begins Here Most advanced device (ASV) used in the 2 nd half of night with dramatic improvement in REM sleep consolidation.

Pt. K.M. 5 th Titration (ASV) Feb 2010: 82 minutes of REM 5 REM periods = 16.4 REM Consolidation Index (REM-CI) All night ASV titration shows stabilization of REM sleep with mean consolidation > 15 minutes per REM period.

Summary Patient failed CPAP during desensitization on first titration night and used BPAP instead. Both BPAP and ABPAP led to modest symptom improvement in insomnia, sleepiness & fatigue. Only after patient was titrated with and then regularly used ASV therapy were improvements marked for insomnia, sleepiness & fatigue. Near optimal to optimal response achieved only with advanced technology (ASV), which correlated with enhanced REM sleep consolidation.

A Unique Perspective on PAP Therapy And I will put breath into you, and you shall live again. Ezekiel 37:14