Psychiatric Sequalae of Sleep Disorders

Mark Brown, M.D.Stanford Sleep Disorders

CenterA.W.A.K.E. Meeting

Presentation Overview Introduction Primary Sleep

Disorders Psychiatry

Summary

Introduction Epidemiology

Common Psychiatric Morbidity Sleep and Psychiatry

Comorbid Difficult to separate Etiology,

consequence, or both?

Primary Sleep Disorders Insufficient Sleep Sleep

Fragmenting Disorders SDB RLS/PLMD

Disorders of Hypersomnolence Narcolepsy

Insufficient Sleep Very common in

today’s society 20% of 1.1 million

Americans sleep less than 6.5 hrs/night

Basal Sleep Need Epi studies indicate

mean need of 8.16 hrs/night

Principles and Practice of Sleep Medicine, 4th Ed. 2005

Insufficient Sleep Neuropsychiatric

Effects Cognitive,

psychomotor, memory

Subjective vs. Objective

Balkin et al. Sleep Loss and Sleepiness. Chest. 134(3):653-660, 2008 Sep.

Insufficient Sleep Individual

differences Stable within

individuals Varies between

individuals Need vs.

Resilience?

Van Dongen et al. “The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation.” Sleep. 2003 Mar 15;26(2):117-26.

Sleep Disordered Breathing (SDB) Obstructive Sleep

Apnea/Hypopnea Syndrome (OSAHS)

Apnea/Hypopnea Index (AHI)

<5 normal 5-15 mild 15-30 moderate >30 severe

Common OSA: 4% of men and

2% of women

Screening Symptoms

Snoring Witnessed apneas Choking arousals Spouse report

Signs BMI Neck

Circumference HTN

SDB and Depression Multiple Studies

Guilleminault et al Reynolds et al Millmann et al Mosko, S et al Aikens et al

Schroder et al. Depression and Obstructive Sleep Apnea (OSA). Annals of General Psychiatry 2005, 4:13, 1-8.

SDB and Depression Review Harris et al

Large prevalence studies

Sleep-EVAL VA database Hordaland Health

Study Correlational

studies Cross-sectional

studies

Prospective longitudinal Studies

Peppard et al Treatment studies

Harris et al. Clinical Review: Obstructive sleep apnea and depression. Sleep Medicine Reviews 13 (2009) 437-444.

SDB and Depression Review

1995-2006 OSA and

Depression/Anxiety

203 total articles Rigorous exclusion

criteria Final total of 55

articles

Results Age 44-69 yrs Median N 54 Median male sex

83% Median AHI 48 Assessment of

Mood Beck, Zung, CES-D,

HADS, STAI, POMS, MMPI, SCL-90, SCID, interview, etc…

Saunamaki T, Jehkonen M. Depression and anxiety in obstructive sleep apnea syndrome: a review. Acta Neurol Scand 2007:116:277-288.

SDB and Depression (cont) Pretreatment

Prevalence Depression 7-63% Anxiety 11-70%

CPAP Treatment 7 rigorous studies

Depression decreased in 4/7 studies

Anxiety decreased in 2/4 studies

Saunamaki T, Jehkonen M. Depression and anxiety in obstructive sleep apnea syndrome: a review. Acta Neurol Scand 2007:116:277-288.

SDB and Depression Sleep Heart Health

Study (SHHS) 6,441 3,078

subjects 2 PSG’s, 5 yrs apart

Quality of Life Mental Component

Summary Scale (MCS) Sample

Age 62 55% female 75% Caucasian

Results Very small changes

over 5 years in RDI, BMI, ESS, PCS, and MCS.

Minimal change in PCS and no change in MCS

Significant association between subjective sleep quality and PCS/MCS.

Not clinically significant changes over 5 years

Silva et al, Sleep Disordered Breathing and Quality of Life. Sleep, 32(8), 1049-1057.

SDB and Cognitive Dysfunction Review Aloia et al

1985-2002 Initial 187 articles Final analysis 37

articles Limitations

Results Impairment >

60% Attention/Vigilance Exec Functioning Memory

Impairment >80% Construction Motor Functioning

Aloia et al. Neuropsychological sequelae of obstructive sleep apnea-hypopnea syndrome: A Critical Review. JINS, 2004, 10, 772-785.

SDB and Cognitive Dysfunction (cont) Treatment

Attention/vigilance (11/17)

Global functioning, executive functioning, and memory (6/10, 7/15, 8/15)

Psychomotor functioning failed to improve (0/6)

Aloia et al. Neuropsychological sequelae of obstructive sleep apnea-hypopnea syndrome: A Critical Review. JINS, 2004, 10, 772-785.

SDB in Children Introduction

ADHD comorbidity Prospective Study

Adenotonsillectomy (AT) cohort and surgical control

N=78, 5-12.9(8.4)yrs Mild-Moderate severity 57% male 95% f/u rate Measurements

Results AT group

Higher scores for hyperactivity, inattention, MSLT, and ADHD at baseline and improved to control rate 1 yr after surgery

However, only sleepiness correlated with PSG

Chervin et al. Sleep disordered breathing, behavior, and cognition in children before and after adenotonsillectomy. Pediatrics. 117(4) 2006 e769-e778.

SDB Summary Complex

relationship 20+ year history

of studies Comorbid Treatment

implications Lack of response ADHD overlap in

children

RLS/PLMD RLS

Definition/Criteria “Unpleasant” Limb

Sensations Motor

Restlessness Precipitated by

REST and Relieved by Activity

Worse in Evening/Night

PLMD Definition/Criteria Repetitive,

stereotypic dorsiflexions of the big toe with fanning of the small toes with flexion of the ankles, knees, & thighs

Recur in intervals

RLS/PLMD Primary RLS Secondary RLS

Iron Deficiency Renal Failure Pregnancy Medications

TCA, SSRI, Dopamine antagonists (compazine, metaclopramide)

Caffeine

PLMD Any cause of RLS Withdrawal of

anticonvulsants, barbiturates, hypnotics

Associated with SDB, CPAP titration, and Narcolepsy

RLS and QoL SHHS 2821 men and

women RLS dx by 8-item

questionnaire and correlated with PSG findings

Health Related Quality of Life SF-36

Decrements in ALL physical domains

Decrements in Psychiatric domains of ‘Mental Health’ and ‘Vitality’ Dose-response

relationship

Winkelman et al. Polysomnographic and Health-related Quality of Life Correlates of Restless Legs Syndrome in the Sleep Heart Health Study. SLEEP 32(6) 2009 772-778.

RLS and Psychiatric Disorders RLS in community

sample of Korean Adults

6,509 subjects Age 18-64 Face-to-face

interview, K-CIDI, CES-D-K and EQ-5D

Prevalence Women (1.3%) Men (0.6%) Increased with

age

Cho et al. Restless Legs Syndrome in a Community Sample of Korean Adults: Prevalence, Impact on Quality of Life, and Association with DSM-IV Psychiatric Disorders. SLEEP. 32(8) 2009 1069-1076.

Results Psychotropics

(12.5% vs. 3%) Anxiety or

depression (21.1% vs. 12.6%)

Mean CES-D score (10.8 vs. 6.4)

Lifetime Prevalence of DSM-IV Disorders

40.3% vs. 27.7% MDD most

common (15.3% vs. 8.3%)

Anxiety disorders increased as well (13.9% vs. 6.7%)

Cho et al. Restless Legs Syndrome in a Community Sample of Korean Adults: Prevalence, Impact on Quality of Life, and Association with DSM-IV Psychiatric Disorders. SLEEP. 32(8) 2009 1069-1076.

RLS and Psychiatric Disorders (cont)

RLS, PLMD and Depression Review Depression more

common in RLS RLS/PLMD

exacerbated in those on SSRI’s/SNRI’s

RLS/PLMD improved or similar to control for buproprion and trazodone

Picchietti and Winkelman. Restless Legs Syndrome, Periodic Limb Movements in Sleep, and Depression. SLEEP. 28(7) 2005 891-898.

Narcolepsy REM Disorder Onset late

childhood to 20’s Signs/Symptoms

EDS Sleep Attacks Cataplexy Hypnagogic

Hallucinations Sleep Paralysis

Secondary Causes Head trauma Stroke MS Brain Tumors NG Disorders CNS infections

Diagnosis PSG with MSLT HLA antigens CSF

Narcolepsy and Psychiatry Psychosocial

Morbidity Study Cross-sectional

questionnaire survey

Children aged 4-18 Narcolepsy,

Behavior, Mood, QoL. And Educational Assessments

Subjects 42 subjects with

Narcolepsy 18 with EDS

without cataplexy 23 control group No demographic

differences between groups

Stores et al. The Psychosocial Problems of Children with Narcolepsy and those with Excessive Daytime Sleepiness of Uncertain Origin. Pediatrics. 118(4) 2006 e1116-e1123.

Narcolepsy and Psychiatry (cont.) Results

Significant differences for peer problems, conduct, emotional symptoms and total problems

Prosocial and hyperactivity not different from controls

CDI increased in Narcolepsy and EDS group

Mental Health QoL affect but not physical or global

Greater educational difficulties

Increased psychosocial morbidity

Narcolepsy and Schizophrenia

Case Series (5) All female, mean

age 39+/-6.8 Tx refractory

schizophrenia and EDS

All selected had narcolepsy tetrad

SANS, SAPS, BPRS Patients 2-5 (not

avail for pt 1) had statistically and clinically significant improvement of SANS, SAPS, and BPRS on stimulants.

Douglas et al. Florid Refractory Schizophrenias that turn out to be Treatable Variants of HLA-Associated Narcolepsy. J Nerv Ment Dis. 179:012-017, 1991, 12-17.

Summary Sleep disorders

are common Sleep disorders

have associated morbidity/mortality

Sleep disorders are under-appreciated

The relationship between sleep disorders and psychiatric disorders appears bi-directional

Identification and treatment of Primary Sleep disorders may improve psychiatric comorbidity

Questions