Cynthia M. Dorsey, Ph.D.

Director, Sleep Research ProgramMcLean Hospital, Belmont, MA

Assistant Professor of Psychology (Dept. of Psychiatry)Harvard Medical School, Boston, MA

Sleep Disturbances in Substance Abuse:

Assessment and Management

Humana LectureHumana Lecture

Sleep Disturbance in Those Who Abuse Drugs

Can Occur During:

• acute use

• chronic use

• withdrawal

Sleep Disturbance in Those Who Abuse Drugs

Can Involve:

• insomnia

• hypersomnia

• disruption of sleep-wake cycle

Differing profile for different drugs

Thompson et al., Biol Psychiatry 1995;38

Sleep Disturbance in Substance Abuse

• Opiates

• Stimulants

• Alcohol

• Hypnotics

Sleep Disturbance:Opiates

Acute/Chronic Use:

• Disrupted sleep: - frequency of awakenings- sleep time, “deep sleep”

• Sleep architecture abnormalities:- REM sleep (supression)

(latency prolonged/amount reduced) Kay et al., Br J Clin Pharmacol 1981;11 Davison et al., Pharmacology and Clinical Implications. 1973

Sleep Disturbance:Opiates

Withdrawal:

• Pronounced insomnia that often contributes to relapse

• Sleep architecture abnormalities- REM (“rebound”):

(latency is shortened/time increased)

Gillin et al. In:Principles and Practice of Sleep Medicine, 2000

Kay, Electroenceph Clin Neurophysiol. 1975.

Sleep Disturbance:Cocaine

Acute/Chronic Use: • Sleep continuity and architecture

abnormalities:- frequency of awakenings- REM sleep supression- disrupted sleep cycle

Sleep Disturbance:Cocaine

Withdrawal:

• hypersomnia

• • Sleep Architecture Abnormalities- REM “rebound”- SWS (deep sleep) is reduced(persists for 3 wks in chronic users)

Kowatch, J Addict Dis 1992

Sleep Disturbance:Alcohol

Acute Use by non-Alcholics:

• latency to sleep• disruption of sleep 2nd 1/2 of night• gastric irritation, headache• sympathetic arousal (tachycardia,

sweating, etc.)• additive effect with sleep deprivation

Lobo et al. 1997

Sleep Disturbance:Alcohol

Chronic Use by Alcoholics:

• insomnia: latency, awakenings• hypersomnia• sleep architecture abnormalities• sleep cycle disturbance• increased frequency/severity of other sleep disorders

Sleep Disturbance:Alcohol

Withdrawal:

• Insomnia latency to sleep, deep sleep

• Disrupted architecture (acute): REM sleep, REM latency

• Sleep disruption often persists and may predict relapse

Brower et al. 1998

Insomnia is a Risk FactorFor Developing Alcohol Abuse:

• Sleep disturbance due to worry higher risk of alcohol-related problems

• Risk highest for those with depression or anxiety

Crum et al, 2004

Insomnia is a Risk FactorFor Developing Alcohol Abuse:

• Insomniacs self-medicate with alcohol

• 10-15% persistent insomnia inthe general population

• 30% persistent insomniacs have used alcohol to help sleep

• 67% of those found it effective Roehrs et al., 2000; Ancoli Israel and Roth, 2000

Insomnia is a Risk Factor for Substance Abuse

0

2

4

6

8

10

12

14

16

18

Depression Anxiety Alcohol Drug

Insomnia n=240

No Insomnia n=739

Incidence (%) over 3.5 years

****

**

* 95% C.I. for Odds Ratio excludes 1.0

Adapted from Breslau N et al. Biol Psychiatry 1996;39.

Od

ds

Rat

io

Substance Abuse is a Risk Factor for Developing Insomnia

• Previous history of insomnia

• Increasing age

• Female gender

• Psychiatric symptoms and disorders

• Medical symptoms and disorders

• Substance abuse/dependence

Insomnia Substance Abuse

Reciprocal Relationship

Prevalence of Insomnia

• Insomnia is the most common sleep complaint in the industrialized world

• Complaints in 30% to 40%

• Complaint with distress or impairment: 8% to 19%

Sateia MJ et al. SLEEP 2000;23.

Prevalence of Insomniain Urban South America

Buenos Aires, Mexico City, Sao Paulo

• Complaints in 23%

• Complaints of moderate or severe insomnia: 6% (26% of sufferers)

• Sufferers who sought help from a physician: 31%

Blanco et al. BMC Fam Pract. 2003;4(1).

Insomniacs Under-Report Sleep Problems to Physicians

Percent of insomniacs who discussed any sleep problems with their physicians

Adapted from Ancoli-Israel S et al. SLEEP 1999;22.

Never discussed (69%)

Discussed sleep during visit for other purpose (26%)

Visited specifically to discuss sleep problem (5%)

What is Insomnia ?A complaint of:

• Difficulty falling asleep

• Difficulty staying asleep

• Poor quality sleep

Associated with:

• Distress

• Impaired function

Insomnia: Daytime Complaints• Fatigue, sluggishness

• Sleepiness

• Somatic complaints

• Worry about insomnia

• Mood disturbances

• Poor concentration

• Impaired performance

Insomnia: Consequences• Decreased quality of life• Increased healthcare costs• Increased absenteeism• Decreased productivity• Increased risk for psychiatric disorders

and substance abuse• Increased accident risk

Chesson A Jr. et al. SLEEP 2000;23.Sateia MJ et al. SLEEP 2000;23.

Assessment: Patient History

• History of sleep complaint

• Daytime symptoms

• Sleep habits (24-hour sleep / wake cycle)

• Risks / Precipitating Factors

• Medical/neurological/psychiatric history

• Medications

• Health habits

Assessment: Sleep/wake Diary

Assessment: Polysomnography• Indications

– Suspect other sleep disorder

– Poor treatment response

• Not routinely indicated for the evaluation of insomnia

Practice parameters for the evaluation of chronic insomnia. SLEEP 2000;23.

Obstructive Sleep ApneaRepetitive upper airway obstruction during sleep:

Symptoms: snoring, sleepiness, witnessed pauses in breathing, increased BMI/neck size

Results: oxygen desaturation,arousal from sleep, increased risk

for HTN, arrhythmia.

Obstructive Apnea on Polysomnogram

Treatment for Obstructive ApneaContinuous Positive Airway Pressure

Over 1 Million People Sleep at Night with CPAP in the U.S.

Flow Generator

Nasal Mask

Tubing

Headgear

Periodic limb movement disorder (PLMD)

•Repetitive stereotyped movements of foot/leg

•Usually only recognized by bedpartner, as “restlessness” or “kicking” during sleep

Pathophysiology of RLS/PLMD

Idiopathic

Familial (30-50%)

Iron Deficiency

Renal Failure

Peripheral Neuropathy

Antidepressants

Fibromyalgia

Rheumatoid Arthritis

Pregnancy

Caffeine

Treatment for RLS/PLMDDopaminergic agents:

Pramipexole .25 – 1.0 mg q8pm or

L-Dopa/Carbidopa 25/100-100/400 qhs

Persistent sleep disruption

Partial response

No response

Add sedative (e.g.,

Trazodone, benzo, gabapentin)

Add gabapentin or opiate

Reassess diagnosis

Clinical Presentation: Psychophysiologic Insomnia

Frustration, fear negative thinking

Intuitive efforts to self-treat:

bad sleep habits develop

Physiological activation

Difficulty sleeping

Evolution of Chronic Insomnia

poor sleep habits

negative cognitions and emotions

bedroom environment elicits wakefulness

• exacerbation of insomnia

growing sense of loss of control

•extreme frustration • trying too hard to sleep

Treatment of Insomnia

Why to do it with patients with substance abuse:

Cognitive-Behavior Therapy

• medication contraindications• pt. preference for a more “natural”

solution• patient sense of self-efficacy• it is effective

Behavioral Treatments

Strengthen bed & bedroom as sleep stimulus

Reset or reinforce biological rhythm Circadian rhythm entrainment

Reduce arousal & decrease anxietyRelaxation training

Address thoughts and beliefs that interfere with sleep.

Cognitive therapy

Restrict time in bed to improve sleep depth & consolidation

Sleep restriction

Stimulus control

Promote habits that help sleep; provide rationale for subsequent instructions.

Sleep hygiene

AimTechnique

Multi-modal CBT Approach

• Outcome Data

• Total WT 69 min. on average;45% improvement rate

• medication use by 59%;9/21 in DDI group became drug free

• treatment gains were maintained at 6 mo.

Key factors for Success :Empower the patient :

• explain rationale of all techniques

• make pt. an active participant

• encourage consistency and motivation

• reinforce therapeutic gains and patient sense of control

Pharmacotherapy

• Benzodiazepine receptor agonists

• Antidepressants

• Antihistamines

• Melatonin

• Others

Benzodiazepinesestazolam (Prosom)flurazepam (Dalmane)quazepam (Doral)temazepam (Restoril)triazolam (Halcion) clonazepam (Klonopin)lorazepam (Ativan)alprazolam (Xanax)diazepam (Valium)

Pharmacotherapy: Benzodiazepine Receptor Agonists

Nonbenzodiazepineszolpidem (Ambien)zaleplon (Sonata)

zopiclone (Imovane)eszopiclone (Lunesta)

Pharmacotherapy: Benzodiazepine Receptor Agonists

Actions

• Hypnotic

• Anxiolytic

• Myorelaxant

• Anticonvulsant

Side effects

• Sedation

• Anterograde amnesia

• Ataxia, falls

• Respiratory depression

• Tolerance, dependence, abuse

Antidepressants: Rationale

• No antidepressant is FDA-approved for treatment of insomnia

• However, some antidepressants have sedative, sleep-promoting effects

• Many insomnia patients have symptoms of depression or anxiety

• Low risk of abuse, but psychological dependence occurs

Pharmacotherapy: Antihistamines

• Mechanism of action– H1 receptor antagonism– Variable antagonism of cholinergic,

serotonergic, adrenergic receptors• Adverse effects

– Sedation, grogginess– Dry mouth– Psychomotor impairment– Delirium

Pharmacotherapy: Melatonin

• Naturally occurring hormone secreted during darkness at night

• Broad range of physiological effects• Inconclusive findings concerning sleep

promotion in insomnia• Not FDA approved or regulated• Potential vasoactive, CNS, and

reproductive side effects• May be useful in shifting circadian phase

Pharmacotherapy: Valerian

• Substance derived from Valeriana officinalis• Not FDA approved or regulated• Mild hypnotic effect (active component

unknown)• Some anxiolytic and muscle relaxant activity• Some studies show improved sleep latency and

quality of sleep, without change in sleep architecture

• No evidence of tolerance or abuse

Other Pharmacologic Agents

• Hormone replacement therapy

• Herbal therapies

• Over-the-counter agents

Pharmacologic Treatment: Specific Populations

• Sleep apnea: consider antidepressant rather than benzodiazepine receptor agonist

• Elderly: low-dose, short-acting benzodiazepine receptor agonist

• Substance abuse history: antidepressant preferred or non-pharmacologic techniques

• Co-morbid depression or anxiety disorder:– SSRI + benzodiazepine receptor agonist– SSRI + trazodone– Nefazodone, mirtazapine

Treatment and Management of Insomnia: A Suggested Approach

• Education and sleep hygiene • Nonpharmacologic approaches when

feasible• Pharmacologic approach:

• low-dose sedating antidepressant • Combination of nonpharmacologic and

pharmacologic methods• Referral to sleep specialist

Summary• Insomnia is prevalent and persistent in

abuse and withdrawal

• Substance abuse is a risk factor for insomnia and insomnia is a risk factor for developing substance abuse

• Efficacious treatment is available