Sleep and Chemical Dependency The Problem and the Solution Mark W. Mahowald, MD The Retreat Wayzata, MN 7/11/2013

Sleep and Chemical Dependency

The Problem and the Solution

Mark W. Mahowald, MDThe Retreat

Wayzata, MN7/11/2013

Disclosure of Potential Conflicts of Interest:

None

OverviewOverview of normal sleep

Function of sleepCircadian rhythms

Definition

Magnitude of the problem

Perspectives Why take the complaint seriously?Why the complaint is ignored

Etiology

Diagnosis and Treatment

Insomnia and Chemical Dependency

Management

Other Sleep DisordersRestless Legs SyndromeDelayed Sleep Phase Syndrome

Somnomythology

©MRSDC4

Somnomythology

Everybody needs 8 hours of sleep every night.

The best sleep occurs before midnight.

I know I'll be a wreck the next day if I don't get enough sleep.

Sleep is negotiable.

Exercise improves sleep.

REM sleep deprivation results in psychological or psychiatric problems.

©MRSDC5

Somnomythology - Dreams

Most dreams are in black and white.

Eating unusual foods results in more dreaming or nightmares.

Dreams occur in a flash.

External stimuli cause dreams.

The eye movements of REM sleep are following dream images.

Blind people don't dream.

Normal Sleep

Sleep requirement

Circadian factors

State dissociation

Function of sleep

Synaptic plasticity

Memory consolidation

Consequences of sleep deprivation

Determinants of Sleep

Homeostatic

Circadian

Total Sleep Requirement

©MRSDC9

Circadian Rhythms

©MRSDC10

Light Entrains the Human Biologic Clock

©MRSDC11

Opponent Process Model

©MRSDCSleep Latency vs. Time of Day

“Forbidden” Zone

State Dissociation

Sleep is not a whole brain, global, phenomenon.

Parts of the brain can be awake while simultaneously, other parts can be asleep.

©MRSDC 13

Function of Sleep

©MRSDC15Almeida Junior: Descanco, (Circa-1882)

What Body Parts Benefit From Sleep ?

©MRSDC16

Function(s) of Sleep

Cognitive

Learning

Memory

Synaptic plasticity

Frank, Rev. Neurosci. 2006

©MRSDC17

Function of Sleep

Sleep is the price we pay for plasticity, and its goal is the homeostatic regulation of the total synaptic weight impinging on neurons.

A full day of wakefulness is associated with a 20% global increase in cerebral blood flow.

And there is a net increase of synaptic strength (requiring increased energy and volume) during wakefulness.

Tononi, Sleep Med. Reviews, 2006

©MRSDC18

Function of Sleep

These changes presumably would not be sustainable indefinitely.

Sleep renormalizes total synaptic weight to an appropriate baseline level – enforcing synaptic homeostasis.

This results in energy and space saving effects.

Tononi, Sleep Med. Reviews, 2006

©MRSDC19

Sleep Deprivation

Impaired sustained attention

Impaired mood

Insomnia

Insomnia - DefinitionRepeated difficulty with:

Sleep initiation

Sleep consolidation or maintenance

Sleep duration

Sleep quality (non-restorative or poor quality)

Occurs despite adequate time and opportunity for sleep

Results in some form of daytime impairment

Magnitude of the Problem

Insomnia affects up to 30% of all Americans.

Insomnia is much more prevalent in the setting of chemical dependency and withdrawal.

Why so Little Information??

1. Assumption that co-morbid sleep problems will remit with treatment of the primary addiction

2. De-emphasized as less important in early treatment

3. Reluctance to address due to concerns about sleep medication addiction

4. Limited awareness of other treatment options

Arnedt,J of Addict Dis, 2007

Behavioral Consequences of Insomnia

Impairment of:

Working memory

Episodic memory

Executive functioning (verbal fluency, cognitive flexibility)

Fortier-Brochu, Sleep Med Rev, 2012

Insomnia in Alcoholics

Insomnia in previous 6 months

General population: 10%

Alcoholics: 18%

Insomnia in residential treatment centers: 36% - 72%.

Insomnia in Alcoholics

It has been estimated that 10% of alcohol-related expenses can be attributed to insomnia.

Insomnia is a “subacute” withdrawal symptom lasting about 5 weeks.

Sleep abnormalities (by formal sleep studies) may persist for 1-3 years after cessation of drinking.

Insomnia and Alcohol: Bidirectional

Alcohol is used by more than 1 in 10 individuals as a hypnotic agent to self-medicate sleep problems.

Insomnia is a risk factor for the development of alcohol problems.

Subjective and objective sleep continuity variables (insomnia) are robust predictors of relapse during recovery from alcohol dependence.

Arnedt,J of Addict Dis, 2007

Insomnia - Consequences

Medical treatment, drugs Reduced productivity Absenteeism Accidents Hospitalization Depression Increased alcohol consumption

©MRSDC 30

Absenteeism

©MRSDC 31

Insomnia and Car Crashes

©MRSDC 32

Insomnia and Primary Care Visits per Year

©MRSDC 33

Insomnia and Risk of Nursing Home Placement

©MRSDC 34

Insomnia and Risk of Alcohol Abuse

Insomnia and Depression

Insomnia and Depression

Non-depressed people with insomnia have a 2-fold risk to develop depression compared to people with no sleep difficulties.

Baglioni, J of Affective Dis, 2011

Association With Depression

In one study, the relative risk of suicide was 3.6 times greater for those with frequent insomnia compared to those without insomnia.

Paffenbarger et al (1994):

Suicide

Chemical dependency and insomnia are both risk factors for suicide.

Insomnia - Causes

Medical

Psychiatric

Psychological

*Other Sleep Disorders

Insomnia

Contrary to popular opinion, insomnia is often not due to psychiatric or psychological problems.

Insomnia likely results from neurophysiologic vulnerabilities

©MRSDC 41

Insomnia – Somnotypes

The basic level of sleepiness / alertness is genetically influenced and is stable over time.

Two "somnotypes" - "sleepy" and "alert"

The "alert" types may be prone to insomnia.

Some people are inherently more "brittle" sleepers than others.

Insomnia - Physiologic Profiles

Insomniacs are in a state of physiologic hyperarousal.

They are often less sleepy during the day than normals.

Insomnia - Hyperarousal

Activation of sympathetic nervous system and HPA axis.

Increased metabolic ratesElevated levels of circulating catecholaminesIncreased body temperatureAltered heart rate variabilityAltered pupillometry patternsIncreased fast activity on EEG

Seminars in Neurol. 2005

Models of Insomnia

Diathesis-stress model (predisposing, precipitating, and perpetuating factors)

Stimulus control model (classical conditioning)

Cognitive models (thoughts, feelings, and beliefs that may interfere with sleep)

Buysse, Drug Disc Today, 2011

Models of Insomnia

Psychobiological inhibition model (selective attention in the development and maintenance of insomnia)

Neurocognitive model (integrates diathesis stress with neurobiological and neurophysiological observations (increased EEG frequency during sleep) Buysse, Drug Disc Today, 2011

Neurobiological Model of Insomnia

Insomnia is one form of state dissociation – with simultaneous occurrence of activity in sleeping and waking neural activity


Proposed Neurobiological Model

Insomnia is a disorder of sleep-wake regulation characterized by persistent wake-like activity in neural structures during NREM sleep…

resulting in simultaneous and regionally specific waking and sleeping neuronal activity patterns.


Proposed Neurobiological Model

Common pharmacologic and behavioral interventions may reverse some of the regionally specific abnormalities in individuals with untreated insomnia.


Insomnia - Diagnosis

History and physicalSleep diaries

Actigraphy

Psychological tests

Formal sleep studies are usually not indicated

Sleep Diary

Actigraphy

The Utility of Actigraphy

Without actigraphy, it is virtually impossible to evaluate complaints of severe insomnia or circadian rhythm disorders.

Severe insomnia – case 1

32 y/o man with complaint of severe insomnia due to pain following spinal surgery.

Current medications: morphine (600 mg / day), fentanyl patch, benzodiazepines.

Case 1

Case 1

©MRSDC 56

Severe insomnia – case 2

40 y/o businessman who reported sleeping only 2 hours per night, despite treatment with myriad sedative hypnotics.

Case 2

©MRSDC 58

Case 2

Sleep State Misperception (Paradoxical) Insomnia

Conditioned Insomnia

©MRSDC 62

Conditioned insomnia - before

©MRSDC 63

Conditioned insomnia - after

Insomnia - Treatment

Pharmacologic

Behavioral

(Often used in combination)

Pharmacologic Treatment

“Natural” remedies

Over-the-counter preparations

Prescription sedative - hypnotics

“Natural” Remedies

Marijuana, cannabis extracts

There are no scientifically valid objective studies to support the often-stated idea that these agents improve sleep.

“Natural” Remedies

Valerian root

Kava

L-tryptophan (5-HT)

Chamomile tea

Passion flower

Coenzyme Q10

Hops

Lemon balm

Lavender

Skull cap

Acupuncture

There is no evidence that acupuncture is an effective treatment for insomnia (or any other medical condition for that matter).

©MRSDC 68

“Acupuncture is Theatrical Placebo”, Colquhoun, Anestheisia-Analgesia, June 2013

OTC Medications

More used than prescription sleep aids

Diphenhydramine (Benadryl, Nytol, Tylenol PM, Advil PM, etc)

Doxylamine (Unisom)

No documented efficacy

Rapid development of tolerance

Next-day sedation – particularly in the elderly

Non-FDA Approved Drugs

Antidepressants

Atypical antipsychotics

Gabapentin (Neurontin)

Carbamazepine (Tegretol)


Antidepressant Medications

Trazodone (Desyrel)

Mirtazepine (Remeron)

Amitriptyline (Elavil)

There is no good evidence that any antidepressant medication is effective in the treatment of insomnia in the absence of co-existing depression.

Wiegand, Curr Opinion, 2008


Atypical Antipsychotic AgentsQuetiapine (Seroquel)

Ziprasidone (Geodon)

Olanzaprine (Zyprexa)

Side effects: weight gain, metabolic syndrome, extrapyramidal symptoms, tardive dyskinesia.

There is no indication for the use of these drugs for insomnia in the absence of severe psychiatric disease.

Wilson,J Psychopharm, 2010

©MRSDC 73

Antipsychotic Agents for Sleep

“Among medications used for sleep, those with the greatest recent growth in use and risk of adverse effects are second-generation antipsychotic agents.” (particularly quetiapine [Seroquel])

Side effects include: weight gain, disturbances in glucose metabolism, hyperlipidemia

Very costly – up to $10 a day

©MRSDC 74

Hermes, Sleep, 2013

FDA Approved Hypnotics

Benzodiazepines

Triazolam (Halcion)

Temazepam (Restoril)

Oxazepam (Serax)

Quazepam (Doral)

“Non”- benzodiazepines

Zolpidem (Ambien)

Zaleplon (Sonata)

Eszopiclone (Lunesta)

Melatonin agonists

Ramelteon (Rozerem)

Doxepin (Sinequan, Silenor)

FDA Approved Sedatives

Doxepin (Sinequan, Silenor) is an old tricyclic antidepressant which in very low doses (3mg, 6mg) has recently been shown to be a very effective treatment for insomnia.

Virtually no side effects.

Absolutely no abuse/dependency potential.

Really cheap - $0.21/10 mg capsule

FDA Approved Sedatives

Melatonin (Ramelteon, Rozerem)

Of questionable value as a sedative

Used primarily in individuals with a delay in biologic clock

On the Horizon

Hypocretin antagonists

Serotonin antagonists and inverse agonists

Sodium oxybate (GHB)

Histaminergic antagonists

Hypocretin/Orexin System

Important role in both sleep and addiction.

Orexin is a hypothalamic neuropeptide that promotes wakefulness (it is absent in patient with narcolepsy)

Orexin receptor antagonists are effective sleep-inducing agents

©MRSDC 79

©MRSDC 80

Hcrt fibers at level of tuberal region of hypothalamus – Peyron, J Neurosci 1998

©MRSDC 81Hypocretin Cells Sutcliffe, Nature Reviews Neurosci. 2002

Hypocretin/Orexin Antagonists

Suvorexant

Effective sedative-hypnotic

No abuse potential

Well tolerated

©MRSDC 82

Hypocretin/Orexin System

Also play an important role in drug addiction and reward-related behaviors

Orexin plays a role in potentiating reward circuits and is necessary for the seeking of various classes of addictive drugs

©MRSDC 83

Mahler, Progr in Brain Res, 2012

©MRSDC 84

Hypocretin ProjectionsMol Neurobiol 2012

Hypocretin/Orexin Antagonists

Hypocretin/Orexin signaling likely plays a critical role in addiction.

It participates in the primary reinforcing and motivational properties of drugs of abuse

Also, involved in the processes that drive relapse to drug seeking

©MRSDC 85

Plaza-Zabala,Mol Neurobiol, 2012

Insomnia – Behavioral Treatments

Major Contributions:

Hyperarousal

Circadian dysregulation and sleep homeostatic abnormalities

Maladaptive behaviors

Dysfunctional thoughts and beliefs about sleep

Pigeon, J Clin Psychology, 2010

Behavioral Treatments

Sleep Hygiene & Education

Stimulus Control Therapy

Sleep Restriction Therapy

Relaxation Training

Cognitive Behavioral Therapy (CBT)

Sleep Hygiene

1. Regular schedule

2. Relaxing pre-sleep rituals

3. Comfortable environment

4. Bedroom for sleep and sex only

5. Avoid napping (if napping interferes with

sleep the next night)

6. Avoid caffeine within 6 hours of going to

bedPigeon, J Clin Psychology, 2010

Stimulus ControlLimits amount of time spent awake in bed and

develops a more consistent sleep schedule

1.Use alarm set for same time every morning

2.No napping

3.Bedroom only for sleep and sex

4.Go to bed only when sleepy

5.No more than 15 minutes in bed awake

6.Return to bed only when sleepy


Sleep Restriction

Limits amount of time in bed that matches the ability to fill this with mostly sleep

1.Determine average total sleep time from sleep diaries or actigraphic study

2.Establish fixed wake-up time

3.Set “sleep window” to total sleep time plus 30 minutes

4.Adjust time in bed based upon sleep diaries


Relaxation Training

Relaxation exercises, such as progressive muscle relaxation, may help you if you lie in bed with your mind racing. Examples include:

Breathing exercises

Guided imagery

Meditation

Progressive muscle relaxation

Cognitive Behavioral Therapy

Positive thinking, or healthy thinking, is a way to help you stay well or cope with a health problem by changing how you think.

Cognitive-behavioral therapy is a type of counseling that can help you understand why you have sleep problems and can show you how to deal with them.

CBT-I: Individual Components

Psycho-education

Behavioral strategies

Cognitive therapy

Relaxation training


CBT-I

Standard delivery: weekly sessions over 6-8 weeks

Individual or group formats

Begins with sleep education and treatment rationale

Then stimulus control

Then sleep restriction

Then sleep hygiene, cognitive therapy, and relaxation training


Cognitive Therapy

Focus on negative thoughts and maladaptive beliefs about sleep, insomnia, and its consequences

Challenge veracity and usefulness of those unhelpful thoughts and beliefs and then to change or modify them

CBT-I

Benefits 70-80% of non-alcoholic insomnia patients

More sustained benefit than medications

CBT-I Study in Adolescents

6-session group treatment:

Stimulus control

Bright light

Sleep hygiene

Cognitive therapy

Mindfulness-based stress reduction

Improved sleep and emotional distress and reduced substance use

Britton, Substance Abuse, 2010

Future CBT-I Directions

Brief behavioral treatments for insomnia (BBTI) appear to be effective (2 sessions followed by 2 phone calls)

Online CBT-I treatment programs for insomnia are being developed.

Integration of mindfulness meditation

Buysse, Arch Int Med, 2011

Vincent, Sleep, 2009

Ong, J Clin Psychology, 2010

CBTI

There are preliminary data supporting the efficacy of telephone-delivered CBTI in the treatment of chronic insomnia.

©MRSDC 99

Arnedt, Sleep, 2013


Transient / short term(< 30 days)

The effective treatment of acute/short-term insomnia may prevent the development of persistent conditioned

insomnia.


Chronic (> 30 days)

Psychological Behavioral Treatments

Pharmaceutical Intervention

Insomnia - Causes

Other Sleep Disorders

Restless Limb Syndrome

Conflict with Circadian Rhythms-i.e. Delayed Sleep Phase Syndrome

Insomnia - Neurologic

Restless Legs Syndrome (RLS)

Unpleasant, subjective sensation in the legs, appearing only at rest - producing an "irresistible need to keep the legs in motion"

RLS - Etiology

RLS is a neurologic movement disorder

Primary abnormality of iron metabolism in CNS

RLS - Treatment

Dopaminergic Agents

Pramipexole (Mirapex)

Ropinirole (Requip)

Opiates

(Benzodiazepines)

(Gabapentin)

Disorders of the

Wake/Sleep Cycle

CategoriesJet lag

Shiftwork

Delayed, advanced sleep phase

syndrome

Irregular or non-24 hour pattern

Delayed Sleep Phase Syndrome

Inability to fall asleep before 2-4am

Would prefer to sleep until 10am or noon

Presents as insomnia

©MRSDC 110

Delayed Sleep Phase Syndrome

Circadian Factors

Melatonin secretion is disrupted during alcohol withdrawal.

Schmitz, Prog Neuro-Psychophar & Biol Psych, 1996

Circadian Factors

In animal studies, alcohol, opiates, and psychostimulants result in a change in circadian rhythm activity

Bergheim, Brain Res, 2012

Circadian Factors

The circadian clock not only regulates the wake/sleep cycle, but is also implicated in other behavioral and physiological processes relevant to substance abuse – such as mood and cognition.

Hasler, Sleep Med Rev, 2012

Delayed Sleep Phase - Rx

Melatonin 3 mg 5 hours before desired sleep onset.

Bright light exposure in the morning.

Other Interesting Sleep-Addiction Relationships

Drugs and Synaptic Plasticity

Addictive drugs cause changes in synaptic function within the striatal complex which can either mimic or interfere with the induction of synaptic plasticity.

These changes may help explain the long-lasting effect of addictive drugs.

Within the striatum, drugs of abuse modify dendritic morphology, glutamate receptors, and synaptic plasticity.

Grueter, Curr Opin in Neurobiol 2011

Neuroplasticity

Addiction may be a pathology of staged neuroplasticity.

Sleep may affect neuroplasticity.

©MRSDC 118

Kalivas, Neuropsychopharmacology, 2008

Learning and Memory

Memories of learned associations between rewarding properties of drugs of abuse and environmental cues contribute to craving and relapse in humans.

Disruption of reconsolidation dampens or even erases previous memories.

©MRSDC 119

Yan, Neuroscience, 2013

Learning and Memory

Addictive drugs may hijack the learning-and-memory machinery to produce persistent behavioral changes.

If so, this may lead to treatment opportunities.

©MRSDC 120

Robinson, Curr Opin in Neurobiol, 2013

Memory

The persistence of maladaptive drug-associated memories may obstruct the attainment of abstinence.

Addiction can be conceptualized as a disorder of aberrant learning.

Sleep may have an effect on memory.

©MRSDC 121

Milton, Neurosci and Biobehav Rev, 2012

Memory

Persistent, unwanted memories may contribute to drug addiction and chronic relapse.

Disruption of these memories by interfering with reconsolidation through amnestic agents during memory retrieval may be possible.

©MRSDC 122

Sorg, Neurosci and Biobehav. Rev, 2012Milton, Curr. Opin. In Neurobiol. 2012

Memory

Persistent maladaptive memories that maintain drug seeking and are resistant to extinction are a hallmark of addiction.

Therefore, disruption of memory consolidation after retrieval has received attention for its therapeutic potential.

If memories can be disrupted after retieval, then this may have potential for treatment of persistent or exaggerated memory in disorders such as PTSD and addiction.

©MRSDC 123

Tronson, Curr Opin in Neurol, 2012

Memory Consolidation

Persistent, unwanted memories may contribute to addiction and relapse.

One proposed function of sleep is memory consolidation.

Possible therapeutic implication:

Disruption of sleep-related memory reconsolidation through delivery of certain amnestic agents during memory retrieval.

Sorg, Neurosci Biobehav Rev, 2012

©MRSDC 125

Reward Activation

Model (RAM)Perogamvros, L and Schwartz, S. Neurosci Biobehav Rev 36: 1934-1951;2012

Mesolimbic Dopaminergic System (ML-DA)

Implicated in reward and emotional functions

Perturbed in schizophrenia, addiction, and depression

Is active during both wakefulness and sleep

Activation of the “Reward Activation Model” (RAM) for sleep and dreaming has implications for addiction

Sleep problems like insomnia may developmentally precede and predict early onset of alcohol, cigarette, and marijuana use in adolescents and young adults

©MRSDC 126

Perogamvros, Neurosci and Biobehav Rev, 2012

©MRSDC 127Neurosci Biobehav Rev 2012

Main ascending ML and NS dopaminergic pathways

Take-Home Message

Insomnia is very common in the setting of substance abuse and abstinence

Insomnia is a risk factor for relapse

Behavioral techniques are very effective in treating insomnia

Some medications with no abuse potential may be very effective in treating insomnia in this population

Other treatable sleep disorders may be masquerading as insomnia (restless legs syndrome, delayed sleep phase syndrome)

Sleep may be playing a role in maladaptive memory consolidation which may predispose to relapse

©MRSDC129

Somnomythology

©MRSDC130

SomnomythologyEverybody needs 8 hours of sleep every night.

The best sleep occurs before midnight.

I know I'll be a wreck the next day if I don't get enough sleep.

Sleep is negotiable.

Exercise improves sleep.

REM sleep deprivation results in psychological or psychiatric problems.

©MRSDC131

Somnomythology - Dreams

Most dreams are in black and white.

Eating unusual foods results in more dreaming or nightmares.

Dreams occur in a flash.

External stimuli cause dreams.

The eye movements of REM sleep are following dream images.


©MRSDC132

Somnomythology

Depression, laziness, boredom, slothfulness, or other defects of character cause sleepiness.

These conditions DO NOT cause physiologic sleepiness.

©MRSDC133

Somnomythology

"Incorporation"

Waking experiences and external stimulation determines dream content.

©MRSDC134

©MRSDC135

Dreaming - Incorporation

There is a relatively small overall

proportion of stimulus incorporation

(24%) and experimental modification

(12%) of dream content.

Therefore, ongoing sleep mentation is

relatively impervious to intrusions from

concomitant external sources.

©MRSDC136


Cognitive responses of some form may occur in both REM and NREM sleep as a result of external stimulation.

Pre-sleep films, both neutral and violent, resulted in incorporation in 8% - with no difference between the incorporation rate of neutral vs. violent.

©MRSDC137


Biological drive frustration (thirst, hunger, social isolation) is incorporated into dreams, but is certainly not universal.

There is no incorporation of the apnea stimulus into dreams of patients with obstructive sleep apnea.

Pain, even in patients with chronic pain conditions, is an infrequent dream sensation.

©MRSDC138

Somnomythology


Blind people don't have rapid eye movements during their REM sleep.

©MRSDC139

Dreaming and Blindness

Blind people do have rapid eye movements during REM sleep.

Congenitally blind people without any history of form vision are able to represent spatial relationships in dream experiences.

©MRSDC140


People with acquired blindness report that

their dream visualization is as their waking

visual experience was before they became

blind.

Moreover, their visual imagery includes

well defined imaginal representations of

people and places known only since

becoming blind.

©MRSDC141


Therefore, the dream is a constructive

cognitive process, rather than a

reproductive perceptual one.

Dreams are not simply simulations of

seeing: they are simulations of living –

not reflecting life as it is perceived,

but representing life as it is imagined.

©MRSDC142

Does Sleep Deprivation

Predispose to Infection ?

(Or, Were Our Mothers Right ? )

©MRSDC143

Sleep and Infection - Summary

There is no evidence in humans

that sleep deprivation

predisposes to infection, or that

sleep enhances recovery from

infection.

©MRSDC144

Does Exercise

Promote Sleep ?

©MRSDC145

Sleep and Exercise

Eight fit male endurance athletes:

Sleep studied after:

No exercise15-k run43.2-km runUltra-triathlon

©MRSDC146

Sleep and Exercise

Sleep patterns following the no exercise day and the 15-km and 43.2-km run days were similar.

Sleep patterns following the ultra-triathlon day showed increased wakefulness, delayed and decreased REM sleep, and no difference in SWS during 1st 6 hours of sleep.

©MRSDC147

Take-Home Message

Exercise has little, if any,

effect upon sleep.

©MRSDC148

Somnomythology

Coma and anesthesia are not on the wake/sleep continuum.

The state during hypnosis and other "altered states" is simply relaxed wakefulness.

OverviewOverview of normal sleep

Function of sleepCircadian rhythms

Definition

Magnitude of the problem

Perspectives Why take the complaint seriously?Why the complaint is ignored

Etiology

Diagnosis and Treatment

Insomnia and Chemical Dependency

Management

Other Sleep DisordersRestless Legs SyndromeDelayed Sleep Phase Syndrome

Somnomythology

Using Dreams

©MRSDC 150

©MRSDC 152

Documents

Sleep and Chemical Dependency The Problem and the Solution Mark W. Mahowald, MD The Retreat Wayzata, MN 7/11/2013