Outline Neurologist Sleep Focus on sleep, light Light Therapy - - PowerPoint PPT Presentation

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Descartes Li, M.D. Clinical Professor University of California, San Francisco descartes.li@ucsf.edu

Focus on sleep, light therapy, bipolar disorder

Relevant Psychiatry for the Neurologist

https://www.lindahall.org/jean-jacques-dortous-de-mairan/

Jean-Jacques d’Ortous de Mairan, engraved portrait (Smithsonian Institution Libraries)

Outline

Sleep Light Therapy Bipolar Disorder

Prior RAIN talks: 2017- MDD v grief, antidepressant selection, AD side effects 2018 – SSRD, including conversion 2020 – Sleep, Light therapy, and Bipolar disorder

Outline

Sleep Light Therapy Bipolar Disorder

Sleep

• Introduction
• Epidemiology
• Foundational concepts
• Diagnosis and assessment of sleep
• Treatment

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Sleep

• Introduction
• Epidemiology
• Foundational concepts
• Diagnosis and assessment of sleep
• Treatment

Industrialization and Hours of Sleep

• Society sleeps 1.5 hours less per hour

per night compared to 100 years ago

1942: average 7.9 hours per night 2001: 6.7 hours per night

• The increase in work performance

demanded by our 24 hour economy has effectively added a 13th month of work compared to the last century

“microsleeps”

Thirty-one percent (31%) of drivers will fall asleep while driving at least once in their lifetime.  100,000 accidents a year happen because of tiredness.

Effect of technology on sleep

Gradisar M, Wolfson AR, Harvey AG, Hale L, Rosenberg R, Czeisler CA. The Sleep and Technology Use of Americans: Findings from the National Sleep Foundation’s 2011 Sleep in America Poll. J Clin Sleep Med. 2013;9(12):1291-1299. doi:10.5664/jcsm.3272

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Sleep

• Introduction
• Epidemiology
• Foundational concepts
• Diagnosis and assessment of sleep
• Treatment

Opponent Process (or Two Process) Model of Sleep

• Sleep Debt and
• Alerting Force

work at the same time

• But they

fluctuate independently

At any given time, the sum is called sleep propensity

What is Sleep Debt?

(aka homeostatic drive or pressure)

What is the Alerting Force?

(aka Circadian rhythm)

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Melatonin Sleep tip#1: Blue Light blocking glasses Raise body temperature (early in the day)

Which leads to a compensatory decrease in core body temperature that night

Sleep tip#2:

Raymann RJEM, Swaab DF, Van Someren EJW. Skin deep: enhanced sleep depth by cutaneous temperature manipulation. Brain. 2008;131(Pt 2):500-

• 513. doi:10.1093/brain/awm315

However, raising skin temperature may also be helpful

see also www.Tuck.com

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Summary: Opponent Process Model of Sleep

• Sleep Debt and
• Alerting Force

work at the same time

• But they

fluctuate independently

Sleep

• Introduction
• Epidemiology
• Foundational concepts
• Diagnosis and assessment of

sleep

• Treatment

Four questions

Question comment

1) How long does it usually take you to fall asleep? Normal sleep latency is about 10 minutes; Be aware of patients with short latencies, such as 2 minutes 2) How many times a night do you wake up? Ask this of the patient's sleep partner as well. 3) After each awakening, how long does it take to fall back asleep? Combined with question #2 gives how much sleep is being lost 4) Do you feel refreshed upon awakening in the morning? Most important question

How much coffee do you drink?

Key Rule outs

• Obstructive sleep apnea
• Narcolepsy
• Restless leg syndrome
• Nocturnal myoclonus
• Caffeinism

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Case Vignette

54-year-old physician reports that she awakens every morning at 4am no matter what time he goes to sleep. Extremely tired/sleepy mid-afternoon which makes it difficult to work productively. Drinks about three cups of coffee throughout the day to stay awake, but this seems to interfere with going to bed at a reasonable time How much caffeine does she have in her by the time she goes to bed? What is the FDA recommended maximum?

Caffeine

(and educational tangent)

Can you drink coffee and then sleep?

Overuse can lead to restlessness, anxiety, cardiac arrhythmias, gi distress, irritability, etc

Caffeine has fascinating pharmacology, see: https://www.psychiatrictimes.com/cme/caffeine- neurobiological-and-psychiatric-implications

How much caffeine in the following products?

110mg 80mg 227mg

(per ounce, = 20 beans)

20-50mg

(but some up to 95mg per cup)

https://www.caffeinei nformer.com/the- caffeine-database

How Much Caffeine?

195mg 260mg 340mg

(Starbucks Featured Dark Roast)

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https://www.fda.gov/food/dietary-supplement-products-ingredients/pure-and-highly-concentrated-caffeine https://www.fda.gov/consumers/consumer-updates/spilling-beans-how-much-caffeine-too-much

How much caffeine is too much?

400mg

How Much Caffeine?

125mg 300mg

(assorted energy drinks and shots)

422mg/1.93 oz

(222mg, the 200mg over 6 hours)

260mg /2 oz

How Much Caffeine?

(tablets OTC)

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What is the half-life of caffeine?

Half-life of caffeine = 3 to 7 hours (in healthy active individuals) Question: If you take 240mg of caffeine at 12noon, how much is still in your body at 10pm?

Answer: 60mg (which is the equivalent of 16oz of Diet Coke)

Assume ½ life = 5hours

Time amount 12noon 240mg 5pm 120mg 10pm 60mg What about another cup of coffee (133mg) at 3pm?

using formula above, that gives another 50mg at 10pm

Total = 60mg+50mg = 110mg

Sleep

• Introduction
• Epidemiology
• Foundational concepts
• Diagnosis and assessment of sleep
• Treatment

– CBT-I – Pharmacotherapy

Test Question

62yo woman with sleep maintenance insomnia for the past six months. Self- prescribed trial of Unisom not helpful. No

• ther medical or psychiatric morbidities.

Which of the following is true*:

• A. Moderate evidence for temazepam
• B. Strong evidence for doxepin+suvorexant
• C. Sufficient evidence for CBT-I as first line

treatment

• D. Moderate evidence that pharmacotherapy

decisions should be independent of CBT-I

*Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. Journal of Clinical Sleep Medicine. 2017;13(02):307-349. doi:10.5664/jcsm.6470

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Test Question

62yo woman with sleep maintenance insomnia for the past six months. Self- prescribed trial of Unisom not helpful. No

• ther medical or psychiatric morbidities.

Which of the following is true*:

• A. Moderate evidence for temazepam
• B. Strong evidence for doxepin+suvorexant
• C. Sufficient evidence for CBT-I as first line

treatment

• D. Moderate evidence that pharmacotherapy

decisions should be independent of CBT-I

*Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. Journal of Clinical Sleep Medicine. 2017;13(02):307-349. doi:10.5664/jcsm.6470

Nonpharmacologic Treatment Strategies: Sleep Hygiene

• Maintain regular bedtime and awakening time1-3
• Exercise regularly, but not before bedtime1,2
• Avoid naps1,3
• Avoid caffeine intake after noon and alcohol

and nicotine in the evening1,2

• Make bedroom comfortable: dark, quiet,

not too hot or too cold1,2

• If hungry, have only a light snack before bedtime2
• 1. Lippmann S et al. Insomnia: therapeutic approach. South Med J. 2001;94:866-873.
• 2. National Heart, Lung, and Blood Institute Working Group on Insomnia. Insomnia: Assessment and Management

in Primary Care. Bethesda, Md: National Heart, Lung, and Blood Institute; September 1998. NIH Publication No. 98- 4088.

• 3. Kupfer DJ, Reynolds CF. Management of insomnia. N Engl J Med. 1997;336:341-346.

Working Group on Insomnia. 1998. NIH Publication 98-4088.

Minimal evidence for sleep hygiene

Sleep Hygiene is different from stimulus control and sleep restriction “…the direct effects of individual recommendations on sleep remains largely untested in the general population.”

From Irish LA, Kline CE, Gunn HE, Buysse DJ, Hall MH. The Role of Sleep Hygiene in Promoting Public Health: A Review of Empirical Evidence. Sleep Med Rev. 2015;22:23-36. doi:10.1016/j.smrv.2014.10.001

Sleep Hygiene

If it worked, then the patient probably wouldn’t be coming to see you.

https://www.originsrecovery.com/addiction- recovery-sleep/

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• Case conceptualization: Night and Day
• Stimulus control/sleep restriction*
• Circadian/rhythm education
• Pre-sleep ‘wind down’/ Roll bedtime forward by 20-30 mins per

week

• Brisk wakeup: overcoming sleep inertia
• Unhelpful beliefs about sleep
• Worry / rumination
• Daytime focus
• Strategies for different kinds of sleep disturbance
• Attention to: Opportunity to sleep and Light/Dark

CBT-I for Bipolar Disorder: Treatment components

8 sessions, 90min each

Sleep Restriction Therapy Rationale: Aims to limit the person’s time in bed to the estimated average amount of nighttime sleep

• Goal 1: Maximize sleep efficiency
• Goal 2: Associate the bed with sleep
• Goal 3: Build homeostatic pressure

to sleep

Stimulus Control Therapy

Rationale:

• Assumes there is a learned association between

wakefulness and the bedroom

• To break this association the patient must not spend

excessive time wide awake in the bedroom

Stimulus Control Therapy

1. The goal is to associate the bed with falling asleep quickly

a) Use your bed and bedroom ONLY for sleep and sex b) Go to bed only when sleepy c) Use the bed only for sleeping and sex – do not read, watch TV, or eat in bed d) Develop a pre-sleep routine e) If unable to sleep (in 20 mins), move to another room. Stay up until really sleepy. Repeat tactic immediately above as often as necessary

2. Awaken at the same time every morning

a) Regardless of total sleep time b) Establish a regular morning rise time.

3. Avoid excessive napping 4. Distinguish between fatigue and sleepiness

Bootzin RR, Epstein DR. Stimulus Control. In: Lichstein KL, Morin CM, eds. Treatment of late-life

• insomnia. Thousand Oaks, Calif: Sage; 2000:167-184.

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A dramatic example of stimulus control: Practice Makes Perfect

Harris J; Lack L; Kemp K; Wright H; Bootzin R. A randomized controlled trial of intensive sleep retraining (ISR): a brief conditioning treatment for chronic insomnia. SLEEP 2012;35(1):49-60.

50 sleep onset trials over a 25- h sleep deprivation period

• On day prior sleep restrict to 5 h (to increase homeostatic

sleep drive)

• 9pm, subject arrives at sleep lab
• One treatment trial every 30min until 11pm the following

night (50 trials)

• Each trial, pt allowed to fall asleep for 3min, then awoken

and kept awake (reading or DVDs) until next trial

• Participants then had a recovery night’s sleep (maximum
• f 8 h).

Harris J; Lack L; Kemp K; Wright H; Bootzin R. A randomized controlled trial of intensive sleep retraining (ISR): a brief conditioning treatment for chronic insomnia. SLEEP 2012;35(1):49-60.

Results and conclusions

Harris J; Lack L; Kemp K; Wright H; Bootzin R. A randomized controlled trial of intensive sleep retraining (ISR): a brief conditioning treatment for chronic insomnia. SLEEP 2012;35(1):49-60.

In the combination treatment group (ISR+SCT), 61% reaching “good sleeper” status. Treatment gains were maintained up to 6 months. Conclusion: ISR for chronic insomnia can produce rapid improvements in sleep, daytime functioning, and psychological variables.

Books on sleep

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What about sleep apps? Sleep

• Introduction
• Epidemiology
• Foundational concepts
• Diagnosis and assessment of sleep
• Treatment

– CBT-I – Pharmacotherapy

Classes of hypnotics

Benzodiazepines Heterocyclics Anticonvulsants OTC Unisom

Orexin receptor agonists: suvorexant (Belsomra) Melatonin agonists: ramelteon (Rozerem) BZD receptor agonist: Eszopiclone (Lunesta) Zolpidem (Ambien) Zaleplon (Sonata)

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Test Question

Which of the following agents may be used for both sleep onset insomnia and sleep maintenance insomnia? (more than one may be correct)

• A. eszopiclone
• B. melatonin
• C. ramelteon
• D. Suvorexant
• E. temazepam
• F. trazodone
• G. zolpidem

Test Question

Which of the following agents may be used for both sleep onset insomnia and sleep maintenance insomnia? (more than one may be correct)

• A. eszopiclone
• B. melatonin
• C. ramelteon
• D. Suvorexant
• E. temazepam
• F. trazodone
• G. zolpidem

Table

Sateia MJ et al. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults Journal of Clinical Sleep Medicine. 2017;13(02):307-349. doi:10.5664/jcsm.6470

Table (continued)

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Case Vignette

54-year-old physician reports that she awakens every morning at 4am no matter what time she goes to sleep. Extremely tired/sleepy mid-afternoon which makes it difficult to work productively. Doesn’t drink coffee Has good sleep hygiene, even tried CBT-I Has taken zolpidem and zaleplon with variable sucess What medication could you try next?

• Best for early morning awakening or

mid-insomnia

• Half life of 15 hours
• probably best to take only 3-4 nights

per week

• 1. Krystal AD, Durrence HH, Scharf M, et al. Efficacy and Safety of Doxepin 1 mg and

3 mg in a 12-week Sleep Laboratory and Outpatient Trial of Elderly Subjects with Chronic Primary Insomnia. Sleep. 2010;33(11):1553-1561.

• 2. Krystal AD, Lankford A, Durrence HH, et al. Efficacy and Safety of Doxepin 3 and 6

mg in a 35-day Sleep Laboratory Trial in Adults with Chronic Primary Insomnia.

• Sleep. 2011;34(10):1433-1442. doi:10.5665/SLEEP.1294

Doxepin

Doxepin formulation cost Silenor (doxepin) 3mg pills, #30 $450 Doxepin liquid (120ml

• f 10mg/ml)

$40 Doxepin generic 10mg caps, #30 $20-40

Prices from Goodrx.com, accessed 1/31/2020

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• Dissolve 10mg in 10cc syringe of

water (or just get the liquid, 10mg/cc)

• Take 2-3mg per night
• Complicating factors:

– Long half-life (15 hours) – Tolerance – Decreased sleep debt

Doxepin: how to use

Sleep is God, go worship

• Jim Butcher

Outline

Sleep Light Therapy Bipolar Disorder

Light Therapy

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Light therapy for MDD

• Daily exposure light box for 30

minutes ASAP after awakening, preferably between 7 and 8 am

(Carex Day-Light Classic, emitting 4000-K white light rated at 10000 lux at 35.56 cm from screen to cornea, with a UV filter

• Patients used the light box at home

and were given standardized verbal and written instructions.

Lam RW et al. Efficacy of Bright Light Treatment, Fluoxetine, and the Combination in Patients With Nonseasonal Major Depressive Disorder A Randomized Clinical

• Trial. JAMA Psychiatry.

2016;73(1):56-63. doi:10.1001/jamapsychiatr y.2015.2235 Goto

www.cet.org

for details

Light Therapy

Check out the Center for Environmental Therapeutics: www.cet.org

Light boxes

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Outline

Sleep Light Therapy Bipolar Disorder

Bipolar disorder

Focus on bipolar depression and early action plans Effectiveness of Antidepressants in Bipolar Depression

• Systematic Treatment Enhancement Program for

Bipolar Disorder (STEP-BD) patients already on mood stabilizer (MS) or atypical antipsychotic (AAP)

• Standard antidepressants tapered by 50% in the

first week and stopped by the second week

• 26 week study

– This is the probably the best study available on this issue

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Lecture: Mood Disorders II: Bipolar Disorder

Source: Sachs, GS et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. NEJM 2007 356 17:1711 -22.

Results

Outcome MS+AD (n=179) MS+placebo (n=187) P value Transient remission 32 (17.9%) 40 (21.4%) 0.40

Durable recovery

42 (23.5%) 51 (27.3%) 0.40 Transient remission or durable recovery 74 (41.3%) 91 (48.7%) 0.23 Affective switch (Aff switch) 18 (10.1%) 20 (10.7%) 0.84 Discontinue because of adverse drug reations 22 (12.3%) 17 (9.1%) 0.32 Response rate in h/o AD-related aff. switch 13.6% Aff switch = 10.2% 25.4% Aff switch = 17.9% 0.10 0.22

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Lecture: Mood Disorders II: Bipolar Disorder

Result: no difference plc vs AD

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Bottom Line

• Antidepressants generally not helpful in bipolar

depression

• Antidepressants may cause switching or rapid-

cycling (10%-30%): TCA/venl>SSRIs

• If your patient is doing well, it’s ok to continue

antidepressants

• For most patients with bipolar depression,

stopping or starting antidepressants don’t do much

• However, if you patient has mixed features or

rapid cycling, you should definitely stop antidepressants

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Lecture: Mood Disorders II: Bipolar Disorder

Case Vignette

• Presents with

depressed mood, anhedonia, low energy, sleeping 12-14 hours per day

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35 y.o. man with bipolar disorder, type I Why is it important to find out when was the last manic episode?

What is the difference between spontaneous depression and post-manic depression (aka biphasic depression)?

Spontaneous Depression (Easier to Treat)

• Hypomania
• Euthymia
• Depression

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Lecture: Mood Disorders II: Bipolar Disorder

Biphasic Depression (Hard to Treat)

• Hypomania
• Euthymia
• Depression

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Lecture: Mood Disorders II: Bipolar Disorder For many patients with bipolar disorder, prevention of mania will lead to absence of depressive episodes

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Spontaneous Depression Versus Biphasic Cycling

Conclusions from the study

– Two types of bipolar depression: spontaneous and biphasic (post-manic) – Biphasic depression: associated with increased risk of manic switch as well as decreased rate of response to either AD or MS

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Lecture: Mood Disorders II: Bipolar Disorder

Previous mood state predicts response and switch rates in patients with bipolar depression. MacQueen GM et al. Acta Psychiatrica Scandinavica. 2002; 105:414-418.

Re-analysis of STEP-BD study

Does recent mania affect response to antidepressants in bipolar disorder? In this study, presence of a manic episode before depression in patients with bipolar disorder did NOT significantly predict response to antidepressants. Alternate hypothesis: mania and depression may

• perate separately

My hypothesis: Some do and some don’t.

Mousavi Z, Johnson S, Li D. Does recent mania affect response to antidepressants in bipolar disorder? A re-analysis of STEP-BD data. Journal of Affective Disorders. 2018;236:136-139. doi:10.1016/j.jad.2018.04.097

Corollary?

• In clinical practice, post-manic

depressions frequently last 6 to 12 months and are often resistant to treatment

• But may also frequently resolve

spontaneously

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Lecture: Mood Disorders II: Bipolar Disorder

What to Do About Bipolar Depression?

• Controversial area in psychiatry
• Avoid antidepressants, unless clear

evidence of benefit

• Prevent mania: start mood stabilizers:

lithium or divalproex

• Anticipate spontaneous recovery in patients

with recent mania

• Psychotherapy of bipolar disorder (another

topic)

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Lecture: Mood Disorders II: Bipolar Disorder

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Clinical Assessment of Bipolar Depression

• What is the baseline? (chronic?)
• When was last mania? Rapid cycling?
• What worked in the past?
• Rule out substance abuse

– Alcohol – Marijuana

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Lecture: Mood Disorders II: Bipolar Disorder For many patients with bipolar disorder, prevention of mania will lead to absence of depressive episodes

More about biphasic depression

Acute (<6m) Chronic (>6m), spontaneous Stop antidepressants Optimize mood stabilizers Taper benzodiazepines Taper atypical antipsychotic Add lamotrigine* Wait/do nothing

Quetiapine, aripiprazole, lurasidone Cytomel supplement (T3) Light therapy (www.cet.org) Electroconvulsive Therapy ?Transcranial magnetic stimulation (TMS)/ketamine ?Modafinil

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*Not an antimanic agent

Remember

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Lecture: Mood Disorders II: Bipolar Disorder

For many patients with bipolar disorder , prevention of mania will lead to absence of depressive episodes

Maintenance Treatment: Medications

• Lithium or divalproex
• Planning for relapse: prn atypical

antipsychotic (the “kryptonite”) Psychotherapy of bipolar disorder

80 Lecture: Mood Disorders II: Bipolar Disorder

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Maintenance Treatment

• Psychotherapy for bipolar disorder: psychoeducation, CBT,

IPSRT, FFT

• Plan for manic relapse

– Remember the Kryptonite: prn antipsychotics

• Mood/medication diary

(life style /attitude changes)

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Lecture: Mood Disorders II: Bipolar Disorder

Evidence-based, psychosocial treatments for bipolar disorder

• 1. Cognitive-behavioral therapy

(CBT)

• 2. Interpersonal and Social rhythm

psychotherapy (IPSRT)

• 3. Family-focussed therapy (FFT)
• 4. Psychoeducation

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Successful Psychosocial Therapy for Bipolar Disorder: What Are the Common Ingredients?

Common, important features of all psychosocial treatments for bipolar disorder:

• 1. Emphasis on medication/treatment adherence.
• 2. Lifestyle regularity
• 3. Early symptom detection and early intervention

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Resources for Bipolar Disorder: Books

• Miklowitz, D. (2002). The Bipolar Disorder

Survival Guide: What you and your family need to know. New York: Guilford Press

• Jamison, K.R. (1995). An Unquiet Mind.

New York: Knopf

• Forney, E. (2012). Marbles: Mania,

Depression, Michelangelo and Me: A Graphic Memoir

• Phelps, J. (2006) Why am I Still Depressed? Recognizing

and Managing the Ups and Downs of Bipolar II and Soft Bipolar Disorder. McGraw-Hill Education

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Summary

• Sleep
• Light therapy
• Bipolar disorder

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