A Practical Approach to the Medication Management of

Dr. Bruce McGee Utah Valley Outpatient Psychiatry Disclaimer

• Represent myself only • I am a psychiatrist without medicine fellowship • Biases Intention/Objectives:

•Quick review of how sleep works •Review of DSM-5 and ICSD [International Classification of Sleep Disorders – 3rd Ed.] •Assess benefits vs. risks of medication management •Discuss considerations in medication selection •Not to dissuade , therapy, CBT-I Not covering, but important • CBT • CBT-I • Stimulus control • Sleep restriction therapy • Cognitive control • Cognitive restructuring • • Paradoxical intention • Relaxation • Progressive muscle relaxation But first, a quick review of sleep Simplified Examples of Sleep Architecture

https://slideplayer.com/slide/9220738/ Actual Examples of Sleep Architecture

https://www.researchgate.net/figure/Hypnogram-before-upper-panel- and-after-treatment-with-5-OH-tryptophan-lower- panel_fig2_42587318 Sleep Architecture

• Stage 1 (5%) • Typically the first 5 minutes; transitional stage • Low arousal threshold • Stage 2 (50-55%) • Typically the next 10-15 minutes • Stage 3 (previously classified as 3 & 4) (20%) • Typically the 20-40 minutes; “delta” slow-wave sleep • REM (Rapid Movement) (20-25%) • Paralyzed, except for the • If you remember a , it happened in REM Dreaming [REM sleep] • are critical for learning and • Dreams often play a key role in emotional healing • disrupt sleep and can be terrifying • Conventional treatments of disturbing dreams/ nightmares include: • Pharmacological interventions [prazosin] • Psychotherapeutic approaches • Exposure • Relaxation • Re-scripting (Rewrite the ending of a repeating dream) REM is necessary

Rats denied REM sleep will die within a few weeks!

Suppression of REM sleep may be caused by: • Excessive • Insomnia • Most • Excessive light • Alarm clock awakenings is part of a greater cycle

Circadian Rhythm

• Circa = About • Dia = Day • Literally translates as “about daily” rhythm • Its is controlled in hypothalmus • Like most everything else… This slide is intended to demonstrate that light exposure affects physiology and behavior. Circadian Rhythm • The average circadian rhythm of is 24h 11min. • After LIGHT exposure, signals travel from the retina to the through the retinohypothalamic tract within the optic nerve. • There the signal enters the suprachiasmatic nuclei (SCN) within the hypothalmus to regulate, reset, or correct the circadian rhythm. • Each SCN is the size of a grain of rice, contains ~20k neurons each, with one on the right, one on the left. Don’t panic on the next slide… Cascading of Protein Interactions After Light Exposure in the SCN Don’t panic on this one either…

It is the concept that is important. produced in DMH, LH, and PH

HYPOTHALAMIC STRUCTURES (in box): LDT = Laterodorsal tegmental nucleus [midbrain] SCN = Suprachiasmatic nuclei PPT = Pedunculopontine tegmental nucleus [] DMH = Dorsomedial hypothalamus VTA = Ventral tegmental area [midbrain] LHA = Lateral hypothalamic area LC = [pons] PH = Posterior hypothalamus DR = Dorsal raphe [midbrain/pons] VLPO = Ventrolateral preoptic area TMN = Tuberomammillary nucleus BST = nucleus of the stria terminalis SNr = pars reticulata [midbrain] http://www.nature.com/nrn/journal/v8/n3/fig_tab/nrn2092_F3.html Wakefulness

Melatonin through the ages…

How do you keep your circadian rhythm in check?

• Zeitgebers (German for “time giver”, synchronizer): External cues that synchronize the circadian rhythm • Bright light, especially blue or green light • Exercise • Temperature changes • Smells (bacon in the morning…) • Social interactions • Medication • Eating HYPOTHALAMIC STRUCTURES (in box): LDT = Laterodorsal tegmental nucleus SCN = Suprachiasmatic nuclei PPT = Pedunculopontine tegmental nucleus DMH = Dorsomedial hypothalamus VTA = Ventral tegmental area LHA = Lateral hypothalamic area LC = Locus coeruleus PH = Posterior hypothalamus DR = Dorsal raphe BST = Bed nucleus of the stria terminalis TMN = Tuberomammillary nucleus VLPO = Ventrolateral preoptic area SNr = Substantia nigra pars reticulata http://www.nature.com/nrn/journal/v8/n3/fig_tab/nrn2092_F3.html International Classification of Sleep Disorders – Third Edition 1. Insomnia 2. Sleep-related breathing disorders 3. Central disorders of hypersomnolence 4. Circadian rhythm sleep-wake disorders 5. 6. Sleep-related movement disorders 7. Other sleep disorders International Classification of Sleep Disorders – Third Edition • Chronic insomnia disorder • type 1 • • Short-term insomnia disorder • Narcolepsy type 2 • Sleep-related • Other insomnia disorder • Idiopathic • Sleep enuresis • OSA, adult • Kleine-Levin syndrome • due to a medical disorder • OSA, pediatric • Central with Cheyne-Stokes • Hypersomnia due to a medical disorder • Parasomnia due to a medication or breathing • Hypersomnia due to a medication or substance • Central sleep apnea due to a medical substance • Parasomnia, unspecified disorder without Cheyne-Stokes breathing • Hypersomnia associated with a psychiatric • Restless legs syndrome • Central sleep apnea due to high altitude- disorder • Periodic limb movement disorder periodic breathing • Insufficient sleep syndrome • Sleep-related leg cramps • Primary central sleep apnea • Delayed sleep-wake phase disorder • Sleep-related • Primary central sleep apnea of infancy • Advanced sleep-wake phase disorder • Sleep-related rhythmic movement • Primary central sleep apnea of prematurity • Irregular sleep-wake rhythm disorder disorder • Treatment-emergent central sleep apnea • Non-24-h sleep-wake rhythm disorder • Benign sleep myoclonus of infancy • Obesity hypoventilation syndrome • Shift work disorder • Propriospinal myoclonus at • Congenital central alveolar • disorder • Sleep-related movement disorder due to a hypoventilation syndrome • Circadian sleep-wake disorder not medical disorder • Late-onset central hypoventilation with otherwise specified • Sleep-related movement disorder due to a hypothalamic dysfunction • Confusional arousals medication or substance • Idiopathic central alveolar Sleep-related movement disorder, hypoventilation • • • Sleep-related hypoventilation due to a • Sleep terrors unspecified medication or substance • Sleep-related eating disorder • Sleep-related hypoventilation due to a • REM sleep behavior disorder medical disorder • Recurrent isolated sleep • Sleep-related hypoxemia disorder • disorder 73>57 DSM-5 Sleep-Wake Disorders

• Insomnia disorder • Hypersomnolence disorder • Narcolepsy • Breathing-related sleep disorders: • • • • Circadian rhythm sleep-wake disorders • Parasomnias: • • • • DSM-5 Sleep-Wake Disorders

• Insomnia disorder • Hypersomnolence disorder • Narcolepsy • Breathing-related sleep disorders: • hypopnea • Central sleep apnea • Sleep-related hypoventilation • Circadian rhythm sleep-wake disorders • Parasomnias: • Non-rapid sleep arousal disorders • • behavior disorder • Restless legs syndrome ~11 Dx DSM-5 Sleep-Wake Disorders

• Insomnia disorder • Substance/medication- induced • Hypersomnolence disorder • Other specified insomnia • Narcolepsy disorder • Breathing-related sleep disorders: • Unspecified insomnia • Obstructive sleep apnea hypopnea disorder • Central sleep apnea • Other specified • Sleep-related hypoventilation hypersomnolence disorder • Unspecified • Circadian rhythm sleep-wake disorders hypersomnolence disorder • Parasomnias: • Other specified sleep-wake • Non-rapid eye movement sleep arousal disorders disorder • Nightmare disorder • Unspecified sleep-wake • Rapid eye movement sleep behavior disorder disorder • Restless legs syndrome 18 Dx Insomnia Disorder A) A predominant complaint of dissatisfaction with sleep quantity or quality 1. Difficulty initiating sleep [DFA] -OR- 2. Difficulty maintaining sleep [DSA] -OR- 3. Early-morning awakening with inability to return to sleep [EMA] B) Distress or impairment C) 3+ nights/week D) 3+ months already E) Adequate opportunity for sleep F) Not due to other sleep disorder G) Not due to a substance or medication H) Not explained by coexisting mental disorders or medical conditions Insomnia Disorder Subtypes

• With non-sleep disorder mental comorbity • With other medical comorbity • With other sleep disorder

• Episodic • Persistent • Recurrent Hypersomnolence Disorder

A) Excessive sleepiness despite a main sleep period lasting at least 7h 1. Recurrent periods of sleep or lapses into sleep within the same day -OR- 2. A prolonged main sleep episode of more than 9h/day that is nonrestorative -OR- 3. Difficulty being fully awake after abrupt awakening B) 3+ nights/week for 3+ months C) Distress or impairment D) Not due to other sleep disorder E) Not due to a substance or medication F) Not explained by coexisting mental disorders or medical conditions Hypersomnolence Disorder Subtypes

• With mental disorder • With medical condition • With another sleep disorder • Acute [<1m] • Subacute • Persistent [>3m] • Mild • Moderate • Severe Narcolepsy Narcolepsy

Sleeping with dead people, right? Narcolepsy

Comes from Greek narkē-lambanein, later narkē-lepsia, meaning numbness-take hold, later numbness-seize Narcolepsy

Or better, “numbness attack” Narcolepsy

Ok, so that’s abusing narcotics, right? Narcolepsy

Nobody asked me in the late 19th century what we should call it. I would have preferred hypnolepsy. from the Greek hupnos-lepsia, meaning sleep attack Narcolepsy

What is the classic triad for narcolepsy – OR – tetrad/quadrad? Narcolepsy

Fire setting, bedwetting, and cruelty to animals… Hypnogogic/ Hallucinations + Sleep Attacks

Cataplexy

https://www.youtube.com/watch?v=gRfysISuVps What causes these phenomena? REM mismatches

Hypnogogic/ Hypnopompic Hallucinations + Sleep Attacks are from REM intrusion

Cataplexy Sleep Paralysis How do you test for narcolepsy? Narcolepsy [DSM-5 Dx]

A) Recurrent periods of an irrepressible need to sleep -OR- lapsing into sleep -OR- multiple within a day; 3x/week, >3 months B) At least one of the following: 1) Cataplexy 2) Hypocretin [orexin] deficiency in CSF [<100pg/mL], not due to TBI, infection, or inflammation 3) PSG w/REM onset within 15min -OR- PSG/MSLT with average sleep latency of 8min -OR- PSG/MSLT with 2+ SOREMs [sleep onset rapid eye movement]

Note: International Classification of Sleep Disorders, 3rd Ed requires PSG/MSLT. http://braindiseases.org/brain-diseases-treatment/narcolepsy-how-to-address-the-sleep-disorder/ Obstructive Sleep Apnea

A) Either 1. AHI>5 on PSG, and either a. Nocturnal breathing disturbances: , snorting/gasping, or breathing pauses during sleep. b. Daytime sleepiness, fatigue, or unrefreshing sleep despite sufficient opportunities to sleep not from other mental disorder or medical condition. 2. AHI>15 on PSG Subtypes of Obstructive Sleep Apnea

• Mild [AHI<15] • Moderate • Severe [AHI >30] Signs and symptoms of OSA •?? Signs and symptoms of OSA

• Witnessed apnea • Large neck • Large girth • Malampati level • Narrow and high arching mouth • • Morning headaches • Family history of OSA sleep

↓BP and ↓HR

Nocturia OSA events

↑ BP and ↑ HR

↑ANF (atrial natriuretic factor)

Malampati Level Central Sleep Apnea

A) Evidence on PSG of 5+ central apneas/hour. B) Not better explained by another sleep disorder.

Specifiers: Idiopathic Cheyne-Stokes breathing CSA comorbid with opioid use Sleep-Related Hypoventilation

A) PSG w/↓ respirations and ↑CO2 B) Not better explained by another sleep disorder

Specify: Idiopathic hypoventilation Congenital central alveolar hypoventilation Comorbid sleep-related hypoventilation Pulmonary disorders Neuromuscular or chest wall disorders Medication induced With obesity Circadian Rhythm Sleep-Wake Disorders

A) Persistent or recurrent pattern of sleep disruption d/t alterations in circadian rhythm or misalignment with sleep-wake schedule [environmental, social, or professional] B) Excessive sleepiness and/or insomnia C) Distress or impairment Circadian Rhythm Sleep-Wake Disorders

Specify: • Delayed sleep phase type • Familial • Overlapping with non-24-hour sleep-wake type • Advanced sleep phase type • Irregular sleep-wake type • Non-24-hour sleep-wake type • Shift work type • Unspecified type • Episodic, Persistent, Recurrent Non-Rapid Eye Movement Sleep Arousal Disorders A) Recurrent episodes of incomplete awakening from sleep, usually occurring during the first third of the major sleep episode: 1) Sleepwalking 2) Sleep terrors B) No or little dream imagery is recalled C) Amnesia for the episodes is present D) Distress or impairment E) Not substance induced F) Co-existing medical or mental disorders do not explain the episodes Non-Rapid Eye Movement Sleep Arousal Disorders [continued] Sleepwalking – Repeated episodes of rising from bed during sleep and walking about. While sleepwalking, the individual has a blank, staring face; is relatively unresponsive to the efforts of others to communicate with him or her; and can be awakened only with great difficulty. Non-Rapid Eye Movement Sleep Arousal Disorders [continued] Sleep terrors – •Recurrent episodes of abrupt terror arousals from sleep, usually beginning with a panicky scream. •Intense fear and signs of autonomic arousal, such as mydriasis, tachycardia, rapid breathing, and sweating, during each episode. •Relative unresponsiveness to efforts of others to comfort the individual during the episodes. Nightmare Disorder

A) Repeated occurrences of extended, extremely dysphoric, and well- remembered dreams that usually involve efforts to avoid threats to survival, security, or physical integrity, and that generally occur during the second half of the major sleep episode. B) On awakening from the dysphoric dreams, the individual rapidly becomes oriented and alert. C) Distress or impairment D) Not substance induced E) Co-existing medical or mental disorders do not explain the episodes Rapid Eye Movement Sleep Behavior Disorder

A) Repeated episodes of arousal during sleep associated with vocalization and/or complex motor behaviors. B) These behaviors arise during rapid eye movement [REM] sleep and therefore usually occur more than 90 minutes after sleep onset, are more frequent during the later portions of the sleep period and uncommonly occur during daytime naps. C) Upon awakening from these episodes, the individual is completely awake, alert, and not confused or disoriented. D) Either of the following: 1) REM sleep without atonia on PSG recording 2) A history suggestive or REM sleep disorder behavior and established dx [e.g. Parkinsons, multiple systems atrophy] E) Distress or impairment F) Not substance induced G) Co-existing medical or mental disorders do not explain the episodes Restless Leg Syndrome

A) An urge to move the legs, usually accompanied by or in response to uncomfortable or unpleasant sensations in the legs, characterized by all of the following: 1) The urge to move the legs begins or worsens during periods of rest or inactivity. 2) The urge to move the legs is partially or totally relieved by movement. 3) The urge to move the legs is worse in the evening or at night than during the day, or occurs in the evening or at night. B) 3x/week, 3+ months C) Distress or impairment D) Not substance induced E) Co-existing medical or mental disorders do not explain the episodes Substance/Medication-Induced Sleep Disorder

Subtypes: Insomnia Daytime Sleepiness Parasomnias Mixed Back to management… What portion of your day is spent seeing mental health issues? CDC QuickStats: Percentage of Mental Health– Related* Primary Care† Office Visits, by Age Group — National Ambulatory Medical Care Survey, United States, 2010 What portion of those patients have insomnia? What should be your first inclination for treatment? Sleep Hygiene

• You can insist that a patient practice sleep hygiene before medicating insomnia. • And you can extend that to CBT-I. How do you incorporate sleep hygiene into your practice?

CBT-I?

Dr’s Orders: 1. No TV in . DO: SLEEP HYGIENE 2. No monitor of any kind after 10pm  Get up at the same time everyday (TV, computer, tablet, phone…)  Go to bed at the same time every night DO NOT:  Expose yourself to sunlight each morning  Take naps (unless for safety)  Make your room dark or use mask (↑)  Get in bed if not sleepy  Make your room silent or use white noise  Watch TV in bed  Make your room cool  Have a TV in your bedroom  Use more if necessary  Work in bed  Reduce amount of time in bed awake  Play in bed  Get out of bed if you can’t fall asleep in ~20min  Read in bed  Do something boring until sleepy out of bedroom  Listen to stimulating music in bed  Avoid bright lights out of bedroom  Converse in bed  Try relaxation exercises  Talk on the phone in bed  Then try breathing exercises  Smoke before bed (2+ hours)  Try a cup of warm milk  Drink alcohol before bed  Try a cup of caffeine free tea  Drink caffeinated beverages after noon  Try a small snack before bed (unless overweight)  Overeat before bed (¡reflux!)  Take a hot bath or shower 2hours before bed  Exercise shortly before bed (2+ hours)  Listen to relaxing music  Stay in bed if not asleep  Develop a routine or a ritual THE BEDROOM IS ONLY FOR  Turn clock away so you cannot see it SLEEP AND SEX!  But, use clock alarm, not phone for alarm A McGee Production For more comprehensive help, download free CBT-I Coach App!

To do:  Medication Pickup  Laboratory Studies  Scheduled Therapy     Follow up in: Caffeine Cycle What, however, is likely the solution that your patient is looking for? GAH….

Medications How many of you have prescribed medications for sleep? What are some bad outcomes for giving sleep medications? What are the risks of giving sleep medications? What are some good outcomes from giving sleep medications? What are the benefits of giving sleep medications? What are some of your arguments for giving or not giving sleep medications or specific types of sleep medications? So, which meds have you prescribed for sleep? Antihistamines: Atarax/hydroxyzine [tab] Barbiturates: Butisol/butabarbital Agonists: Vistaril/hydroxyzine [cap] Seconal/Secobarbital Requip/Ropinirole Benadryl/diphenhydramine Benzodiazepines: Xanax/alprazolam Mirapex/pramipexole Unisom/doxylamine SARI: Desyrel/trazodone Halcion/triazolam NaSSA: Remeron/mirtazapine Prosom/estazolam Antimalarial: Melatonin agonists:Rozarem/ramelteon Dalmane/flurazepam Tonic water [quinine] Hetlioz/tasimelteon Ativan/lorazepam [83mg/L] Antiepileptics/ Depakote/divalproex Na+ Restoril/temazepam Mood stabilizers: Neurontin/gabapentin Klonopin/clonazepam TCAs: Silenor/doxepin Elavil/amitriptyline Serax/oxazepam Pamelor/nortriptyline Doral/quazepam Non BZDs: Ambien/zolpidem IR Tranxene/clorazepate Lunesta/eszopiclone IR Librium/chlordiazepoxide Ambien CR/zolpidem CR Non-BZDs: Zolpimist/zolpidem IN Sonata/zaleplon Intermezzo/zolpidem SL Orexin inhibitor: Belsomra/suvorexant Dopamine agonist: Mirapex/pramipexole Edular/zolpidem SL

Requip/ropinirole GABAB modulator: Xyrem/sodium oxybate[GHB salt] What considerations do you ponder when choosing a sleep medication for your patients? FDA Approved Drugs What do you consider when choosing… What do you • What kind of insomnia? consider when choosing… What do you • What kind of insomnia? consider when • What is their metabolic status? Weight/BMI? choosing… • What kind of insomnia? What do you • What is their metabolic status? Weight/BMI? • Temporal details: time to onset, half-life, next consider when day sedation choosing… • What kind of insomnia? • What is their metabolic status? Weight/BMI? What do you • Temporal details: time to onset, half-life, next consider when day sedation choosing… • What are their other medical/mental issues? • What kind of insomnia? • What is their metabolic status? Weight/BMI? • Temporal details: time to onset, half-life, next day sedation What do you • What are their other medical/mental issues? consider when • Pain • Nightmares choosing… • Sleep behaviors • Loosening of associations • RLS • HTN, LH’d, fall hx, headaches, etc. Which meds would be better for DFA?

[Difficulty falling asleep] Which meds would be better for DSA?

[Difficulty staying asleep] McGEE MEDICATION MANAGEMENT OF INSOMNIA

INSOMNIA

DFA DSA EMA Non-Restorative [DFA] Which meds are addictive? [DFA] Which meds are not addictive? [DSA] Which meds do not cause weight gain? [DSA] Which meds work better for causing weight gain? McGEE MEDICATION MANAGEMENT OF INSOMNIA

INSOMNIA

DFA DSA EMA Non-Restorative

PSG addiction no addiction heavy skinny potential concern MSLT MEDICATION MANAGEMENT OF INSOMNIA

Other considerations: Loosening of associations Non-REM behaviors INSOMNIA Nightmares Pain RLS DFA DSA EMA Non-Restorative

PSG

addiction no addiction heavy skinny potential concern MSLT MEDICATION MANAGEMENT OF INSOMNIA

Other considerations: The No-No List Loosening of associations Non-REM behaviors INSOMNIA Nightmares Pain RLS DFA DSA EMA Non-Restorative

PSG

addiction no addiction heavy skinny potential concern MSLT MEDICATION MANAGEMENT OF INSOMNIA

Other Considerations: The No-No List Loosening of Associations Non-REM Behaviors INSOMNIA Nightmares Pain Exceptions DFA DSA EMA Non-Restorative

PSG

addiction no addiction heavy skinny potential concern MSLT MEDICATION MANAGEMENT OF INSOMNIA DFA DSA EMA Non-Restorative addiction no addiction potential concern heavy skinny SSRIs PSG +/- MSLT +/- Antiψs Atarax/ Ambien trazodone Remeron Vistaril ↓ ↓ ↓øSI OSA PLMD ↓ Lunesta Silenor Elavil ↓ ↓ Benadryl ↓ ↓ (2D6) PAP Neurontin ↓ Ambien CR Pamelor Mirapex doxylamine Narcolepsy Requip The No-No List: ↓ Quinine ~Xyrem (GHB) (Tonic Water) Rozarem suvorexant Chloral hydrate§ ~Klonopin Xanax† Serax* ↓ ↓ Halcion† Doral REMEMBER: tasimelteon Sonata Prosom† Tranxene Medication management Valium Librium should augment therapy Melatonin: Many OTC †TriazoloBZD melatonin formulations *LOT BZD Dalmane Zolpimist IN and good sleep hygiene, as do not have melatonin in ~ exceptions for Non- Ativan* Intermezzo SL needed. It is not a them. REM Behaviors ~Restoril* Edular SL substitute. § no FDA indication at all PAIN NIGHTMARES LOOSE Non-REM Behaviors -Neurontin/Lyrica -Minipress -Seroquel -Klonopin -Elavil (2D6) -Catapres -Abilify -Restoril

-Pamelor augmentation A McGee Production MEDICATION MANAGEMENT OF INSOMNIA DFA DSA EMA Non-Restorative addiction no addiction potential concern heavy skinny SSRIs PSG +/- MSLT +/- Antiψs Atarax/ Ambien trazodone Remeron Vistaril ↓ ↓ ↓øSI OSA PLMD (RLS) ↓ Lunesta Silenor Elavil ↓ ↓ Benadryl ↓ ↓ (2D6) PAP Neurontin ↓ Ambien CR Pamelor Mirapex doxylamine Narcolepsy Requip The No-No List: ↓ Quinine ~Xyrem (GHB) (Tonic Water) Rozarem suvorexant Chloral hydrate§ ~Klonopin Xanax† Serax* ↓ ↓ Halcion† Doral REMEMBER: tasimelteon Sonata Prosom† Tranxene Medication management Valium Librium should augment therapy Melatonin: Many OTC †TriazoloBZD melatonin formulations *LOT BZD Dalmane Zolpimist IN and good sleep hygiene, as do not have melatonin in ~ exceptions for Non- Ativan* Intermezzo SL needed. It is not a them. REM Behaviors ~Restoril* Edular SL substitute. § no FDA indication at all PAIN NIGHTMARES LOOSE Non-REM Behaviors -Neurontin/Lyrica -Minipress -Seroquel -Klonopin -Elavil (2D6) -Catapres -Abilify -Restoril

-Pamelor augmentation A McGee Production What warnings do you give patients when starting them on sleep medications? For All Sleep Medications NEXT DAY OVERSEDATION/OVERSEDATION: • This drug is intended to make it easier for you to get to work. • Not harder. • If it is harder to get to work, then that’s a problem. • Your safety comes first. • You would never want to hurt yourself, or hurt or kill someone else because you were too sedated. DO NOT DRIVE OR DO ANYTHING DANGEROUS WHEN OVERSEDATED. How many of you have prescribed trazodone for sleep? Managing next day sedation, trazodone example

• Usually, there is a dose that helps without causing next day sedation. You just need to dial it in. You may need to give more flexible range in non-controlled medications. • Remember, it is not addictive; so be flexible. • Example 1: 25-200mg of trazodone 1-2h a sleep. • Consideration: start on FRI night, start with minimum doses and build up incrementally, a bit more each night. Trazodone [not all inclusive]:

• Priapism • Dry mouth • Syndrome – if not familiar, better get familiar • Nasal and sinus congestion • Lightheadedness, hypotension, syncope, ataxia • Headache, nervousness, blurry vision, confusion • Belly pain, nausea, vomiting, diarrhea, flatulence, constipation • Myalgia, tremor, muscle twitches How many of you have prescribed Remeron for sleep? Managing next day sedation, Remeron example

• Example 2: 15mg of Remeron > 7.5mg > 3.75mg, 1-2h before bed. • Consideration: start on FRI night, if too much, reduce to 7.5mg, if too much, reduce to 3.75mg. • If not enough, consider 30mg at next appt, then 45mg. • Note: it may have paradoxical reverse effect at higher doses. Remeron [not all inclusive]:

• Fatigue, poor energy • Increased , weight gain, increased appetite • ↑ LDL, ↑TGs • Dry mouth, dry eyes, constipation, urinary retention, flushing, blurry vision • Lightheaded, fainting, hypotension, conversely hypertension • Constipation • Edema How many of you have prescribed an antihistamine for sleep? How many of you have prescribed an antihistamine for sleep?

As well as other meds that are antihistaminic? Antihistamines [not all inclusive]:

• Dry mouth, dry eyes, constipation, urinary retention, flushing • Blurry vision • Weight gain, increased appetite • Tolerance typically builds quickly • QT prolongation/torsades de pointes • Lightheaded, tachycardia, palpitations, hyperthermia • Paradoxical CNS stimulation • Benadryl has too many to even list… Antihistamines [not all inclusive]:

• Dry mouth, dry eyes, constipation, urinary retention, flushing • Blurry vision • Weight gain, increased appetite REMEMBER: • Tolerance typically builds quickly is the main excitatory • QT prolongation/torsades de pointes in • Lightheaded, tachycardia, palpitations, hyperthermia the brain in regards • Paradoxical CNS stimulation to wakefulness. • Benadryl has too many to even list… Doxepin [not all inclusive]:

• Would include Silenor [doxepin] in antihistamine group. • Dose is so small, in my opinion: • You should not have to give tricyclic warnings • Same warnings as antihistamines How many of you have prescribed an for sleep? Tricyclic Antidepressants [not all inclusive]: • You may not be able to give safely to suicidal patients! • Drug withdrawal • Weight gain, increased appetite, metabolic changes [HTN, HLD] • Dry mouth, dry eyes, constipation, urinary retention, flushing, blurry vision [Hot as a hare, blind as a bat, dry as a bone, red as a beet, mad as a hatter] • Lightheaded, fainting, hypotension, conversely hypertension • Sexual SEs: [women too], low libido, anorgasmia/delayed • QT prolongation/torsades de pointes, cardiotoxic [KISS principal] • Reduces seizure threshold, decreases REM sleep • Peripheral neuropathy, seizure, paresthesia's, galactorrhea, gynecomastia , tinnitus, NMS, angle- closure glaucoma, hepatitis, bone marrow depression, alopecia, ataxia, hyperthermia, purpura, belly cramps, ileus, stomatitis, cardiomyopathy, arrhythmias, tachycardia, palpitations, edema, HTN, MI, CVA How many of you have prescribed an antipsychotic for sleep? Why do providers prescribe antipsychotics?

Sedation through multiple pathways: • Antihistaminic primarily • seemingly less tolerance building than antihistamines, non-paradoxical • Anticholinergic antagonism • Dopamine 2 antagonism • Serotonin 2a antagonism • α1/α2 antagonism

Depending on your antipsychotic, 6 possible ways to sedate a patient. Antipsychotics warnings [not all inclusive]: • Increased appetite, weight gain, slow metabolism • Metabolic syndrome [HLD, HTN, DMt2] • Increased sleep apnea • Lightheadedness/fainting > falls > TBI or death • Dry mouth, dry eyes, constipation, urinary retention, flushing, blurry vision • Tachycardia, hyperthermia, blurry vision • NMS [neuroleptic malignant Syndrome] • Dystonia • Akathisia D acronym • Tardive Dyskinesia A is helpful • EPS [extrapyramidal symptoms] • Tremors T • Muscle rigidity E • Muscle initiation difficulties > falls > TBI or death How many of you have prescribed a benzodiazepine for sleep? Benzodiazepines warnings [not all inclusive]: • Death • Reduced stage 3 sleep • Overdose • Overdose with narcotics or alcohol • Not feeling rested/refreshed • Delirium tremens in withdrawal • Reduced growth and repair of bones and • Falls tissues [difficult for body to repair itself] • Sooner than non-users for all causes • Brain gets less of a nightly “wash” • Early [?anoxia] • Decreased glucose metabolism • Dependency and addiction • Decreased short-term memory • Detoxification/Rehabilitation • Decreased long-term memory • Jonesing/Re-enforces its own use • Decreased ability to learn • Controlled medication • Poor considerations • Alzheimer’s, heart disease, strokes, • Increased sleep apnea diabetes… ?everything… • Dangerous with other sedating meds, such as opioids and alcohol. • Disinhibited behaviors [explored later] How many of you have prescribed a non-benzodiazepine for sleep? Non-benzodiazepines warnings [not all inclusive]: • Disinhibited behaviors • Inappropriate purchases • Inappropriate phone calls • Sexting • Killing your in-laws, etc. • Could lead to being taken advantage of as well • Sleepwalking behaviors: • Somnambulism • Sexsomnia • Somnophagia • ?Reduced life expectancy • Controlled medication considerations • Lunesta: dysgeusia Non-benzodiazepines [not all inclusive]: • Disinhibited behaviors WHAT • Inappropriate purchases • Inappropriate phone calls WARNINGS • Sexting • Killing your in-laws, etc. COULD YOU GIVE • Could lead to being taken advantage of as well TO GREATLY • Sleepwalking behaviors: DECREASE THESE • Somnambulism • Sexsomnia BEHAVIORS? • Somnophagia • ?Reduced life expectancy • Controlled medication considerations • Lunesta: dysgeusia How many of you have prescribed suvorexant [Belsomra] for sleep? Belsomra [not all inclusive]:

• Contraindicated in narcolepsy • Narcoleptic symptoms: • Sleep paralysis • Hypnagogic/hypnopompic hallucinations • Cataplexy • All the same sleepwalking and disinhibited behaviors of non-benzodiazepines • Controlled medication considerations How many of you have prescribed melatonin or a melatonin agonist for sleep? Melatonin agonists [not all inclusive]:

• Melatonin [OTC]: • headache, confusion, fragmented sleep • ?Inhibit future melatonin production or pineal dysregulation • Ramelteon [Rozerem]: • Lightheaded, nausea, fatigue, dysgeusia, myalgia, arthralgia • Debated on how helpful it actually is • M1/M2 agonist, not M3 agonist • Tasimelteon [Hetlioz]: • Headache [17%] • Abnormal dreams, UTI, increased ALT, URI How many of you have prescribed a dopamine agonist for sleep? Dopamine agonists [not all inclusive]:

• ! [hallucinations, delusions], poor impulse control, aggressiveness • Hypotension, lightheadedness, syncope • Hypertension, edema, chest pain, flushing, palpitations, Afib, tachycardia, headaches, sweating • Narcolepsy, amnesia, EPS, ataxia • Nausea, vomiting, belly pain, xerostomia, diarrhea, constipation, flatulence • Muscle weakness, pain, paresthesia, hypoesthesia • UTI, ED, increased AlkPhos, visual disturbances, dry eyes • Nasopharyngitis, sinusitis, bronchitis, cough, dyspnea How many of you have prescribed Neurontin [gabapentin] for sleep? Neurontin [not all inclusive]:

• Some capacity for addiction/dependence/abuse/diversion • Now controlled in Utah • Why? Deaths from gabapentin + opioids • Withdrawal syndrome [hostility] • Weight gain • Lightheadedness, fatigue, fever [kids] • Emotional lability, altered thinking, amnesia, depression • Ataxia, tremor, nystagmus, asthenia, diplopia • Nausea, vomiting, diarrhea, xerostomia, constipation, dyspepsia • Bronchitis, nasopharyngitis, URI, pneumonia, cough, dry throat How many of you have prescribed Minipress [prazosin] for nightmares? Minipress [not all inclusive]:

• Increasing tolerances • Lightheadedness/hypotension > syncope/falls • Fatigue, weakness • Palpitations, angina • Nausea, vomiting, diarrhea, xerostomia, constipation • Headache • Blurry vision • Edema, rash, urinary frequency, priapism • Dyspnea, epistaxis, nasal congestion How many of you have prescribed Catapres [clonidine] for sleep or nightmares? Catapres [not all inclusive]:

• Increasing tolerances • Lightheadedness/hypotension > syncope/falls • Fatigue • Rebound hypertension, withdrawal syndrome • Bradycardia, edema • Headache, , nightmares, emotional disturbance, depression, , agitation, , delusions, hallucinations, tremor • Rash, xerostomia, abdominal pain, constipation, anorexia, paresthesia, parotid pain, alopecia, incontinence, ED, sexual SEs, myalgias, arthralgias, otalgia, fever How many of you have prescribed Xyrem [sodium oxybate, AKA GHB] for sleep? Xyrem [GHB]

• Very controlled • “Date rape” drug, probably only with alcohol though • Has REMS program • Leave it to the doctor • Basically medical food • Massive salt load Hopefully you are not even considering: • Xyrem/sodium oxybate (salt of gamma hydroxy butyrate) • Barbiturates • Triazolobenzodiazepines • Xanax/alprazolam • Halcion/triazolam • Prosom/estazolam • Intranasal or sublingual nonbenzodiazepines • Tonic water How many of you have prescribed a PAP therapy or an oral appliance for sleep? Positive Air Pressure [not all inclusive]:

• Contact dermatitis • Aerophagia [try raising head of bed, or BiPAP] • Xerostomia > cavities > abscesses > encephalitis/meningitis • Dry nose, nosebleeds • Exposure to mold [if PAP machine not kept clean] • Headaches Oral appliance therapy, OAT [not all inclusive]:

• TMJ • Change in bite • Tooth pain > cavities > abscesses > encephalitis/meningitis • Drooling Case Example from Thursday [before]

57yoMWF BYU Professor w/insomnia, depression, anxiety [w/permission]: • -Do not take Sonata [zaleplon], or Ambien, or Lunesta together. • -Stop doxepin. • -Start trazodone 50-200mg po qhs for insomnia, 1-2h before bed. • -Continue Lunesta 3mg po qhs immediately before bed for insomnia, stop if any sleepwalking. • -Continue Mirapex 0.125mg po qhs 1-2h before bed for RLS. • -Try Viagra 50mg po daily PRN for ED. • -Continue Prozac 40mg po daily for depression and anxiety. • -Continue modafinil 200mg po daily PRN for wakefulness [~1x/wk] Case Example from Thursday [after]

57yoMWF BYU Professor w/insomnia, depression, anxiety [w/permission]: -Sleep regimen: • -Start melatonin 10mg po qhs 3h before bed for insomnia. • -Start Catapres 0.1mg po qhs 1-2h before bed for insomnia. • -Continue doxepin 10mg po qhs 1-2h before bed for insomnia. • -Continue Mirapex 0.125mg po qhs 1-2h before bed for RLS. • -Continue Lunesta 3mg po qhs immediately before bed for insomnia, stop if any sleepwalking. • -Start Fish Oil 1gm po bid, continue Vitamin D and Calcium. • -Continue Viagra 50mg po daily PRN for ED. • -Continue Prozac 40mg po daily for depression and anxiety. • -Continue modafinil 200mg po daily PRN for wakefulness [less now] Case Example from Thursday [?really] 57yoMWF BYU Professor w/insomnia, depression, anxiety [w/permission]:

• Notably, this is a patient with no suicide attempts

• Sleep regimen: THAT IS 5 MEDS! Case Example from Thursday [?really] 57yoMWF BYU Professor w/insomnia, depression, anxiety [w/permission]:

• Notably, this is a patient with no suicide attempts

• Sleep regimen: THAT IS 5 MEDS! • Why not just give Seroquel? Case Example from Thursday [after]

57yoMWF BYU Professor w/insomnia, depression, anxiety [w/permission]: -Sleep regimen: • -Start melatonin 10mg po qhs 3h before bed for insomnia. THESE 5 MEDS ARE • -Start Catapres 0.1mg po qhs 1-2h before bed for insomnia. LESS LIKELY TO HURT HER THAN AN • -Continue doxepin 10mg po qhs 1-2h before bed for insomnia. ANTIPSYCHOTIC. • -Continue Mirapex 0.125mg po qhs 1-2h before bed for RLS. • -Continue Lunesta 3mg po qhs immediately before bed for insomnia, stop if any sleepwalking. • -Start Fish Oil 1gm po bid, continue Vitamin D and Calcium. • -Continue Viagra 50mg po daily PRN for ED. • -Continue Prozac 40mg po daily for depression and anxiety. • -Continue modafinil 200mg po daily PRN for wakefulness [less now] What are some other sleep medication dilemmas that you run into? Questions??? Thank you for your attention