Sleep Medications in Primary Care Disclosure • No Real Or Potential

Sleep Medications in Primary Care

Disclosure Sleep Medications in Primary Care • No real or potential conflict of Margaret A. Fitzgerald, interest to disclose. DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC, FNAP President, • No off-label, experimental or Fitzgerald Health Education Associates, North Andover, MA investigational use of drugs or Family Nurse Practitioner, Greater Lawrence (MA) Family Health Center devices will be presented. Editorial Board Member The Nurse Practitioner Journal, The Prescriber’s Letter, American Nurse Today Member, Pharmacy and Therapeutics Committee Neighborhood Health Plan, Boston, MA

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Objectives Objectives (continued) • Upon completion of the learning • Upon completion of the learning activity the participant will be able to: activity the participant will be able – Describe the process of naturally- to: (cont.) occurring sleep. – Recognize the anticipated sleep – Identify the pharmacokinetics and outcomes with select medications pharmacodynamics of medications and commonly prescribed or used to herbal products to enhance sleep. enhance sleep as well as the risks associated with these products.

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Sleep Defined Insomnia: The Cost of the Problem (Or Best Defined in its Absence?) • Difficult to define and characterized • Costs the average American worker by observable changes in behavior – 11.3 days per year, $2,280 in lost and responsiveness productivity each year – Decreased activity • Presenteeism vs. absenteeism – Recognizable posture •Entire USA – Brain is less attentive to external stimuli – $63.2 billion in lost productivity – Source: http://healthland.time.com/2011/09/01/the-high-cost- – Altered consciousness yet easily aroused of-bad-sleep-63-billion-per-year/ –Source: http://healthysleep.med.harvard.edu/healthy/science/what/characteristics

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Insomnia: The Cost of the Problem The focus of this program is medications (continued) used to induce/maintain sleep. • In primary care • Not addressed in program – Up to 1/3 of all patients have a complaint of – Sleep apnea, central disordered sleep or obstructive – One in 6 patients – Restless leg syndrome describing problem – Parasomnias, sleepwalking, as “serious or severe” sleep terrors – One in 12 patients –Narcolepsy describing problem –Others as “chronic” – Source: http://www.medscape.org/viewarticle/478849

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Insomnia Disorders (continued) Insomnia Disorders • Defined – Complaint of difficulty in falling asleep, Source: maintaining sleep (awakening frequently http://www.dsm5.org/File%20Library/Psychiatrists/Pract during the night), or an inability to easily ice/DSM/APA_DSM-5-Sleep-Wake-Disorders.pdf fall back asleep – Dissatisfaction with sleep – Significant negative impact on daytime functioning

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Insomnia Disorders Insomnia Disorders (continued) (continued) • Dissatisfaction with sleep defined • Significant negative impact on daytime functioning defined – Difficulty initiating and/or maintaining sleep – Significant fatigue – Non-restorative sleep – Sleepiness – ≥3 nights per week for ≥3 months, – Poor concentration despite adequate opportunity to sleep – Low mood – Impaired ability to perform social, occupational or caregiving responsibilities • Not explained by other health issues

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Cognitive Behavioral The focus of this program is medications Therapy (CBT) for Insomnia used to induce/maintain sleep. Consider medications as an aid to gap while working with patient on CTB. Assumed that the NP has Resources: appropriately assessed the patient http://www.mentalhealth.va.gov/coe/cih- and that a sleep medication is a visn2/Documents/Provider_Education_Handouts/CBT_for_Inso prudent clinical action with risks mnia_Information_Sheet_for_BHPs_Version_3.pdf and benefits shared with patient http://www.sleepeducation.org/treatment-therapy/cognitive- behavioral-therapy

Caffeine’s Pharmacokinetics One Culprit of Modern-day Life Clinical Significance? Caffeine • MW=194.19 • Lipophilic

•T½ range=1.5−9 h

•Cmax=~15−100 mins • Minimum first-pass effect • CYP 450 substrate 1A2 Source image: https://en.wikipedia.org/wiki/Caffeine – Source: http://books.nap.edu/openbook.php?isbn=0309082587

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True or false? Caffeine PK

• When compared with a healthy • Common 1A2 inhibitors? 40-year-old adult, CYP 450 isoenzyme – Remember the “Cs” levels can drop by up to 30% in elders •Ciprofloxacin after age 70 years. • Cimetidine • Common 1A2 inducer? • CYP 450 1A2’s activity is influenced by – Nicotine the presence or absence of estrogen in women. – And remember to advise when cutting down…

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Sleep Architecture Non-REM: Stages 1 and 2 Naturally-occurring Sleep’s 2 Stages •Stage 1 1. Non-rapid eye movement (NREM) – Easily awakened –Stage 1 − Transitional “muscle jump” –Stage 2 − Light sleep (hypnic myoclonia) –Stage 3 − Deep sleep •Stage 2 –Stage 4 − Deepest sleep – Heart rate slows, body 2. Rapid eye movement (REM) temperature drops – 50% of total sleep time

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Non-REM: Stage 3 Stage 4: “Deep Sleep”

•Stage 3 •Stage 4 –Delta waves –Delta waves exclusively, (slow waves) difficult to arouse, –Moving to no eye movement or deeper sleep muscle activities –When interrupted, “groggy and disoriented” –Stage of bedwetting, night terrors or sleepwalking occur during deep sleep

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REM Sleep Sleep Stages 20% of Adult Sleep Movement Through 5 Stages • Rapid, irregular and • Adults actively shallow breathing move through the • Rapid eye jerks in sleep process from various directions NREM stages 1−4 • Temporary paralysis to REM of limb muscles – Complete cycle • Increased HR, BP typically 90−100 minutes • Penile erections – Complete 4−5 • Most vivid dreams cycles per night

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Sleep Stages Circadian Rhythm Movement Through 5 Stages (continued) • Biologic “internal clock” •Length of REM –Housed in sleep becomes suprachiasmatic nucleus progressively in anterior hypothalamus longer and time – Fully developed by age in deep sleep 25 years –Source: decreases http://www.howsleepworks.com/ho throughout w_circadian.html the night

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Sleep-Wake Homeostasis

Potential Influence of Sleep Aids • The pressure to sleep on Sleep Architecture: – Also known as sleep drive Potential Increase in Stage 1, Stage 2 Sleep • Unable to overcome Potential Reduction in Stage 3, Stage 4, – With use of stimulants, can only mask REM Sleep need to sleep Consider as short-term therapy! – With medications, can mildly promote or enhance sleep drive Source: http://www.medscape.com/viewarticle/723907_2

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Pharmacology of Insomnia Treatment Pharmacology of Insomnia Treatment Therapeutic Approaches Therapeutic Approaches (continued) • Stimulate/activate sleep-promoting system • Suppress the wake-promoting systems –GABA –Histamine • Inhibitory neurotransmitter (NT) – Cholinergic • Main hypothalamic NT, projects to several sleep-regulating centers of the brain – Serotonin – Increase in GABA inhibits (“blocks”) the wake- –Orexin promoting chemicals –Melatonin

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In particular, for sleep medications T that induce sedation, what is the ½ medication’s half-life (T )? ½ • Time required for the amount of drug How much of the medication will be in the body to be reduced or eliminated on board upon AM awakening? by ½

Onset of action? • Also known as elimination or biological T½ Peak of action? –3−5 T½ needed to reach steady state –3−5 drug-free T needed to eliminate Reference: ½ PL Detail-Document, Comparison of Insomnia Treatments. drug from body Pharmacist’s Letter/Prescriber’s Letter. May 2012.

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What % is left of original drug dose? True or false?

•1 T½ •The T½ of a medication is a predictable – 50% left number regardless of the patient’s age, •2 T½ – 50% of 50%=25% left gender, and overall state of health.

•3 T½ • If a sleep med is taken at 10 PM and has – 50% of 50% of 50%=12.5% left a T½ of about 2 h, then approximately •4 T½ 6.5% of the original dose will be on board – 50% of 50% of 50% of 50%=6.25% left with 6 AM awakening. •5 T½ – 50% of 50% of 50% of 50% of 50%=3.125% left

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True or false? With Many if Not Most Sleep Meds

• In order to exploit optimal PK, all • When coadministered with alcohol sleep medications should be taken – Additive psychomotor impairment on an empty or near-empty • Habituation/misuse stomach. – Reported in most clinical trials • When taken with a meal, the onset – Controlled substance of sleep latency with many sleep • Most are Schedule 4 with exception of meds will be delayed by 1.5−3.5 h. psychotropics used for conditions other than sleep, OTCs, herbal products

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What would you want to prescribe, if Sleep Medications with GABA-generic appropriate, for the patient who states, Effect=Enhances Sleep Promotion • “I have an 8-h overnight flight where I • Non-benzodiazepines need to walk off the plane and go right • GABA role= Blocks action of to an important meeting. Can I have excitatory brain chemicals – Zolpidem (Ambien®, something to help me get some shut-eye Intermezzo®) on the plane?” – Zaleplon (Sonata®) • “My patient is in a subacute care hospital – Eszopiclone (Lunesta®) for a few days and cannot fall asleep. Once asleep, he stays asleep fairly well.”

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Short T½ Onset of Action=~30 mins Peak=~1h •Zaleplon FDA Advisory about Zolpidem Dose – Ultra-short, T½=1h • Zolpidem FDA Drug Safety Communication: Risk of next- –Short, T½=2−2.5 h morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem, available at http://www.fda.gov/drugs/drugsafety/ucm334033.htm

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Zolpidem Tartrate From FDA Advisory Specifically Labeled for Middle-of-the-night •Dosing Awakening with ≥4 h Sleep Duration Available – Recommended zolpidem immediate-release •Dose dose: 5 mg for women and either 5 mg or 10 mg for men –Men=3.5 mg – Recommended zolpidem extended-release – Women=1.75 mg dose: 6.25 mg for women and either 6.25 or • Only one dose per night, only if needed 12.5 mg for men – Source: Intermezzo® Prescribing Information, available at http://app.purduepharma.com/xmlpublishing/pi.aspx?id=i – CR formulation=Special warning about next-day performance issues – Higher doses should be used with caution.

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Longer T½ Onset of Action=~30 mins What would you want to prescribe, if Peak=~1h appropriate, for the patient who states, • Eszopiclone “I fall asleep with that sleep med you –T =6 h in adults, 9 h in elders gave me, but I do not stay asleep. ½ I am back up at 4 AM.” • Taken at 10 PM=50% of dose on board at 4 AM – Dose=Start with 1 mg, can increase to NB: Consider possible 2−3 mg if needed contribution of depression.

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FDA Warning in Patient Drug Information • “…sedative-hypnotic drug products, a class of drugs used to induce and/or maintain sleep, Common to all Sedative-hypnotics: strengthen their product labeling to include FDA Advisory stronger language concerning potential risks. These risks include severe allergic reactions and complex sleep-related behaviors, which may include sleep-driving. Sleep-driving is defined as driving while not fully awake after ingestion of a sedative-hypnotic product, with no memory of the event.” – Source: http://www.fda.gov/drugs/drugsafety/ucm352085.htm

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Sleep Medications with GABA-generic Zaleplon 1 Half-life (hours) Effect=Enhances Sleep Promotion Zolpidem 2 • Benzodiazepines Triazolam 3 • -pam suffix Eszopiclone 6 – Temazepam Temazepam Restoril® 11

Estazolam Prosom® 10-24 – Triazolam

Quazepam Doral® 39 – Estazolam

Flurazepam Dalmane® 74 –Flurazepam

0 20406080 –Quazepam

All brand names are the property of their respective owners. Source: Dikeos DG, Soldatos. Primary Care Companion. J Clin Psychiatry. 2002;4(suppl 1):27-32.

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BZD Pharmacokinetics Pharmacology of Insomnia Treatment Appropriate Sleep Aids? Therapeutic Approaches Dose Half-life in equivalent hours • Suppress the wake-promoting systems Alprazolam (Xanax®) 0.5 6−20 –Histamine ® Chlordiazepoxide (Librium )1030−100 – Cholinergic Clonazepam (Klonopin®)0.2518−50 – Serotonin Clorazepate (Tranxene®)7.530−100 –Orexin Diazepam (Valium®)530−100 Lorazepam (Ativan®)110−20 Oxazepam (Serax®)158−12 Source: http://www.vhpharmsci.com/vhformulary/tools/benzodiazepines-comparison.htm . 51 Fitzgerald Health Education Associates 52 Fitzgerald Health Education Associates. 51

Suvorexant Suvorexant (Belsomra®) Mechanism of Action Mechanism of Action (continued) • What is it? • Blocking the binding – Orexin-receptor of neuropeptides antagonist orexin A and orexin • Any drug that occupies B to receptors OX1R a receptor site and and OX2R=Thought prohibits its activation to suppress the is an antagonist. wake drive Source of image: https://en.wikipedia.org/wiki/Or exin#/media/File:1CQ0_crystallo graphy.png

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Suvorexant Suvorexant C-IV PK Information • Indication • Peak plasma time • Zolpidem – For treatment of – 2 h post dose –T =2.6 h insomnia characterized ½ – With high-fat meal= • 2.6 h × 3=7.8 h, take by difficulties with sleep 1.5-h delay at 10 PM, approx. onset and/or sleep 12.5% of dose on maintenance in adults •T½=12 h board at 6 AM age ≥18 years – As a result, when –Time to Cmax=1.6 h • What would you expect taking at 10 PM, for PK? 50% of the dose still on board at 10 AM

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Suvorexant Suvorexant Precaution Recommended Dose Do we have this information on older meds? • How supplied • Per FDA-required study – 5 mg, 10 mg, 15 mg, and 20 mg tablets – Exposure to suvorexant increased in • Recommended daily dose obese compared to non-obese patients

– 10 mg, taken ≥30 mins prior to bedtime, •AUC and Cmax increased by 46% and 25% only if ≥7 h of sleep time available, only 1 respectively compared to nonobese females dose per night – Women compared to men • If 10 mg dose is well-tolerated but not • Consistent with warnings about other sleep effective, dose can be increased up to a aids including zolpidem maximum dose of 20 mg daily.

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Suvorexant Adverse Effects and Precaution (continued) • Patient advised about these in handout provided with medication Antidepressants as Sleep Medications – CNS depressant effects and Potential Advantages: Not scheduled, daytime impairment possibly less abuse potential, low cost – Abnormal thinking and behavioral changes Potential Disadvantages: Adverse effects – Worsening of depression/suicidal ideation – Sleep paralysis, hallucinations, cataplexy- like symptoms

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Two Patients Commonly-prescribed Possible TCA or Trazodone Candidates Psychotropic Medications • A 60-year-old woman with DM neuropathy • Tricyclic antidepressants (TCA) with partial improvement with pregabalin, – Block reuptake of NE, 5-HT difficulty initiating and maintaining sleep • Amitriptyline, nortriptyline in part due to leg burning • Issues with use • A 56-year-old man with 30-year hx alcohol – Significant AE in overdose abuse, now sober × 5 years, difficulty – Sedating, possibly helpful with chronic pain initiating and maintaining sleep –Inexpensive

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Action of Psychotropic Medications TCA as Sleep Aids (Katzung, 2014) • Nortriptyline, amitriptyline Sedation or Anti- Drug activation cholinergic Serotonin NE Dopamine – Onset of action=1−3 h Sedation –Time to peak=7−8 h Amitriptyline +++ ++++ +++ ++ 0 –T =24−31 h Activation 0 ½ Sedation ++ Nortriptyline ++ +++ ++ 0 • Perhaps helpful Activation 0 – Chronic painful conditions such as DM Sedation Trazodone +++ 00/+00 neuropathy, recurrent headache, others Activation 0 • Perhaps problematic Mirtazapine Sedation +000 ++++ – Daytime drowsiness Activation 0

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Adverse Effects Meds with Anticholinergic Effect • Dry as a bone (dry mouth) • Red as a beet (flushing) American Geriatrics Society Updated Beers • Mad as a hatter (confusion) Criteria for Potentially Inappropriate • Hot as a hare (hyperthermia) Medication Use in Older Adults • Can’t see (vision changes) • Can’t pee (urinary retention) Available at: http://onlinelibrary.wiley.com/doi/10.1111/jgs • Can’t spit (dry mouth) .13702/abstract • Can’t (something that rhymes with spit) (constipation)

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® Doxepin (Silenor®) Doxepin (Silenor ) (continued) • Tricyclic antidepressant • Recommended dose – FDA-approved as sleep aid – 3 mg (elder) or 6 mg (adult) – Significant systemic anticholinergic effect • Per Beers Criteria, do not Rx ≥6 mg in the • PK parameters older adult

–Tmax=3.5 h post dose when taken on an – Take within 30 mins of going to bed empty stomach – Do not take within 3 h of a meal • Doubled when taken with a high-fat meal, •Alters PK labeled warning

–T½=15.3 h

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Doxepin Tetracyclic Antidepressant (continued)

• Pharmacogenomics •Trazodone warning – FDA-approved for treatment of depression • Effect on cholinergic and serotonin – Poor CYP2C9, 2C19 neurotransmitters metabolizers will – Seldom used to treat depression due to sedation likely have greater – Pharmacokinetics doxepin exposure. •Peak=1−3 h

•T½=7−8 h

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Mirtazapine (Remeron®) Q and A • Mechanism of action α • When using trazodone or a TCA to aid – Blocks presynaptic 2-adrenergic autoreceptor; sleep, the drug should be optimally blocks 5-HT2, 5-HT3 taken _____ prior to sleep. • Net effect, enhance serotonin and NE activity •Dose A. Immediately – 7.5–15 mg at bedtime for sleep helpful B. 15–45 minutes • More sedating at lower dose C. 1–2 hour – Depression dose=45−60 mg/d D. 2–3 hours •PK –Peak=2 h

–T½=20−40 h

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Mirtazapine Action of Psychotropic Medications th (continued) (Katzung and Trevor, Basic and Clinical Pharmacology, 13 ed. 2014) Sedation or Anti- • Not FDA-approved for insomnia Drug activation cholinergic Serotonin NE Dopamine Sedation – Some evidence on reducing insomnia in Amitriptyline +++ ++++ +++ ++ 0 depression, especially early in treatment Activation 0 Sedation ++ Nortriptyline ++ +++ ++ 0 – Increases the risk of restless leg Activation 0 syndrome and periodic limb movements Sedation in sleep Trazodone +++ 00/+00 Activation 0 Mirtazapine Sedation +000 ++++ Activation 0

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SGAs as Sleep Aids Second-generation Antipsychotics (SGA, AKA Atypicals) • The evidence as Sleep Aids – Particularly more sedating members of the class demonstrated to be helpful in Sleep-inducing due to largely the presence of schizophrenia antihistamine and serotonin effect. – Not extensively studied in unipolar Potential drugs of abuse (“Baby Heroin,” etc.) depression as a sleep aid Is there a therapeutic indication – Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC487011/ for use of these meds beyond sleep?

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SGA: Most Sedating= Less Sedating SGA=Less Antihistaminic Greater H1 Antagonism Effect=Less Weight Gain • H1 antagonism=possible weight gain • But how helpful for sleep? – Clozapine (Clozaril®) – Ziprasidone (Geodon®) • Seldom used for sleep due to need for WBC – Aripiprazole (Abilify®) monitoring due to neutropenia risk – Asenapine (Saphris®) – Olanzapine (Zyprexa®) – Lurasidone (Latuda®) – Quetiapine (Seroquel®) ® ® – Paliperidone (Invega ) – Risperidone (Risperdal ) – Source: Comparison of atypical antipsychotics. Pharmacist’s – Source: Comparison of atypical antipsychotics. Pharmacist’s Letter/Prescriber’s Letter. July 2015;310701. Letter/Prescriber’s Letter. July 2015;310701.

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SGA PKs: SGA PKs: When should the med be When should the med be taken if used to enhance sleep? taken if used to enhance sleep? (continued) • Olanzapine PK • Risperidone – Plasma peak=6 h post dose – PK related to CYP 2D6 activity –T =21‒54 h ½ • Plasma peak in extensive metabolizers=3 h •Quetiapine • Plasma peak in poor metabolizers=17 h

– Plasma peak with IR formulation=1.5 h •T½ in extensive metabolizers= 3 h •T in poor metabolizers=20 h –T½=6 h ½

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Source: Ann Pharmacother. 2012;46:718-22.

• “There are potential safety concerns Antihistamines when using low-dose quetiapine for Sold OTC, Significant Anticholinergic Effect treatment of insomnia. These concerns Avoid in elders. should be evaluated in further prospective studies. Based on limited Dangerous in overdose data and potential safety concerns, use Best candidate is younger adult of low-dose quetiapine for insomnia is with temporary issue with sleep. not recommended.”

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Antihistamines as Sleep Aids Antihistamines as Sleep Aids (continued) • Potential tolerance • Hydroxyzine (Vistaril®, Atarax®) – Most often noted with ≥10 nights/use •Rx only – Consider an “off” night after three days –Dose 10−50 mg at bedtime

of use to reduce tolerance.. – Onset of action=15−30 mins – Avoid using more than ten days without –Peak=2 h

consulting a healthcare professional. –T½=3−7 h

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Antihistamines as Sleep Aids Antihistamines as Sleep Aids (continued) (continued) • Diphenhydramine (Benadryl®) •Doxylamine • In the majority of OTC sleep aids – Dose 12.5−25 mg at bedtime – Dose=12.5−50 mg • In OTC sleep aids that do not have – Onset of action=15−30 mins diphenhydramine as a primary ingredient

–Peak=2 h –T½=10 h

–T½=2−8 h –Tmax=2 h • Up to 13 h in elderly

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Role of Melatonin in Sleep Melatonin as Sleep Aid • Produced endogenously by pineal gland • Available OTC – Released in rhythm that is largely in – Be aware of quality of nutraceutical synch with the body’s circadian rhythm – Choose USP-verified with distinctive label – Signals darkness, brain and body should •Dose get ready for sleep – 0.3 to 3 mg, usually taken around the • Sleep-enhancing time a reasonable person would expect to – Consider this as a sleep facilitator rather be getting sleepy than sedating medication. • For example, around 9 PM for a person who – Source: http://www.ncbi.nlm.nih.gov/pubmed/12622846 will go to bed at 10 PM and get up at 6 AM

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Melatonin as Sleep Aid Ramelteon (Rozerem™) (continued) • • Best suited for What is it? person with – FDA-approved for treatment of insomnia – Jet lag, AKA characterized by sleep-onset difficulty desynchronosis –Dose – Chronic circadian • 8 mg dose taken within 30 mins of bedtime disorder – Avoid use with high-fat meal • Adverse effects • Studied in long-term use – Vivid dreams reported – Not a controlled substance

Source: – Initially promoted as without abuse potential https://en.wiki2.org/wiki/Pok%C3%A9mon_Jet#/media/Fil e:Pokemon_Jets.jpg – Source: Hirai et al., 2005

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Ramelteon PD Ramelteon PK • Highly selective, nonspecific • Rapidly absorbed MT1/MT2 agonist within 0.5−1.5 h – 6- and 3-fold higher affinities for MT and 1 –Tmax=0.75 h MT2 than melatonin, respectively •T½ • No measurable affinity for a large – 1.36 h (1−2.6 h) number of tested ligand binding sites • Metabolized (i.e., including GABAA receptors, dopamine receptors, opiate receptors, – CYP1A2 isozyme ion channels and transporters)

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Easily-found Online Tasimelteon (Hetlioz®) “Ramelteon (Rozerem™) Poppers” • “The usual dosing is in 8 mg tablets, • Indication but people seeking “ramelteon – Treatment of Non-24-Hour Sleep-Wake (Rozerem™) highs" might take as much Disorder (Non-24) as a total of 24−32 mg at a time, mix it • Most commonly noted in people who are blind who do not get light/dark signals with booze or other anti-anxiety benzos • Mechanism of action or sleep aids (such as zolpidem)… a wonderful weed-like high that lasts – Agonist at melatonin MT1 and MT2 receptors • Receptors believed to be involved in circadian about 1 h.” rhythm control – Source: http://www.urbandictionary.com/define.php?term=rozerem

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Tasimelteon (continued) •Dosage – 20 mg per day taken before bedtime, at Plant-based Products as Sleep Aids the same time every night – Effect typically not seen until weeks or months of regular use

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Kava Kava as Sleep Aid Kava Kava as Sleep Aid (continued) • Efficacy • Mechanism of action –Mixed as sleep aid or – Kavalactones act on treatment of anxiety limbic system •Caution – Mixed evidence of impact –Hepatoxicity on GABA, dopamine or opioid receptors • Increased when taken with acetaminophen • Dose as sleep aid • Noted in absence of – 180−210 mg at bedtime underlying liver disease –Source: https://naturalmedicines.therapeuticresearch.com/databases/ food,-herbs- supplements/professional.aspx?productid=872#background

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Valerian Root Anesthesia and Herbal Products Avoid Concomitant Use • Mechanism of action – Not clearly understood, likely •Valerian, kava via multiple mechanisms • Kava kava •Dose – Potential for prolongation of anesthesia – 400−900 mg aqueous extract – Source: Nutritional Supplements and Perioperative Evaluation, up to 2 h prior to bedtime available at https://www.aao.org/complimentary-therapy- assessment/nutritional-supplements-perioperative-implications –Source: https://naturalmedicines.therapeuticresear ch.com/databases/food,-herbs- supplements/professional.aspx?productid= 870#background

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• Images/illustrations: Unless otherwise noted, all images/illustrations are from End of Presentation open sources, such as the CDC or Thank you for your time and attention. Wikipedia or property of FHEA or author. Margaret A. Fitzgerald, • All websites listed active at the DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC, FNAP time of publication.

www.fhea.com [email protected]

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Copyright by Fitzgerald Health Education Associates • The information in this program has been thoroughly All rights reserved. No part of this publication may be reproduced or transmitted researched and checked for accuracy. However, clinical in any form or by any means, electronic or mechanical, including photocopy, practice and techniques are a dynamic process and new recording or any information storage and retrieval system, without permission from Fitzgerald Health Education Associates information becomes available daily. Prudent practice dictates that the clinician consult further sources prior to Requests for permission to make copies of any applying information obtained from this program, whether part of the work should be mailed to: in printed, visual or verbal form.

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