Insomnia, Drowsiness and Fatigue

Presentation of Insomnia

Difficulty falling sleep

Frequent awakening with difficulty falling back asleep

Early morning awakening with difficulty falling back asleep

Disturbed quality of sleep with unusual or troublesome dreams

Poor sleep in general

Impaired daytime functioning

Duration of sleep may be normal compared to average, but it may taken them longer to fall asleep

Quality of life is negatively impacted

Other: fatigue, drowsiness, anxiety, irritability, depression, decreased concentration, memory impairment.

Exclusions for Self Care

• <12 years

• > 65 years of age

• Pregnancy

• Frequent nocturnal awakenings or early morning awakenings (may be associated with depression)

• Chronic insomnia > 3weeks (OTC options aren’t generally helpful)

• Sleep disturbances secondary to psychiatric or general medical disorders

Treatment goals

• Improve duration and quality of sleep

• reduce fatigue and drowsiness during the day

• Improve daytime functioning

• Minimize adverse effects of treatment

• Improve the pateint’s presenting symptoms

• Improve quality of life

Nonpharmacologic treatment

Recommended for transient and short-term insomnia with no underlying medical or psychiatric conditions that cause insomnia

• sleep hygiene

• Establish a normal sleep cycle: go to bed and wake up at the same time every day, including weekends

  • Make the bedroom comfortable for sleeping

  • Engage in relaxing activities before bed

  • Use bed for sleep and intimacy only

  • Avoid caffeine, alcohol and nicotine 4-6 hours before bed

  • Exercise regularly but avoid late-night exercise (2-4 hrs before bed)

  • Eat a snack if hungry but avoid late-night heavy meals 2 hrs before bed

  • Avoid daytime napping

  • Remove environmental distractions (noise, lighting, uncomfortable temperatures, new surroundings)

  • Don’t lay in bed if unable to fall asleep, get up and perform a relaxing activity until tired

  • Do not watch the clock

Pharmacologic Treatment: Diphenhydramine MOA

MOA:Competes with histamine for H1-Receptors sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract; anticholinergic and sedative effects are also seen

• Indication

  • Symptomatic management of transient and short-term sleep difficulty (particularly sleep latency)

  • Use of diphenhydramine as a sleep aid should be limited according to the 2017 American Academy of Sleep Medicine (AASM) guidelines

• Dosing

50 mg at bedtime, some patients benefit from 25 mg at bedtime

• After 3 days take an “off” night to assess sleep

• Tolerance develops ~ 4 days

• Use for no more than 7- 10 consecutive nights as insomnia

may be secondary to a serious medical or psychiatric conditi

Pharmacologic Treatment:Diphehydramine Side effects

Anticholinergic: dry mouth/ throat, constipation, urinary retention, blurred vision and tinnitus; anticholinergic toxicity may occur

Drowsiness

Drug interactions

• Other medications that can cause drowsiness→2D6 inhibitor

Kinetics

• Max sedations in 3-6 hours after the dose

• Half-life is 2.4-9.3 hours

Anticholinergic side effects

Salivation

Lacrimation

Urination

Defecation

can pee cant see cant spit cant shit

Pharmacologic Treatment: Diphenhydramine

Counseling Points

• Avoid driving, cooking,operating heavy machinery until they know they are effected

• Do not drink alcohol while taking

• Paradoxical excitation may occur (most frequent in children, elderly, those with mental illness

Contraindications

• Older men with BPH and trouble urinating

• Angle-closure glaucoma

• Patients with angina or arrhythmias

• Patients with decreased cognition/dementia

1st Generation Antihistamines

Doxylamine→ safety and efficacy as a sleep aid not fully established

First Generation Antihistamines often cause drowsiness!The side effects seen are similar to those common with diphenhydramine- Anticholinergic

Pharmacologic Treatment: Doxylamine& Ethanol

Doxylamine

• Safety and efficacy have not been fully established

• Commonly available in sleep aid products

• DO not recommend - less efficacy data than diphenhydramine

Ethanol

• Commonly used by patients to induce sleep

• Associated with hazardous drinking

• Initially improves sleep in patients who do not abuse alcohol

• High dose:sleep disturbances occur in the second half of the night

• Tolerance develops quickly→leads to using higher doses

• Chronic uses causes disorganization of sleep, restless sleep, reduced sleep duration

• Present in some OTC products (10%)

Pharmacologic Treatment CAM - Melatonin- Strongest Evidence

• Benefits are limited -May be effective for some types of insomnia

• Usual dose is 0.3-5 mg at bedtimes (30 minutes prior)

  • AASM data based on 2 mg

  • Conflicting data

• BEST evidence seen in patients with neurological disorders, elderly, depression or jet lag

Pharmacologic Treatment CAM 5-Hydroxytryphan (5-HTP)

• Immediate precursor to serotonin

• Efficacy is not established; May be linked to eosinophilia-myalgia syndrome (EMS)

• Do not recommend

Pharmacologic Treatment CAM Valerian (valeriana officinalis)

• Limited benefit

• Trials have used doses of 400-900 mg

• Continuous nightly use for days- weeks is needed for effects (not useful in acute insomnia)

• withdrawal can occur when large doses are taken for many years, discontinue slowly via taper

Pharmacologic Treatment CAM Kava

• Associated with serve hepatotoxicity

• do not recommend

• Chamomile, ginseng, lavender, hops, lemon balm, passion flower

• Inadequate evidence

Special Populations insomnia

Pregnancy

• Benefit vs. risk→refer to medical provider

• Diphenhydramine: pregnancy catergory B

Breastfeeding

• Increased risk CNS effects in breastfed infants whose mothers ingest sedating antihistamines

• Use of low dose after daytimes feeding may lessen the effects

• Drowsiness can be seen in infants whose mothers ingest larger doses of sedating antihistamines for sustained periods

Special populations continues insomnia

Children/ Adolescents:

• May present with insomnia secondary to circadian rhythm disorder

• Use behavioral interventions/ sleep hygiene first

• Diphenhydramine/ doxylamine are not indicated for insomnia in children <12

• Diphenhydramine may cause paradoxical excitation in younger children

• Do not use both oral and topical diphenhydramine in children (toxicity)

Teenagers:

• Ask about use of caffeine/ alcohol

Older Adults:

▪ Beers criteria recommends avoiding anticholinergics in older adults

▪ Diphenhydramine may cause cognitive impairment/ falls -> refer to medical provider

Patient Counseling

• Practice good sleep hygiene-this may resolve insomnia on its own!

▪ Review the dosage guidelines and duration of therapy if recommending a pharmacologic option

▪ Review adverse effects, drug interactions, precautions and warnings for

recommended pharmacologic options

▪ Educate on the signs and symptoms that indicate the patient should see their provider (i.e. sleep has not improved within 10 days)

▪ Discourage the use of more than 1 concomitant pharmacologic insomnia option (due to increased risk of adverse effects)

▪ AASM’s weak recommendation against the use of diphenhydramine for treatment of sleep-onset and sleep-maintenance insomnia is based on low-quality evidence in patients receiving 50 mg doses

Drowsiness and Fatigue Basics

▪ Most often caused by inadequate sleep (duration and quality)

▪ increase risk of workplace and transportation accidents-

▪ increase accidents in drivers who report <7 hours of sleep per night

▪ Adversely effects on mood, productivity, and overall health

▪ May affect 22% of the population

Caffeine

▪ The most commonly used stimulant worldwide

▪ Average caffeine intake is 227 mg daily

▪ Caffeine is in multiple OTC drugs, Rx drugs, dietary

supplements and beverages

Sleep and Wakefulness

Sleep and wakefulness is affected by

1. Homeostatic mechanisms

2. Circadian rhythms

3. Medications

▪ CNS depressants, benzodiazepines, hypnotics, antihistamines,

antipsychotics, antidepressants, mood stabilizers, alcohol,

anticonvulsants, opioids, dopamine agonists, antibiotics, antihypertensives

4. Diseases

▪ Depression, cancer, anemia, hypothyroidism, chronic pain, overexertion,

imbalances in diet/ exercise

Presentation of Drowsiness and Fatigue

• Sleepiness

• Yawning

• Eye rubbing

• Tendency to fall asleep

• Decreased ability to focus and concentrate.

Exclusions for self Care

▪ <12 years of age

▪ Pregnancy

▪ Breastfeeding

▪ Heart disease

▪ Anxiety

▪ Medication-induced drowsiness (refer to prescriber for dose adjustment)

▪ Chronic fatigue (refer to PCP to rule out hypothyroidism, sleep apnea, other

medical conditions)

Treatment Goals

▪ Identify and eliminate the underlying cause

▪ Improve mental alertness and productivity

▪ Maintain wakefulness

Nonpharmacologic treatment for drowsiness and fatigue

• Sleep Hygiene

• See insomnia

Pharmacologic Treatment: Caffeine

▪ Caffeine cannot compensate for inadequate sleep!!!

▪ MOA: Increases levels of 3'5' cyclic AMP by inhibiting phosphodiesterase; CNS stimulant which increases medullary respiratory center sensitivity to carbon dioxide, stimulates central inspiratory drive, and improves skeletal muscle contraction(diaphragmatic contractility); prevention of apnea may occur by competitive inhibition of adenosine

▪ Indication

▪ Occasional use to restore mental alertness or wakefulness

▪ Low-moderate caffeine doses increase arousal, decrease fatigue and elevate mood; High

doses are associated with anxiety, nausea, and nervousness

▪ Dosing

▪ 100- 200 mg every 3-4 hours as needed; rapid tolerance is seen

Pharmacologic treatment Caffeine

Side Effects

▪ Withdrawal may occur with abrupt discontinuation, symptoms include throbbing headache, fatigue, decreased alertness, drowsiness, depressed mood and irritability

▪ Aggravation of peptic ulcer disease (PUD), gastric reflux and esophagitis

▪ Increase in blood pressure and heart rate

▪ Increased risk of kidney stones in at risk patients

▪ Delayed sleep onset

▪ Drug Interactions

▪ Cigarette smoking may increase the clearance of serum caffeine (1A2) by >50%

▪ What do you need to tell someone who is trying to quit smoking?

▪ Table 8 -> additional drug-drug interactions

▪ Kinetics

▪ Peak concentration in 30- 75 min

▪ Elimination half-life is 3- 6 hrs

Pharmacologic Treatment: Caffeine

Contraindications

▪ Patients taking monoamine oxidase inhibitors (MAOIs)

▪ Patients with existing coronary artery disease (CAD)

▪ Uncontrolled hypertension

▪ Preexisting arrhythmias

Additional Counseling

▪ Caution use of dietary supplements and weight-loss supplements which often do not list

caffeine amount

▪ Symptoms of excessive intake

▪ Irritability, tremor, rapid pulse, dizziness and heart palpitations

Pharmacologic Treatment-CAM

▪ Ginseng

▪ Contradictory evidence exists regarding ginsengs ability to boost mental and physical energy

▪ Strongest evidence for Chronic Fatigue Syndrome (not a self-care condition)

▪ Cola nut, guarana, yerba mate

▪ Often found in caffeine-containing dietary supplements

▪ Risk of additive adverse effects and toxicity when taken in excess

Special populations

Pregnancy

▪ Caffeine: pregnancy category B; Freely crosses placenta

▪ Moderate consumptions ≤ 200 mg/ day is acceptable

Breastfeeding

▪ Consume caffeine in small-moderate amounts, preferably after breast-feeding to reduce infant exposure

Children

▪ More susceptible to cardiovascular and CNS effects

▪ Maximum recommended intake is 2.5 mg/kg/day

▪ Nonprescription caffeine products are not indicated for children <12 years of age

Older adults

▪ Elimination half-life of caffeine is prolonged

▪ May experience an exaggerated pharmacologic effect and sleep interference-Avoid after dinner

Patient counseling

▪ Practice good sleep hygiene

▪ Eliminate factors that interfere with normal sleep

▪ Review dosage guidelines for caffeine products

▪ Review adverse effects, drug interactions, precautions and warnings for caffeine products including irritability, tremor, rapid pulse, dizziness and heart palpitations (especially in older adults)

▪ Educate on the signs and symptoms of caffeine withdrawal

▪ Excessive sleepiness is a warning of inadequate sleep which is potentially LIFE THREATENING

▪ Educate on the signs and symptoms that indicate the patient should see their provider (i.e.increased pulse, headache, anxiety, etc)