Pharmacotherapy of sleep disorders Flashcards
DISEASE STATES, MEDICATIONS, SUBSTANCES ASSOCIATED WITH INSOMNIA
Anxiety, Hyperthyroidism, Caffeine, Modafinil, Amphetamines,Beta‐agonists,Beta‐blockers, Nicotine, Thyroid meds, Bupropion,Decongestants, Methylphenidate
DSM‐5 – INSOMNIA DISORDERS
Difficulties with sleep initiation (latency), sleep maintenance, and/or early‐morning awakening Takes place at least 3 nights per week Present for at least 3 months
Treatment of insomnia disorders
First‐line treatment is non‐pharmacological,Sleep hygiene principles are necessary and should be counseled by the pharmacist
The z‐hypnotics (zolpidem, eszopiclone, zaleplon) are the most commonly used sleep medications:
Initial dose of zolpidem is lower in women and elderly – 5 mg
Eszopiclone (Lunesta®) is FDA‐approved for long‐term (6 months) use – patients
complain of metallic taste
3A4 substrates – metabolism is impacted by 3A4 inhibition and induction
Somnolence, dizziness, ataxia, headaches
Can cause parasomnias – unusual actions while a person is sleeping – is a warning on all medications used for sleep
Controlled substances – potential for misuse
Additive effects with other CNS depressants
BNZ and insomnia
Temazepam is the benzodiazepine used for sleep
Drowsiness, dizziness, cognitive impairment, increased fall risk
All medications FDA‐approved for insomnia have sleep behaviors warning
Melatonin receptor Agonists
Ramelton:Contraindicated with fluvoxamine, GI upset, next day somnolence, hyperprolactinemia, prolactinoma
Tassimelton: FDA‐approved for non‐24 sleep‐ wake disorder in adults
1A2 substrates: watch for 1A2 inducers and inhibitors
Suvorexant
Orexin receptor Antagonists at least 7 hours to sleep
Contraindicated in narcolepsy – causes narcolepsy‐like side
effects 3A4 substrate
Lemborexant
OREXIN RECEPTOR ANTAGONISTS at least 7 hours to sleep,Contraindicated in narcolepsy – causes
narcolepsy‐like side effects 3A4 substrate
Daridorexant
OREXIN RECEPTOR ANTAGONISTS at least 7 hours to sleep Contraindicated in narcolepsy – causes narcolepsy‐like side effects3A4 substrate
Doxepin (Silenor®)
TCA – low doses exert effect through H1 receptor antagonism
Anticholinergic side effects
Trazodone
Not FDA‐approved for insomnia
Long half‐life – may see daytime hangover
Quetiapine
Low dose quetiapine is not recommended for use in insomnia unless there is a co‐morbid psychiatric disorder
Mirtazapine
Clinically used as a sleep agent, especially in patients with depression who have difficulty sleeping
Diphenhydramine/Doxylamin
Not recommended by AASM
Melatonin/Valerian/Chamomile
Melatonin can be considered in jet lag and patients with low melatonin levels; 1A2 substrate
German chamomile contains a BZD‐like compound; allergic reactions in patients with daisy or ragweed allergies
Kava may be used by patients but is not recommended due to hepatotoxicity
What is first line for sleep disorders
CBT and behavioral
therapies are first‐line
DSM‐5 CRITERIA OBSTRUCTIVE SLEEP APNEA
Patient must have evidence of at least 5 obstructive apneas per hour of sleep confirmed by polysomnography
Symptoms include excessive daytime sleepiness, snoring, pauses in breathing during sleep, headache, irritability, sore throat, erectile dysfunction, impaired memory, GERD, mood disturbance
Clinically, there is greater recognition that many patients have both apnea and insomnia – both need to be treated with apnea treated first
AASM GUIDELINE 2017 DIAGNOSTIC TESTING FOR SLEEP APNEA
Polysomnography only if there is significant cardiorespiratory disease, potential respiratory muscle weakness due to a neuro‐muscular condition, sleep‐related
hypoventilation, chronic opioid medication use, history of stroke, or severe insomnia
Tx sleep apnea
Weight loss (adjunctive rather than curative), smoking cessation, avoid alcohol and CNS depressants, sleep on side rather than back
If a patient is overweight/obese and comes for evaluation for insomnia, consider assessment for sleep apnea prior to initiating medications
CPAP – continuous positive airway pressure
Excessive daytime sleepiness (EDS) can be treated with modafinil or armodafinil –
need to review CPAP adherence first and possibility of RLS or PLMS
When considering treating apnea and insomnia, ensure that the obstructive apnea is addressed before recommending sedative/hypnotic drug therapy
DSM‐5 CRITERIA: NARCOLEPSY
Recurring episodes of irresistible need to sleep, fall asleep, or nap; three times per week over the past 3 months (excessive daytime sleepiness)
THE NARCOLEPSY TETRAD
EDS – Occurs in 100% of patients, generally more severe in Type I narcolepsy
(narcolepsy with cataplexy or hypocretin deficiency syndrome)
Cataplexy – sudden loss of muscle tone triggered by emotion – 75% of patients
Hallucinations – 30% ‐ 60% of patients
Sleep paralysis – 25% ‐ 50% of patients
All four symptoms – 10% ‐ 33% of patients
Tx of narcolepsy
Cataplexy: Sodium oxybate (Xyrem®) – GHB – high sodium content
Xywav® ‐ For adults and children aged 7 or older, also approved for idiopathic hypersomnia in adults – lower sodium content
Lumryz® ‐ For adults only – ER dosage form, once nightly dosing, high sodium content
Excessive daytime sleepiness: Modafinil/armodafinil: associated with possible life‐threatening rash
Sodium oxybate
Pitolisant and solriamfetol recently FDA‐approved for EDS
Pilosant
Used to tx narcolepsy
H3 receptor antagonist/ inverse agonist
Contraindicated in severe hepatic impairment
Prolongs QT interval
2D6/3A4 substrate
Weak 3A4 inducer – may reduce effectiveness of oral contraceptives
Avoid use with centrally‐acting H1 receptor antagonists (OTC antihistamines
Shift work sleep disorder
Modafinil and armodafinil are the drugs of choice, taken 1 hour before the work period starts during “wake time”
SOLRIAMFETOL
used to tx narcolepsy
Dopamine norepinephrine reuptake inhibitor (DNRI)
Indicated for improvement in wakefulness in adults with excessive daytime sleepiness due to narcolepsy or obstructive sleep apnea
- Moderate renal impairment – start 37.5 mg, may increase to 75 mg after at least 7 days; severe renal impairment – starting and max dose = 37.5 mg
- Warnings: B/P and HR increases – avoid in unstable CV disease and arrhythmias; use caution in patients with a history of psychosis or bipolar disorder – decrease dose or discontinue if psychiatric symptoms develop; use with caution with dopaminergic drugs
Restless Legs syndrome
Gabapentin enacarbil – prodrug of gabapentin, FDA‐approved for RLS, growing evidence base for effectiveness, may be considered first‐line
Dopamine agonists (IR formulation) – pramipexole or ropinirole
Iron supplementation may be considered
