Insomnia: Updates in Medical Management Michael Newnam M.D.
Sleep Neurobiology Delicate balance of excitatory and inhibitory neurotransmitters that control the switch between wakefulness and sleep
Circadian Rhythm
Insomnia Dissatisfaction with quantity or quality of sleep causing daytime symptoms. (DSM-5) 50-70 million chronic sleep/wake disorders More common in women 50% of elderly patients
National Health Interview Survey 62% of the adult population getting 7-8 hours of sleep 28% revealed sleeping less than 6 hours
Co-morbid conditions contributing to insomnia OSA RLS CVD DM Arthritis Chronic pain COPD Fibromyalgia Mood disorders
Treatment Goals To improve quantity and quality of sleep Improve daytime function
Factors to help guide treatment choices Symptom pattern Past treatment response Patient preference Costs Co-morbid conditions Contraindications Concurrent medications
Medications Benzodiazepines Benzodiazepine receptor agonists (BZA s) Melatonin agonists Antidepressants (TCA s/heterocyclics) Orexin Receptor agonists Atypical Antipsychotics Antihistamines
Benzo s Short Acting: Triazolam (Halcion)- 2 hour Intermediate acting: Temazepam (Restoril)- 9 hour Estazolam (Prosom) Long Acting: Quazepam (Doral)- 39 hours Fluazepam (Dalmane)
Off Label Benzo s Alprazolam (Xanax)- 1/2 life of 6-11 hours Clonazepam (Klonopin)- 1/2 life of 30-40 hours Lorazepam (Ativan)- 1/2 life 10-20 hours Diazepam (Valium)- up to 40 hours
Evidence Grade B with good evidence of short term effectiveness (decreased sleep latency, sleep duration)
Adverse Effects Psychomotor retardation Memory impairments Tolerance/Dependence Decreased REM sleep
Tips on the Benzo s Would not choose them 1st line unless another comorbidity like anxiety or parasomnias Stay with longer acting agents if possible Caution with Elderly Caution with opioids
Bezodiazapine receptor agonists (Z drugs) GABA alpha1 subunit (more specific than the nonselective Benzo s that effect multiple sites) Zolpidem (Ambien) 5-10 mg or ER 6.25-12.5 mg Eszopiclone (Lunesta) 1-3 mg Zaleplon (Sonata) 10-20 mg
Z-hypnotics
Melatonin Supplemental melatonin at 1-10 mg Ramelteon (Rozerem) 8mg, Melatonin agonist, very short 1/2 life for sleep onset insomnia No effect on GABA
TCA s/heterocyclic s Doxepin (Silenor) 6-50 mg sleep maintenance insomnia, safe in the elderly, take on empty stomach
Off Label TCA/Heterocyclic s Trazodone 25-100 mg, 5HT2A (serotonin) Blockade and H1 antagonism, anticholinergic side effects as you increase dose Mirtazapine (Remeron) 7.5-30 mg, H1 receptor antagonist, weight gain Amitriptyline, Imipramine, Nortryptaline anticholinergic side effects, orthostatic hypotension, slow cardiac conduction
Orexin Receptor Agonist Suvorexant (Belsomra) 10-20 mg 30 minutes before bed Not likely to cause dependence or tolerance Costly
Atypical Antipsychotics Quetiapine (Seroquel) 25-200mg Olanzapine (Zyprexa) 5-20 mg Risperidone (Risperdal).05-2 mg 5Ht2 (serotonin blocker) and H1 antagonist Metabolic Syndrome SE s (weight gain, dyslipidemia, hyperglycemia)
Antihistamines Most OTC products use sedating antihistamines as the active ingredient (sominex, unisom, Zquil, PM products) Rapid tolerance, Residual drowsiness and anticholinergic side effects Lack evidence of efficacy Doxylamine (Unisom), Diphenhydramine (Zquil, sominex, Tylenol PM, Advil PM)
The public has spoken!
The public has spoken! Forget randomized controlled studies which drug has the most likes?
Summary Insomnia is a common disorder with multiple comorbidities Medical therapy targets neurotransmitters that regulate the sleep/wake cycle including histamine, serotonin, melatonin, orexin. Therapy should be individually tailored to the patient taking into consideration symptoms, comorbidities, costs and side effects. Adverse effects of sleep aids can include drowsiness, memory issues, anticholinergic effects, dependence, tolerance