Health.amTable 89-2 Medications for sleep disorders | ||||||
Effects on sleep | ||||||
Drug class | Examples and typical doses | Subjective | Objective | Adverse effects | Indications | Comments |
Benzodiazepine receptor agonists (includes benzodiazepines and nonbenzodiazepines such as the imidazopyridine zolpidem and the pyrazolopyrimidine zaleplon) | Marketed as hypnotics: estazolam 1-2 mg; quazepam, flurazepam, temazepam 7.5-30 mg; triazolam 0.125-0.25 mg; zolpidem 5-10 mg; zaleplon 5-6 mg Marketed as anxiolytics: diazepam 5-10 mg; lorazepam 1-3 mg; chlordiazepoxide 10-30 mg Others: clonazepam 0.5-2 mg | Shorten sleep latency Decrease awakenings Increase sleep duration | Shorten sleep latency Decrease wakefulness Increase sleep duration Decrease (benzodiazepines) or no change (zolpidem, zaleplon) in Stage 3/4 sleep Decrease REM sleep (slight) Increase sleep spindles Decrease periodic limb movements and associated arousals Increase apnea and oxyhemoglobin desaturations (slight) | Sedation Ataxia Confusion Falls Memory and psychomotor performance impairment Tolerance, dependence, withdrawal possible | 1. Primary insomnia 2. Restless legs syndrome (as secondary treatment) 3. Periodic limb movement disorder 4. Insomnia related to another mental disorder (as adjunct in mood, anxiety, psychotic disorders) 5. Narcolepsy (as adjunct for nocturnal sleep disruption) 6. Parasomnias (nightmares, sleep terror disorder, sleepwalking disorder, REM sleep behavior disorder) 7. Circadian rhythm sleep disorder (shortterm use) 8. Secondary sleep disorder due to a medical condition (in selected conditions) | Shortterm, intermittent use preferred for insomnias Longer-term use may be appropriate for periodic limb movements, parasomnias, some insomnia Use lowest effective dose Avoid in patients with substance abuse history Cautious use in the elderly Taper and discontinue gradually Effects and adverse effects vary with dose, half-life, duration of action |
Tricyclic antidepressants | Amitriptyline, doxepin, trimipramine, imipramine, clomipramine, desipramine 25-250 mg; nortriptyline 10-150 mg; protriptyline 10-60 mg; amoxapine 25-400 mg | Individual agents vary from strongly sedating (doxepin, amitriptyline) to alerting (protriptyline, desipramine) May increase or decrease dreaming | Effects on sleep latency, wakefulness vary for specific drugs Little change or slight increase in Stage 3/4 sleep REM suppression ranges from strong (clomipramine) to weak (trimipramine) Decrease apnea (slight) May increase leg movements Anomalous sleep stages (e.g., eye movements during NREM sleep) Can promote parasomnias in some individuals | Anticholinergic (dry mouth, urinary retention, constipation) α-Adrenergic antagonist (sedation, orthostatic hypotension) Cardiac conduction delay Sexual dysfunction Confusion, delirium Withdrawal syndrome Psychomotor impairment Can be lethal in overdose | 1. Primary insomnia (patients with personal or family history of mood disorder, substance abuse) 2. Insomnia related to another mental disorder (mood, anxiety disorders) 3. Substance-induced sleep disorder, insomnia type (patients at risk for benzodiazepine misuse) 4. Narcolepsy (as adjunct for cataplexy, sleep paralysis, sleep-related hallucinations) 5. Breathing-related sleep disorder (as adjunct for sleep sedation with CPAP) 6. Parasomnias (nightmares, sleep terror disorder, sleepwalking disorder) | Individual agents have widely different chemical and clinical profiles Nightly (as opposed to intermittent) use generally preferred Elderly more sensitive to effects and side effects Preferred in patients with substance abuse history Use for insomnia poorly validated in controlled studies |
Selective serotonin reuptake inhibitors | Fluoxetine 10-60 mg; sertraline 50-200 mg; paroxetine 20-50 mg; citalopram 20-40 mg; fluvoxamine 50-300 mg | Usually experienced as alerting (fluoxetine > sertraline > paroxetine > citalopram > fluvoxamine) May disrupt nocturnal sleep Some patients report sedation | Dose-related increase in wakefulness Decrease in REM sleep (slight) Increase in periodic limb movements Decrease in apnea, hypoxemia (slight) Eye movements during NREM sleep | Agitation, anxiety GI upset Sexual dysfunction Dizziness Headache | 1. Primary insomnia (patients with personal or family history of mood disorder) 2. Insomnia related to another mental disorder (mood, anxiety disorders) 3. Substance-induced sleep disorder, insomnia type (patients at risk for benzodiazepine misuse) 4. Narcolepsy (as adjunct for cataplexy) | Some patients have initial change in sleep duration, which then subsides Effects on sleep, insomnia do not appear to result from sedation May inhibit hepatic metabolism and increase levels of other drugs, including benzodiazepines |
Other antidepressants | Trazodone 25-400 mg; nefazodone 200-500 mg; mirtazapine 15-60 mg | Trazodone and low-dose mirtazapine very sedating; higher-dose mirtazapine and nefazodone mildly sedating Nefazodone infrequently causes insomnia | Improve sleep continuity (decrease wakefulness during sleep, increase sleep efficacy) No change or slight increase in REM with trazodone or nefazodone Increase in Stage 3/4 sleep with trazodone | Sedation, headache, GI upset, constipation, dry mouth; hypotension, potential for ventricular ectopy, priapism (trazodone); weight gain, rare agranulocytosis (mirtazapine) | 1. Insomnia related to another mental disorder (mood, anxiety disorders) 2. Primary insomnia (trazodone) 3. Primary insomnia in patients with personal or family history of mood disorder (mirtazapine, nefazodone) 4. Substance-induced sleep disorder, insomnia type (patients at risk for benzodiazepine abuse) 5. Breathing-related sleep disorder (as adjunct for sleep with CPAP) | Mirtazapine more sedating at lower doses Trazodone only agent evaluated in primary insomnia |
Stimulants | Pemoline 37.5-131.5 mg; methylphenidate, dextroamphetamine, methamphetamine 10-60 mg; modafinil 100-400 mg | Decrease sleepiness, increase alertness Increase wakefulness during night sleep Dreams, nightmares during withdrawal (traditional stimulants) | Dose-related decrease in daytime sleepiness, increase in nocturnal wakefulness Decrease in Stage 3/4 sleep (slight) Decrease in REM sleep | Traditional stimulants: agitation, anxiety Paranoia, psychosis in very high doses Increased heart rate, blood pressure GI upset, anorexia, weight loss Abnormal involuntary movements (tics) Withdrawal hypersomnia Abuse, tolerance, dependence possible Modafinil: Headache Insomnia GI upset Pemoline: Rare liver failure | 1. Primary hypersomnia 2. Narcolepsy 3. Insomnia related to another mental disorder (as adjunct for hypersomnic depression) | Lowest effective dose recommended Periodic "drug holidays" may decrease tolerance, dependence for traditional stimulants Diagnosis should be verified with sleep studies |
Dopaminergic agents | Pergolide 0.05-0.25 mg; pramipexole 0.125-0.75 mg; carbidopa-levodopa 25/100-50/200 mg; bromocriptine 2.5-10 mg | Little effect at low doses Insomnia at higher doses Increased dreams, nightmares at high doses | Decrease wakefulness at low doses, increase wakefulness at higher doses Increase REM sleep at low doses, decrease REM sleep at higher doses Decrease restless legs symptoms, periodic limb movements, and association arousals | Agitation, delirium at high doses GI upset, nausea Abnormal involuntary movements (tics, dyskinesias) Hypertension, hypotension Headache | 1. Restless legs syndrome 2. Periodic limb movement disorder | May require second dose in middle of night or sustained-release preparation Restless legs symptoms may be displaced into daytime |
Opioids | Propoxyphene 65-130 mg; codeine 30-90 mg | Sedation | Variable effects on wakefulness Decrease in REM sleep | Sedation Potential for tolerance, dependence, withdrawal syndrome GI upset | 1. Restless legs syndrome 2. Periodic limb movement disorder | Risk of dependence, abuse Should be reserved for treatment-resistant cases |