Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

nonrapid eye movement (NREM) parasomnia

1st line – safety modifications and correction of predisposing factors

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ONGOING
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nonrapid eye movement (NREM) parasomnia
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confusional arousals or sleep terrors
1st line – 

safety modifications and correction of predisposing factors

Confusional arousals or night terrors generally do not require pharmacologic therapy.

Simple reassurance that the condition is not harmful and is likely to resolve over time is indicated.

Simple measures such as removing objects that may cause harm to the patient from the sleeping areas and avoiding precipitants such as sleep deprivation are warranted, especially if episodes are frequent.

Physical restraint during a confusional arousal or night terror is not indicated.

Consider – psychotherapy

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ONGOING
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nonrapid eye movement (NREM) parasomnia
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confusional arousals or sleep terrors
Consider – 

psychotherapy

Treatment recommended for SOME patients in selected patient group

If safety modifications and correction of predisposing factors fail to work, psychotherapy (cognitive behavioral therapy or hypnosis) is added.​[66][68]

2nd line – benzodiazepine

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nonrapid eye movement (NREM) parasomnia
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confusional arousals or sleep terrors
2nd line – 

benzodiazepine

If confusional arousals or night terrors persist despite observation, benzodiazepines are used.[66]​ Benzodiazepines are not approved for use in confusional arousals or night terrors and are used only exceptionally for these parasomnias. Such use should be supervised by a qualified sleep specialist, preferably one with special expertise in the management of parasomnias.

Pharmacologic therapy should only be instituted in chronic and severe cases that cause significant disruption in the patient's sleep or injury to the patient or bed partner.

Patients receiving benzodiazepines should be cautioned about the potential for daytime drowsiness. The addition of alcohol or other central nervous system depressant drugs to benzodiazepines increases the risk of drowsiness and sedation, and patients must be cautioned about this potential for interaction. Withdrawal of benzodiazepine treatment is associated with recurrence of symptoms.

Clonazepam, temazepam, oxazepam, or diazepam may be used for confusional arousals or night terrors.

Patients should be seen in close follow-up soon after treatment is started and assessed for efficacy, adverse effects, need to change dose or stop treatment, and change to a different treatment. Monitor regularly and reassess after 4 weeks.

Doses should be started low and increased gradually according to response.

Primary options

clonazepam: 0.5 to 2 mg orally once daily at bedtime

OR

temazepam: 15-30 mg orally once daily at bedtime

OR

diazepam: 5-10 mg orally once daily at bedtime

OR

oxazepam: 10-20 mg orally once daily at bedtime

3rd line – selective serotonin-reuptake inhibitor or tricyclic antidepressant

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ONGOING
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nonrapid eye movement (NREM) parasomnia
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confusional arousals or sleep terrors
3rd line – 

selective serotonin-reuptake inhibitor or tricyclic antidepressant

If benzodiazepines are not effective, selective serotonin-reuptake inhibitors (SSRIs) (e.g., fluoxetine, citalopram, paroxetine, sertraline), or even tricyclic antidepressants (e.g., clomipramine, imipramine), are occasionally used.

SSRIs and tricyclic antidepressants are not approved for use in confusional arousals or night terrors and are used only exceptionally for this parasomnia. Such use should be supervised by a qualified sleep specialist, preferably one with special expertise in the management of parasomnias.​[66][71]

Antidepressants increase the risk of suicide in children, adolescents, and young adults according to studies with such medications in depressed patients. Patients must be warned of this risk, as well as the other adverse effects of antidepressants.

Patients should be seen in close follow-up soon after treatment starts and assessed for efficacy, adverse effects, need to change dose or stop treatment, and change to a different treatment and monitored regularly.

Doses should be started low and increased gradually according to response.

Primary options

fluoxetine: 20-60 mg orally once daily

OR

citalopram: 20-60 mg orally once daily

OR

paroxetine: 20-50 mg orally (immediate-release) once daily

OR

sertraline: 25-200 mg orally once daily

Secondary options

clomipramine: 25-100 mg orally once daily at bedtime

OR

imipramine: 10-50 mg orally once daily at bedtime

1st line – safety modifications and correction of predisposing factors

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ONGOING
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nonrapid eye movement (NREM) parasomnia
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sleepwalking
1st line – 

safety modifications and correction of predisposing factors

Avoiding or correcting predisposing factors and triggers (e.g., sleep deprivation, school or home stress, environmental noise), and making safety modifications of the sleep environment to avoid injury (e.g., locks on doors and windows) are first-line therapies.

Pharmacologic therapy should not be instituted unless these measures have failed and the sleepwalking is chronic and/or severe enough to cause significant disruption in the patient's sleep.

Consider – psychotherapy

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ONGOING
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nonrapid eye movement (NREM) parasomnia
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sleepwalking
Consider – 

psychotherapy

Treatment recommended for SOME patients in selected patient group

If safety modifications and correction of predisposing factors fail to work, psychotherapy (cognitive behavioral therapy or hypnosis) is added.[66]

2nd line – benzodiazepine

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ONGOING
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nonrapid eye movement (NREM) parasomnia
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sleepwalking
2nd line – 

benzodiazepine

Benzodiazepines are not approved for use in sleepwalking and should be used only exceptionally for this parasomnia. Consequently, such use should be supervised by a qualified sleep specialist, preferably one with special expertise in the management of parasomnias.

Benzodiazepines should only be used in severe cases of sleepwalking that do not respond to simple measures (i.e., correction of predisposing factors, safety modifications, and psychotherapy), or if the sleepwalking is placing the patient or bed partner in harm’s way. Clonazepam and diazepam are the benzodiazepines of choice for this indication; however, clonazepam is usually tried first.

Patients receiving benzodiazepines should be cautioned about the potential for daytime drowsiness. The addition of alcohol or other central nervous system depressant drugs to benzodiazepines increases the risk of drowsiness and sedation, and patients must be cautioned about this potential for interaction. Withdrawal of benzodiazepine treatment is associated with recurrence of symptoms.

Patients are seen in close follow-up soon after treatment starts and assessed for efficacy, adverse effects, need to change dose or stop treatment, and change to a different treatment. Monitor regularly and reassess after 4 weeks.

Doses should be started low and increased gradually according to response.

Primary options

clonazepam: 0.5 to 2 mg orally once daily at bedtime

Secondary options

diazepam: 5-10 mg orally once daily at bedtime

3rd line – selective serotonin-reuptake inhibitor or tricyclic antidepressant

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ONGOING
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nonrapid eye movement (NREM) parasomnia
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sleepwalking
3rd line – 

selective serotonin-reuptake inhibitor or tricyclic antidepressant

Antidepressants are not approved for use in sleepwalking and are only used exceptionally for this parasomnia. Consequently, such use should be supervised by a qualified sleep specialist, preferably one with special expertise in the management of parasomnias.

Tricyclic antidepressants are only used in severe cases of sleepwalking that do not respond to simple measures (i.e., correction of predisposing factors and safety modifications) or use of benzodiazepines.

The selective serotonin-reuptake inhibitor sertraline may be considered as an alternative to tricyclic antidepressants for the management of sleepwalking if tricyclic antidepressants are not tolerated, or as third-line treatment if other options prove to be ineffective.[71]

Monitor regularly and reassess after 4 weeks.

Doses should be started low and increased gradually according to response.

Primary options

sertraline: 25-200 mg orally once daily

Secondary options

clomipramine: 25-100 mg orally once daily at bedtime

OR

imipramine: 10-50 mg orally once daily at bedtime

1st line – topiramate

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nonrapid eye movement (NREM) parasomnia
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sleep-related eating disorder
1st line – 

topiramate

Anticonvulsant therapy with topiramate has been shown to be effective in some patients with sleep-related eating disorder.[5][69][70]

Duration of treatment is variable and depends on the response to treatment, adverse effects, and physician/patient choice. The treatment may need to be long term in patients with this parasomnia.

Doses should be started low and increased gradually according to response.

Primary options

topiramate: 25-150 mg orally once daily at bedtime

2nd line – dopamine agonist

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nonrapid eye movement (NREM) parasomnia
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sleep-related eating disorder
2nd line – 

dopamine agonist

Dopamine agonists are indicated if topiramate therapy fails.[73][74]

Pramipexole and ropinirole therapy have been reported to cause sudden sleep in patients even while they are engaged in activities during the day. Patients must be warned about the potential for this adverse effect, especially with regard to driving and operating heavy machinery.

Patients should also be warned that hypotension, especially orthostatic hypotension, may occur. Some patients have described visual hallucinations.

Duration of treatment with pramipexole or ropinirole is variable and depends on the response to treatment, adverse effects, and physician/patient choice. The treatment may need to be long term. Treatment should be withdrawn gradually, as abrupt withdrawal may result in acute worsening of symptoms.

Doses should be started low and increased gradually according to response.

Primary options

pramipexole: 0.125 to 1.5 mg orally once daily at bedtime

OR

ropinirole: 0.5 to 8 mg orally (immediate-release) once daily at bedtime

rapid eye movement (REM) parasomnia

1st line – sleep environment modification

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ONGOING
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rapid eye movement (REM) parasomnia
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rapid eye movement sleep behavior disorder (RBD)
1st line – 

sleep environment modification

Safety precautions to prevent injury to the patient and the bed partner should be instituted in conjunction with pharmacotherapy. Furniture, mirrors, and other objects that could harm the patient if he or she left the bed should be removed. The bedroom door should be closed to avoid danger from staircases or wandering around the house.​[37][68]​​​ A bed alarm can be considered.[75]

Consider – melatonin or clonazepam

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ONGOING
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rapid eye movement (REM) parasomnia
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rapid eye movement sleep behavior disorder (RBD)
Consider – 

melatonin or clonazepam

Treatment recommended for SOME patients in selected patient group

Melatonin (immediate-release) and clonazepam are recommended as first-line pharmacologic options.[23][37][75][76][77][78][79]​​​​​​​​​​

Melatonin has a favorable adverse-effect profile especially in patients with a risk of falls, comorbid sleep apnea, underlying liver disease, and those receiving polypharmacy with other medications.[37][68][78]​​

Clonazepam is highly effective.[37][68][75]​​[76]​​​​​ No other benzodiazepines are reported to have the level of efficacy that clonazepam has in this disorder. Patients receiving clonazepam should be cautioned about the potential for daytime drowsiness.[37] The addition of alcohol or other central nervous system depressant drugs to benzodiazepines increases the risk of drowsiness and sedation, and patients must be cautioned about this potential for interaction. Withdrawal of benzodiazepine treatment is associated with recurrence of symptoms. 

Doses should be started low and increased gradually according to response.

Primary options

melatonin: 3-12 mg orally (immediate-release) once daily at bedtime

OR

clonazepam: 0.5 to 2 mg orally once daily at bedtime

2nd line – pramipexole or rivastigmine

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rapid eye movement (REM) parasomnia
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rapid eye movement sleep behavior disorder (RBD)
2nd line – 

pramipexole or rivastigmine

If refractory to melatonin or clonazepam, other medications such as pramipexole and rivastigmine may be beneficial.​[37]

Pramipexole (a dopamine agonist) has shown benefits in patients with isolated RBD based on several observational studies.[37][75][80][81][82]​ It was most effective in patients with periodic limb movements, suggesting that the effect of pramipexole may be through improving ancillary motor activity. Adverse effects may include orthostatic hypotension, daytime sleepiness, nausea, confusion, and impulse control disorder.[37]

Transdermal rivastigmine (a cholinesterase inhibitor) can be used for isolated and secondary RBD based on a randomized controlled clinical trial showing reduced dream enactment behaviors in patients with mild cognitive impairment and in patients with Parkinson disease.[37][83][84]​​​​ Adverse effects include skin irritation, nausea, headache, and bradycardia.[37] Because transdermal rivastigmine may cause bradycardia, an electrocardiogram may be considered before starting treatment.

Safety precautions to prevent injury to the patient and the bed partner should be instituted in conjunction with pharmacotherapy.

Doses should be started low and increased gradually according to response.

Primary options

pramipexole: 0.125 to 1.5 mg orally once daily at bedtime

OR

rivastigmine transdermal: 4.6 mg/24 hour to 13.3 mg/24 hour patch once daily

1st line – discontinue causative drug

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rapid eye movement (REM) parasomnia
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drug-induced rapid eye movement sleep behavior disorder
1st line – 

discontinue causative drug

For patients with drug-induced REM sleep behavior disorder, typically due to selective serotonin-reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors, discontinuing the offending drug may be helpful, if possible. However, risks of stopping the drug, such as in worsening the underlying mood disorder, needs to be weighed against the potential benefits, particularly given that it may take months to see RBD symptom improvement.[37]

1st line – reassurance and positional therapy

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ONGOING
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rapid eye movement (REM) parasomnia
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recurrent isolated sleep paralysis
1st line – 

reassurance and positional therapy

Patients should be reassured that isolated sleep paralysis is very common and has no untoward consequences.[5]​ Positional therapy to promote sleep in non-supine positions can be considered because it usually occurs during arousals from supine sleep.[25]

2nd line – cognitive behavioral therapy

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ONGOING
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rapid eye movement (REM) parasomnia
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recurrent isolated sleep paralysis
2nd line – 

cognitive behavioral therapy

Cognitive behavioral therapy can be tried (e.g., sleep hygiene, relaxation techniques during episodes, coping strategies for frightening hallucinations, disputation of catastrophic thoughts, imaginary rehearsal of successful resolution of episodes).[25]

3rd line – selective serotonin-reuptake inhibitor or tricyclic antidepressants

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ONGOING
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rapid eye movement (REM) parasomnia
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recurrent isolated sleep paralysis
3rd line – 

selective serotonin-reuptake inhibitor or tricyclic antidepressants

In recurrent isolated sleep paralysis, the selective serotonin-reuptake inhibitor (SSRI) escitalopram has shown benefit in a small number of case reports.[85]

In persistent cases, other SSRIs (e.g., fluoxetine, citalopram, paroxetine, sertraline) and tricyclic antidepressants (e.g., clomipramine, imipramine) can be considered since they have shown benefit in sleep paralysis due to narcolepsy. However, recurrent isolated sleep paralysis drug treatment options lack good quality evidence since there are no RCTs.[25]

Doses should be started low and increased gradually according to response.

Primary options

escitalopram: 10-20 mg orally once daily

Secondary options

fluoxetine: 20-60 mg orally once daily

OR

citalopram: 20-60 mg orally once daily

OR

paroxetine: 20-50 mg orally (immediate-release) once daily

OR

sertraline: 25-200 mg orally once daily

Tertiary options

clomipramine: 25-100 mg orally once daily at bedtime

OR

imipramine: 10-50 mg orally once daily at bedtime

1st line – cognitive behavioral therapy

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ONGOING
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rapid eye movement (REM) parasomnia
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nightmares
1st line – 

cognitive behavioral therapy

Cognitive behavioral therapy includes systemic desensitization and relaxation techniques.

Nightmare-focused cognitive behavioral therapy (imagery rehearsal therapy and exposure, relaxation, and rescripting therapy) resulted in better treatment outcomes than indirect methods such as relaxation and recording of nightmares.[18][67][86]​​​​

Nightmares that recur enough to interfere with sleep health and patient well-being are managed with these techniques.​[18]

2nd line – prazosin

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ONGOING
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rapid eye movement (REM) parasomnia
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nightmares
2nd line – 

prazosin

The alpha-blocker prazosin, when used in nightmares associated with post-traumatic stress disorder, has shown beneficial efficacy in several studies in civilian and military settings. Although one large clinical trial failed to show improvement, subsequent meta-analyses incorporating it still show net benefit.[18][87]

Primary options

prazosin: 1 mg orally once daily at bedtime initially, increase gradually according to response, maximum 15 mg/day

other parasomnias

1st line – reassurance and treatment of underlying sleep disorder

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ONGOING
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other parasomnias
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exploding head syndrome, sleep-related hallucinations
1st line – 

reassurance and treatment of underlying sleep disorder

A group of other parasomnias can arise from both REM and NREM sleep (or wakefulness) and typically have a characteristic pathognomonic symptom (loud bang or flash of light, vivid hallucinations).

Patients with exploding head syndrome or sleep-related hallucinations should be reassured that this parasomnia is not associated with any serious consequences.[5]

Sleep-related hallucinations management involves eliminating or reducing known triggers (e.g., sleep deprivation, tobacco smoking, drugs [e.g., adrenergic antagonists, sedative hypnotics, antidepressants]).[5]

Treatment of an underlying comorbid sleep disorder, such as sleep apnea, may also improve these parasomnias.[5][92]

Consider – tricyclic antidepressant

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ONGOING
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other parasomnias
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exploding head syndrome, sleep-related hallucinations
Consider – 

tricyclic antidepressant

Treatment recommended for SOME patients in selected patient group

Tricyclic antidepressants (e.g., amitriptyline, clomipramine) may also be beneficial in patients with exploding head syndrome.[5][92]

Doses should be started low and increased gradually according to response.

Primary options

clomipramine: 25-100 mg orally once daily at bedtime

OR

amitriptyline: 10-150 mg orally once daily at bedtime

1st line – behavioral therapy

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ONGOING
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other parasomnias
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enuresis
1st line – 

behavioral therapy

Behavioral therapy is supported by clinical and anecdotal data, but no randomized trials are available to validate its efficacy. Nevertheless, it has very few drawbacks and should be attempted as first line. It includes a strict bowel regimen to avoid hard stools or constipation, as this may cause or worsen enuresis; increasing fluid intake during the morning and early afternoon hours, and limiting it during the evening and night time; encouraging the patient to avoid holding urine and to void at least once every 2 hours; and biofeedback to help relax the pelvic floor muscles.[5][17]

2nd line – alarm therapy

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ONGOING
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other parasomnias
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enuresis
2nd line – 

alarm therapy

Has only been studied in children, and has been shown efficacious in multiple trials. It involves using a moisture-sensitive alarm that goes off and awakens the child at the moment of bedwetting.[5][17]

3rd line – pharmacotherapy

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ONGOING
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other parasomnias
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enuresis
3rd line – 

pharmacotherapy

The drugs that have randomized trial support for efficacy include anticholinergics (e.g., oxybutynin, tolterodine), desmopressin, tricyclic antidepressants (e.g., imipramine), and verapamil. Rarely, medications can be used in combination.[5][17]

Primary options

desmopressin: 0.2 to 0.6 mg orally 1 hour before bedtime

OR

oxybutynin: 5 mg orally once daily at bedtime

OR

tolterodine: 4 mg (extended-release) orally once daily at bedtime

OR

imipramine: 25-75 mg orally once daily at bedtime

OR

verapamil: 80 mg orally once daily at bedtime

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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