insomnia
INSOMNIA
Treatment Guideline Chart

Insomnia can be either having difficulty in initiating sleep, maintaining sleep or experiencing early morning awakening wherein returning to sleep is not easily attained.

These disturbances can cause significant distress and impairment in daytime functioning.

It is the most prevalent sleep disorder in the general population thus accurate diagnosis and effective treatment is necessary.

Insomnia Treatment

Principles of Therapy

  • If there are comorbidities, clinical judgment should decide whether the insomnia or the comorbid condition is treated first or they can be treated at the same time
    • Choice of agent should be based on type of insomnia and presence of comorbidities
      • Concomitant treatment of insomnia and psychiatric disorders is recommended to accelerate recovery and increase the likelihood of sustained response
      • Other sleep disorders such as obstructive sleep apnea and restless leg syndrome may present with insomnia but will most likely not improve without treatment of the specific disorder
      • Insomnia due to nocturia, pain or shortness of breath will most likely not improve without treatment of the medical disorder
Primary Treatment Goals
  • Improve sleep quality and quantity
  • Improve insomnia-related daytime dysfunction

The following may be measured using a sleep log and specific questionnaires to determine treatment outcomes:

  • Sleep onset latency (time to fall asleep following bedtime)
  • Total sleep duration
  • Number of nighttime awakenings
  • Sleep efficiency
  • Satisfaction with sleep and reduction in sleep-related distress
  • Daytime functioning
  • Wake time after sleep onset
  • When patient forms a clear association between the bed and sleeping
  • ISI may be used to monitor the effect of treatment interventions

Pharmacotherapy

  • Considered as adjunctive therapy to non-pharmacological therapy
  • Prescribe the lowest effective dose and do not exceed the maximum recommended dose
  • Individualized drug regimen may be short-term or long-term but intermittent
  • Can be offered if cognitive behavioral therapy is not sufficiently effective or not available or when patient is not motivated
  • Good sleep hygiene is still necessary
  • Avoid long-term nightly use
  • Regular follow-up is recommended to ensure effectiveness, monitor for side effects, dependence (both psychological and physiological), and assess continuing need for medication

Benzodiazepines

  • Most commonly prescribed agents for treatment of insomnia
    • May be used as adjunctive therapy with behavioral therapy
  • Proven effective for short-term insomnia treatment
    • Reduce time to sleep onset; prolong stage 2 sleep; prolong total sleep time; may slightly reduce rapid eye movement sleep
    • Decrease anxiety; impair memory; prevent seizure occurrence
  • Use is usually limited to ≤4 weeks 
    • Long-term use increases chances of habituation and withdrawal symptoms
    • Tolerance to hypnotic effects develops on repeated administration
  • Rebound insomnia has occurred
  • Short-acting: Triazolam
    • Has been associated with rebound anxiety and is therefore not first line for insomnia
    • Suggested as treatment for sleep onset insomnia
  • Intermediate-acting: Estazolam, Temazepam
    • Temazepam is suggested as treatment for sleep onset and sleep maintenance insomnia
  • Long-acting: Flurazepam, Quazepam
  • Diazepam is generally not used in the treatment of insomnia due to its long duration of effect and possibility of accumulating active metabolites

Non-benzodiazepine Hypnotics

  • Decrease sleep latency and number of awakenings
  • Improve sleep duration and sleep quality

Eszopiclone

  • Longest half-life among non-benzodiazepine hypnotics: 5-7 hours
  • Effective for sleep onset and maintenance insomnia

Zaleplon

  • Suggested for treatment of sleep onset insomnia
  • Effective for patients with difficulty in falling asleep but not in patients with difficulty in maintaining sleep

Zolpidem

  • Suggested for treatment of sleep onset and sleep maintenance insomnia
  • Does not alter normal sleep patterns and is usually not associated with rebound insomnia

Zopiclone

  • Decreases sleep latency when compared to placebo and generally increases sleep duration without changing normal sleep patterns

Melatonin Receptor Agonist

Melatonin

  • Clinical trials data have shown that prolonged-release Melatonin improves sleep onset latency and quality in patients >55 years old
  • Limited clinical data on use for chronic insomnia
  • May be beneficial to patients with delayed sleep phase syndrome and in a subgroup of patients with low melatonin level
    • Limit use to a maximum of 3 months
Ramelteon
  • Effective for sleep onset insomnia
  •  Has no short-term usage restriction
  •  Has not been associated with hypnotic side effects, withdrawal or rebound insomnia


Dual Orexin Receptor Antagonists (DORAs)

  • Eg  Daridorexant, Lemborexant, Suvorexant
  • Daridorexant and Lemborexant were recently approved for the treatment of insomnia in adults that have difficulties with sleep onset and/or sleep maintenance
  • Suvorexant was suggested for treatment of sleep maintenance insomnia
Other Agents1
Antidepressants
  • Eg Amitriptyline, Dothiepin, Doxepin, Mirtazapine, Trazodone 
  • Tricyclic antidepressants (TCAs) have been used in lower doses to treat insomnia in patients with comorbid depressive disorders but are dangerous when overdosed
  • Low dose Doxepin is a suggested treatment for sleep maintenance insomnia
  • Trazodone should not be used as a treatment for sleep onset or sleep maintenance insomnia
    • In some studies, low-dose Trazodone in conjunction with another full-dose antidepressant have moderate efficacy in improving sleep quality and/or duration
Antiepileptics
  • Eg Gabapentin, Pregabalin
  • Limited evidence for efficacy in the treatment of chronic insomnia
  • Gabapentin may be used in patients with insomnia associated with restless leg syndrome, neuropathic pain and substance use disorders (eg alcohol use disorder)
  • Pregabalin has been found to improve sleep but the mechanism of action is unclear
  • Gabapentin and Pregabalin may also be used for the treatment of insomnia with comorbid pain condition

Antihistamines

  • Eg Diphenhydramine, Doxylamine
  • Generally less effective than benzodiazepines and are associated with daytime drowsiness
  • Not recommended for insomnia due to limited evidence of efficacy

Antipsychotics
  • Eg Quetiapine
  • Quetiapine is the most frequently prescribed antipsychotic for insomnia but should only be considered in patients with insomnia and comorbid psychotic disorder (eg schizophrenia, bipolar disorder)
1Some of these agents are intended for off-label usage and should be used with caution. 

Non-Pharmacological Therapy

Use of non-pharmacological therapy alone or in combination with pharmacotherapy clinically improves insomnia

Cognitive Behavioral Therapies for Insomnia (CBT-I)

  • Multicomponent treatment recommended for chronic insomnia in adults of any age
  • Combines cognitive therapy with behavioral treatments (eg sleep restriction, stimulus control, and sleep hygiene education) and relaxation therapy
  • Reduces sleep onset latency and nocturnal awakenings, and improve sleep efficiency 
  • Studies have shown improvement in functional outcomes when used as adjunct to pharmacotherapy in patients with insomnia with psychiatric or medical comorbidities
  • May reduce the need for pharmacologic therapy; hence, may decrease the risk of drug-related adverse events
  • CBT-I requires patients to be engaged with a multisession approach (usually 4-8 sessions) with a trained clinician/therapist
  • Brief therapies for insomnia (typically 1-4 sessions) include abbreviated versions of CBT-I with emphasis on the behavioral components
Sleep Hygiene Education/Psychoeducation
  • Targets environmental and lifestyle factor to build good habits which facilitate good sleep
  • Sleep hygiene alone is ineffective for insomnia, but is more beneficial when incorporated into CBT-I
  • Sleep hygiene suggestions
    • Maintain a regular-sleep wake schedule
    • Avoid naps lasting >1 hour or later than 3 pm and decrease the time spent in bed not sleeping (eg work, telephone, internet)
    • Avoid excessive liquids or heavy evening meals
    • Avoid caffeine and nicotine 4-6 hours prior to bedtime
    • Do not use alcohol as a sleep aid
    • Avoid exercising within 3 hours of bedtime, but daytime physical activity particularly exercising 4-6 hours prior to bedtime is encouraged to facilitate sleep onset
    • Minimize light, noise and excessive temperatures
    • Avoid watching the clock
    • Place digital devices far away from the bed to minimize intrusions to bedtime
    • Engage in a relaxing bedtime routine 30 minutes before sleep such as reading, listening to music, warm bath, light snack or stretching
    • Avoid excessive worrying during bedtime, including sleep-related worries
Stimulus Control Therapy
  • Based upon the theory that insomnia is a conditioned response due to temporal (bedtime) and environmental (bedroom/bed) cues that are associated with sleep
  • Aims to re-associate the bed/bedroom with sleep and to re-establish a consistent sleep-wake schedule
  • Bed and bedroom should be associated with rapid onset of sleep
    • Go to bed only when sleepy
    • Use bed only for sleep (or sex)
    • Get out of bed and go to another room when unable to fall asleep within 20 minutes and return only when sleepy
    • Keep to a regular wake time regardless of duration of sleep the night before
    • Avoid daytime naps

Relaxation Therapy

  • Insomnia patients tend to have high levels of cognitive, physiologic, and/or emotional arousal both day and night
  • Two common techniques for relaxation therapy include progressive muscle relaxation and relaxation response
  • In progressive relaxation, patient gently contracts facial muscle for 1-2 seconds and then relaxes it
    • This process is repeated several times and then used in other muscle groups in the following sequence: Jaw and neck, upper arms, lower arms, fingers, chest, abdomen, buttocks, thighs, calves, and feet
  • In relaxation response, patient begins by lying or sitting comfortably
    • With eyes closed, patient allows relaxation to spread throughout the body
    • A relaxed breathing pattern is established and thoughts are directed away from intrusive worries and toward a neutral word or image
  • Different relaxation methods work for different people; it may take some trial and error and practice before the best method for the patient can be identified

Cognitive Therapy

  • Identify faulty beliefs and attitudes about sleep and replace them with more helpful ones
  • Goal is to provide reassurance to patients regarding beliefs about sleep
    • Attempt to decrease the cycle of insomnia, emotional distress and dysfunctional thoughts which can cause further sleep disturbances
Sleep Restriction Therapy
  • Goal is to decrease the amount of time in bed thereby increasing the percentage of time spent in bed asleep
  • Helpful for patients who have been increasing their time in bed hoping to increase their actual sleep time
  • Creates mild sleep deprivation which promotes shorter sleep onset and longer time asleep
  • It is recommended that sleep diaries be used for sleep time estimation, both before starting sleep restriction therapy and also during follow-ups
  • Patient should stay in bed only as long as their average sleep time; but no less than 4 hours per night
    • Allowable time in bed is increased by 15-20 minutes as sleep efficiency improves
    • Time in bed is increased over a period of weeks until optimal sleep duration is achieved
    • Usually keep wake-up time the same and adjust bedtime
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