Insomnia Treatment

• 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

• 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

• 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

• 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
  

• 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

• 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

• 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)

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

• 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

• 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

• 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