Insomnia Management

Evaluation 

Common Comorbid Medical Disorders and Conditions

• Neurological
  • Stroke, Parkinson's disease, dementia, Seizure disorders, Headache disorders, Traumatic brain injury, Chronic pain disorders, Peripheral neuropathy, Neuromuscular disorders
• Cardiovascular
  • Angina, Congestive heart failure
• Pulmonary or Respiratory
  • Chronic obstructive pulmonary disease (COPD), Emphysema, Asthma, Laryngospasm
• Gastrointestinal (GI)
  • Reflux, Peptic ulcer disease, Cholelithiasis, Colitis, Irritable bowel syndrome (IBS)
• Genitourinary
  • Incontinence, benign prostatic hypertrophy, interstitial cystitis
• Endocrine
  • Hyperthyroidism, hypothyroidism, diabetes mellitus
• Musculoskeletal
  • Rheumatoid arthritis, osteoarthritis, fibromyalgia, Sjogren syndrome, kyphosis
• Reproductive
  • Pregnancy, menopause, menstrual cycle variations
• Sleep disorders
  • OSA, central sleep apnea, restless leg syndrome, periodic limb movement disorder, circadian rhythm sleep disorders, parasomnias
    • For obstructive sleep apnea, screen using STOP Bang questionnaire: Snoring, tiredness during the day, observed apneic episodes, high blood pressure, body mass index (BMI) >30kg/m2, age >50 years, neck circumference >40 centimeters, and male gender

Common Comorbid Psychiatric Disorders

• Mood disorders
  • Major depressive disorder (MDD), bipolar disorder
• Anxiety disorders
  • Generalized anxiety disorders, panic disorder, post-traumatic stress disorder, obsessive-compulsive disorder
• Psychotic disorders
  • Schizophrenia, schizoaffective disorder
• Amnestic disorders
  • Alzheimer’s disease, other dementias

Common Medications or Substances Contributing to Insomnia

• Antidepressants
  • Fluoxetine, Paroxetine, Sertraline, Venlafaxine, Duloxetine, monoamine oxidase inhibitors (MAOIs)
• Stimulants
  • Caffeine, Methylphenidate, amphetamine derivatives, Ephedrine and derivatives, cocaine
• Decongestants
  • Pseudoephedrine, Phenylephrine, Phenylpropanolamine
• Narcotic analgesics
  • Oxycodone, Codeine
• Cardiovascular medications
  • Beta-blockers, alpha-receptor agonists and antagonists, lipid-lowering agents
• Respiratory medications
  • Theophylline, Albuterol
• Alcohol
• Corticosteroids

Principles of therapy 

In treating insomnia with underlying comorbidities, clinical judgement should decide whether insomnia or the comorbid condition is treated first, or they can be treated at the same time. The choice of agent should be based on the type of insomnia and the presence of comorbidities. The 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.

The primary treatment goals are to improve sleep quality and quantity and to improve insomnia-related daytime dysfunction.

During treatment, 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
• 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

Pharmacological therapy 

Pharmacological therapy is considered as adjunctive to non-pharmacological therapy. Drugs are started at their lowest effective dose and the maximum dose is not exceeded. Drug regimens are individualized which may be short-term or long-term but are intermittent. Pharmacological therapy can be offered if cognitive behavioral therapy is not sufficiently effective or not available or when the patient is not motivated. It must be remembered that good sleep hygiene is still necessary. Long-term nightly use should be avoided. Lastly, regular follow-up is recommended to ensure effectiveness, monitor side effects and dependence (both psychological and physiological), and assess continuing need for medication.  

Benzodiazepines

Benzodiazepines are the most commonly prescribed agents for the treatment of insomnia. They may be used as adjunctive therapy with behavioral therapy. They have been proven effective for short-term insomnia treatment. They reduce time to sleep onset, prolong stage 2 sleep; prolong total sleep time, and may slightly reduce rapid eye movement (REM) sleep. Benzodiazepines decrease anxiety and prevent seizure occurrence but impairs memory. The use of benzodiazepines is usually limited to 4 weeks because long-term use increases the chances of habituation and withdrawal symptoms and tolerance to hypnotic effects develops upon repeated administration. There are reports of rebound insomnia occurring. The short-acting benzodiazepine Triazolam has been associated with rebound anxiety and is therefore not the first line for insomnia. However, it has been suggested as a treatment for sleep onset insomnia. Temazepam, an intermediate-acting benzodiazepine, has been suggested as treatment for sleep onset and sleep maintenance insomnia. Lastly, Diazepam is generally not used in the treatment of insomnia due to its long duration effect and possibility of accumulating active metabolites.  

Nonbenzodiazepine Hypnotics

Nonbenzodiazepine hypnotics decrease sleep latency and number of awakenings. These drugs improve sleep duration and sleep quality.

Eszopiclone  

Eszopiclone has the longest half-life among benzodiazepine-like hypnotics with a half-life of 5-7 hours. It is effective for sleep onset and maintenance insomnia.  

Zaleplon

Zaleplon is suggested for the treatment of sleep onset insomnia. It is effective for patients with difficulty in falling asleep but not in patients with difficulty in maintaining sleep.  

Zolpidem  

Zolpidem is suggested for the treatment of sleep onset and sleep maintenance insomnia. It does not alter normal sleep patterns and is not usually associated with rebound insomnia.  

Zopiclone  

Zopiclone decreases sleep latency when compared to placebo. It also increases sleep duration without changing normal sleep patterns.  

Melatonin Receptor Agonists

Melatonin  

Clinical trial data have shown that prolonged-release Melatonin improves sleep onset latency and quality in patients >55 years old. However, there is limited clinical data on the use for chronic insomnia. It may be beneficial to patients with delayed sleep phase syndrome and in a subgroup of patients with low melatonin levels. Use of Melatonin is limited to a maximum of 3 months.  

Ramelteon  

Ramelteon is effective for sleep onset insomnia. It has no short-term usage restriction and has not been associated with hypnotic side effects, withdrawal, or rebound insomnia.  

Dual Orexin Receptor Antagonists (DORAs)

Example drugs: 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. On the other hand, Suvorexant was suggested for the treatment of sleep maintenance insomnia.  

Other Agents¹

Antidepressants

Example drugs: 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. In some studies, low-dose Trazodone in conjunction with another full-dose antidepressant have moderate efficacy in improving sleep quality and/or duration.

Antiepileptics

Example drugs: Gabapentin, Pregabalin  

The use of antiepileptics in the treatment of chronic insomnia has limited evidence for efficacy. However, Gabapentin may be used in patients with insomnia associated with restless leg syndrome, neuropathic pain, and substance abuse disorders (eg alcohol use disorder). Pregabalin has been found to improve sleep, but the mechanism of action is still unclear. Gabapentin and Pregabalin may also be used for the treatment of insomnia with comorbid pain condition.  

Antihistamines

Example drugs: Diphenhydramine, Doxylamine  

Antihistamines are generally less effective than benzodiazepines and are associated with daytime drowsiness. They are not recommended for insomnia due to limited evidence of efficacy.
 
Antipsychotics

Example drug: 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.

Nonpharmacological

It must be noted that the use of non-pharmacological therapy alone or in combination with pharmacotherapy clinically improves insomnia.

Cognitive Behavioral Therapy for Insomnia (CBT-I)

CBT-I is a multicomponent treatment recommended for chronic insomnia in adults of any age. It combines cognitive therapy with behavioral treatments (eg sleep restriction, stimulus control, sleep hygiene) and relaxation therapy. CBT-I reduces sleep onset latency and nocturnal awakenings and improves sleep efficiency. Studies have also shown improvement in functional outcomes when used as adjunct to pharmacotherapy in patients with insomnia with psychiatric or medical comorbidities. It also may reduce the need for pharmacologic therapy. Hence, it 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 or therapist. Brief therapies for insomnia, typically 1-4 sessions, include abbreviated versions of CBT-I with emphasis on the behavioral components.

Sleep Hygiene Education or Psychoeducation

This targets environmental and lifestyle factors to build good habits which facilitate good sleep. Sleep hygiene is ineffective for insomnia, but when incorporated into CBT-I, it becomes more beneficial. 

Sleep hygiene suggestions include:

• 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 heaving 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 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

Stimulus control is based on the theory that insomnia is a conditioned response due to temporal (bedtime) and environmental (bedroom or bed) cues that are associated with sleep. This aims to reassociate the bed or bedroom with sleep to re-establish a consistent sleep-wake schedule. Bed and bedroom should be associated with rapid onset of sleep. 

Take note of the following:

• 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 sleep the night before
• Avoid daytime naps

Relaxation Therapy

Insomnia patients tend to have a high level of cognitive, physiologic and/or emotional arousal both day and night. The two common techniques for relaxation therapy include progressive muscle relaxation and relaxation response. 

In progressive relaxation, patients would gently contract their facial muscles for 1-2 seconds and then relax it. This process is then repeated several times and then used in other muscle groups in the following sequence: Jaw and neck, upper arms, lower arms, chest, abdomen, buttocks, thighs, calves and feet.

In relaxation response, the patient begins by lying or sitting comfortably. With their eyes closed, patients allow relaxation to speed throughout the body. A relaxed breathing pattern is then established, and thoughts are directed away from intrusive worries and toward a neutral word or image. It must be noted that different relaxation methods work for different people, and it may take some trial and error and practice before the best method for the patient can be identified.

Cognitive Therapy

In cognitive therapy, faulty beliefs and attitudes about sleep are identified and are replaced with more helpful ones. The goal is to provide reassurance to patients regarding beliefs about sleep. Efforts to decrease the cycle of insomnia, emotional distress, and dysfunctional thoughts which can cause further sleep disturbances are attempted. 

Sleep Restriction Therapy

The goal of sleep restriction therapy is to decrease the amount of time in bed thereby increasing the percentage of time spent in bed asleep. This is helpful for patients who have been increasing their time in bed hoping to increase their actual sleep time. It creates a mild sleep deprivation which promotes shorter sleep onset and longer time asleep. Sleep restriction therapy is recommended that sleep diaries be used for sleep time estimation, both before sleep restriction therapy and during follow-ups. During the course of the therapy, the patient is recommended to stay in bed only as long as their average sleep time, but no less than 4 hours per night. The allowable time in bed is then increased by 15-20 minutes as sleep efficiency improves. The time in bed is increased over a period of weeks until optimal sleep duration is achieved. The wake-up time is usually kept the same time while adjusting the bedtime.