Today, our attention will be directed towards the second segment of our Insomnia curriculum. This session will concentrate on the management of insomnia, which involves addressing underlying and comorbid conditions, implementing behavioral interventions, Cognitive Behavioral Therapy for insomnia (CBT-i), and the use of medications.
Today's Content Level: All levels (Beginner, Intermediate, Advanced)
Treatment of Insomnia - An Introduction
•Insomnia = inadequate quality or quantity of sleep, characterized by difficulties falling asleep (sleep initiation), staying asleep (sleep maintenance), waking up too early in the morning (early morning awakenings), or some combination of these symptoms. Secondary insomnia refers to difficulty falling asleep or staying asleep due to an underlying cause, such as a medical condition, mental health disorder, medications, or substance use. In contrast, primary insomnia refers to sleep disturbances that are not directly attributable to any underlying health condition. See day # 153 for a full discussion on the etiologies and assessment of insomnia.
•Proper treatment of insomnia hinges on identifying and addressing the underlying causes rather than reflexively writing prescriptions for hypnotic medications or addressing insomnia in isolation. As discussed in the previous post, insomnia often coexists with other medical, psychiatric, or stress-induced conditions, making it critical to evaluate and manage these comorbidities as part of an effective treatment strategy.
•In addition to addressing any underlying disorder, the management of insomnia includes behavioral interventions, a structured therapy called Cognitive Behavioral Therapy for Insomnia (CBT-i), and short-term sleep medications if necessary. Each will be discussed in detail below.
Behavioral Interventions 1
•Non-pharmacological methods are prioritized as initial treatments for insomnia, with a focus on sleep hygiene and behavioral strategies.
•Sleep Environment Modifications: Ensuring that the bedroom is dark (consider blackout curtains or sleep masks), cool (optimal sleeping temperature for most people is between 60–72°F), quiet, and comfortable helps signal the brain that it’s time for rest.
•Sleep Hygiene: Teaching patients sleep hygiene techniques can promote better sleep habits. Key elements include:
Establishing a consistent sleep schedule (bed time and wake time).
Limiting caffeine (particularly after midday) and avoiding nicotine and alcohol.
Reducing screen time before bed (30min - 2 hrs).
Limiting naps, particularly after midday.
Perform consistent exercise, but avoid vigorous exercise late in the evening.
Using the bed only for sleep and sex to condition the mind for sleep in bed.
Reducing the amount of time spent awake in bed. Do not force sleep, leave the bed if not asleep after ~30 mins.
May engage in relaxing pre-bedtime rituals such as reading, calming music, deep breathing, meditation, or progressive muscle relation.
•CBT-I is a specialized form of cognitive-behavioral therapy designed to treat chronic insomnia. This therapy focuses on behavioral strategies to improve sleep efficiency as well as identifying and challenging negative thoughts and behaviors that perpetuate insomnia.
•CBT-I is generally more effective than medications, especially for those with primary/chronic insomnia. It has been shown to decrease insomnia by 50% and, unlike medications, 50%-70% of patients have lasting effects even after discontinuation of therapy.
•CBT-I involves techniques like:
Sleep Restriction: Initially limiting the amount of time spent in bed to align with actual sleep duration enhances sleep efficiency by gradually extending bed time as efficiency improves, restoring a steady sleep-wake cycle. Sleep efficiency = ratio of time spent sleeping versus time spent in bed. Initially, it may lead to increased fatigue, but in the long term reduces sleep-related anxiety and improves sleep quality.
Stimulus Control: Focuses on strengthening the association between the bed and sleep by limiting activities in the bedroom to only sleep and sex (e.g. no reading or watching TV in bed). Additionally, this involves going to bed only when sleepy, getting out of bed if unable to sleep, and maintaining a consistent wake-up time to reset the body's sleep-wake cycle.
Paradoxical Intention: Technique where patients are instructed to try to stay awake instead of trying to sleep. By focusing on staying awake, the anxiety and pressure associated with falling asleep are reduced, breaking the cycle of sleep anxiety. This counterintuitive approach helps to ease tension and allows sleep to occur naturally.
Cognitive Restructuring: Helping patients challenge unrealistic expectations about sleep and reduce the pressure they place on themselves to fall asleep.
CBT-I also includes psychoeducation regarding sleep hygiene, environment modifications, and relaxation techniques discussed in the behavioral interventions section.
•Though highly effective, access to therapists skilled in CBT-I may be limited. Self-guided apps and online CBT-I programs can serve as alternatives for patients who cannot access in-person therapy. I often recommend the free mobile app CBT-i Coach developed by the VA to help patients manage insomnia with CBT-I tools, sleep logs, and relaxation exercises.
•Pharmacologic options for insomnia should be considered when behavioral interventions and treating comorbid conditions are insufficient. Hypnotic medications are best used short-term, while the underlying causes of insomnia are addressed. A wide range of medications may be used depending on the patient’s specific situation. Medications will be discussed by class, and if they received a recommendation in the guidelines by the American Academy of Sleep Medicine (AASM), that will be highlighted in green.
Benzodiazepines
Examples: Temazepam (sleep onset & maintenance), triazolam (sleep onset), clonazepam, lorazepam.
Mechanism: Enhances the activity of gamma-aminobutyric acid (GABA), the brain's primary inhibitory neurotransmitter, by binding to specific allosteric sites on the GABA-A receptor. This enhances GABA's inhibitory effects, leading to sedation, decreased sleep latency, and fewer nocturnal awakenings.
Efficacy: As effective as CBT during short periods of treatment (2–4 weeks); insufficient evidence to support long-term efficacy.
Risks: Development of dependence, tolerance, withdrawal and side effects like daytime drowsiness, dizziness, falls (especially in older adults), rebound insomnia, anterograde amnesia, cognitive impairment, and respiratory depression. Paradoxical reactions (irritability, agitation) can occur in at-risk patients including younger patients, the elderly, and those with heady injury or organic brain syndromes.
Non-Benzodiazepines "Z-drugs”
Examples: Zolpidem (Ambien & Ambien CR) (sleep onset & maintenance), eszopiclone (Lunesta) (sleep onset & maintenance), and zaleplon (Sonata) (sleep onset).
Mechanism: Selective GABA-A alpha-1 subunit agonists.
Efficacy: Like BZDs, there is evidence to support the effectiveness for short-term treatment. Intermittent (prn) use likely extends the period over which Z-drugs and benzodiazepines are effective as hypnotics.
Risks: Generally preferred over BDZs due to lower risk of dependence and next-day grogginess. Risks still include dependence, tolerance, and side effects like headaches, dizziness, falls, anterograde amnesia, cognitive impairment, and complex sleep-related behavior (sleep-driving, cooking, eating, phone calls).
Melatonin and Melatonin Agonists
Examples: Melatonin (over-the-counter [OTC]), ramelteon (Rozerem) (sleep onset).
Melatonin: Hormone that is naturally produced in the pineal gland and plays a key role in preparing the body for sleep. See days #151 and #152 for a thorough description of the role of melatonin in the sleep-wake cycle. Melatonin can be purchased OTC as a “dietary supplement.” It is recommended to take melatonin supplements 1-2 hours before the desired bedtime as this timing aligns with the natural increase in melatonin levels in the evening as the body prepares for sleep. The quality, purity, and dosing can vary significantly among brands. Some brands may contain impurities or widely inaccurate dosages, so it’s important to choose reputable brands that adhere to quality standards. Dosing recommendations differ and there is no clear guidance, but more recent data suggest that less is more with melatonin. It is generally recommended to start with a low dose (anywhere from 0.25 – 1mg), which better mimics biological dosing. Doses higher than 5 or 6 mg are generally not recommended for insomnia.
Ramelteon: Melatonin receptor agonist. FDA approved for sleep onset insomnia and also used off label for the entire spectrum of Circadian Rhythm Sleep-Wake Disorders (CRSWDs). Consider that OTC melatonin (which ramelton mimics) may do the same job at a lower price. Of note, guidelines from the AASM and VA/DoD CPG recommend Ramelteon as an option for sleep onset insomnia but recommend against the use of melatonin.
Compared to other hypnotics, melatonin and ramelteon have no evidence of abuse potential or physical dependence and pose a lower risk for respiratory depression and morning grogginess. The efficacy of these agents, however, are controversial. Common side effects may include headache, dizziness, nausea, vivid dreams, paradoxical activation, and daytime drowsiness. Very rare side effects include hormonal effects (unexplained amenorrhea, decreased libido, fertility problems), anaphylaxis, angioedema, and complex sleep-related behaviors.
Orexin Antagonists
Examples: Suvorexant (Belsomra) (sleep maintenance), lemborexant (Dayvigo), daridorexant (Quviviq).
Mechanism: Dual orexin (OX1 and OX2) receptor antagonists (DORAs for short). They treat insomnia by inhibiting the activity of orexin, a neurotransmitter that promotes wakefulness.
Efficacy: The widespread adoption of these newer medications is hindered by their overall cost and the absence of long-term data. More research is required to assess their effectiveness in comparison to other medications among diverse populations.
Risks: Common side effects: morning grogginess, headache, abnormal dreams, dry mouth. Rare but serious side effects: impaired alertness and motor coordination, sleep paralysis (inability to speak or move for up to a few minutes during the sleep-wake transition), hypnagogic/hypnopompic hallucinations (including vivid and disturbing perceptions), and cataplexy-like symptoms (leg weakness for seconds up to a few minutes both in the nighttime and daytime). Avoid in patients with narcolepsy.
Antidepressants
Certain antidepressants are used for their sedating properties, especially when insomnia coexists with depression or anxiety.
Doxepin (Silenor) (sleep maintenance): Tricyclic antidepressant (TCA) that has been repurposed for its antihistamine properties and FDA approved for the treatment of insomnia. Side effects may include somnolence, nausea, dry mouth, constipation, and orthostasis at higher doses. To maximize effectiveness, avoid taking within 3 hours of eating. Amitriptyline is another TCA that is sometimes used for insomnia, particularly in patients with comorbid chronic pain conditions.
Mirtazapine: Sedating antidepressant with a complex mechanism of action (blocks central alpha-2 adrenergic receptors, potent serotonin antagonist (5HT2 and 5HT3), blocks histamine receptors (H1)). Quite effective for insomnia, but probably under-prescribed likely due to concerns about increased appetite and weight gain. It is particularly useful in depressed patients with comorbid anxiety or insomnia, those who have had sexual side effects with other antidepressants, and those who may benefit from appetite stimulation (e.g., elderly, cancer patients). Use lower doses for insomnia (7.5 or 15mg). If patients experience too much sedation at initial lower dose, consider increasing the dose; mirtazapine has increased noradrenergic effect relative to antihistaminergic effect at high doses.
Trazodone: Technically an antidepressant but most commonly used for insomnia. Shown to decrease nighttime awakenings and improves sleep quality perception.
However, it is not recommended by the AASM for chronic (primary) insomnia due to a lack of clear evidence of improvement in sleep efficiency. Commonly used in insomnia secondary to depression or anxiety. Side effects may include drowsiness, dry mouth, dizziness or lightheadedness, orthostatic hypotension, headache, blurred vision, nausea, or vomiting. Serious but rare: may cause priapism (estimated incidence <0.1%), which is a painful erection lasting over 6 hours, requiring urgent treatment, such as surgery or medication like epinephrine, and may lead to impotence or permanent erectile dysfunction.
Antipsychotics
Antipsychotics, most commonly quetiapine, are sometimes prescribed off-label for insomnia.
Prescribing quetiapine for insomnia is controversial due to the risk of metabolic side effects in long-term use. I tend to avoid prescribing antipsychotics for patients with insomnia unless there is a clear comorbid condition that could also benefit (e.g. bipolar disorder, MDD with psychotic features).
Using quetiapine for insomnia can be a concern in malpractice cases, particularly if it is prescribed off-label without considering potential risks. Common issues include failure to address the underlying condition that may be contributing to insomnia and neglecting the known side effects of the medication. Malpractice claims may arise if a patient experiences significant adverse effects or if the prescribing physician does not follow established guidelines or document the rationale for off-label use adequately.
Antihistamines
Examples: diphenhydramine (Benadryl; found in ZzzQuil, Unisom SleepGels, Advil PM, Tylenol PM), doxylamine (Unisom SleepTabs, NyQuil), hydroxyzine.
Mechanism: Blocking H1 receptors leads to drowsiness but doesn’t necessarily improve sleep quality.
Efficacy: Can be effective for some patients and has a low risk of drug tolerance, dependence, or abuse. AASM guidelines and VA/DoD CPG recommend against antihistamines for the treatment of insomnia.
Risks: Patients commonly experience significant morning grogginess. They have secondary anticholinergic effects, which can cause dry mouth, constipation, blurred vision, tachycardia, urinary retention, as well as cognitive impairment in elderly patients. Observational studies have found that long-term use of anticholinergic drugs are associated with a higher risk of dementia.
Miscellaneous
Antiadrenergics like prazosin (alpha-1 antagonist) and clonidine (alpha-2 agonist) causes a reduction of sympathetic nervous system activity. This decreases heart rate, relaxes blood vessels, and lowers blood pressure but it also reduces the release of norepinephrine, which can have a sedative and calming effect. Data is mixed/evolving, but there is evidence that they may be helpful for patients with insomnia linked to PTSD or nightmares.
Gabapentin and pregabalin can be beneficial for patients with insomnia and comorbid pain or neuropathy, although there is limited direct data for its use in insomnia.
Conclusion
•The optimal approach to managing insomnia is personalized and multifaceted, focusing on treating the underlying cause of the sleep disturbance while incorporating behavioral and, if necessary, pharmacologic interventions. For most patients, non-pharmacological therapies such as CBT-I and sleep hygiene are the cornerstones of treatment, with medications reserved for short-term use or when non-pharmacologic measures fail. By focusing on the root causes of insomnia and promoting healthy sleep habits, you can help patients achieve long-term relief from sleep disturbances without reliance on chronic medication use.
•In the upcoming lesson, we will cover narcolepsy and other hypersomnias.
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