Evidence-Based Treatment of Insomnia: The Role of the Family Physician

Introduction

Insomnia is a health disorder that impairs quality of life and affects 8–18% of people worldwide. A large proportion of patients consult their family physician because of this condition. At first glance, the treatment of a sleep disorder may not appear particularly complicated; however, this condition often presents challenges for family physicians and even specialists in the field.

Insomnia is associated with decreased satisfaction with sleep duration or quality. Impaired sleep duration and quality are related to one or more components of insomnia: inability to fall asleep, inability to remain asleep without awakening, or waking unusually early. This health disorder causes stress throughout the body and impairs the patient’s ability to effectively perform everyday activities. Chronic insomnia is diagnosed when the sleep disturbance occurs at least 3 nights per week and persists for at least 3 months and cannot be explained by other causes, such as the use of medications or other substances or comorbid diseases. In addition, insomnia can only be diagnosed when a person complains of sleep disturbance despite having adequate conditions for sufficient, good-quality sleep. It is always important to ask the patient about this because the information helps the physician distinguish insomnia from sleep deprivation, which has entirely different causes and consequences and requires different measures and methods to address it. Insomnia has been found to frequently coexist with other sleep-wake disorders, psychiatric disorders, and other health problems. It is important to note that acute insomnia is characterized by the same signs and symptoms as chronic insomnia, but is of shorter duration, and its causes and treatment may differ.

The characteristics of insomnia may sometimes help identify the cause of the sleep disturbance. Inability to fall asleep is characteristic of restless legs syndrome and anxiety disorders, whereas patients with obstructive sleep apnea, nocturia, or pain syndromes are often unable to remain asleep for a sufficient length of time and awaken frequently. Early awakening is characteristic of depression. Table 1 presents a brief algorithm for the examination, assessment, and treatment of a patient presenting with insomnia.

Assessment of Insomnia

The family physician plays a major role in evaluating a patient presenting with a sleep disorder because the family physician performs the initial assessment and determines the most appropriate strategy for further treatment.

The diagnosis of insomnia is based on the patient’s complaints, medical history, and information provided by the bed partner. Various questionnaires and sleep diaries are used to assess the severity of insomnia, identify potential causes of the sleep disturbance, and monitor the effects of treatment. Two insomnia assessment tools that can easily be used in clinical practice are the Insomnia Severity Index and the Consensus Sleep Diary. Both can be completed quickly, within 2–3 minutes, either at home or in the physician’s office, and the information they provide helps the treating physician select an appropriate treatment strategy.

Cognitive Behavioral Therapy

When initiating treatment for chronic insomnia, the American College of Physicians (ACP) recommends cognitive behavioral therapy (CBT). The ACP emphasizes that the patient should actively participate in decision-making. If CBT is ineffective, the physician and patient should jointly discuss the cost, potential benefits, and expected harms of pharmacological treatment.

Various methods involving cognitive and behavioral interventions are used in CBT for insomnia. One component of treatment is patient education, including information about normal sleep habits and discussion of expectations. Patients are also taught stimulus control, restriction of time spent in bed, and relaxation techniques. CBT is an effective treatment, with a long-term therapeutic effect observed in 70–80% of patients. Patients receiving CBT use fewer hypnotic medications. CBT may be provided by appropriately trained and qualified specialists or undertaken by the patient using automated computer programs available online, such as SHUTi and Sleepio. This treatment effectively reduces sleep-onset latency, increases sleep duration, and improves sleep quality.

Some centers use Brief Behavioral Treatment for Insomnia. This evidence-based treatment was developed on the basis of CBT and can be delivered either in person or by telephone. It consists of 4 brief behavioral interventions designed to improve sleep quality and duration. The goals of treatment are to strengthen the association between bed and sleep, restore the sleep rhythm, and reduce arousal. The following principles are applied: it is important to spend as little time as possible lying in bed regardless of sleep duration; the patient should get up at the same time every day; the patient should not go to bed unless sleepy; and it is important to get out of bed as soon as sleepiness decreases. Once sleep parameters improve, the patient can gradually increase the amount of time spent in bed, thereby finding the optimal balance between sleep continuity and duration.

Pharmacological Treatment

Pharmacological treatment is most appropriate for patients with acute insomnia (Table 1). In chronic insomnia, pharmacological treatment is used only after discussing its potential benefits and harms with the patient and only when CBT is ineffective.

Hypnotic Medications

Hypnotic medications do not cure insomnia because they do not eliminate its underlying cause. They only alleviate the symptoms of the disorder. Table 2 presents the main recommendations for treatment with hypnotic medications.

Non-benzodiazepine hypnotics, such as eszopiclone, zolpidem, and zaleplon, are considered to have a lower potential for dependence. Benzodiazepines are associated with the development of tolerance, meaning that progressively higher doses are required to achieve the same effect. However, clinical studies have shown that insomnia can be successfully treated with non-benzodiazepine hypnotics even over prolonged periods of 6–12 months without the development of signs characteristic of tolerance. Such treatment improves patients’ quality of life and ability to work and reduces the overall insomnia index.

Treatment with immediate-release zolpidem is initiated at 5 mg before bedtime in women and 5–10 mg before bedtime in men. If extended-release zolpidem is selected, treatment is initiated at 6.25 mg before bedtime in women and 6–12.5 mg before bedtime in men. The immediate-release formulation is used for patients who have difficulty falling asleep, whereas the extended-release formulation is prescribed for patients who have difficulty maintaining good-quality sleep. However, treatment with the extended-release formulation may impair the patient’s ability to operate various types of machinery, including driving a car, because a significant concentration of the drug may still be present in the blood plasma in the morning.

If eszopiclone is selected, the initial dose is 1 mg immediately before bedtime, and the anticipated duration of sleep should be at least 7–8 hours. If necessary, the dose may be increased to 2 mg in older patients and 3 mg in non-elderly patients. This medication is used in patients who have difficulty maintaining sufficiently good sleep quality, i.e., those who awaken frequently.

Zaleplon has a very short half-life of 1 hour. Therefore, it is used in patients who have difficulty falling asleep. A dose of 5–20 mg is administered. It may also be used in patients who occasionally awaken during the night and are unable to fall asleep again. In such cases, the patient may take a tablet, but at least 4 hours must remain before the planned time of awakening; otherwise, the sedative effect of the medication may still be experienced during the day.

Patients with severe or treatment-resistant insomnia and those with chronic diseases may sometimes require long-term treatment with hypnotic medications. However, during follow-up visits, the appropriateness, effectiveness, and adverse effects of such treatment should be continuously assessed. Treatment may be administered as needed when the patient’s condition worsens or before every sleep period. Patients receiving long-term pharmacological treatment should also receive CBT.

The risk of dependence associated with such treatment using non-benzodiazepine hypnotics is not high; however, these medications should be avoided in patients diagnosed with substance dependence.

Abrupt discontinuation of hypnotic medications often results in recurrence of insomnia symptoms. This phenomenon is more frequently observed among patients who have used short-acting medications or high doses. The risk of recurrent insomnia can be reduced by using low medication doses, gradually discontinuing the medication, or combining pharmacological treatment with CBT.

Orexin Receptor Antagonists

Suvorexant belongs to this group of medications. It is used to treat insomnia characterized by difficulty falling asleep and frequent awakenings during the night. The recommended dose is 10 mg before bedtime.

Melatonin Receptor Agonists

These medications bind to and activate melatonin receptors. Ramelteon is used to treat insomnia and is not associated with signs of abuse. Ramelteon is used in patients who have difficulty falling asleep. It may be used in older patients and in those with a history of substance abuse. The recommended dose is 8 mg before bedtime. It is important to note that ramelteon is not an appropriate choice for patients who experience frequent awakenings during the night.

Antidepressants

There is limited evidence-based information on the use of sedating antidepressants for the treatment of primary insomnia when no mood disorder has been diagnosed. Sedative effects are characteristic of tricyclic antidepressants (amitriptyline, nortriptyline, and doxepin) and tetracyclic antidepressants (mirtazapine).

In clinical practice, it is often assumed that sedating antidepressants cause fewer adverse effects than non-benzodiazepine hypnotics such as zolpidem, eszopiclone, or zaleplon; however, this assumption is incorrect. These medications may cause daytime drowsiness, dry mouth, hypotension, weight gain, and cardiac rhythm disturbances. The safety and efficacy of doxepin were evaluated in 2 randomized, double-blind, placebo-controlled trials. Its effect is thought to be mediated through histamine receptors. Studies have shown that doxepin does indeed improve sleep quality in patients with insomnia.

Antihistamines

Antihistamines are readily available without a prescription and are often included in medications used to treat the common cold. First-generation H1 receptor blockers have hypnotic effects; however, their effectiveness in treating insomnia has not been evaluated in high-quality scientific studies. Therefore, they are not recommended for the treatment of insomnia.

Melatonin

Melatonin is a hormone naturally secreted by the human pineal gland and is readily available from pharmacies without a prescription. The pineal gland regulates melatonin metabolism in the body: its highest blood concentrations are observed at night and its lowest concentrations during wakefulness. The timing of melatonin administration is important. It has been found that taking melatonin in the early evening increases sleep duration, whereas taking it 30 minutes before bedtime does not produce a beneficial effect.

Data from clinical trials evaluating the effects of melatonin are inconsistent, and the study designs were not optimal. Several studies have investigated the effects of melatonin in older patients. According to their results, melatonin improves conventional sleep parameters in patients older than 65 years. It is important to note that most of these studies were relatively short and included only small numbers of patients. Given that the safety and efficacy profile of melatonin has not been well established, experts from the American Academy of Sleep Medicine do not recommend melatonin for the treatment of patients with chronic insomnia.

Herbal Preparations and Other Remedies

The herbal preparations most commonly used to treat insomnia contain valerian root. A number of clinical studies have investigated the effects of valerian on sleep quality. The results of meta-analyses are inconsistent. A 2010 meta-analysis found that valerian preparations improved sleep quality according to patients’ subjective assessments. However, the conclusions of a 2006 meta-analysis emphasized that some clinical trials of valerian root had substantial methodological limitations. Evaluation of objective sleep parameters showed that valerian preparations did not improve them.

Scientific studies have failed to demonstrate any beneficial effect of St. John’s wort in the treatment of insomnia, while naturally derived substances such as mulberry, alcohol, or L-tryptophan may cause various adverse effects and may be harmful. Therefore, experts from the American Academy of Sleep Medicine do not recommend these remedies for the treatment of insomnia.

Acupuncture

There is scientific evidence suggesting that acupuncture may be beneficial in the treatment of insomnia and that its therapeutic effect may persist after treatment has been discontinued. However, these studies included small sample sizes and had short follow-up periods.

Device-Based Treatment

In 2016, the U.S. Food and Drug Administration approved the Cereve Sleep system for the treatment of insomnia. The system consists of a bedside device connected to a special pad that cools the forehead during sleep. The mechanism of action is based on research showing increased electrical activity in the frontal cerebral cortex at night in people with insomnia. Cooling this area suppresses electrical activity, thereby improving sleep quality. The effectiveness of the device has been demonstrated in 3 clinical trials.

Diet and Physical Activity

Dietary recommendations specify which foods should be avoided and when meals should be consumed. In the afternoon and evening, patients with insomnia should avoid beverages high in caffeine because caffeine has a stimulating effect and disrupts sleep. In addition, patients seeking to improve sleep quality should avoid alcoholic beverages in the evening. Large evening meals should also be avoided, particularly in patients who also have gastroesophageal reflux disease (GERD).

Exercise or other physical activity performed in the late afternoon or early evening may improve sleep quality, but such exercise or activities should be performed at least 6 hours before bedtime. If a person exercises vigorously late in the evening, for example, less than 6 hours before the planned bedtime, such physical activity may worsen insomnia.

Treatment of Insomnia in Older Patients

Sleep quality deteriorates with age. Aging itself should not be used to explain insomnia. In older patients, deterioration in sleep quality may be caused by various factors, including nocturnal urination, pain syndromes, chronic diseases such as heart failure, chronic obstructive pulmonary disease, and Parkinson’s disease, as well as restless legs syndrome, sleep apnea, and dementia. Various social factors, such as retirement, disappointment, and financial difficulties, may also contribute to insomnia. These conditions promote the development of anxiety disorders and depression. Both anxiety disorders and depression may also cause insomnia.

When treating older patients, preference should be given to non-pharmacological treatments, including various psychological and behavioral interventions. If these measures are ineffective and treatment with hypnotic medications is chosen, it is important to use the lowest medication doses. Because metabolism is slower in older patients, the duration of action of various medications may be prolonged and their elimination from the body may be slower. Hypnotic medications increase the risk of falls and bone fractures in older patients and may impair their ability to perform daily activities and reduce daytime alertness.

Summary

Insomnia is a common health disorder encountered by family physicians in clinical practice. Although insomnia is often initially treated with benzodiazepines in everyday clinical practice, international experts recommend a different treatment strategy. Treatment of chronic insomnia should begin with non-pharmacological measures, with the best results achieved using CBT. Pharmacological alternatives should only be considered when psychotherapeutic treatment methods are ineffective, and even then, treatment with medications that do not belong to the benzodiazepine group is recommended. Other treatment methods may also be appropriate for certain groups of patients.

Family physicians should be able to independently manage short-term sleep disturbances; however, specialist consultation is often required when treating chronic insomnia. In all cases, particular emphasis should be placed on the principles of sleep hygiene and the importance of diet and physical activity. If a patient has a comorbid condition that may cause insomnia, consultation with an appropriate specialist, such as a pulmonologist, cardiologist, or psychiatrist, is often required. Patients with depression should receive appropriate antidepressant treatment. Particular caution should be exercised when treating older patients. Pharmacological interventions should be avoided whenever possible, and when they are necessary, lower-than-usual medication doses should be used…

Prepared according to: Buysse DJ, Rush AJ, Reynolds CF 3rd. Clinical Management of Insomnia Disorder. JAMA. 2017 Oct 23; Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008 Oct 15;4(5):487-504; supplemented with information provided in the Medscape and UpToDate databases.

Read more in Internistas, No. 6, 2018.

Justas Simonavičius, MD

Vilnius University Hospital Santaros Klinikos