How Effective Is Zolpidem for Insomnia?

Common symptoms are difficulty falling asleep, decreased sleep quality and reduced sleep time, decreased memory and attention.

• Sleep mode

2018-11-04 12:11 Regarding late night insomnia, I have something to say 2018-11-04 12:11

Segmented sleep has even become the theme of the 2013 Sleep Conference, the annual meeting of the United Professional Sleep Association. This idea has caused a lot of repercussions, and scholars have concluded that the most common insomnia, "late night insomnia", may not be a disease, but a natural sleep pattern. ... more

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Basic Information

English name

insomnia

Visiting department

Department of Neurology, Psychology

Common causes

Caused by mental stress, psychosocial factors, certain chronic diseases, etc.

Common symptoms

Difficulty falling asleep, low sleep quality, easy to wake up; forgetfulness, daytime sleepiness

Causes of insomnia

According to the etiology, insomnia can be divided into two types: primary and secondary.

Primary insomnia

Usually there is no clear etiology, or the symptoms of insomnia still remain after excluding the causes that may cause insomnia, including psychophysiological insomnia, idiopathic insomnia and subjective insomnia. The diagnosis of primary insomnia lacks specific indicators, and is mainly an exclusion diagnosis. After the cause that may cause insomnia is eliminated or cured, the insomnia symptoms can be considered as primary insomnia. Psychophysiological insomnia is clinically found that its etiology can be traced to the influence of a certain or long-term event on the stability of the patient's limbic system function. The imbalance of the stability of limbic system function eventually leads to disturbance of brain sleep function and insomnia.

2. Secondary insomnia

Insomnia caused by physical diseases, mental disorders, drug abuse, etc., and insomnia related to sleep disordered breathing, sleep movement disorders, etc. Insomnia often occurs simultaneously with other diseases, and sometimes it is difficult to determine the causal relationship between these diseases and insomnia, so the concept of comorbidinsomnia has been proposed in recent years to describe insomnia that is accompanied by other diseases.

Clinical manifestations of insomnia

The clinical manifestations of insomnia patients are mainly the following:

1. disorders of the sleep process

Difficulty falling asleep, decreased sleep quality, and reduced sleep time.

2. Daytime cognitive dysfunction

Reduced memory function, decreased attention function, and decreased planning function lead to drowsiness during the day and decreased work ability, and prone to daytime sleepiness when stopping work.

3. Autonomic dysfunction of the limbic system and its surroundings

The cardiovascular system is characterized by chest tightness, palpitations, blood pressure instability, and disturbance of peripheral vasoconstriction; the digestive system is manifested by constipation or diarrhea, and the stomach is bloated; the motor system is manifested by neck and shoulder muscle tension, headache, and low back pain. Reduced ability to control emotions, easy to get angry or unhappy; males are prone to impotence, and females often have reduced sexual function.

4. Other system symptoms

Prone to short-term weight loss, decreased immune function and endocrine disorders.

Insomnia diagnosis

The Guidelines for the Diagnosis and Treatment of Chinese Adult Insomnia sets out the diagnostic criteria for Chinese adults with insomnia: insomnia manifests difficulty falling asleep, falling asleep longer than 30 minutes; the quality of sleep declines, the quality of sleep is impaired, the number of awakenings throughout the night 2 times, early Waking and sleep quality decrease; Total sleep time Total sleep time decreases, usually less than 6 hours.

On the basis of the above symptoms accompanied by daytime dysfunction. Sleep-related daytime functional impairments include: fatigue or general discomfort; loss of attention, ability to maintain attention or memory; decreased ability to study, work and / or socialize; mood swings or irritability; daytime thinking Sleep; loss of interest and energy; increased tendency to error during work or driving; nervousness, headache, dizziness, or other physical symptoms related to lack of sleep; excessive attention to sleep.
Insomnia is divided into: acute insomnia with a course of 1 month; subacute insomnia with a course of 1 month and <6 months; chronic insomnia with a course of 6 months.

The standard process and clinical path for diagnosing insomnia are as follows:

1. Medical history collection

Clinicians need to inquire carefully about the medical history, including specific sleep conditions, medication history and possible substance dependence, physical examination and assessment of mental state. The specific content of sleep status data acquisition includes insomnia manifestations, work and rest rules, sleep-related symptoms, and the effects of insomnia on daytime functions. Medical history data can be collected through a variety of means including self-assessment scale tools, family sleep records, symptom screening forms, mental screening tests, and family member statements. The recommended medical history collection process (1 to 7 are necessary evaluation items and 8 are recommended evaluation items) are as follows:

(1) Determine whether there are diseases of the nervous system, cardiovascular system, respiratory system, digestive system, and endocrine system through systematic review, and also check whether there are various other types of physical diseases, such as skin itching and chronic pain;

(2) Determine whether the patient has mood disorders, anxiety disorders, memory disorders, and other mental disorders through questioning;

(3) Review the history of drug or substance application, especially the history of abuse of antidepressants, central excitatory drugs, analgesics, sedatives, theophylline, steroids, and alcohol;

(4) Review the overall sleep status in the past 2 to 4 weeks, including the incubation latency (time from bed to sleep), number of awakenings during sleep, duration and total sleep time. It should be noted that the average estimated value should be taken when inquiring the above parameters, and it is not appropriate to use the sleep status and experience of a single night as a diagnostic basis; it is recommended to use a body motion sleep detector for a 7-day cycle of sleep assessment;

(5) For sleep quality assessment, you can use the Pittsburgh Sleep Quality Index (PSQJ) questionnaire and other scale tools. It is recommended to use a physical sleep detector for a 7-day cycle of sleep assessment, and finger vein oxygen monitors to monitor nighttime blood. oxygen;

(6) Evaluate daytime function through consultation or with the aid of a scale tool to exclude other diseases that impair daytime function;

(7) For patients with daytime sleepiness, combined with screening for sleep disordered breathing and other sleep disorders;

(8) It is best to assist patients and family members to complete a 2-week sleep diary before the first system assessment, record daily bedtime, estimate sleep latency, record the number of nightly awakenings and the time of each awakening, and record the time from bedtime to wake up Total bedtime between, estimated actual sleep time based on morning awake time, calculated sleep efficiency (ie actual sleep time / bed time × 100%), recorded abnormal symptoms at night (abnormal breathing, behavior and exercise, etc.), daytime energy and The extent to which social functions are affected, and lunch breaks. Day medication and self-experience.

2. Scale assessment

(1) Systematic review of medical history: It is recommended to use the Cornell Health Index for a semi-quantitative review of medical history and current status, and to obtain evidence supporting relevant physical and emotional data.

(2) Evaluation of Sleep Quality Scale: Insomnia Severity Index; Pittsburgh Sleep Index; Fatigue Severity Scale; Quality of Life Questionnaire; Sleep Belief and Attitude Questionnaire, Epworth Sleeping Scale Assessment.

(3) Emotions include self-assessment and other assessments of insomnia: Beck; depression scale; status trait anxiety questionnaire.

3. Cognitive function assessment

Note that IVA-CPT is recommended for functional evaluation; Wechsler memory scale is recommended for memory function.

4. Objective assessment

Patients with insomnia are more prone to deviations in their self-assessment of sleep conditions, and need to be evaluated by objective assessment methods when necessary.

(1) Sleep monitoring All night polysomnography (PSG) is mainly used for the evaluation and differential diagnosis of sleep disorders. PSG assessment can be performed in the differential diagnosis of patients with chronic insomnia. Multiple sleep latency tests are used for the diagnosis and differential diagnosis of narcolepsy and daytime sleep disorders. The body motion recorder can be used as an alternative to evaluate patients' total sleep time and sleep pattern in the absence of PSG monitoring conditions. Finger pulse blood oxygen monitoring can understand the blood oxygen condition during sleep, and it should be performed before and after treatment. Before treatment, it is mainly used to diagnose the existence of hypoxia during sleep. The main purpose of treatment is to judge the effect of drugs on breathing during sleep.

(2) Limb system stability check Event-related evoked potential check can provide objective indicators for the diagnosis of emotional and cognitive dysfunction. Neurofunctional imaging opens up new fields for the diagnosis and differential diagnosis of insomnia. Due to the expensive equipment, it cannot be promoted in clinical practice.

(3) Etiological exclusion test Because the occurrence of sleep disorders is often related to endocrine function, tumors, diabetes, and cardiovascular disease, it is recommended to perform thyroid function tests, sex hormone level tests, tumor marker tests, blood glucose tests, and dynamic ECG night heart rate variability. Sex analysis. Some patients require head imaging.

Insomnia treatment

Overall goal

Make the cause as clear as possible to achieve the following purposes:

(1) Improve sleep quality and / or increase effective sleep time;

(2) Restore social functions and improve patients' quality of life;

(3) reduce or eliminate the risk of physical diseases associated with or related to insomnia;

(4) Avoid the negative effects of drug intervention.

2. Mode of intervention

Interventions for insomnia include drug treatment and non-drug treatment. For patients with acute insomnia, drug treatment should be applied early. For patients with subacute or chronic insomnia, whether it is primary or secondary, drug therapy should be supplemented with psychological behavior therapy, even for those who have been taking sedative hypnotics for a long time. The most effective psychological and behavioral therapy for insomnia is cognitive behavioral therapy (CBT-I).

At present, there are relatively few professional resources capable of engaging in psycho-behavioral therapy in China, and there are not many personnel with professional qualification certification in this area. CBT-I alone will also face compliance issues, so drug intervention still occupies a dominant position in insomnia treatment. In addition to psycho-behavioral therapy, other non-drug treatments, such as diet therapy, aromatherapy, massage, homeopathy, and light therapy, lack a convincing large-scale controlled study. Traditional Chinese medicine has a long history of treating insomnia, but it is difficult to evaluate it with modern evidence-based medicine due to its special individualized medical model. The importance of sleep health education should be emphasized, that is, on the basis of establishing good sleep hygiene habits, psychological behavior therapy, drug treatment and traditional medical treatment should be carried out.

3. Medication for insomnia

Although there are many drugs with hypnotic effects, the main purpose of most of them is not to treat insomnia. The current drugs for clinical treatment of insomnia mainly include benzodiazepine receptor agonists (benzodiazepine receptors agonists, BZRAs), melatonin receptor agonists and antidepressants with hypnotic effects. Although antihistamines (such as diphenhydramine), melatonin, and valerian extract have hypnotic effects, the existing clinical research has limited evidence and should not be used as routine drugs for insomnia. General treatment recommendations: eszopiclone, zolpidem, zolpidem-CR, zopiclone. Drugs for insomnia are complex and numerous, including estazolam, flurazepam, quazepam, temazepam, triazolam, and alprazolam ), Chlordiazepoxide, diazepam, lorazepam, midazolam, zolpidem, zolpidem-CR, zopipam Clone (zopiclone), eszopiclone and zaleplon, ramelteon, tasmellteon (stage III clinical, tasimelteon), agomelatin ), Tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibition (SNRIs), low-dose mirtazapine, low-dose trazodone, etc. . Due to the possibility of dependence on some drugs, long-term use is generally not recommended.

4. Physical therapy

Repetitive transcranial magnetic stimulation is a new type of non-drug treatment for insomnia. Transcranial magnetic stimulation is a new technology that provides magnetic stimulation to a specific part of the human skull. It refers to the process of giving repeated stimulation to a specific cortical part. Repetitive transcranial magnetic stimulation can affect local and functionally related distal septal cortical functions, achieve regional reconstruction of cortical functions, and affect neurotransmitters and their transmission in the brain, and multiple receptors including serotonin in different brain regions. The gene expression of body and neuron excitability has a significant effect. It can be combined with drugs to quickly block the occurrence of insomnia, and is especially suitable for women's insomnia treatment during breastfeeding, especially insomnia caused by postpartum depression.

5. Drug treatment for patients with special types of insomnia

(1) Elderly patients Non-drug treatments are preferred for elderly patients with insomnia, such as sleep hygiene education, with particular emphasis on receiving CBT-I (grade I recommendation). When the treatment of the primary disease does not relieve the symptoms of insomnia or cannot comply with non-drug treatment, drug treatment can be considered. Elderly patients with insomnia are recommended to use non-BZDs (non-benzodiazepines) or melatonin receptor agonists (grade II recommendation). It is necessary to be cautious when using BZDs (benzodiazepines). If ataxia, confusion, abnormal movements, hallucinations, or respiratory depression occur, the drug should be discontinued immediately and properly handled. At the same time, the muscle tension caused by taking BZDs should be paid attention Reduction may cause accidental injury such as a fall. The dosage of drug treatment for elderly patients should start from the minimum effective dose, short-term application or intermittent therapy is not recommended, and large doses are not recommended. Adverse drug reactions should be closely observed during the medication.

(2) There is no data on the safety of sedative and hypnotic drugs for pregnant women during pregnancy and lactation . Because zolpidem has no teratogenic effect in animal experiments, it can be taken for a short time if necessary (level IV recommendation). The use of sedative and hypnotic drugs and antidepressants during breastfeeding needs to be cautious to prevent the drug from affecting the baby through milk. Non-pharmacological intervention is recommended to treat insomnia (grade I recommendation). Existing experiments show that transcranial magnetic stimulation is a promising method for treating insomnia during pregnancy and lactation, but the exact effect needs to be observed in a large sample.

(3) Perimenopausal and menopausal women. For perimenopausal and menopausal insomnia women, they should first identify and deal with common diseases affecting sleep in this age group, such as depression, anxiety disorders, and sleep apnea syndrome. The necessary hormone replacement therapy is given according to the symptoms and hormone levels. The treatment of insomnia in this part of patients is the same as that of ordinary adults.

(4) BZDs with respiratory diseases are used with caution in patients with chronic obstructive pulmonary disease (COPD) and sleep apnea-hypopnea syndrome due to adverse reactions such as respiratory depression. Non-BZDs receptors are highly selective, and the incidence of residual effects in the next morning is low. Zolpidem and zopiclone have been used to treat patients with mild to moderate COPD in the stable stage of insomnia. No respiratory adverse reactions have been reported, but zalep The efficacy of Long on patients with insomnia with respiratory diseases has not been determined.

Insomnia may be the main complaint in elderly patients with sleep apnea, and there are more people with complex sleep disordered breathing. Short-acting sleep-promoting drugs such as zolpidem alone can reduce the incidence of central sleep apnea. Application of non-invasive ventilator therapy can improve compliance And reduce the possibility of inducing obstructive sleep apnea. BZDs should be disabled in patients with acute exacerbation of COPD with acute hypercapnia and decompensated periods of restricted ventilatory dysfunction. If necessary, they can be applied and closely monitored with mechanical ventilation support (invasive or noninvasive). Remelton, a melatonin receptor agonist, can be used to treat patients with sleep disordered breathing and insomnia, but further research is needed.

(5) Patients with comorbid mental disorders often have insomnia symptoms, and psychiatric practitioners should treat and control the primary disease according to the special principles, while treating insomnia symptoms. Depression disorders often co -exist with insomnia, and cannot be treated in isolation to avoid the dilemma of the vicious circle. The recommended combination treatment methods include: CBT-I treatment CBT-I treatment with insomnia and the application of antidepressants with hypnotic effects (such as docepine , Amitriptyline, mirtazapine, or paroxetine, etc.); antidepressant antidepressant (single drug or combination) plus sedative hypnotic drugs, such as non-BZDs drugs or melatonin receptor agonists (grade III recommended) . It should be noted that the use of antidepressants and hypnotic drugs may increase sleep apnea syndrome and periodic leg movements. When insomnia exists in patients with anxiety disorders, anti-anxiety drugs are mainly used, and sedative hypnotic drugs are added before bedtime if necessary. When insomnia exists in patients with schizophrenia, antipsychotic drugs should be the main treatment, and sedative and hypnotic drugs can be used to treat insomnia if necessary.

6. Psycho-behavioral treatment of insomnia

The essence of psychobehavioral therapy is to change the patient's belief system, exert its self-efficacy, and then improve the symptoms of insomnia. To achieve this goal often requires the involvement of a professional physician. Psycho-behavioral therapy has good effects on primary and secondary insomnia in adults, and usually includes sleep hygiene education, stimulation control therapy, sleep restriction therapy, cognitive therapy and relaxation therapy. These methods are used alone or in combination for the treatment of adult primary or secondary insomnia

(1) Sleep hygiene education Most insomnia sufferers have bad sleep habits, disrupting normal sleep patterns, forming the wrong conception of sleep, which leads to insomnia. Sleep hygiene education is mainly to help patients with insomnia to recognize the important role of poor sleep habits in the occurrence and development of insomnia, analyze and find the causes of bad sleep habits, and establish good sleep habits. Generally speaking, sleep hygiene education needs to be carried out simultaneously with other psycho-behavioral treatment methods. It is not recommended to apply sleep hygiene education as an isolated intervention.
The contents of sleep hygiene education include:

Avoid using excitable substances (coffee, strong tea or smoking, etc.) for several hours before bedtime (usually after 4 pm); Do not drink alcohol before bedtime, alcohol can interfere with sleep; regular physical exercise, but avoid strenuous exercise before bedtime Exercise; Do not eat or drink or eat food that is difficult to digest before going to bed; Do not do excitement mental labor or watch books and film programs that cause excitement for at least 1 hour before going to bed; The bedroom environment should be quiet and comfortable , The light and temperature are suitable; maintain a regular schedule.

(2) Stress, tension and anxiety are the common factors that induce insomnia. Relaxation therapy can alleviate the adverse effects caused by the above factors, so it is the most commonly used non-drug therapy for insomnia. Its purpose is to reduce alertness in bed and reduce nighttime awakening. Techniques to reduce awakening and promote nighttime sleep include progressive muscle relaxation, guided imagination, and abdominal breathing exercises. Patients plan to practice 2-3 times a day after relaxation training. The environment should be clean and quiet. The initial stage should be performed under the guidance of professionals. Relaxation therapy can be used as an independent intervention for insomnia treatment (Class I recommendation).

(3) Stimulation control therapy Stimulation control therapy is a set of behavioral interventions to improve the interaction between the sleeping environment and the tendency to sleep (sleepiness), restore the function of bedridden as a signal to induce sleep, make it easy for patients to fall asleep, and rebuild the sleep-wake biological rhythm . Stimulation control therapy can be applied as a stand-alone intervention (Class I recommendation). Specific content: Go to bed only when you have sleepiness; If you can't fall asleep for 20 minutes in bed, you should get up and leave the bedroom, you can engage in some simple activities, and then return to the bedroom to sleep when you feel sleepy; Do not do sleep-related activities in bed , Such as eating, watching TV, listening to the radio, and thinking about complex issues; Regardless of how much sleep the night before, keep a regular wake-up time; Avoid napping during the day.

(4) Sleep restriction therapy Many patients with insomnia try to increase their chances of sleep by increasing their bed time, but often they are contrary to their wishes, and they further reduce the quality of sleep. Sleep restriction therapy improves sleep efficiency by shortening the time spent in bed and increasing the drive to fall asleep. The specific contents of the recommended sleep restriction therapy are as follows (Class II recommendation): Reduce the bed time to match the actual sleep time, and only increase the bed time by 15-20 minutes if the sleep efficiency in a week exceeds 85%. Time; When the sleep efficiency is less than 80%, reduce the bedtime by 15-20 minutes; when the sleep efficiency is between 80% and 85%, keep the bedtime unchanged; Avoid napping during the day and keep the time of getting up regularly.

(5) Cognitive-behavioral therapy Insomnia patients often fear the insomnia itself, pay too much attention to the adverse consequences of insomnia, often feel nervous when they are close to sleep, and worry about poor sleep. These negative emotions make sleep worse, and the worsening of insomnia is. It affects the patient's mood, and the two form a vicious circle. The purpose of cognitive therapy is to change the cognitive bias of patients with insomnia, and to change their irrational beliefs and attitudes about sleep problems. Cognitive therapy is often used in combination with stimulation control therapy and sleep restriction therapy to form CBT-I for insomnia. The basic content of cognitive behavioral therapy: maintain reasonable sleep expectations; do not attribute all problems to insomnia; keep falling asleep naturally and avoid excessive subjective intentions to fall asleep (forcing yourself to fall asleep); do not pay too much attention to sleep; Don't get frustrated because you didn't sleep well for one night; Cultivate tolerance to the effects of insomnia. CBT-I is usually a combination of cognitive therapy and behavioral therapy (stimulation control therapy, sleep restriction therapy). It can also be combined with relaxation therapy and supplemented with sleep hygiene education. CBT-I is the core of psychobehavioral therapy for insomnia (Class I recommendation)

(6) Comprehensive intervention for insomnia : 1) The short-term effect of drug intervention on insomnia has been confirmed by clinical trials, but long-term application still needs to bear potential risks such as adverse drug reactions and addiction. CBT-I not only has short-term effects, but its effects can be maintained for a long time during follow-up observation. CBT-I combined with non-BZDs can get more advantages, and the latter can be changed to intermittent treatment to optimize the effect of this combination therapy. 2) The recommended combination therapy (grade II recommendation) is the combination of CBT-I and non-BZDs (or melatonin receptor agonist). If the symptoms are controlled in the short term, non-BZDs will be gradually stopped, otherwise non-BZDs BZDs were changed to intermittent medication, and CBT-I intervention was maintained throughout the treatment (grade II recommendation).