Sleep disturbance: treatment

Treatment of insomnia

Insomnia is a symptom of a disturbed sleep, which can be a manifestation of various diseases. Therefore, the first step towards the treatment of insomnia should be persistent search for the cause of sleep disorders. Only when establishing the cause of insomnia can develop an effective strategy for its therapy. Since the reasons are different, then the treatment can vary significantly. In some cases, patients first of all need to help cope with stress - this may require the advice of a psychotherapist or psychologist. In cases where poor sleep habits or wrong actions of patients contribute to sleep disturbances, it is important to convince them to follow the rules of sleep hygiene. If sleep disorders are associated with somatic or neurological disease, substance abuse, drug use, then correction of these conditions is the most effective way to normalize sleep.

Insomnia often develops against a background of mental disorders, especially depression. If a patient is diagnosed with a major depression, he is always carefully examined for insomnia. For example, in the Hamilton Depression Rating Scale, often used to assess the severity of depression, 3 out of 21 points are devoted to sleep disorders. They evaluate the difficulties of falling asleep, awakening in the middle of the night, premature morning awakenings. On the other hand, a patient with insomnia should always exclude depression. It is widely believed that with a decrease in depression, sleep also improves. Although this pattern is confirmed by clinical experience, there are very few special studies that would evaluate changes in sleep against a background of depression. A recent study in which patients with depression was treated with the method of interpersonal psychotherapy (without the use of medication) showed that a decrease in the severity of depression was accompanied by a deterioration in some sleep indices - for example, the degree of fragmentation and delta activity in a slow sleep. In addition, it was found that low delta activity in slow sleep in patients who achieved remission, was associated with a higher risk of recurrence. These data show that the relationship between sleep physiology and depression should be taken into account when assessing the condition of patients.

In recent years, a fairly large number of new antidepressants have appeared. Although their effectiveness is comparable, they differ significantly in a number of pharmacological properties. The mechanism of their action is associated with the effect on various neurotransmitter systems of the central nervous system, primarily noradrenergic, serotonergic and dopaminergic. Most antidepressants change the activity of one or more of these systems, blocking the reverse capture of the mediator by presynaptic endings.

One of the properties by which antidepressants differ significantly from one another is selectivity. Some antidepressants (for example, tricyclics) have a wide pharmacological profile, blocking various types of receptors in the brain - histamine (N1), muscarinic cholinergic receptors, alpha-adrenergic receptors. The side effects of tricyclic antidepressants are often explained by a non-selective effect on many types of receptors. For example, such drugs as amitriptyline and doxepin have a pronounced sedative effect, which, at least in part, is due to their ability to block histamine H1 receptors. Tricyclic antidepressants with sedative action are often recommended to prescribe to patients suffering from depression and insomnia. Some studies have shown that these drugs shorten the latent period of sleep and reduce the degree of its fragmentation.

Other antidepressants have a more selective effect, mainly affecting only one neurotransmitter system. An example is selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. Insomnia is one of the most common side effects of SSRIs, occurring in 20-25% of cases. In several studies involving the use of PSG, the adverse effect of SSRIs on sleep was shown: on the background of their administration, a decrease in the efficiency of sleep, an increase in the number of complete or partial awakenings was observed. It is suggested that the influence of SIOSH on sleep is mediated by increased stimulation of serotonin 5-HT2 receptors. In favor of this point of view, the fact that two antidepressants - nefazodone and mirtazapine - that improve sleep, according to preclinical studies, effectively block 5-HT2 receptors. Little is known about the effect on sleep of mirtazapine. However, the effect on sleep of nefazodone has been studied in sufficient detail - both in healthy and in patients with depression. In one study in patients with depression and sleep disturbance, a comparative study of the effects of nefazodone and fluoxetine was conducted. The effect of drugs on sleep was assessed with the help of PSG. Both drugs led to a significant and comparable reduction in depressive symptoms, but their impact on sleep was different. In patients taking fluoxetine, lower sleep efficacy and a higher number of awakenings were noted than in patients taking nefazodone.

These results demonstrate that different antidepressants have different effects on the physiology of sleep, despite the fact that they have approximately the same antidepressant effect. Choosing a drug to treat a patient with depression and insomnia, you should consider its impact on the architectonics of sleep. Many clinicians prefer to combine an antidepressant with an activating action (eg, fluoxetine) with a hypnotic in patients with depression and insomnia. Although this practice is widespread and supported by many specialists, its effectiveness and safety have not been studied in controlled trials using objective estimation methods such as PSG. In practice, a combination of trazodone, an antidepressant with a pronounced sedative effect (usually at very low doses) with an activating drug, such as fluoxetine, is often used. Despite the popularity of such a combination and the belief of many doctors in its effectiveness, there is no data that would prove the effectiveness of such a strategy.

Medicinal treatment of insomnia

For many patients with insomnia, medication is the most important, if not obligate, component of treatment. Over the past decades, a number of drugs have been used to treat insomnia. In the past, barbiturates (for example, secobarbital) or barbiturate-like hypnotics, such as chloral hydrate, have been widely used in the treatment of insomnia. Currently, they are rarely used because of the frequent side effects, high risk of drug dependence and withdrawal syndrome with prolonged use.

At present, antidepressants with sedative action, such as amitriptyline and trazodone, are often used to treat insomnia. The effectiveness of these drugs in the treatment of a combination of depression and insomnia is beyond doubt. However, many doctors prescribe antidepressants with sedative effect in relatively small doses and those with insomnia who do not suffer from depression. This practice, at least in part, is due to the desire to avoid long-term use of sleeping pills, which is associated with a risk of dependence and withdrawal syndrome. Clinical experience shows that small doses of antidepressants do cause symptomatic improvement in many patients with chronic insomnia. This effectiveness and safety of this method of treatment is not proved in clinical trials. It should also be taken into account that this class of drugs can cause serious side effects, even if small doses are not observed so often.

Benzodiazepines

Currently, benzodiazepines are most widely used for the treatment of insomnia, including triazolam, temazepam, quazepam, estazolam, flurazepam, and the imidazopyridine derivative zolpidem.

Benzodiazepine hypnotics differ, first of all, by the speed of action (the rate of onset of the effect), the half-elimination period and the number of active metabolites. Among benzodiazepine hypnotics, triazolam, estazolam, flurazepam have a more rapid effect. Slowly acting temazepam; quazepam occupies an intermediate position. In some cases, knowledge of this characteristic of the drugs is important for the choice of treatment. For example, if the patient is disturbed by falling asleep, in this case, the drug with a quick action will be more effective. The rapidity of the drug should be sure to inform the patient. The drug with a quick action of the patient should be taken shortly before going to bed, if he takes it too soon, he puts himself at risk of falling or other accidents.

The duration of the drug is determined by the duration of the half-elimination period and the presence of active metabolites. From these indicators depends the ability of drugs to support sleep and the likelihood of certain side effects. Benzodiazepines are usually divided into short-acting drugs (T1 / 2 not more than 5 hours), intermediate (medium) action (T1 / 2 from 6 to 24 hours) and long-acting (T1 / 2 for more than 24 hours). According to this classification, triazolam is referred to as short-acting drugs, estazolam and temazepam - to intermediates, flurazepam and quazepam - to long-acting drugs. But the duration of action depends on active metabolites. For example, quazepam and flurazepam are classified as long-acting drugs, taking into account the half-elimination of primary substances, and their active metabolites have an even longer half-elimination period. Because of this, both drugs can be accumulated in the body during repeated admission.

Benzodiazepines of short and long-term action differ in a number of properties that need to be considered in the treatment of insomnia. Thus, short-acting benzodiazepines are not characterized by the phenomenon of aftereffect, which can be expressed in daytime drowsiness, slowing down of psychomotor reactions, violation of the memory of other cognitive functions. In addition, upon repeated admission, they practically do not tend to accumulate. Shortcomings of short-acting drugs include low efficiency for sleep disorders (frequent night wakes, premature morning waking), as well as the possibility of developing tolerance and ricochet insomnia. Long-acting drugs are effective in disorders of sleep maintenance, have anxiolytic effect in the daytime. With their application, there is less risk of developing tolerance and ricochet insomnia. Disadvantages of drugs with long-term action are, first of all, the possibility of developing daytime drowsiness, memory impairment, other cognitive and psychomotor functions, as well as the danger of cumulation during repeated admission.

The efficacy and safety of benzodiazepines permitted for insomnia has been extensively studied in prospective controlled clinical trials using PSG. In clinical trials, it was noted that benzodiazepines improve the quality of sleep, which is manifested in a shortening of the latent period of sleep, a decrease in the number of awakenings per night. As a result, the patient feels more rested and cheerful. Side effects include mainly daytime drowsiness, memory impairment, other cognitive and psychomotor functions, dizziness and ricochet insomnia. The probability of side effects depended on the pharmacological properties of the drug, primarily on the half-elimination period and the ability to form active metabolites.

According to PSG, benzodiazepines shortened the latent period of falling asleep, reduced the degree of fragmentation of sleep, reduced the number of complete or partial awakenings and the duration of wakefulness after the onset of sleep, increased sleep efficiency. Against the backdrop of benzodiazepines, there has been some change in the physiology and architectonics of sleep. For example, in the II stage EEG revealed a significant increase in the representation of carotid spindles, but the clinical significance of this effect is unknown. With long-term admission of benzodiazepines, slow sleep and sleep with BDG are suppressed, but it is not known whether this has any adverse effects.

Ricochet insomnia occurs with varying frequency after long-lasting benzodiazepines have been abruptly abolished. This phenomenon has been well studied using PSG. Ricochet insomnia occurs more often after the abolition of short-acting benzodiazepines than long-acting drugs. This complication is of great clinical importance. Thus, a patient suffering from severe insomnia is likely to notice improvement with benzodiazepine. With prolonged use of it over time, some tolerance to the drug will develop, but overall the quality of sleep will continue to be better than it was before the treatment. If the patient suddenly stops taking the medication or absentmindedly misses the next appointment, then there will be a ricochet insomnia (especially if the patient took short-acting benzodiazepine). Although this is a pharmacologically induced reaction, the patient decides that this is an increase in the illness itself, which is due to the lack of treatment. When he re-starts taking benzodiazepine, he feels an almost immediate improvement. Thus, although the emergence of insomnia was just a reaction to the abolition of the drug, the patient concludes that he must constantly take the drug to maintain a good sleep. This development of events strengthens the patient's opinion that long-term use of sleeping pills is necessary. In this regard, patients should be warned about the possibility of ricochet insomnia when skipping a dose and recommend a gradual withdrawal of the drug within 3-4 weeks, as well as certain psychological techniques that reduce discomfort if ricochet insomnia nevertheless developed.

Patients should also be warned about the dangers of a combination of benzodiazepines with alcohol, which can lead to severe respiratory depression with possible fatal outcome. Benzodiazepines should be avoided or used with extreme caution in patients with obstructive sleep apnea, as these drugs depress the respiratory center and enhance muscle atony during sleep, increasing the degree of airway obstruction. Caution should be given to benzodiazepines and to elderly people who often have intermittent nighttime sleep. If they take benzodiazepine before bedtime, then, waking up in the middle of the night to go to the toilet, they can fall, as the drug causes confusion, disorientation and dizziness. In addition, the elderly often take several drugs, which makes possible the interaction of benzodiazepines with other drugs. First of all, it is necessary to take into account the possibility of interaction of benzodiazepines with blockers of histamine H1 and H2 receptors and other psychotropic agents. For example, an antidepressant nefazodone, metabolized by the hepatic microsomal enzyme CYPII D-4, can interact with triazolobenzodiazepines (including triazolam, which is metabolized by the same enzyme).

Benzodiazepines act on a number of zones called benzodiazepine receptors. The benzodiazepine receptor is a component of the GABA-receptor. GABA is a macromolecular receptor complex containing sites to which other neuroactive substances bind, in particular ethanol, barbiturates, and convulsant picrotoxin. With stimulation of the GABAA receptor, the influx of chlorine ions into the cell increases, which leads to hyperpolarization of the cell membrane-this mechanism mediates the inhibitory effect of GAM K. When stimulating the binding site of benzodiazepines, the reaction to GAM K increases, which leads to more significant hyperpolarization in the presence of a fixed amount of GABA. In the absence of GABA or in the inactivation of the GABAA receptor, stimulation of the benzodiazepine receptor will not cause a physiological reaction.

The GABA-receptor consists of five separate subunits. They can be combined in various ways, which predetermines the variability of the GABAA receptor population and, accordingly, of benzodiazepine receptors. From the pharmacological point of view, we can talk about several types of benzodiazepine receptors. Thus, benzodiazepine receptors of the first type are localized mainly in the brain and, apparently, mediate the anxiolytic and hypnotic effects of benzodiazepines. Benzodiazepine receptors of the second type are concentrated in the spinal cord and provide a miorelaxing effect. Benzodiazepine receptors of the third type (peripheral type of receptors) are found both in the brain and in peripheral tissues; whether they provide any aspect of the psychotropic effects of benzodiazepines or not, remains unclear.

Benzodiazepines can cause a variety of behavioral effects in representatives of various biological species, including a dose-dependent sedative effect, which makes it possible to use them as hypnotics. For many years, benzodiazepines have been used as anxiolytic agents - this effect was predicted on the laboratory stress model, which demonstrated the anti-conflict effect of these drugs. In addition, benzodiazepines have an anticonvulsant and muscle relaxant effect, which also finds application in the clinic.

[1], [2], [3], [4], [5]

Nebenzodiazepine hypnotics

Although some new sleeping pills are structurally different from benzodiazepines, their effect is also realized via benzodiazepine receptors. At the same time, there are some differences in the mechanism of action of benzodiazepine and nonbenzodiazepine hypnotics. If benzodiazepines bind to virtually all types of benzodiazepine receptors in the brain, nonbenzodiazepine hypnotics selectively interact only with type 1 receptors. This has an important physiological and clinical significance. If benzodiazepines cause comparable sedation and miorelaxing effects with minimal muscle relaxation, in non-benzodiazepine receptors (eg, zolpidem), the sedative effect is significantly superior to myorelaxation. In addition, nonbenzodiazepine receptors are less likely to cause side effects than benzodiazepines. However, the selectivity of the action of zolpidem, as shown by experimental studies, manifests itself only in low doses and disappears when high doses are used.

In clinical trials of zolpidem, zaleplon and zopiclone, it is noted that they shorten the latent period of sleep and, to a lesser extent, reduce the degree of its fragmentation. They are characterized by a rapid onset of action, a relatively short period of half-elimination (in zolpidem - about 2.5 hours), the absence of active metabolites. Unlike benzodiazepines, zolpidem and zaleplon in a minimum degree suppress slow sleep and sleep with BDG, although the data on this occasion are somewhat contradictory.

With the cessation of zolpidem and zaleplone, the risk of ricochet insomnia is extremely small. In one study, patients with insomnia for 4 weeks were treated with either triazolam or zolpidem, after which the drugs were replaced with placebo. In patients taking triazolam, when switching to placebo, there was a more pronounced ricochet insomnia than in patients taking zolpidem. To assess the ability of nonbenzodiazepine hypnotics to reduce manifestations of ricochet insomnia, additional controlled trials are necessary.

Although nonbenzodiazepine hypnotics significantly improve sleep, with violations of sleep maintenance and premature morning awakenings, they are inferior in effectiveness to benzodiazepines. In comparison with benzodiazepines, they rarely cause the phenomenon of aftereffect, which is partly explained by a shorter half-elimination period. They interact less with alcohol and depress respiration in patients with obstructive sleep apnea. However, more research is needed to confirm these promising preliminary results.

Knowing the pharmacological features of various sleeping pills helps to choose the most effective and safe drug.

Barbiturates

Some barbiturates, especially medium and long-acting (eg, secobarbital and amobarbital), are still used for insomnia. Thanks to the sedative effect, they shorten the latent period of sleep and reduce the degree of its fragmentation. However, most somnologists advise them to appoint in extremely rare cases because of the high risk of side effects. Essential disadvantages of barbiturates are: high probability of development of tolerance and physical dependence, severe withdrawal syndrome with sudden discontinuation of the drug, the possibility of deep respiratory center depression in combination with alcohol and death in overdose.

[6], [7], [8]

Antihistamines

Diphenhydramine and other antihistamines are widely used for insomnia. Many hypnotic-release sleeping pills contain an antihistamine as the main active ingredient. Antihistamines with sedative action can be really useful for insomnia, but only a small number of clinical trials have shown their moderate effectiveness in this condition. However, the hypnotic effect of antihistamines often develops tolerance, sometimes for several days. Moreover, when they are used, serious side effects are possible, including paradoxical agitation and cholinolytic effects. This creates a special problem for elderly patients who often take other drugs with anticholinergic action.

[9], [10], [11], [12],

Neuroleptics

A number of neuroleptics (for example, chlorpromazine) have a pronounced sedative effect. Neuroleptics with sedative effect are shown, mainly, in sleep disorders in patients with active psychosis and marked arousal. However, given the risk of serious side effects, including late dyskinesia, they are not recommended for use in everyday insomnia treatment.

Tryptophan

Tryptophan is an essential amino acid, the precursor of serotonin. Since serotonin participates in sleep regulation, including during the asleep phase, it has been suggested that tryptophan may be useful as a hypnotic. Interest in tryptophan has increased especially after experimental studies have shown that the administration of large doses of tryptophan increases the concentration of serotonin in the brain. Thus, the use of tryptophan could increase the activity of serotonergic systems in the brain and induce a hypnotic effect. In several clinical trials, a moderate hypnotic effect of tryptophan was confirmed, mainly expressed in the shortening of the latent period of sleep. However, several years ago, studies in the United States were discontinued after reports of the development of some serious side effects, including eosinophilia and myalgia, with tryptophan, were also fatal. Later it was found out that these side effects were caused by an admixture to the preparation, and not by the amino acid itself. Nevertheless, after this history, tryptophan in the US is almost not used, although in some European countries it is used on a limited scale for the treatment of insomnia.

Melatonin

Thanks to advertising in the press, melatonin has gained popularity as a new effective tool for treating insomnia. However, to date, only a small number of studies have been conducted that evaluated its effectiveness and safety. Probably the most impressive results were obtained with the use of melatonin for the treatment of insomnia in the elderly. Since melatonin has the status of a dietary supplement, it is often taken by patients who have not undergone an adequate examination. The efficacy and safety of melatonin has yet to be demonstrated in more thorough clinical trials. It should be borne in mind that since the drug is dispensed without a prescription, some patients may take it at a higher dose than that studied in controlled trials.

Treatment of chronic insomnia

Although specialists usually recommend using sleeping pills for a limited time, usually not more than 3-4 weeks, insomnia often has a chronic course. Therefore, after the withdrawal of sleeping pills, symptoms of insomnia in many patients will inevitably return, even if non-pharmacological methods of treatment are additionally used.

If the patient continues to take sleeping pills, then with time the effectiveness of the drug decreases, its effect on the physiological mechanisms of sleep manifests itself, which leads to a decrease in the quality of sleep. This kind of concern arose in connection with the results of the study of benzodiazepines: some patients developed tolerance or physical dependence on these drugs, ricochet insomnia and other manifestations of withdrawal syndrome.

Of course, long-term use of sleeping pills is associated with a certain risk. However, a real problem arises in front of a doctor: how to help a patient with chronic insomnia who, due to a disturbed sleep, develops severe emotional disturbances, decreases efficiency, etc. Moreover, chronic sleep disorders are accompanied by increased mortality. In this regard, for each patient, it is necessary to weigh the pros and cons of one or another method of treatment in order to develop the most optimal therapy plan. It is necessary to inform the patient in detail about the dangers associated with the use of sleeping pills, and how to avoid them. First of all, you should warn that you can not suddenly stop or skip the drug. It is necessary to use non-pharmacological methods of treatment as much as possible.

There are only limited data on the safety and efficacy of hypnotics in long-term use, but some of them are encouraging.

In one study, patients with insomnia within 360 days took zolpidem. During the study, the effectiveness of the drug did not decrease, and side effects, if any, were usually light. Further research is needed on the efficacy and safety of long-term therapy in order to develop optimal recommendations for the use of hypnotics in patients with chronic insomnia.

Treatment of other sleep disorders

Treatment of increased daytime sleepiness

Increased daytime sleepiness may be a manifestation of obstructive sleep apnea, narcolepsy, idiopathic hypersomnia, or a consequence of disturbing nighttime sleep or lack of sleep (regardless of their cause).

Obstructive sleep apnea

Obstructive sleep apnea is an important public health problem, but the importance of pharmacological agents in treating this condition is small. To correct obstructive sleep apnea at a different time, acetazolamide, nicotine, strychnine, medroxyprogesterone and some antidepressants, especially protriptyline, were suggested. It was suggested that medroxyprogesterone may be useful due to the stimulating effect on the respiratory center. Antidepressants (such as protriptyline) could benefit from the oppressive effect on sleep with BDG, during which most episodes of apnea occur.

Unfortunately, the results of clinical trials of these agents with obstructive sleep apnea have been disappointing. To date, the following methods are most often used in the treatment of this condition: position therapy (the patient is taught how to avoid lying on his back during sleep), the use of intraoral devices (including the warning of tongue lancing), surgical procedures (for example, tonsils and adenoids , tracheostomy, uveopalatopharyngoplasty), the use of devices to create a constant positive pressure in the upper respiratory tract. The latter method is used especially widely and is often considered as a method of choice for obstructive sleep apnea.

Fundamental studies on the pathophysiology of respiratory distress in sleep, mainly study the role of various neurotransmitter systems in the regulation of activity of the muscles of the upper respiratory tract. It is shown that the serotonergic neurons of the caudal seam nucleus are projected onto motoneurons controlling the activity of the muscles of the upper respiratory tract. Pharmacological agents that would affect these serotonergic pathways could increase the effectiveness of sleep apnea treatment.

Narcolepsy

Narcolepsy is a disease characterized by increased daytime drowsiness accompanied by cataplexy and other characteristic symptoms. His treatment is mainly based on the use of psychostimulants in combination with drugs that improve night sleep, which is often violated in narcolepsy. In some cases, patients are advised to take short breaks during sleep during the daytime. With patients it is important to discuss issues related to the possibility of driving a car, as well as problems arising from a disease at work or at school.

In narcolepsy, psychostimulants dextroamphetamine, methylphenidate, pemoline or antidepressants with an activating action, such as protriptyline and fluoxetine, are often used. Psychostimulants mainly correct daytime drowsiness and bouts of falling asleep, but have little effect on cataplexy. Antidepressants reduce the manifestations of cataplexy, but are much less effective with respect to daytime sleepiness.

Although psychostimulants have a significant therapeutic effect in narcolepsy, in many cases facilitating the life of patients and improving their quality of life, however, the use of these drugs encounters a number of significant limitations. They can adversely affect the cardiovascular system, contributing to the acceleration of heart rate and increased blood pressure, can cause insomnia, anxiety, agitation, anxiety, less often - other mental disorders. In addition, with their long-term use, there is a risk of developing tolerance and dependence, and with a sudden discontinuation of their reception, a marked withdrawal syndrome is possible. To prevent the development of tolerance, it is recommended that the dose of the stimulant is reduced regularly (for example, every 2-3 months) or canceled at all, by arranging a medicinal vacation.

The problems associated with prolonged use of psychostimulants force us to seek new drugs for the treatment of narcolepsy. In recent years, with narcolepsy, modafinil is increasingly being used. In controlled trials, it has been shown that modafinil effectively reduces daytime sleepiness, but has no significant effect on cataplexy. Therefore, modafinil may be the drug of choice in patients with pronounced daytime drowsiness, but relatively mild cataplexy. In the same cases, when the manifestations of cataplexy are expressed in patients, a combination of modafinil and protriptyline, effective in cataplexy, appears promising. However, clinical trials are needed to evaluate the efficacy and safety of such a combination.

Modafinil has obvious advantages over other psychostimulants due to a more favorable profile of side effects. When it is used, headache and nausea are common; at the same time, side effects from the cardiovascular system, excitation, are much less common; In addition, the risk of developing tolerance, dependence and withdrawal syndrome is lower.

It is suggested that the effect of psychostimulants (for example, amphetamine and methylphenidate) is explained by the increased release of noradrenaline and dopamine in those areas of the brain that are involved in the wakefulness process, the so-called "wake-up centers". The risk of developing drug dependence may be related to an increase in dopaminergic activity. In preclinical studies, it was shown that modafinil activates "wake centers" without having a significant effect on catecholaminergic neurotransmitter systems. Perhaps this explains the low risk of drug dependence. The main mechanism of action of modafinil remains unknown.

Periodic limb movements in a dream. The prevalence of periodic limb movements in a dream increases significantly with age and is greatest in the elderly. This condition is often combined with restless legs syndrome.

Periodic limb movements can lead to fragmentation of sleep, which is usually expressed in patients' complaints of insomnia, restless sleep and daytime sleepiness.

To reduce the periodic movements of limbs in a dream with different success, several means are used. Most often use long-acting benzodiazepine, for example, clonazepam. Clinical studies of the effectiveness of benzodiazepines with periodic limb movements in sleep have produced mixed results. At the same time, it is shown that clonazepam reduces the number of awakenings, improves sleep quality (by subjective sensations), reduces daytime sleepiness. Since benzodiazepines can themselves induce daytime sleepiness, when applied, it is important to ensure that the side effect does not outweigh the possible benefits of treatment.

Another direction in the pharmacological treatment of periodic limb movements is the use of dopaminergic drugs, such as L-Dopa or dopamine receptor agonists (bromocriptine, pramipexole, ropinirole). Several studies have shown that these drugs reduce the periodic movements of limbs in a dream and facilitate the manifestation of restless legs syndrome. However, when they are used, it is possible to develop ricochet symptoms on the day after taking the drug in the form of anxiety, agitation, and insomnia. Occasionally, in the presence of L-Dopa, patients develop psychotic symptoms.

To treat the periodic movements of limbs in a dream, opioids are also used. It has been reported that opioids reduce periodic limb movements in sleep and manifestations of restless legs syndrome. But, since their use is fraught with the risk of abuse and the development of drug dependence, they should be used with caution, only if the benzodiazepines are ineffective, L-Dopa preparations or dopamine receptor agonists are used.

Behavioral disorders in sleep

A number of vegetative or behavioral changes can occur sporadically or increase during sleep. To refer to psychomotor phenomena specifically associated with different phases of sleep, the term "parasomnias" is used. Parasomnias arising in the phase of slow sleep include sleepwalking (somnambulism) and night terrors. Disorder of behavior in a dream with BDG, as the name implies, presupposes certain actions, sometimes violent and aggressive, that arise during sleep with BDG and often reflect the content of dreams. These conditions must be differentiated with nocturnal epileptic seizures. Differential diagnosis is often impossible without PSG, which in patients with seizures can reveal epileptic activity.

As with other sleep disorders, treatment of behavioral disorders in sleep is more effective if their causes are known. In patients with nocturnal epileptic seizures, a treatment regimen should be chosen that is most effective in the established form of epilepsy. In the disorder of behavior in sleep with BDG, clonazepam is effective. In these patients, an additional examination should be conducted to exclude focal lesions of the midbrain or other parts of the trunk. If its cause is established, then therapy of the underlying disease is necessary. With parasomnias, the effectiveness of drug therapy is limited. The greatest effect in these cases is psychological counseling and behavior modification techniques.

[13], [14], [15], [16]

Sleep disorders associated with circadian rhythm disorders

This group of sleep disorders includes endogenous circadian rhythm disorders, for example, premature sleep and delayed sleep phase syndromes, irregular sleep and wake cycles (with a duration other than 24 hours), as well as sleep disorders caused by shift work or the change of time zones.

Treatment of these disorders, first of all, involves psychological counseling and correction of behavioral stereotypes, aimed at adapting to a changed circadian rhythm. In sleep disorders associated with circadian rhythm disturbances, phototherapy is also used. Light exposure is performed at certain periods of the 24-hour cycle in order to shift it in the desired direction. For example, the light effect in the evening allows you to move the endogenous rhythm in such a way that sleep occurs at a later time, and light exposure in the early morning allows you to shift the rhythm in such a way that sleep comes earlier. Apparently, the effect of light on the endogenous circadian rhythm is mediated by a change in the secretion of melatonin.

From the pharmacological point of view, the use of melatonin is a promising new direction in the therapy of sleep disorders associated with circadian rhythm disturbances, however, further studies are needed to evaluate its effectiveness. The ability of melatonin to cause a phase shift in the sleep and wake cycle is shown in both experimental and clinical studies. Several preliminary reports have been published on the beneficial effect of melatonin on sleep disorders caused by shift work or the change of time zones. It is noted that melatonin causes a phase shift and has a direct hypnotic effect. How to optimize the balance between the influence of melatonin on the circadian rhythm and sleeping pills is a question that needs to be addressed. Currently, among the chemical analogs of melatonin, a search is being made for such a compound that would be superior to melatonin by selectivity, efficacy and safety.

Other methods of treating insomnia

Approximately half of insomnia patients can not establish the cause even after careful examination. Treatment in such cases, considered as idiopathic insomnia, has a predominantly symptomatic nature and is aimed at preventing a new coil in the further development of a sleep disorder. Most experts believe that hypnotic drugs in most patients with insomnia should be used with extreme caution. Recently, a number of methods have been proposed that can serve as an alternative or complement to the medical treatment of insomnia. Some of them are described below.

1. The rules of sleep hygiene. Discussion with the patient of various aspects of sleep hygiene often contributes to changing his behavioral stereotypes, favorably affecting the quality of sleep. In order to work out the most effective measures, the patient is recommended to spend some time a detailed "sleep diary", having analyzed which, it is possible to reveal important regularities.
2. Control of incentives. This is one of the methods of behavior modification, which reduces the likelihood of insomnia and helps the patient to cope with the stress that insomnia carries. For example, control of stimuli suggests that the patient should go to sleep only when he feels a marked drowsiness. If you can not fall asleep within a reasonable time, then he is invited not to wait for the onset of sleep, but to get up and go to another room. It is also important not to sleep during the day.
3. Relaxation methods. Various relaxation techniques, including biological feedback, meditation, deep muscle relaxation techniques, allow one to achieve relaxation, which is especially important in situations of increased stress. It is important to teach the patient the methods of relaxation, with which he can fall asleep more quickly.
4. Cognitive therapy. Although initially the method of cognitive therapy was developed for the treatment of depression, it can be useful in patients with sleep disorders. Many patients with sleep disorders have a tendency to catastrophic perception of symptoms, which can contribute to chronic insomnia. Identification of negative ideas associated with the disease, and the development of a more rational attitude towards it can significantly improve the condition of patients.
5. Restriction of sleep therapy. A recently developed method that limits the time spent in bed at night (for example, from 1.00 to 6.00). Getting up from bed at 6.00, the patient in every way avoids daytime sleep, no matter how much he managed to sleep the previous night, and goes to bed no earlier than 1.00. Thus, gradually accumulating a deficiency of sleep, due to which over time the patient falls asleep more quickly, and his sleep becomes stronger. After achieving a sustainable improvement, the length of stay in bed is gradually increased. This method, which is quite rigid in relation to patients, often gives good results.
6. Psychotherapy. Many people have insomnia due to serious psychosocial or personal problems. In these cases, the patient should be referred to a specialist for psychotherapy. If the inability to identify and effectively solve their psychological problems, a person is doomed to relapse of sleep disorders.

It is important for a doctor to have an idea of the various methods of non-drug treatment of insomnia. A number of popular books about these methods have been published. In some cases, it is advisable to refer patients to psychotherapists or somnologists who are well versed in non-drug methods of treating sleep disorders.