Waking up with stress

Ph.D. Poluektov M.G.: - Yes, you can say that.

Academician of the Russian Academy of Medical Sciences, Professor Ivashkin V.T.: – Insomnia. Insomnia is such an interesting thing, yes.

Ph.D. Poluektov M.G.: - Good afternoon, dear colleagues! We continue the story about insomnia now. Last time we talked about different forms of insomnia. And now we will talk about the most mysterious form of insomnia, or insomnia, how to say it correctly - about acute insomnia, or stress insomnia. Why is this condition so mysterious? Because in clinical practice, it actually does not occur. The patient does not come with complaints that he had stress and began to sleep badly. He complains to his family, he himself is experiencing this condition, but rarely enough he comes to the doctor with such complaints. And it comes more often with complications of this condition, most often these complications are associated with the development of drug dependence with improper use of sleeping pills.

So, a little about the terminology: what is the correct name for insomnia? Well, the founder of the Russian clinical direction, Alexander Moiseevich Vein, insisted on the term insomnia - he considered it more academic. Because the term insomnia is what? This is a negative term when the patient believes that he is not sleeping at all. He suffers from this. Although this term is historical. In principle, for example, in the modern translation of the International Classification of Diseases of the 10th revision, insomnia is still called insomnia of inorganic and organic etiology. That is, it is not so important, in fact, how to call this state.

Another term is dyssomnia. They tried to introduce it artificially enough, but it did not take root. Dyssomnia is like a combination of several types of sleep disorders, including insomnia, but now it is not used. Now, if we are talking about making a diagnosis, we are talking about insomnia. In everyday life, this condition is called insomnia.

What is insomnia? Insomnia is not a disease. This is a clinical syndrome. This is not nosology. And the main characteristics of this clinical syndrome are: firstly, a violation of sleep itself, this is a violation of the initiation of sleep, a violation of its duration; violation of its consolidation, that is, quality, and here is the feeling of sleep. These disturbances occur despite having the opportunity to sleep. And these violations are manifested by violations of daily activities of various types. Any sleepy person will tell us several violations of daily activities at once. And there are nine nosological types of insomnia. That is, insomnia is not a disease. And insomnia is not a disease, it is a clinical syndrome. As, for example, a cerebral stroke is not a disease, but a clinical syndrome.

Distribution of insomnia in the population. The prevalence figures depend on which question you ask. If you ask the question of whether or not a person has a sleep disorder, then somewhere around one third of the people in the population will say that they are unhappy with their sleep. If we use more stringent criteria, add to this also complaints about the presence of daytime disturbances associated with sleep disturbance, then about 10 percent will tell us that they are unhappy with their sleep in this way. If we use the most stringent criterion, which will be evaluated by a specialist, a doctor - this is the criterion for the American psychiatric classification DSM-4, then at least 6 percent of the general population have insomnia, insomnia. And in this graph, we see that women at their most active age - 40, 50, 60 years old - are twice as likely to have a sleep disorder than men. Women are more prone to insomnia.

In our recent study, which we conducted in Chuvashia, it was shown that the prevalence of insomnia in the domestic population is also quite high. 20 percent of respondents answered the question "Do they have frequent or persistent sleep disturbances?" affirmatively. And one more thing that alerted us, which we received as a result of this study, is that very many of the respondents were constantly taking sleeping pills. 4.5 percent of the Russians included in this sample took sleeping pills. While, for example, according to foreign studies, in the general population, sleeping pills are often taken by 0.2 percent of patients. That is, excessive prescription of sleeping pills exists in the Russian Federation.

I have spoken of nine clinical forms of insomnia. Here, the so-called primary insomnias are highlighted in green, which occur without connection with any diseases. And insomnias are highlighted in red in the structure of any other diseases. Most often, these are mental illnesses, most often it is the abuse of drugs, and less often it is a somatic and neurological pathology.

And now there are six special primary forms of insomnia, in the first place among which is adaptive insomnia, or stress insomnia, or acute insomnia. What is this insomnia? Firstly, I would like to say a little more about the temporary criteria for insomnia, when, nevertheless, a person has the right to complain about his sleep disturbance: the next day after he did not sleep, three days after insomnia, a month after he sleep badly. According to international criteria, we can diagnose insomnia syndrome when the sleep disturbance lasts at least one week and the frequency of this disturbance is at least three nights a week. If insomnia lasts less than three months, it is acute insomnia. If more than three months - this is chronic insomnia. Most often, of course, in clinical practice we deal with chronic insomnia. Patients with acute insomnia rarely come to the doctor. They most often try to use some non-drug methods, some over-the-counter drugs, but if this fails, then in the end they become patients more often than a neurologist, probably, than a psychiatrist.

How do scientists now imagine the genesis of insomnia? Why can't a person sleep? Why can't he go into deep sleep? The main cause of insomnia is the presence of constant hyperactivation, increased activity of the activating systems of the brain. Many activating systems are now open in the brain. And almost everyone has their own mediator. There are activating systems that work on acetylcholines, the activating effect of which is associated with the release of acetylcholine. There are histaminergic activating systems - serotonin, dopamine are involved in brain activation. The new orexin system, the so-called, was discovered not so long ago, at the turn of the century. Glutamate, a universal excitatory amino acid, is also involved in the activity of the activating systems of the brain. Aspartate.

What are all these activation systems doing? Firstly, they constantly stimulate the cerebral cortex, enable a person to realize that he is, enable him to carry out active mental activity. In addition, these systems quite bizarrely interact with each other, interact with sleep centers and prevent a person from falling asleep. And when one of these systems, several of these systems work with excessive activity, load - then the normal alternation of sleep and wakefulness is disturbed, then this person cannot completely relax, go to sleep. The most common cause of this hyperactivation is anxiety. And most often, sleep disturbance is, of course, associated with some kind of mental disorder, more often with anxiety or depressive disorders.

The presence of such hyperactivation in insomnia, insomnia was confirmed by modern methods of neuroimaging, methods of positron emission tomography. For example, in one of the studies it was shown that during sleep, indeed, in patients with insomnia (insomnia) the metabolism is worse, the metabolism is worse in those parts of the brain that are responsible for the emotional response to stress. That is, they are too excited, react too strongly to external stimuli. And this level of metabolism does not decrease in them compared to healthy ones. But at the same time, when awake, these same patients have areas of the brain that work worse than in healthy people. These are the areas of the brain that are associated with cognitive processes, with the processes of acquiring new skills, assimilating information, remembering it - these are areas of the prefrontal cortex. That is, people with sleep disorders, with insomnia, have proven disorders of brain functions associated with certain parts of the brain that are primarily involved in the response to stress.

The presence of a reaction of the autonomic nervous system, in particular, the sympathetic, primarily its department, to stress, to sleep disturbance during insomnia is shown. So, in one of the studies it was shown that in patients with insomnia, compared with healthy people, the ratio of low-frequency and high-frequency components of the spectral power of heart rate variability is disturbed. The low-frequency component, as is commonly believed, reflects sympathetic influences on the heart rhythm; and the high-frequency component reflects parasympathetic influences on the heart rhythm. It turns out that in people with insomnia this ratio is shifted to the region of low-frequency, sympathetic components. They are dominated by the activity of the sympathetic division of the autonomic nervous system. And this graph shows that the activity of this department predominates both in the state of wakefulness and in all stages of sleep - in the first stage of sleep, in the second stage of sleep; in the phase of REM sleep, the so-called sleep with rapid eye movements. That is, there is hyperactivation in patients with insomnia and at this level - at the level of the autonomic nervous system.

The presence of such hyperactivation was also confirmed at the hormonal level. The level of cortisol, if we compare the daily secretion of cortisol in a healthy person and in a patient with insomnia - in the evening, at 20-22 hours, there is an increase in cortisol secretion, while in a healthy person the level of cortisol secretion is minimal. That is, instead of a person being able to relax before going to bed so that the production of stress hormones decreases, it, on the contrary, increases. The daily rhythm of cortisol secretion is distorted in the presence of this hyperactivation.

So, we talked about one of the most common forms of insomnia - acute insomnia. Well, now it is more often called adaptive insomnia. We are talking about the fact that the adaptation of the body is disrupted as part of the reaction to the action of some stress factor. What stress factors are the most common causes of sleep disorders? This is an interpersonal conflict often: a person has a fight with someone, cannot move away from this for a long time, goes to bed; thinks about what happened; thinks about how he could turn the conversation around, what could happen. And it really increases the level of brain activation, does not allow him to go into deep sleep. Work stress, constant workload, "manager's syndrome" - also, if a person cannot disconnect from these thoughts, a high level of activation is maintained, a person cannot go into a state of deep sleep. Changes in the external environment, moving, hospitalization are a very common cause of adaptive insomnia. New people, new conditions, an unusual regime - all this disrupts the normal course of sleep. And events with a positive emotional sign can also cause sleep disturbance - this should be remembered.

Adaptive insomnia is the most common “domestic” insomnia. When population studies were conducted, it turned out that 15-20 percent of people in the general population during the year have this disorder. That is, every fifth person experiences problems of stress insomnia during the year. Who is more likely to experience these problems? These are people who have already had sleep disorders, are more prone to sleep disorders; it is women, as we have already said, who are twice as likely to have a sleep disorder; these are older people; these are people with some manifestations of depression and anxiety, which do not reach the level of psychopathology, however, in response to the impact of stressful situations, they can significantly increase.

When should adaptation insomnia go away? Or when we can no longer make this diagnosis? On this slide, it is not quite correct, unfortunately, it is noted. From the moment the stress factor ends, no more than three weeks, but three months should pass. It is believed that after three months the connection between the impact of a stress factor is lost, if it stopped acting three months ago, and sleep, or thoughts about whether a person will fall asleep or not fall asleep. And this graph shows how the main symptoms of this adaptation syndrome, the so-called, or stress syndrome, change over time. Worst of all, disturbing thoughts change. Even after a few months - this is the last column on the right - they remain somewhere at the level of 12 percent. About 12 percent of people even after a few months think about their stress, it haunts them. But sleep disturbance is already showing fairly rapid dynamics. After one month, usually only 10 percent of people who have been exposed to this stress have this connection with a stressor. In a few months - already after three months, for example - this connection is completely leveled, lost. That is why the criterion of 3 months was proposed. Because here we are sure that this insomnia is no longer associated with stress, but has some other causes.

Clinical manifestations of adaptive insomnia are: lengthening of the time to fall asleep may be, there may be frequent awakening at night, long periods of wakefulness at night, a decrease in the total duration of sleep, dissatisfaction with the quality of one's sleep. Any sleep disturbance can occur against a background of acute stress.

During the day, what manifestations can be due to disturbed night sleep? This is fatigue, this is a violation of attention, concentration, memorization, this is a manifestation of social dysfunction, mood disorder, irritability, daytime sleepiness, decreased motivation and initiative, a tendency to make mistakes while driving and at work, muscle tension, headache, gastrointestinal disorders, concern about the state of one’s own sleep. Again, I emphasize that any sleepy person can easily list several such categories of daytime disturbances, since this is a universal such reaction to a lack of nighttime sleep.

In one of the studies, which was conducted on the basis of our department, it was shown how the structure of sleep changes during acute emotional stress. This graph shows, for example, how strongly those changes in the structure of sleep that are noted during experimental modeling of stress stand out (highlighted in green). This or that characteristic can even increase several times. For example, the time spent awake during sleep can increase several times due to stress. Maybe the number of awakenings will double. The latent period of the first stage, in fact, the time to fall asleep, also doubles against the background of stress. That is, sleep responds to stress as one of the first physiological indicators.

How should this adaptive insomnia, acute insomnia, be dealt with? To do this, behavioral techniques are used, psychologists often offer their own ways to deal with stress, sedatives use and use, of course, sleeping pills. First of all, we can say about non-drug methods of exposure - what is available to every person. It is recommended, for example, if there is some kind of stress associated with relationships, with the solution of some problems, to state those issues that bother a person on paper - paper will endure everything - before going to bed. Food rich in carbohydrates and tryptophan increases serotonergic transmission, serotonin calms, reduces the level of internal tension. Exclusion of alcohol, coffee, smoking before bedtime. It is necessary to reduce, not increase, and so the basic high anxiety, anxiety that occurs with this form of insomnia in the evening. Distracting monotonous activities can contribute to falling asleep, relaxing baths before bedtime; massage as much as possible at home. Here is one of the new directions - this is local warming. There are self-heating eye patches (eye warmer), which really also give a switch, a pleasant tactile sensation - a person switches from his disturbing thoughts. One very important factor is the presence of a clock in the bedroom. No one - neither a healthy person nor a sick person - is recommended to look at his watch at night, because he will not extract any useful information from this, soothing.

And another direction is the use of special preparations, hypnotic preparations, the action of which is directed at certain cerebral systems of the brain. A universal inhibitory neurotransmitter is gamma-aminobutyric acid. Here are the main centers that are associated with GABAergic transmission. And it is the effect on GABAergic transmission that contributes to such a pharmacological induction of sleep. And most sleeping pills just act through GABAergic mechanisms.

GABA _A receptor complex is the main target of classic hypnotic drugs, benzodiazepine hypnotics. Consists of five subunits. Between, for example, alpha and beta subunits binds, in fact, gamma-aminobutyric acid and changes the permeability of this channel, its permeability to chloride ions. And what does a benzodiazepine agonist do, what does sleeping pills do? It is attached between the alpha and gamma subunits and contributes to a change in the conformation of this entire complex in such a way that the affinity of the receptor for gamma-aminobutyric acid increases. And gamma-aminobutyric acid begins to have a stronger effect. That is, benzodiazepine hypnotics are modulators of the activity of gamma-aminobutyric acid.

What are these preparations? These are classic benzodiazepines. Why benzodiazepines? Because their structure includes one benzene ring, one diazepine ring. The most typical representative is diazepam. They act on the alpha ₁ subunits, which are responsible for the hypnotic effect, and act on other subunits of the GABA _A complex, which are responsible for other actions. Effects of benzodiazepines: anticonvulsant, sedative, anxiolytic, muscle relaxant.

A new generation of sleeping pills, the so-called Z-drugs, have a more selective effect. They are mainly [inrzb] only to the alpha ₁ subunit, which promotes hypnotic, sedative effects and minimally interacts with other subunits, and therefore they are called selective hypnotic drugs. Selective sleeping pills can indeed significantly improve the state of sleep under stress. Again, in the cited study, both the drug zopiclone and midazolam were used - this made it possible in both cases to significantly level the effects of stress on the structure of sleep. Here, the bars, for example, yellow and gray, show that certain indicators of sleep became on the background of the use of a hypnotic drug in healthy subjects who were introduced into a state of stress, these indicators became in fact the same as they were in the background. That is, the timely use of sleeping pills has a protective property. Do not hesitate, do not defend your sleep, because it contributes to the fastest recovery from stress.

Why is it now being tried to eliminate the use of benzodiazepine hypnotics for virtually all forms of insomnia? Because benzodiazepine sleeping pills have problems. This is addiction, the need to increase the dose, this is the development of dependence. Dependence is a situation when, when trying to stop the drug, an abstinence syndrome develops, a withdrawal syndrome. Just in this case, benzodiazepine drugs have such a negative effect. Worsening of sleep apnea syndrome. If a person snores, if he has breath holding during sleep, the use of benzodiazepine hypnotic drugs, which promote muscle relaxation, increase breathing problems during sleep. Decreased memory, attention, reaction time - this is important for actively working people. This is the so-called cognitive toxicity effect. Due to the fact that sleeping pills, many benzodiazepine drugs remain in the blood for a long time, in the morning a person has not yet fully woken up, his attention is still reduced - this is important for drivers, of course. Ataxia is another undesirable effect of benzodiazepine hypnotic drugs, especially for older people who do not walk very well anyway. In the morning, they may have big problems with gait, and problems with daytime sleepiness, of course. This is why benzodiazepine drugs are used with caution in various forms of insomnia.

There is another direction of pharmacological induction of sleep - this is the effect on other brain symptoms, for example, on the activating histamine system. This graph shows projections of histaminergic neurons. The main source of histamine is the tuberomamillary nucleus, located in the hypothalamus. And we see how the influence from this nucleus is projected on the cerebral cortex, first of all, and on other important brain centers: on the substantia nigra, on the aminergic and cholinergic groups of neurons, on the trigeminal nerve and motor nuclei of neurons. We see that this is one of the universal activating systems. If it is blocked with the help of certain pharmacological influences, then those brain systems that are responsible for the induction of sleep begin to have a stronger effect, and the possibility of the onset of sleep will increase. That is, in this case, we act not through the stimulation of GABA transmissions, not through the inhibition of the brain centers, but, on the contrary, through the inhibition of the activating brain systems.

One of the most effective drugs in this group, central blockers of histamine receptors, is doxylamine or donormil. In one study, the comparative efficacy of doxylamine was shown to be comparable to, for example, that of zolpidem in the treatment of sleep disorders. After about two weeks of using this drug, there is a significant improvement in clinical sleep parameters according to the Spiegel questionnaire. And this improvement is comparable to the same improvement that was noted with the use of a typical such hypnotic Z-drug zolpidem.

Donormil increases the duration and quality of sleep, while it does not affect the structure of sleep. It acts not only as a sleeping pill, but also has a calming effect. Again, this is important when stressed. This increases the protection of the body, reduces stress. This is one of the few sleeping pills that have no contraindications regarding the possibility of developing sleep apnea. Even if a person snores, if there is any suspicion of having sleep apnea, we can still use this sleeping pill for him. And there are no signs of the development of drug dependence or withdrawal syndrome when using donormil. Thank you for your attention.

How do you get better sleep when you're stressed? Expert advice on how to get rid of insomnia

Events in the world are developing unpredictably. Disturbing news makes many people feel a lot of stress, anxiety, and anxiety. Constant nervous tension negatively affects sleep. Some begin to experience problems falling asleep, others wake up at night and then cannot fall asleep, and others develop chronic insomnia.

Sleep disturbance against the background of severe stress is a physiological reaction of the body, the so-called adaptive insomnia Nervous tension passes, sleep normalizes. However, if the stressful situation continues for a long time, it can lead to persistent sleep disorders, as well as the development of somatic pathologies.

In this article, I will give some recommendations that will help you cope with stress, reduce nervous tension, and normalize sleep.

Sleep is a physiological state that is characterized by a reduced reaction to the outside world, relaxation of all body systems. Stress is a defensive reaction to potential or real danger, accompanied by intense emotional and physical stress.

The higher the level of stress, the more pronounced sleep disturbances ^2.3 . The lower the quality of sleep, the stronger the anxiety ⁴ . As a result, we get a vicious circle that just needs to be broken. If this is not done, then the consequences for health will be the most negative. Read more about how insomnia affects the state of the body in our article on sleep biohacking.

The importance of sleep in human life and its relationship with stress has been studied in many studies. Most scientists agree that one of the most important functions of normal physiological sleep is the relaxation of the nervous system, ensuring the full functioning of the body during wakefulness.

As the researchers suggest, this may be due to the cessation of stress during sleep, a decrease in cortisol levels, and the production of melatonin, which has an anti-stress effect.

After scientists discovered the phases and stages of sleep, a large number of experiments were conducted to study the effect of nervous tension on its structure. The vast majority of studies have proven the negative impact of emotional stress on sleep. Thus, the time of falling asleep, the number of awakenings increased in the subjects, the representation of delta sleep and the overall efficiency of sleep decreased, i.e., the changes were of a maladaptive nature.

One of the latest studies, conducted at the Moscow Somnology Center, was devoted to the study of the effect of acute and chronic stress on sleep ⁶ . The experiment involved healthy men and women aged 21 to 33 years, as well as patients with insomnia caused by chronic emotional stress, aged 21 to 40 years.

As a result of the study, it was found that under the influence of acute stress in all healthy participants of the experiment, regardless of the psychological characteristics of the personality, the parameters of sleep changed: the time to fall asleep, the number of awakenings, and the total time of wakefulness within sleep increased. In patients who were under the influence of chronic emotional stress, gross violations of all indicators of the sleep structure were revealed: there was an increase in the number of awakenings, wakefulness, duration of the first stage of sleep, as well as a decrease in the duration and representation of delta sleep.

Another Saudi Arabian study also found a statistically significant relationship between stress and sleep quality. The experiment involved male and female medical students from the King Saud bin Abdulaziz University of Medical Sciences in Riyadh. The results were assessed using the Pittsburgh Sleep Quality and Stress Index and the Kessler Psychological Stress Scale.

The study showed a high prevalence among students of sleep disorders (76%) and stress (53%) with a statistically significant relationship (p<0.001). Logistic regression found that students who did not suffer from stress were less likely to have poor sleep quality (OR=0.28, p<0.001), and the risk of insomnia was almost four times higher for those students whose cumulative GPA was less than 4. 25 (OR=3.83, p=0.01) ⁷ .

Sleep disorders caused by nervous tension require an integrated approach. Taking sedatives and sleeping pills can help in the short term, but if they are canceled, the problem will return, so in order to achieve a lasting result, you need to adjust your lifestyle:

• Limit information flow. Reduce time spent watching news broadcasts. Before going to bed, completely eliminate the use of gadgets for 1-2 hours. If you find it hard to stop reading the news, you can limit yourself to headlines for a few days. So, you will be aware of what is happening, but do not go headlong into the negative.

• To refuse from bad habits. Alcohol and nicotine destroy the nervous system, and if you abuse them, you will inevitably encounter sleep disorders. If possible, give up bad habits completely. If it is extremely difficult for you to do this right now, at least try to minimize the use of alcohol and smoking.

• Add physical activity. Any moderate physical activity is good for the nervous system. You don't have to train to the point of exhaustion. To sleep better, daily jogging and moderate exercise appropriate for your fitness level will suffice.

• Eliminate eating disorders. Improper nutrition can also cause insomnia, especially if you like to eat before bed. Review your diet and nutrition system. Eliminate heavy fatty foods, canned, fried foods, fast food from the diet. Eat more vegetables and fruits. Eat dinner 2-3 hours before you go to bed.

• Provide additional support to the nervous system. Some vitamins, minerals, plant extracts, amino acids have mild sedative properties, contribute to the normalization of metabolic processes in neurons. The complex intake of dietary supplements with calming components can help reduce nervous tension and improve sleep quality.

With a pronounced stress response, three types of disorders are most common: difficulty falling asleep, interrupted sleep, early awakening ⁸ . During the period of increased anxiety, all of these disorders can be observed.

If you are having difficulty falling asleep, I recommend paying attention to the following complexes:

• Reason with Melatonin is a soluble hot drink to improve sleep based on vitamins, minerals, amino acids and beneficial plant extracts. The complex has a high degree of assimilation. To achieve a therapeutic effect, it is enough to dissolve 1 sachet in a glass of hot water and drink a drink 30-40 minutes before bedtime.

• "Sleep Formula Express" - a complex based on plant extracts of passionflower and griffonia (source of 5-HTP), which have a mild sedative and hypnotic effect ^9.10 . Course reception of the complex can accelerate falling asleep, have a positive effect on the duration and depth of sleep. Adults are advised to take 2 tablets of the complex 30-40 minutes before bedtime. In case of awakening, it is allowed to dissolve 2 additional tablets at night.

• "Magnesium chelate" - contains readily available magnesium in a chelated form, helps support the nervous system, increase stress resistance, and normalize the emotional background. Taking magnesium regularly can help reduce levels of subjective anxiety and stress ¹¹ , thereby improving the quality of sleep. Adults and children over 14 years of age "Magnesium chelate" is recommended to take 1-2 tablets per day. The duration of admission is at least 1 month.

If you often wake up at night, then a complex intake of bioadditives can help you: "Reason with 5-HTP", "Sleep Formula" and "Magnesium Chelate". The regimen and dosage are similar to those recommended above.

Those who suffer from early awakenings can try this combination: Phyto-Melatonin Boosted Sleep Formula, PhytoHypnosis and Magnesium Chelate. "PhytoHypnosis" is recommended to take 2 tablets immediately before falling asleep, "Sleep Formula" 2 capsules in the evening, "Magnesium Chelate" 1 tablet daily in the afternoon.

All components that make up dietary supplements are well combined, enhancing each other's action. The duration of any course depends on the individual characteristics of the body and the severity of sleep disorders, but on average it ranges from 1 to 3 months. Before starting the reception, it is advisable to consult with a specialist.

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² Relationships Among Nightly Sleep Quality, Daily Stress, and Daily Affect. Jessica M Blaxton, Cindy S Bergeman, Brenda R Whitehead, Marcia E Braun, Jessic D Payne, May 2017 Agorastos Agorastos, Miranda Olff, September 2021.
⁴ Sleep and stress. K N Strygin, April 2011 Sleep and stress. Ros. physiol. magazine them. I. M. Sechenova, 2011, 97(4): 422-32.
⁶ Strygin K.N. Influence of stresses of different modality on the sleep-wake cycle of a healthy person. Dis. … cand. honey. Sciences. Moscow, 2007: 27.
⁷ The prevalence and association of stress with sleep quality among medical students. Almojali A.I., Almaki S., Alotman A.S., Masuadi E.M., Alakil M.K. J Epidemiol Glob Health. 2017 Sep;7(3):169-174. doi: 10.1016/j.jegh.2017.04.005 . Epub 2017 May 5. PMID: 28756825; PMCID: PMC7320447.
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¹⁰ Anxiety, depression, and insomnia. Larzelere M. M., Wiseman P. Prim Care. 2002 Jun;29(2):339-60, vii. doi: 10.1016/s0095-4543(01)00003-3 . PMID: 12391715.
¹¹ The Effects of Magnesium Supplementation on Subjective Anxiety and Stress - A Systematic Review.