What anti-anxiety medications are there and how do they work?

Sedatives are medications that reduce increased irritability, conflict, nervous tension, and have a slight calming effect by reducing the excitability of the nervous system.

Despite the wide selection of drugs with a pronounced sedative effect (tranquilizers), sedatives are used very actively, especially in cases of high nervous excitability, irritability, sleep disturbances, especially associated with negative emotions, and neurosis-like conditions that are accompanied by heart pain.

Unlike tranquilizers, sedatives, especially herbal ones, do not have such a pronounced calming effect. At the same time, sedatives are well tolerated by patients, they do not have serious negative effects - they do not cause muscle relaxation, gait disturbances, a feeling of lethargy, or a decrease in the speed of mental reactions.

To sedatives, addiction does not develop (decrease in effect with long-term use) and drug dependence (an irresistible need to use the drug again and again).

Due to these advantages, sedatives are very widely used throughout the world.

Indications for use

Sedatives are used to treat neurasthenia - conditions that are accompanied by increased irritability, absent-mindedness, conflict, and nervous tension.

In addition, sedatives are used in the complex treatment of diseases that are easily aggravated by stress - angina pectoris (oxygen starvation of the heart), hypertension (persistently high blood pressure), gastric and duodenal ulcers, pruritic neurodermatoses (skin diseases that are accompanied by itching). ), migraine.

In addition, sedatives are used for hysteria, menopausal syndrome, and vegetative-vascular dystonia.

Psychiatry Psychiatry and psychopharmacotherapy named after. P.B. Gannushkina No. 06 2021

The article discusses the state of affairs with anxiolytics, hypnotics and sedatives in the clinical practice of a psychiatrist in Russia at the present time. Topical issues of the applied use of drugs, their features, and prescription tactics are covered.

Keywords:

anxiolytics, hypnotics and sedatives, benzodiazepine tranquilizers, tranquilizers in Russia, anxiolytics in Russia.
For citation:
Maslov K.A. Anxiolytics, hypnotics and sedatives in Russia in modern clinical practice of a psychiatrist. Issues of applied practical application. Psychiatry and psychopharmacotherapy. 2019; 21 (6): 4–10.

Anxiolytics, hypnotic drugs and sedatives in Russia, in modern clinical practice of the psychiatrist. Questions of applied practical application

K.A. Maslov

Evgrafov Regional Mental Hospital, Penza, Russia

[email protected]

Abstract

In the article there is a speech about a situation with anxiolytics, hypnotic drugs and sedatives in clinical practice of psychiatry in Russia now. Relevant issues of applied use of these drugs, their features, appointment tactics.

Key words:

anxiolytics, hypnotic drugs and sedatives, benzodiazepine tranquilizers, tranquilizers in Russia, anxiolytics in Russia.
For citation:
Maslov KA Anxiolytics, hypnotic drugs and sedatives in Russia, in modern clinical practice of the psychiatrist. Questions of applied practical application. Psychiatry and Psychopharmacotherapy. 2019; 21 (6): 4–10.

Introduction

Anxiolytics - drugs that reduce anxiety and restlessness, according to the international (recommended by the World Health Organization - WHO) anatomical-therapeutic-chemical classification belong to group "N" (drugs for the treatment of diseases of the nervous system), namely N5 (psycholeptics), subgroup - N05B (anxiolytics) [1]. The group of psycholeptics also includes subgroups N05A (antipsychotic drugs) and N05C (hypnotics and sedatives). A somewhat outdated name for anxiolytic drugs is tranquilizers, and an even more outdated one is the so-called “minor tranquilizers” (“major tranquilizers” were previously called antipsychotic drugs) [2–5]. Currently, the overwhelming number of anxiolytics are representatives of the group of benzodiazepines, the mechanism of action of which is based on the effect on a certain area (site) of one of the types of receptors for gamma-aminobutyric acid (GABA), namely the GABAA receptor. As a result, the affinity of the GABA inhibitory transmitter of the central nervous system (CNS) to these receptors increases and its effect increases (increasing the inhibitory postsynaptic potential), the excitability of neurons in the CNS, as well as in the periphery (in spinal cord cells and peripheral tissues), decreases. These receptors are sometimes called benzodiazepine receptors [6]. Nowadays, the most common and prescribed group of anxiolytics in Russia and in the world are benzodiazepine derivatives (the so-called benzodiazepine tranquilizers, or benzodiazepines) [7–9], so further we will mainly talk about them.

A Brief History of Anxiolytics, Hypnotics and Sedatives

The first fairly powerful representatives of the group (except for bromine and valerian preparations) were derivatives of barbituric acid (the so-called barbiturates), namely barbital, which has been used in clinical practice since 1903 [10], with a mechanism of action somewhat similar to benzodiazepines ( including modulating the GABAA receptor). Then, from the 2nd half of the 1950s, benzodiazepines appeared (one of the first, chlordiazepoxide, synthesized in 1955, entered clinical practice in 1960) [11]. Subsequently, a large number of benzodiazepines appeared, the most successful of which, and subsequently the “gold standard,” was diazepam, which entered clinical practice in 1963 [12]. In the 1950s, the problem of barbiturate addiction was recognized worldwide [13]. The advent of benzodiazepines by the 1970s significantly reduced the distribution and prescription of barbiturates, almost completely replacing them with benzodiazepine tranquilizers in the treatment of anxiety and sleep disorders, shifting barbiturates to the niche they occupy to this day (mainly as drugs for anesthesia and for the treatment of epilepsy) [11]. In the 1980s, benzodiazepines suffered the same fate as barbiturates, and the problem of dependence on them was recognized [14]. Since the 1980s, the so-called “Z-drugs” (non-benzodiazepine benzodiazepine receptor agonists) entered clinical practice: zopiclone - since 1986, zolpidem - since 1992, zaleplon - since 1999, which partially replaced benzodiazepines from therapy sleep disorders and have firmly occupied the niche of selective sleeping pills [15]. Currently, there are drugs with a mechanism of action not related to the effect on benzodiazepine receptors, such as hydroxyzine (used in clinical practice since 1956) [16, 17], etifoxine (since the 1960s) [18], buspirone ( since 1986) [19–21]. It is also necessary to note the presence on the Russian market of such popular non-benzodiazepine drugs as tetramethyltetraazabicyclooctanedione (in clinical practice in Russia since 1978) [29], preparations of valerian rhizomes and fabomotizol (in clinical practice in Russia since 2005) [30].

Treatment and side effects

Anxiolytics, hypnotics and sedatives (mainly the benzodiazepine group) have four main therapeutic effects [22, 23]: • hypnotic; • anxiolytic; • anticonvulsant; • muscle relaxant; • sedative1; • vegetative stabilizing1. The downside of the therapeutic effects are side effects and complications, the most common are excessive sedation and drowsiness, the risk of falls, memory and concentration problems, withdrawal symptoms and the risk of addiction, disruption of sleep architecture, dizziness, paradoxical effects in the form of reactions of intoxication and arousal. and aggression [22]. The degree of severity and the relationship between therapeutic and side effects determines the range of clinical use of the drug. The main clinically significant problems with the use of benzodiazepine tranquilizers and tactics for their prevention and correction are presented in Table. 1.

Currently in Russia (according to some estimates) [7–9], the most popular anxiolytics in clinical practice are (in descending order) tofisopam, tetramethyltetraazabicyclooctanedione, bromodihydrochlorophenylbenzodiazepine, diazepam, fabomotizol. Of the hypnotics and sedatives, the most popular in clinical practice in Russia [7–9] are (in descending order) melatonin and zopiclone. For comparison, currently in the USA (according to some estimates) [26], the most popular among the group of anxiolytics in clinical practice are (in descending order) alprazolam, clonazepam (according to the anatomical-therapeutic-chemical classification, it is assigned to group N03 - antiepileptic drugs, although in fact is a benzodiazepine tranquilizer and has a powerful anti-anxiety effect), lorazepam, buspirone, hydroxyzine, diazepam. Of the hypnotics and sedatives, the most popular in clinical practice in the United States [26] is zolpidem.

Classifications

There are several classifications of anxiolytics, hypnotics and sedatives. Some experts in the field of psychiatry propose a classification of drugs (in particular antipsychotics) based on their receptor mechanism of action [31]. This approach is logical and consistent, and also perfectly complements clinical classifications. Obviously, a similar approach would be relevant for the classification of drugs from the group of anxiolytics, hypnotics and sedatives (we can distinguish, for example, benzodiazepine receptor agonists and a group of drugs with non-benzodiazepine receptor action). Perhaps in the future, researchers will attempt a similar classification of these drugs. Based on the duration of action (half-life - T1/2), anxiolytics, hypnotics and sedatives are divided into several groups. There are several approaches to classification by duration of action. Domestic researchers identify drugs with short (up to 5 hours), medium (5–24 hours) and long-acting (more than 24 hours) effects [24]. American and European researchers distinguish [32, 33] drugs with short (up to 6 hours), medium (6–24 hours) and long (more than 24 hours) action. Australian researchers identify drugs with ultrashort (up to 6 hours), short (6–12 hours), medium (12–24 hours) and long (more than 24 hours) action [25]. It should be noted that these classifications overlap in many ways. Taking into account the average WHO recommended sleep duration [34] and the average daylight hours in the Northern Hemisphere in the European part of Russia, the classification of researchers from Australia seems to be the most suitable for clinical practice [25]. The classification of anxiolytics, hypnotics and sedatives by duration of action (T1/2 of the drug and T1/2 of its active metabolites in ascending order) is presented in Table. 2. The advantages, disadvantages and optimal tactics for using anxiolytics, hypnotics and sedatives are presented in table. 3.

In addition to classification by duration of action, the strength of the drug is of important clinical importance, and therefore the concept of the so-called diazepam equivalent [39] (similar to “chlorpromazine equivalent”) has been introduced into clinical practice since 1985 [37, 38]. Diazepam equivalent is a dose of the drug equivalent to 10 mg of diazepam in terms of therapeutic effect [37]. The classification of anxiolytics, hypnotics and sedatives by strength (in descending order) is presented in Table. 4 [37, 38].

Non-benzodiazepine tranquilizers

Currently in Russia, in psychiatric clinical practice, there are three main non-benzodiazepine tranquilizers - hydroxyzine, etifoxine, buspirone, sometimes tofisopam is also conditionally included in this group, although it is a benzodiazepine derivative, but according to its stated properties it is classified as a so-called atypical benzodiazepine. The advantages of these drugs are that they are devoid of the main side effects of benzodiazepine tranquilizers, such as daytime sleepiness (with the exception of hydroxyzine), risks of addiction and withdrawal syndrome, cognitive toxicity, but at the same time they also have a much weaker anxiolytic effect, due to with which they are often used when withdrawing benzodiazepine tranquilizers, if it is impossible to use benzodiazepines (in case of individual intolerance, risks of developing dependence syndrome or withdrawal syndrome), if it is necessary to drive a vehicle while taking therapy (with the exception of hydroxyzine), in elderly patients (since they do not suppress cognitive processes, memory and attention, do not cause an increase in tolerance, withdrawal syndrome, dependence syndrome, do not have a sedative and relaxing effect, suppress fear and anxiety). I would like to note that in addition to the above medications, non-benzodiazepine drugs also include tetramethyltetraazabicyclooctanedione, melatonin, fabomotizol, and valerian rhizome preparations. However, in scientific studies for the indications stated by the manufacturers in the instructions, the effectiveness of these drugs has not been confirmed (either there are low-quality studies on their effectiveness, or there is reliable data on ineffectiveness) [40–45], and given that the last two drugs are widely sold in pharmacy chains Russia and are over-the-counter, they can be conditionally classified as drugs of the so-called “preclinical” stage (most often, patients take them independently before seeking medical help, i.e., use them for self-medication). Drugs such as bromizal, bromides and others are not discussed in the article, since they have very limited use in Russia, and there are no high-quality studies confirming their clinical effectiveness.

Application tactics

Taking into account the officially registered instructions for the use of drugs, there are currently several main established tactics for the use of anxiolytics, hypnotics and sedatives in the clinical practice of psychiatry in Russia.

1. Outpatient tactics: a) treatment of anxiety as part of complex therapy - an anxiolytic is prescribed in short courses (usually up to 2 weeks, maximum 3 weeks, with a break between courses of at least 1 month) in small or medium doses in combination with treatment of concomitant psychiatric or somatic pathologies; b) covering the antidepressant (the so-called “benzodiazepine bridge tactics”) - an anxiolytic is prescribed in a short course (usually up to 2 weeks, maximum 3 weeks, in small or medium doses) for the period of development of the action of the antidepressant in order to quickly relieve anxiety, as well as relieve possible undesirable effects phenomena of the initial stage of antidepressant therapy; c) treatment of sleep disorders - an anxiolytic or hypnotic and sedative drug is prescribed in a short course (usually a maximum of 2 weeks) in small or medium dosages once before bedtime, followed by transition to episodic use against the background of complex therapy of sleep disorders (drug and psychotherapeutic treatment of comorbid psychiatric pathology , drug treatment of somatic pathology); d) treatment of panic attacks (an anxiolytic is prescribed for occasional use in small or medium doses to relieve panic attacks in addition to the main therapy); e) correction of anxiety, sleep disorders, neuroleptic complications, to improve compliance (adherence to therapy) in patients receiving antipsychotic therapy - an anxiolytic is prescribed in small or medium doses, in short courses of up to 1 month, followed by withdrawal during periods of selection of antipsychotic therapy and during periods exacerbations with increasing dosages of antipsychotic drugs. 2. Stationary tactics. Rapid relief of psychomotor agitation, agitation, severe anxiety (an anxiolytic is prescribed more often in injection form in medium or above average doses in a short course of up to 1 week, maximum 2 weeks, in addition to the main therapy, usually antipsychotics or antidepressants until their main effect develops and for its potentiation); mainly used are 2 drugs available for parenteral administration - bromodihydrochlorophenylbenzodiazepine and diazepam. Of all existing anxiolytics, hypnotics and sedatives in Russia (according to the State Register of Medicines) [7], at least 13 names of anxiolytics and at least 10 names of hypnotics and sedatives are registered, not counting drugs that are classified as drugs from other groups (for example, clonazepam). Anxiolytic, hypnotic and sedatives currently registered in Russia, taking into account trade names, are presented in Table. 5 (with the exception of trade names of the form “international nonproprietary name” - INN or “INN-manufacturer”) [7]. In addition to classification by duration (T1/2) of action and strength (diazepam equivalent), important parameters for clinical practice are the price and availability of the drug (legislative regulation of drug prescribing, pharmacy chain policies), but they are largely subject to change (price changes, legislative practice national health care system), the final decision on prescribing a particular drug is made by the attending physician, taking into account the indications, contraindications, clinical profile of the drug, its pharmacodynamics, pharmacokinetics, individual characteristics of the patient and the above parameters. Important aspects of the use of anxiolytics, sedatives and hypnotics are the age at which they are approved for use, the effect on driving and activities requiring increased concentration, as well as use during pregnancy and lactation (according to official instructions for drugs)2 [7 ]. Most of these drugs currently used in Russia (namely: diazepam, chlordiazepoxide, hydrazinocarbonylmethylbromophenyldihydrobenzdiazepine, etifoxine, bromodihydrochlorophenylbenzodiazepine, diazepam + cyclobarbital, nitrazepam, zopiclone, zaleplon, melatonin), are approved for use from 18 years of age, are not recommended for use during driving vehicles and is contraindicated during pregnancy (especially in the first trimester) and lactation. However, for other drugs of these groups, these aspects (according to the instructions for use) [7] are somewhat different; they are presented in table. 6 2.

Conclusion

Despite its “venerable” age (more than half a century from the discovery of the first representatives of the group of benzodiazepine tranquilizers) and the large number of modern antidepressants and other psychotropic drugs that affect anxiety and have an anxiolytic effect that have appeared in clinical practice (including in Russia) in recent decades , benzodiazepine receptor agonists (mostly benzodiazepine tranquilizers), as typical representatives of anxiolytics, hypnotics and sedatives, firmly occupy their niche in psychiatric practice, which can be briefly described as “short-term complex treatment of anxiety and sleep disorders.” Their therapeutic effect, side effects and associated problems of use and ways to overcome them have been well studied in numerous scientific studies, many of them are included in the WHO Model List of Essential Medicines [46] and currently remain widely used drugs in modern psychiatric practice in Russia , and all over the world.

1. Additionally highlighted by researchers in Russia [23, 24]. 2. The data may differ significantly (depending on the manufacturer - trade name of the drug, release form, dosage, according to the instructions for the drug officially registered in Russia at the time of writing), it is necessary to clarify the information in each specific case according to the instructions.

About the author

Maslov Konstantin Andreevich – psychiatrist, State Budgetary Healthcare Institution “OPB named after. K.R. Evgrafova. Email

Classification of sedatives

Based on their origin, sedatives that are widely used in clinical practice are grouped into the following classes:

• herbal preparations: valerian extract, motherwort tincture, peony tincture, hawthorn tincture, passionflower extract, mint herb, lemon balm herb and combinations thereof;
• synthetic drugs: sodium bromide, potassium bromide, magnesium lactate, magnesium sulfate, phenobarbital.

In addition, many psychoactive substances can have a sedative effect and reduce the level of irritability. These drugs include anxiolytics (tranquilizers), antidepressants, some antipsychotics, as well as antiarrhythmic and antihypertensive drugs (for example, the β-blocker propranolol) and antihistamines and antiallergic drugs (for example, diphenhydramine).

What sedatives can you buy without a prescription?

The “simple” and cheapest sedatives are usually sold without prescriptions:

• soothing tablets and tinctures based on valerian, motherwort, mint, peony, St. John's wort;
• combination preparations on a plant basis - Fitosed, Persen, Novo-passit, Algoven-relax, Dormiplant;
• drugs to improve heart function that have a mild sedative effect - Valocordin, Corvalol, Zelenin Drops, Adonis Bromine, Bromcamphor;
• homeopathic medicines – Notta, Leovit, Gelarium, Edas, etc.

Inexpensive sedatives based on natural raw materials can also be purchased in “whole” form. Pharmacies sell dried valerian roots, mint leaves, motherwort herb, and special soothing mixtures that can be brewed and drunk like tea. To relax after a busy day, these infusions can be added to evening baths.

Natural sedatives

Another type of safe sedatives are aromatic oils of jasmine, bergamot, sage, rose, orange, tangerine, ylang-ylang, and lavender. They are used for:

• saturating the air with aroma. For this purpose, water is poured into the aroma lamp, into which a few drops of the selected oil (or mixture) are dripped. The water and oil are heated by the candle, causing the oil to evaporate intensively;
• taking baths Since the oil does not dissolve in water, it is better to drip it onto sea salt. This will help reduce the oil droplets and distribute them more evenly in the water.

Sedative medicinal herbs may be allergens

When using over-the-counter herbal sedatives, make sure you are not allergic to any of the ingredients.

Note! The number of poisonings with sedatives is second only to poisonings with sleeping pills. Therefore, you should not exceed the dosage recommended by your doctor. If after taking a high dose of the drug you experience the following symptoms, you should immediately consult a doctor:

• a decrease in heart rate of less than 60 beats per minute at rest in an adult, 70 in children from one to 6 years of age, 100 in infants;
• fogginess, loss of consciousness;
• motor dysfunction;
• nausea, heartburn, indigestion, thirst, dry mouth;
• allergic rashes;
• weakness, lethargy, unmotivated fatigue, dizziness, headache.

While you wait for the ambulance to arrive, rinse your stomach and drink adsorbent.

Basics of sedative treatment

Sedatives are safe even with long-term use, so they are classified as over-the-counter medications.

The effectiveness of sedatives does not decrease with prolonged use. There is no physical or mental dependence on these drugs – an irresistible need to take them constantly.

Sedatives usually do not reduce daytime performance; moreover, they can even increase it, relieving excessive irritability and emotional stress.

Sedative effects of alcohol

Some people drink alcohol thinking it helps relieve stress and relax.
This is a common misconception. In fact, alcohol in large doses is a depressant. It depresses the functioning of the nervous system, so its use only aggravates stress. In small doses, alcoholic drinks can have a calming effect on the body. However, you should not calm down with the help of alcohol. By making it a system, you can fall into a trap. Each time, the body's sensitivity to alcohol will increase, so in order to achieve sleep, you will have to constantly increase the dose of alcohol, which is a direct path to alcohol dependence.

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Features of the treatment of neurasthenia

Tinctures and alcohol extracts contain ethanol, which causes the main side effects - general weakness, fatigue, indifference to the environment, weakened memory, drowsiness.

In addition, alcohol-containing sedatives reduce physical and mental abilities, so they are not recommended for use by patients whose work requires quick mental, behavioral and emotional reactions - drivers, dispatchers, operators, etc., as well as people with alcohol addiction. Such patients need to choose drugs without alcohol, for example, dry plant extracts or combinations thereof.

All sedatives enhance the effect of other drugs that depress the central nervous system - antipsychotics, tranquilizers, anticonvulsants.

Most sedatives cause a decrease in libido and potency.

What sedatives are there?

According to the type of effect on the body, sedative tablets, drops and mixtures are divided into:

• Sedative drugs. These are natural sedatives based on valerian, mint, lemon balm, motherwort, and combination preparations. This group also includes bromine-based drugs.
• Tranquilizers. Drugs that affect the psyche. They are needed when a person needs to get rid of unmotivated anxiety, fear, emotional stress, and various mental disorders.
• Neuroleptics. Strong sedatives used in psychiatry.
• Normotimics. Psychotropic drugs that doctors prescribe to patients with mental illness.

Soothing agents are of natural and artificial origin

When a person wants to buy a good sedative without a prescription, he will most often be recommended a sedative. Compared to tranquilizers, neuroleptics and mood stabilizers, such drugs are weaker, but they are relatively harmless - they work gently and have a minimal number of side effects. However, you should not extend the recommended course - addiction to sedatives may occur.