Depression is a widespread illness affecting approximately 20% of people in developed countries. Her therapy includes an integrated approach, including the use of medications. A new generation tranquilizer Grandaxin for depression is prescribed in case of moderately severe symptoms. It gently affects the psycho-emotional background of the patient, while showing a minimum of side effects.

Pharmacological group

Grandaxin is classified as an anxiolytic ( anti-anxiety ) agent or tranquilizer. Most representatives of this group, in addition to the anti -anxiety effect, also show others, including:

• sedative – a decrease in mental and motor activity;
• hypnotic;
• anticonvulsant;
• muscle relaxant – relaxing.

Such effects make it impossible to take such drugs during the day, while driving.

Grandaxin is a fundamentally new tranquilizer with a pronounced anxiolytic effect. Its active ingredient is tofisopam , an atypical benzodiazepine derivative. It is synthesized as a result of the transformation of the molecular structure of diazepam. Due to this feature, it is not able to cause addiction and withdrawal syndrome.

The action of benzodiazepines is based on an increase in the sensitivity of receptors to GABA – gamma-aminobutyric acid. This is the main mediator that causes inhibition in the brain and thereby stops excitation and has a calming effect. However, its excess provokes the opposite reaction – hyperactivity, anxiety, trembling in the arms and legs.

All benzodiazepines are divided into 3 classes, taking into account the predominant action:

• with anxiolytic ;
• with sleeping pills;
• with anticonvulsant effect.

Most representatives have all of the listed properties with one pronounced. Grandaxin , on the other hand, has an anti-anxiety effect, and other manifestations are practically absent.

Given that the drug does not cause a feeling of drowsiness, relaxation and lethargy, does not interfere with concentration, it is called a daytime tranquilizer and it is allowed to combine its use with driving, but only after consulting a doctor.

How to recognize depression

As already mentioned, the drug helps to get rid of depression, but not all of its forms. Grandaxin is taken only for mild to moderate disease with moderate symptoms.

During the course of the disease, several syndromes are distinguished:

1. Emotional disorders: low mood, melancholy, anxiety and internal tension, pessimistic mood; self-flagellation, lack of interest in the outside world, inability to have fun.
2. Behavioral reactions: solitude, reduced activity; bad habits;
3. Cognitive functions: inability to concentrate, mental retardation, decreased memory and perception; pessimistic thoughts, suicidal thoughts, low self-esteem.
4. Vegetative disorders: poor sleep, appetite perversions, weakness and malaise, malfunctions in the intestines; discomfort in the region of the heart and other organs, headaches.

A specific indication for the use of the drug is reactive depression. It develops in response to the action of some traumatic factor. The condition is characterized by a stably reduced emotional background and obsession with the problem.

The patient reproaches and blames himself for what happened, his conversations are directed only at the problem. And, constantly analyzing it, he seeks support from others.

The person is worried about insomnia. And he is fully aware of his condition.

Bouts of despair and demonstrative tantrums are possible. Excitation reaches a state called ” melancholic raptus “. At the same time, a person aimlessly rushes about, sobs, screams, suicide attempts are not ruled out.

This state can be replaced by a depressive stupor, when the patient “freezes” in one position, not reacting to what is happening.

Impact of Grandaxin

The main effect of the drug is manifested in the anxiolytic effect. It helps eliminate feelings of anxiety and fear, reduce emotional stress, anxiety and excitement, both mental and motor.

To a high degree , Tofisopam exhibits a vegetative- stabilizing property. With him, it is expressed to the greatest extent compared to other tranquilizers:

• normalizes sleep – eliminates insomnia, promotes rapid falling asleep;
• restores blood pressure;
• stabilizes the heart rate;
• reduces sweating;
• improves the functioning of the digestive tract, eliminates constipation.

The vegetostabilizing effect is achieved by establishing a balance between the sympathetic and parasympathetic systems.

The stress -protective effect of Grandaxin protects the central nervous system from the effects of a destructive factor. It gives the patient a state of psychological comfort, provides an adequate assessment of what is happening. Protects against the development of unwanted vegetovascular reactions: tachycardia, vascular spasms, destruction of the gastrointestinal mucosa. Eliminates arousal.

To some extent , Tofisopam has a coronary lytic effect:

• improves coronary circulation;
• reduces the need of the heart muscle for oxygen;
• normalizes metabolism in cardiac tissues;
• increases the amount of oxygen delivered to the heart.

This ability of Tofizopam is widely used in the treatment of coronary heart disease. The drug stabilizes the work of both parts of the autonomic nervous system, and this improves the electrical conductivity of the heart muscle.

The psychostimulating effect of the drug helps to restore the mental and physical activity of the patient. Helps to improve cognitive functions, restores mental abilities, improves mood. Enhances the ability to withstand the effects of undesirable environmental factors.

Grandaxin is recommended to be included in complex therapy as:

• enhancing the action of antidepressants;
• to eliminate anxiety and panic attacks, which can be triggered by the start of taking antidepressant drugs;
• in cases where the dosage of antidepressants is insufficient, and its increase is impossible due to the risk of adverse reactions.

As a monotherapy , the use of the drug is undesirable.

Grandaxin and other tranquilizers

Due to its mild and selective effect, the drug has a minimum of side effects, unlike other anxiolytics . It does not cause the negative consequences inherent in most representatives of this group. The main ones are:

1. “Behavioral Toxicity”. Manifested by increased daytime sleepiness, weakness and malaise. Characterized by a decrease in the speed of reactions and the inability to concentrate. Coordination of movements is disturbed, confusion may occur.
2. Addiction. A common problem when taking tranquilizers. There is a possibility of its aggravation up to substance abuse. But more often addiction develops with prolonged treatment with such drugs, with an unauthorized increase in the dose or parallel use of alcohol.
3. Withdrawal syndrome is manifested by a sharp refusal to use a tranquilizer. At the same time, the symptoms of the disease return to the patient in a more pronounced or even complicated form.

Grandaxin does not show such complications. It is low toxic , and repeated exposure to it does not develop resistance. Therefore, it is taken during the daytime.

The drug does not reduce physical and mental activity, does not lead to drowsiness. It does not suppress the effectiveness of perception, speed of reactions, does not interfere with professional activities.

Limitations and adverse reactions

Contraindications to the use of the drug are:

• severe forms of depression – with them there is a high probability of suicidal thoughts and actions;
• phobias, obsessions – possibly increased aggression;
• allergic reactions;
• uncompensated respiratory failure.

With caution, the drug is prescribed to elderly people due to their increased susceptibility to it. It is not advised to use it at this age for too long a time.

For children under 18 years of age, the remedy is contraindicated. It is possible to take it only in rare cases after a careful weighing of the need and risks. In this case, therapy should be short-term.

The drug is contraindicated in the 1st trimester of pregnancy. It easily crosses the placental barrier and can cause malformations in the child. Grandaxin is able to penetrate into breast milk, so you should stop breastfeeding during treatment with the drug.

Otherwise, when it enters the child’s body, it accumulates and causes a sedative effect. In a newborn, the severity of the sucking reflex decreases, he cannot fully suck out milk, and loses weight.

Despite the mild effect of the drug, it still shows some side reactions:

• headaches, agitation and aggressiveness;
• sleep problems;
• confused mind;
• increased frequency of seizures in epileptic patients;
• breathing disorders;
• poor appetite, thirst, digestive problems;
• jaundice;
• muscle hypertonicity , muscle pain;
• allergic manifestations.

In such cases, the reception of funds is canceled.

How to take

Grandaxin is a small tablet, round, disc-shaped, with the GRANDAX logo. They are white or gray in color and practically odorless. Are located on the blister on 10 pieces.

The dosage of 1 tablet is 50 mg. The package contains 20 or 60 tablets.

Once in the digestive tract, Grandaxin is rapidly absorbed into it. Undergoing transformation in the liver, enters the bloodstream. Here it reaches its maximum concentration 2 hours after ingestion. It is excreted by the kidneys and does not accumulate in the body.

The dose of the drug depends on the severity of the condition. It is calculated and prescribed only by a doctor. Self-medication is unacceptable. Usually the scheme is as follows: 1-2 tab. 1 to 3 times a day.

The maximum dose per day is 300 mg, in children – 200 mg.

Due to the fact that the drug accumulates in the liver and is evacuated through the kidneys, patients with renal and hepatic insufficiency are prescribed with caution. In such patients, a change in the severity and duration of the effect, as well as the development of side effects, is possible. In this regard, the dose is reduced by half. The same scheme is used for the elderly.

In case of an overdose of the drug, complications in the form of vomiting, a change in consciousness, coma, convulsive seizures and impaired respiratory function are possible.

Grandaxin is not used in parallel with cyclosporine and immunosuppressants such as tacrolimus , sirolimus .

Tablets are able to intensify the effect of drugs that depress the activity of the central nervous system: analgesics, sedatives and hypnotics, etc.

The use of Grandaxin along with alcohol, smoking, barbiturates, together with antiepileptic therapy reduces its activity.

It is strongly recommended to take Grandaxin before 17.00 to avoid insomnia.

The drug is dispensed by prescription. The cost of 20 tablets averages 400 rubles, 60 tablets – 900 rubles.

Reviews and opinions

Reviews about the drug Grandaxin are twofold. Many note its ability to calm and eliminate unwanted physiological reactions, for example, in the form of tachycardia. Grandaxin gives calmness, does not let you get annoyed over trifles.

Begins to act on the first day of admission. Patients note the ease and clarity of perception without distorting reality. Appetite is restored, mood improves. And all this happens smoothly, without splashes.

An interesting feature of the remedy was even noticed: it helps to lose weight. Which is a plus to some extent.

Now about the side . In patients with chronic bronchitis, breathing difficulty was observed, a feeling of “filled bronchi” appeared. In such cases, you should be extremely careful, given all the contraindications for the use of the drug.

In another case, patients suffered from insomnia. There were problems with falling asleep, and sleep was short. Some are concerned about back pain and dyspeptic disorders.

In general , Grandaxin is successfully used to treat depressive conditions, eliminating tension and irritability, and normalizing the emotional background. It gently and smoothly acts on the body. But, given that the drug is still classified as a psychotropic drug, it is taken only with the permission of the doctor and under his supervision.

Amitriptyline ( Amitriptyline )

The scientific information provided is general and cannot be used to make a decision on the possibility of using a particular medicinal product.

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Dosage form

Release form, packaging and composition of the drug Amitriptyline

Tablets from white with a grayish to white with a yellowish tint, flat-cylindrical shape with a chamfer.

1 tab.
amitriptyline hydrochloride	28.3 mg
which corresponds to the content of amitriptyline	25 mg

Excipients : lactose monohydrate (milk sugar) – 51.1 mg, potato starch – 14.47 mg, microcrystalline cellulose – 4 mg, colloidal silicon dioxide ( aerosil ) – 0.08 mg, gelatin – 1.05 mg, calcium stearate – 1 mg.

10 pieces. – cellular contour packaging (5) – packs of cardboard.
50 pcs. – polymer cans (1) – packs of cardboard.

pharmachologic effect

An antidepressant from the group of tricyclic compounds, a derivative of dibenzocycloheptadine .

The mechanism of antidepressant action is associated with an increase in the concentration of noradrenaline in synapses and / or serotonin in the central nervous system due to inhibition of neuronal reuptake of these mediators. With prolonged use, it reduces the functional activity of β – adrenergic receptors and serotonin receptors in the brain, normalizes adrenergic and serotonergic transmission, restores the balance of these systems, disturbed during depressive states. In anxiety-depressive conditions, it reduces anxiety, agitation and depressive manifestations.

It also has some analgesic effect, which is believed to be associated with changes in the concentrations of monoamines in the central nervous system, especially serotonin, and the effect on endogenous opioid systems.

It has a pronounced peripheral and central anticholinergic effect due to its high affinity for m- cholinergic receptors ; a strong sedative effect associated with affinity for histamine H 1 receptors, and alpha – adrenergic blocking action.

The mechanism of therapeutic action in bulimia nervosa has not been established (possibly similar to that in depression). Amitriptyline has been shown to be clearly effective in bulimic patients both without depression and in its presence, while a decrease in bulimia can be observed without a concomitant weakening of the depression itself.

Efficacy in bedwetting appears to be due to anticholinergic activity leading to increased bladder distensibility, direct β-adrenergic stimulation, α-adrenergic agonist activity accompanied by increased sphincter tone, and central blockade of serotonin uptake.

It has an antiulcer effect, the mechanism of which is due to the ability to block histamine H 2 receptors in the parietal cells of the stomach, as well as to have a sedative and anticholinergic effect (in case of gastric ulcer and duodenal ulcer, it reduces pain, accelerates the healing of the ulcer).

During general anesthesia, it lowers blood pressure and body temperature. Does not inhibit MAO.

Antidepressant action develops within 2-3 weeks after the start of use.

Pharmacokinetics

The bioavailability of amitriptyline is 30-60%. Plasma protein binding 82-96%. V d – 5-10 l / kg. Metabolized to form the active metabolite nortriptyline .

T 1/2 – 31-46 hours. Excreted mainly by the kidneys.

Active ingredient matches for Amitriptyline

Depression (especially with anxiety, agitation and sleep disorders, including in childhood, endogenous, involutional, reactive, neurotic, drug, with organic brain damage, alcohol withdrawal), schizophrenic psychoses, mixed emotional disorders, behavioral disorders (activity and attention), bulimia nervosa, tension headache, migraine, neuropathic pain, chronic pain in cancer patients, rheumatic pain, nocturnal enuresis (with the exception of patients with bladder hypotension), peptic ulcer of the stomach and duodenum.

Open list of ICD-10 codes

ICD-10 code	Indication
B02.2	Herpes zoster with other nervous system complications
F20	Schizophrenia
F21	schizotypal disorder
F22	Chronic delusional disorders
F23	Acute and transient mental disorders
F25	Schizoaffective disorders
F29	Nonorganic psychosis, unspecified
F32	depressive episode
F33	recurrent depressive disorder
F40	Phobic anxiety disorders (including agoraphobia, social phobias)
F41.2	Mixed anxiety and depressive disorder
F50.2	bulimia nervosa
F90.0	Activity and attention disorders
F91.9	Conduct disorder, unspecified
F98.0	Enuresis of inorganic nature
G43	Migraine
G44.2	Tension-type headache
G50.1	Atypical facial pain
G53.0	Neuralgia after herpes zoster (B02.2)
G60	Hereditary and idiopathic neuropathy
G61	Inflammatory polyneuropathy
G62.1	Alcoholic polyneuropathy
G63.2	Diabetic polyneuropathy
K25	stomach ulcer
K26	Duodenal ulcer
M79.2	Neuralgia and neuritis, unspecified
R52.2	Other persistent pain (chronic)

Dosing regimen

The method of application and dosing regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. Compliance of the dosage form of a particular drug with indications for use and dosing regimen should be strictly observed.

For oral administration, the initial dose is 25-50 mg at night. Then, within 5-6 days, the dose is individually increased to 150-200 mg / day (most of the dose is taken at night). If there is no improvement within the second week, the daily dose is increased to 300 mg. With the disappearance of signs of depression, the dose is reduced to 50-100 mg / day and therapy is continued for at least 3 months. In elderly patients with mild disorders, the dose is 30-100 mg / day , usually 1 time / day at night, after achieving a therapeutic effect, they switch to the minimum effective dose – 25-50 mg / day .

With nocturnal enuresis in children aged 6-10 years – 10-20 mg / day at night, at the age of 11-16 years – 25-50 mg / day .

V / m – the initial dose is 50-100 mg / day in 2-4 injections. If necessary, the dose can be gradually increased to 300 mg / day , in exceptional cases – up to 400 mg / day .

Side effect

From the nervous system: drowsiness, asthenia, fainting, anxiety, disorientation, agitation, hallucinations (especially in elderly patients and in patients with Parkinson’s disease), anxiety, motor restlessness, manic state, hypomanic state, aggressiveness, memory impairment, depersonalization , increased depression, reduced ability to concentrate, insomnia, nightmares, yawning, activation of psychotic symptoms, headache, myoclonus , dysarthria, tremor (especially of the hands, head, tongue), peripheral neuropathy (paresthesia), myasthenia gravis, myoclonus , ataxia, extrapyramidal syndrome, increased frequency and intensification of epileptic seizures, changes in the EEG.

From the side of the cardiovascular system: orthostatic hypotension, tachycardia, conduction disturbances, dizziness, non-specific changes on the ECG (ST interval or T wave), arrhythmia, blood pressure lability, intraventricular conduction disturbance (expansion of the QRS complex, changes in the PQ interval, blockade of the legs of the His bundle ).

From the digestive system: nausea, heartburn, vomiting, gastralgia , increased or decreased appetite (increase or decrease in body weight), stomatitis, change in taste, diarrhea, darkening of the tongue; rarely – liver dysfunction, cholestatic jaundice, hepatitis.

On the part of the endocrine system: testicular edema , gynecomastia, mammary gland enlargement, galactorrhea , changes in libido, decreased potency, hypo- or hyperglycemia, hyponatremia (decreased vasopressin production), syndrome of inappropriate ADH secretion.

From the hemopoietic system: agranulocytosis, leukopenia, thrombocytopenia, purpura, eosinophilia .

Allergic reactions: skin rash, pruritus, urticaria, photosensitivity, swelling of the face and tongue.

Effects due to anticholinergic activity: dry mouth, tachycardia, disturbances of accommodation, blurred vision, mydriasis , increased intraocular pressure (only in individuals with a narrow anterior chamber angle of the eye), constipation, paralytic ileus, urinary retention, decreased sweating, confusion, delirium or hallucinations.

Other: hair loss, tinnitus, edema, hyperpyrexia , swollen lymph nodes, pollakiuria, hypoproteinemia .

Contraindications for use

Acute period and early recovery period after myocardial infarction, acute alcohol intoxication, acute intoxication with hypnotics, analgesics and psychotropic drugs, angle -closure glaucoma, severe disorders of AV and intraventricular conduction (blockade of the bundle of His bundle, AV blockade of II degree), lactation period, children under 6 years of age (for oral administration), children under 12 years of age (for intramuscular and intravenous administration), simultaneous treatment with MAO inhibitors and the period 2 weeks before their use, hypersensitivity to amitriptyline.

Use during pregnancy and lactation

Amitriptyline should not be used during pregnancy, especially in the first and third trimesters, unless absolutely necessary. Adequate and strictly controlled clinical studies of the safety of the use of amitriptyline during pregnancy have not been conducted.

Amitriptyline should be gradually discontinued at least 7 weeks before expected delivery to avoid the development of a withdrawal syndrome in the newborn.

In experimental studies, amitriptyline had a teratogenic effect.

Contraindicated during lactation. It is excreted in breast milk and may cause drowsiness in infants.