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From a chemical point of view, amitriptyline belongs to the category of tricyclic antidepressant drugs. This class of drugs received such a name because of the characteristic form of the molecule consisting of three carbon rings. The principle of action of amitriptyline is based on the inhibition of the reuptake of various neurotransmitters, such as dopamine, norepinephrine and serotonin. This means that the drug does not allow nerve cells to retain these neurotransmitters at the moment of impulse transmission. As a result, the total number of neurotransmitters in the region of synaptic connections between neurons increases. As a result, neural connections become more stable, the work of adrenergic and serotonin systems of the body is normalized.
Why is it so important in case of depression? It is no secret that depression is not just a blues or a bad mood. This is a serious disease of the nervous system, in which neural connections do not function properly, and in the nervous system there is a lack of various neurotransmitters and a violation of the transmission of impulses between different parts of the central nervous system. And the disease can be cured only by taking special medicines, including amitriptyline.
This drug has not only antidepressant effect. It also provides:
moderate analgesic effect of central genesis,
anticholinergic (central and peripheral),
alpha adrenergic blocking
antiarrhythmic (due to slower ventricular conduction),
anxiolytic (anti-anxiety) action.
In addition, amitriptyline causes a decrease in appetite. Due to all these properties, the positive effect of the drug is not only manifested in mental disorders. Also drug:
helps to reduce pain,
has an anti-ulcer effect (due to the blocking of histamine receptors in the parietal cells of the stomach),
contributes to the normalization of urination (due to the anticholinergic effect and increase the degree of stretching of the bladder).
The drug does not inhibit MAO. When general anesthesia reduces body temperature, blood pressure level.
Amitriptyline does not have an instant effect. In order for its therapeutic effects to manifest, it takes some time, at least 2-3 weeks.
The effect of the drug depends on the dose. With small doses, below the therapeutic threshold, the drug has only a slight sedative effect, and the antidepressant effect is absent. With an increase in dose, the antidepressive effect is manifested, with the sedative effect giving way to a stimulating one. At a dose close to the maximum, sedation reappears, and the antidepressant effect is somewhat weakened. It should be borne in mind that the intervals in which these effects occur are individual for different patients.
In general, compared with other tricyclic antidepressants, sedative properties of the drug predominate. Because of this, such side effects characteristic of antidepressants with a stimulating effect, such as delirium and hallucinations, are uncharacteristic for amitriptyline.
Especially effective drug for anxiety and depressive states. Treatment with amitriptyline in such cases successfully removes not only the depression itself, but also anxiety, psychomotor agitation (agitation), internal tension and fear, normalizes sleep.
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The main scope of the drug are diseases of the psyche and the central nervous system. These primarily include:
depression of various origins, in the first place, endogenous;
neurogenic pain syndrome;
behavioral disorders, including in children;
bulimia nervosa (excessive appetite for nerves);
chronic pain syndrome (migraine, rheumatism, cancer, neuralgia and neuropathy);
peptic ulcer and duodenal ulcer;
neurogenic urinary incontinence (except for cases with bladder hypotension).
For depressions, the drug can be used as part of monotherapy, with other diseases most often amitriptyline is used as part of complex therapy.
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There are two forms of the drug release – tablets and solution for parenteral administration. There are tablets with a dosage of 10, 25 and 50 mg. 1 ml of solution contains 10 mg of amitriptyline. Prescription drug is available.
Structural analogues of Amitriptyline are:
In addition, there are other antidepressant drugs. Imipramine and clomipramine are also included in the tricyclic antidepressant group. However, of course, it is the prerogative of a psychotherapist, a neurologist or a neurologist to choose the necessary remedy for depression, and self-medication is inappropriate and even dangerous.
Amitriptyline is contraindicated in:
severe forms of heart and kidney failure;
decompensated heart defects;
hypertension in severe form;
acute or subacute forms of myocardial infarction;
acute alcohol intoxication, hypnotics, analgesics and psychoactive substances;
atrioventricular block 2 of article;
under the age of 6 years;
while taking MAO inhibitors.
During pregnancy, the drug can be prescribed only in the absence of another alternative, after the doctor weighs all the pros and cons. As shown by experiments on animals, the drug has a teratogenic effect. Newborns born to women who took the drug during pregnancy may for some time suffer from increased drowsiness or tearfulness. Also, the drug is not allowed during lactation due to its ability to penetrate into breast milk. Children of nursing mothers taking Amitriptyline may also suffer from excessive drowsiness.
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The drug, in addition, is contraindicated for people who drive vehicles and perform work that requires concentration.
The drug is prescribed with caution when:
problems with the cardiovascular system (in particular, ischemic heart disease, arrhythmias, heart failure),
decrease in intestinal motor function,
presence of convulsive symptoms in history
renal and hepatic pathologies,
urinary retention and bladder hypotension,
Treatment of patients with severe endogenous depression and a high risk of suicidal behavior should be carried out only in a hospital setting.
The most common undesirable sleeping pills side effects side effects resulting from taking the drug include:
drowsiness or insomnia;
allergic reactions (skin – urticaria, rash or itching, or systemic – anaphylactic shock, angioedema);
abdominal pain, nausea, diarrhea, constipation;
blood pressure jumps (most often – hypotension, due to the drug’s alpha-blocking effect);
drop in pressure when rising or moving the body from a lying to a sitting position (orthostatic hypotension);
increased intraocular pressure.
In epilepsy, the use of amitriptyline in doses of more than 150 mg per day can cause a decrease in the seizure threshold. When used in children and young people up to 24 years old, it may increase the risk of suicidal behavior. Prolonged use increases the incidence of caries.
From the side of the central nervous system can also be observed:
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noise in ears,
development of mania,
increased epileptic seizures,
reduced ability to concentrate
Hallucinations are more common in the elderly and those with Parkinson’s disease.
The appearance of epileptiform convulsions is most often manifested when taking the drug in high doses, in patients with epilepsy or in patients with head injuries in history. In such cases, dose adjustment or the appointment of anticonvulsants is required.
On the part of the cardiovascular system are also possible:
impaired cardiac conduction
changes in the QT interval on the ECG (requires dose reduction or constant monitoring of the parameter),
feeling of heartbeat.
Side effects caused by anticholinergic effects:
accommodation disturbance (blurred vision),
intestinal obstruction (mainly in the elderly and in patients with a tendency to constipation).
On the part of the digestive system are also possible:
development of hepatitis and jaundice,
increased appetite (usually the drug, on the contrary leads to a decrease in appetite),
On the part of the endocrine system, the following phenomena are possible:
swelling of the testicles
gynecomastia (breast enlargement, in women and men),
decreased or increased libido,
change in potency.
Also the following side effects are not excluded:
darkening of the tongue
swollen lymph nodes
hand tremor (associated with stimulation of the beta-adrenergic system, is removed by taking beta-blockers),
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changes in the blood composition (leukopenia, eosinophilia, thrombocytopenia), fluctuations in blood glucose.
With the abolition of the drug the following phenomena are possible:
Therefore, before the abolition of the drug requires a gradual dose reduction. These symptoms are usually transient and are not evidence of drug dependence.
Instructions for use
The initial dose in tablets is 25-50 mg (1-2 tablets 25 mg) per day. The drug in such a case, it is desirable to take at bedtime. Then the dose is gradually increased (25 mg daily) to 150-200 mg. In this case, the daily dose should be divided into three doses. The greatest amount of the drug should be taken at night.
In mild cases, in patients taking the drug for the first time, in patients with severe somatic diseases, in elderly or adolescent age, a slower dose escalation is recommended (25 mg in 2-3 days). In severe, suicidally dangerous depressions, on the contrary, should begin immediately with large daily doses (100 mg).
The maximum daily dose for outpatient treatment is 200 mg, for inpatient treatment it is 300 mg. In some cases, with severe depression and good tolerability of the drug may increase the maximum daily dose of 400-450 g.
In case of nervous bulimia, emotional disorders, schizophrenia, aggravated by psychosis, alcohol withdrawal begins with a dose of 25-100 mg (1-4 tablets of 25 mg) at night. After reaching the therapeutic effect, it is necessary to switch to the minimum effective dose – 10-50 mg per day.
Prevention of migraine, chronic neurogenic pain, ulcerative diseases of the gastrointestinal tract require daily doses of 10-100 mg (the dose is prescribed by a doctor based on specific circumstances). Moreover, most of the dose is taken at night.
In the treatment of depressive conditions in children 6–12 years old, a dose of 10–30 mg per day is required. Or you can calculate the dosage based on the weight – 1.5 mg / kg.
In case of nocturnal enuresis, children of 6–12 years old are prescribed 10 mg each, less often 20 mg each. Children over 12 years old – up to 50 mg. The drug is taken once at night.
The duration of treatment depends on many factors — the patient’s condition, the type of illness, and can vary from a few months to one year.
With impaired renal function requires dose adjustment. Also, dose adjustment is required for older people.
In order to avoid adverse reactions, the drug should be taken immediately after a meal.
With the abrupt cancellation of the drug may cause withdrawal. Therefore, it is recommended to gradually reduce the dosage of the drug before the end of the course.
Parenterally (intramuscularly or intravenously) the drug can be administered only in the hospital, under the supervision of a physician. Usually the dosage is 20-40 mg 4 times a day. At the first opportunity, you must go to oral intake.
With an overdose possible:
Necessary gastric lavage, symptomatic therapy. Hemodialysis is ineffective.
Interaction with other substances
The drug is incompatible with alcohol. Therefore, during the course of therapy it is necessary to give up alcohol. You should not take the drug with other tricyclic antidepressants. Use with antidepressants of a group of selective serotonin reuptake inhibitors can lead to serotonin syndrome.
Absolutely incompatible with another class of antidepressants – MAO inhibitors. When applied simultaneously with MAO inhibitors, severe seizures and hypertensive crises can develop, which often result in the death of the patient. Therefore, the interval between treatment courses with amitriptyline and MAO inhibitors should be at least 2 weeks.
With simultaneous appointment with benzodiazepines, mutual enhancement of the therapeutic effect can be observed. When used with other antidepressants, barbiturates, sedatives, benzodiazepines, general anesthetics, the inhibitory effect on the central nervous system increases, the hypotensive effect develops, and respiratory depression is possible.
Amitriptyline also enhances the effect on the cardiovascular system of epinephrine, ephedrine and similar agents, resulting in the risk of tachycardias, arrhythmias and arterial hypertension. Therefore, when performing anesthesia (epinephrine is usually included in anesthetics), the physician should be informed of the patient taking this antidepressant drug to adjust the dose of anesthetics.
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Increases the therapeutic effect of anticholinergic, antihistamines, which can lead to increased side effects. Amantadine increases the anticholinergic effect.
The drug reduces the effectiveness of alpha-blockers, anticonvulsants and antihypertensive drugs. Clonidine and antihistamines increase the inhibitory effect on the central nervous system, atropine increases the risk of intestinal paralysis. In this case, clonidine and methyldopa decreases the hypotensive effect.
Barbiturates, nicotine reduce the effectiveness of the drug. Cocaine increases the risk of arrhythmias. In local adrenomimetics, the vasoconstrictive effect increases. The use of thyroid hormones together with the drug increases both the mutual therapeutic effect and toxic effects.