Pharmacological properties
Amitriptyline ((3-(10,11-dihydro-5H-dibenzo-[a,[d]cyclohepten-5ylidene)-n/n-dimethylpropylamine hydrochloride) is a tricyclic antidepressant. Amitriptyline has a thymolytic, antidepressant, anxiolytic, sedative and antidysuric effect. Inhibits the reuptake of neurotransmitters (noradrenaline, serotonin, etc.) by presynaptic nerve endings of neurons, causes the accumulation of monoamines in the synaptic cleft and enhances postsynaptic impulses. With prolonged use, it reduces the functional activity (desensitization) of β-adrenergic and serotonin receptors of the brain, normalizes adrenergic and serotoninergic transmission, restores the balance of these systems, which is disturbed in depressive states. Blocks m-cholino- and histamine CNS receptors.
Well absorbed in the digestive tract, metabolized in the body with the formation of desmethylamitriptyline (nortriptyline). The maximum concentration in the blood of amitriptyline after oral administration is reached after 2-7.7 hours. The therapeutic concentration in the blood for amitriptyline is 50-250 ng / ml, for nortriptyline - 50-150 ng / ml. About 95% binds to plasma proteins. Amitriptyline, like nortriptyline, penetrates histohematological barriers, including the placental and blood-brain barriers, as well as into breast milk. The half-life is 40-75 hours. In the liver, it undergoes biotransformation (demethylation, hydroxylation, n-oxidation) and forms active (nortriptyline, 10-hydroxyamitriptyline) and inactive metabolites. Excreted by the kidneys (mainly in the form of metabolites) within several days; partially - with feces.
Indication
Depressive phase of manic-depressive psychosis, other types of endogenous depressions, involutional depressions, depressive syndrome in schizophrenic psychoses (against the background of ongoing therapy with neuroleptics), depressions in organic brain damage, depressions after treatment with reserpine, reactive depressions, neurotic depressions, enuresis, irritable bowel syndrome. depressions in childhood, including emotional disorders specific to children, accompanied by anxiety and fear, increased sensitivity of the nervous system, timidity and fear of others. mixed emotional disorders and behavioral disorders with a predominance of feelings of anxiety, inferiority and obsessive states; enuresis in children (especially primary), except in cases of bladder hypotension; encopresis; psychogenic anorexia. In anxiety-depressive states, it reduces anxiety, agitation, and depressive manifestations.
Application
Usually, at the beginning of treatment, the drug is prescribed at 25-50 mg before bedtime, then, depending on the clinical effect and tolerability, the dose is gradually increased over 5-6 days to 150-200 mg/day, with most of the daily dose being taken at night. If the condition does not improve during the second week, the daily dose is gradually increased to 300 mg, and then it is gradually reduced to 50-100 mg. Therapy is continued until the symptoms of depression disappear completely. As a rule, the course of treatment lasts at least 3 months.
Elderly patients or those with milder forms of depression are prescribed 50-100 mg of the drug per day, usually in one dose at night.
For enuresis, children are usually prescribed 12.5-25 mg of amitriptyline once a day before bedtime. In psychiatric practice, school-age children are usually prescribed 12.5-25 mg of amitriptyline 1-3 times a day. The therapeutic effect of the drug usually appears 7-10 days after the start of the course.
The tablet is swallowed without chewing, with liquid.
Amitriptyline should be taken regularly at a certain time of day (usually in the evening).
Amitriptyline is not recommended for use for more than 6-8 months.
Contraindication
Hypersensitivity to the drug, simultaneous treatment with MAO inhibitors or their administration less than 14 days after discontinuation of amitriptyline, glaucoma, paralytic ileus, epilepsy, pyloric stenosis, bladder atony, decompensated heart failure, coronary artery disease, paroxysmal tachycardia, pregnancy and breastfeeding, age up to 6 years. Relative contraindications are prostatic hypertrophy with impaired urodynamics, gastric and duodenal ulcer.
Side effects
Dry mouth, mydriasis, accommodation disorders, urinary retention, drowsiness, dizziness, tremor of the upper extremities, paresthesias, allergic reactions, arrhythmias. Side effects are mild and, as a rule, do not require discontinuation of the drug, but patients should be warned about their possible development.
Special instructions
Patients taking the drug should refrain from all potentially dangerous activities that require increased attention and speed of reaction. During the period of treatment with the drug, it is necessary to exclude the use of alcohol. Treatment with amitriptyline should be considered ineffective if the patient's condition does not improve after 3 weeks of treatment. The onset of antidepressant action can be accelerated by the combined administration of amitriptyline and nortriptyline.
If treatment is stopped suddenly after long-term treatment, withdrawal syndrome may develop.
Incompatible with MAO inhibitors. Potentiates the effect of compounds that depress the central nervous system (including sedatives, hypnotics, alcohol), sympathomimetics, antiparkinsonian drugs, weakens the effect of hypotensive and anticonvulsant drugs. Inducers of microsomal oxidation (barbiturates, carbamazepine) reduce, and cimetidine increases the concentration of the drug in the blood plasma.
Overdose
Possible intensification of the described side effects. Acute poisoning with amitriptyline is life-threatening for the patient, even with a satisfactory general condition and preservation of respiratory function. Convulsions and severe disorders of vital body functions can occur suddenly. A sign of severe cardiotoxic effect - prolongation of the QRS complex on the ECG - may appear only after a 3-5-day latent period after taking a toxic dose.
Treatment: gastric lavage and use of activated charcoal. In case of cardiac disorders, ECG monitoring is performed. If necessary, symptomatic therapy is performed; digoxin or β-adrenergic blockers should not be used. If convulsions occur, diazepam is prescribed intravenously, in severe cases, anesthesia. In the presence of pronounced anticholinergic symptoms, physostigmine is used.
Storage conditions
In a dry place, protected from light, at room temperature.
