Amitriptyline - instructions for use, dose, side effects, contraindications

Antidepressant (tricyclic antidepressant). Anxiolytic. Sedative. Analgesic (central genesis). Antiulcer: m-cholinoblocking, antihistamine (blockade of H2 receptors of parietal cells of the stomach), antiserotonin. Antiarrhythmic. Decreased appetite; elimination of bedwetting.

Pharmacokinetics:

F - 30-60%, its metabolite, nortriptyline, - 46-70%. Relationship with plasma proteins 90%. Therapeutic blood concentrations for amitriptyline are 50-250 ng / ml, for nortriptyline 50-150 ng / ml. Passes (including nortriptyline) through the BBB. Biotransformation in the liver (CYP1A2, 2C9, 2C19, 2D6), active metabolites - nortriptyline and 10-hydroxy-amitriptyline. T1 / 2 amitriptyline - 10-26 h, nortriptyline - 18-44 h. Elimination of metabolites by the kidneys - 80%, in part - with feces.

Indications:

Depression (especially with anxiety, agitation and sleep disorders, including in childhood, endogenous, involutional, reactive, neurotic, medicated, with organic brain lesions, alcohol withdrawal). The efficacy of dysthymia is 75-200 mg / day.

Schizophrenic psychosis. Reliable information is not enough to recommend or reject the use of antidepressants in schizophrenic depression.

Mixed emotional disorders, behavioral disorders (activity and attention).

Nocturnal enuresis (except in patients with hypotension bladder), bulimia nervosa, chronic pain syndrome (chronic cancer pain, migraine, rheumatic diseases, atypical facial pain, post-herpetic neuralgia, post-traumatic neuropathy, diabetic or other peripheral neuropathy), headache pain (10-30 mg / day), gastric ulcer and duodenal ulcer.

ICD-10

I.B00-B09.B02.2 Shingles with other complications from the nervous system

V.F20-F29.F20 Schizophrenia

V.F20-F29.F21 Chrysotile disorder

V.F20-F29.F22 Chronic delusional disorders

V.F20-F29.F23 Acute and transient psychotic disorders

V.F20-F29.F25 Schizoaffective disorder

V.F20-F29.F29 Inorganic psychosis, unspecified

V.F30-F39.F32 Depressive episode

V.F30-F39.F33 Recurrent depressive disorder

V.F40-F48.F40 Phobic anxiety disorders

V.F40-F48.F41.2 Mixed anxiety and depressive disorder

V.F50-F59.F50.2 Nervous bulimia

V.F90-F98.F98.0 Enuresis of inorganic nature

VI.G40-G47.G43 Migraine

VI.G60-G64.G60 Hereditary and idiopathic neuropathy

VI.G60-G64.G61 Inflammatory polyneuropathy

VI.G60-G64.G62.1 Alcoholic polyneuropathy

VI.G60-G64.G63.2 * Diabetic polyneuropathy (E10-E14 + with common fourth sign .4)

XI.K20-K31.K25 Stomach ulcer

XI.K20-K31.K26 Duodenal ulcer

XVIII.R50-R69.R52.2 Another constant pain

Contraindications:

Hypersensitivity, application in conjunction with MAO inhibitors and 2 weeks before the start of treatment, myocardial infarction (acute and subacute periods), acute alcohol intoxication, acute intoxication with hypnotic, analgesic and psychoactive drugs, ZUG, severe disorders of atrioventricular and intraventricular conduction (blockage of the legs of the bundle Gysa, AV-blockade of the II degree), breast-feeding, children's age (up to 6 years - oral forms, up to 12 years with a / m and / in the introduction). Carefully! Chronic alcoholism, bronchial asthma, manic-depressive psychosis, oppression of bone marrow hematopoiesis, cardiovascular diseases (angina pectoris, arrhythmia, heart block, CHF, myocardial infarction, AH), stroke, decreased motor function of the digestive tract (risk of paralytic intestinal obstruction), intraocular hypertension, hepatic and / or renal failure, thyrotoxicosis,hyperplasia of the prostate, urinary retention, bladder hypotension, schizophrenia (possible activation of psychosis), epilepsy, pregnancy (especially I trimester), advanced age.

Carefully:

Used with caution in IHD, arrhythmia, heart block, heart failure, myocardial infarction, arterial hypertension, stroke, chronic alcoholism, thyrotoxicosis, against the background of thyroid medication.

On the background of amitriptyline therapy, orthostatic hypotension is possible.

Pregnancy and lactation:

Pregnancy

Recommendations FDA category C. Passes through the placenta. Teratogenic effect in animals develops with the use of doses many times higher than therapeutic doses for humans.

Lactation

Penetrates into breast milk.

Dosing and Administration:

Dosing regimen. Inside, not liquid, after eating. The initial dose for adults is 25-50 mg per night, then it is increased for 5-6 days to 150-200 mg / day in 3 divided doses (the maximum dose is taken at night). If within 2 weeks there was no improvement, 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 treatment is continued for at least 3 months.In the elderly, with mild disorders, it is prescribed in a dose of 30-100 mg / day (at night), after reaching a therapeutic effect, pass to the minimum effective doses of 25-50 mg / day. In / m or in / in (inject slowly) at a dose of 20-40 mg 4 times a day, gradually replacing the ingestion. Duration of treatment is no more than 6-8 months.

Use in children

Depression. Inside. 16-18 years: 30-75 mg / day (possible at night), gradually increasing the dose to 150-200 mg / day.

Children's enuresis. Inside. 6-10 years: 10-20 mg / day. 11-16 years: 25-50 mg / day (except for children with bladder hypotension) - the effect stops after the end of the admission.

As an antidepressant. Inside. From 6 to 12 years: 10-30 mg or 1-5 mg / kg per day is divided. 12-18 years: 10 mg 3 times a day (if necessary, up to 100 mg / day).

Side effects:

Anticholinergic: a disorder of accommodation, photophobia, constipation, urinary retention, dry mouth> 10%; dizziness, psychosis (including delirium, paranoid-hallucinatory conditions), extrapyramidal disorders, late dyskinesias, tachycardia or bradycardia, conduction disorders, orthostatic hypotension, increased appetite, weight gain, sexual disorders.

Rarely: agranulocytosis, allergic reactions, alopecia, cholestatic jaundice, syndrome of inappropriate secretion of ADH.

Overdose:

Drowsiness, disorientation, confusion, dilated pupils, fever, dyspnea, dysarthria, agitation, hallucinations, seizures, muscle rigidity, vomiting, arrhythmia, lowering blood pressure, heart failure, respiratory depression, sopor, coma.

Treatment is symptomatic: with severe anticholinergic effects (hypotension, arrhythmia, coma, myoclonic seizures) - physostigmine hydrochloride 1-3 mg IM or IV every 1-2 hours. It is impossible to remove during hemodialysis.

Interaction:

Alcohol, other drugs that depress the central nervous system, - potentiation oppression of the central nervous system, respiratory depression, hypotension.

Antithyroid drugs - the risk of agranulocytosis.

MAO inhibitors are incompatible: hyperpyretic, hypertensive crises, convulsions, death.

Clonidine, guanethidine - the weakening of their hypotensive effect, increasing the sedative effect of clonidine.

Sympathomimetics (norepinephrine, epinephrine, including in the form of eye drops and when administered with local anesthetics) - increased action, risk of heart rhythm disturbances, tachycardia, severe AH.

Phenothiazine or thioxanthene antipsychotics - strengthening and lengthening of sedative and anticholinergic action, increased convulsive readiness.

Phenothiazine derivatives and tricyclic antidepressants inhibit each other's metabolism, increase the risk of developing a malignant neuroleptic syndrome.

Cimetidine - depression of the metabolism of amitriptyline, increasing its concentration and toxicity.

Special instructions:

There is insufficient information to recommend or reject depression treatment in Parkinson's disease (3 CI, 106 patients), treatment of tinnitus with TCAs (5 CI, 525 patients), trigeminal neuralgia (9 CI, 223 patients). Further randomized clinical trials are needed.

TCAs and SSRIs (venlafaxine) are comparable in effectiveness in the treatment of neurogenic pain (NNT-3). Further research is required (61 CI, 3293 patients).

During treatment should not be consumed ethanol. Tricyclic antidepressants (including amitriptyline), intensify the action of ethanol, especially during the first few days of therapy.

During the treatment period it is necessary to refrain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Assign no earlier than 14 days after the abolition of MAO inhibitors.

With a sudden discontinuation after long-term treatment, the syndrome of "withdrawal" may develop.

Effective with dysthymia (75-200 mg / day, there is no difference in the effectiveness of antidepressants of different groups), neurotic bulimia (starting at 50 mg / day and gradually increasing to 200-300 mg / day); at a posttraumatic stress disorder (50-300 mg / day).

Amitriptyline in doses above 150 mg / day reduces the threshold of convulsive activity (should take into account the risk of seizures in predisposing patients).

Instructions

Amitriptyline (Amitriptylinum)