Description
Amitriptyline Pharmacodynamics
Amitriptyline is a tricyclic antidepressant (TCA) from the group of non-selective inhibitors of neuronal takeover of monoamines.
Pharmacodynamics
Amitriptyline, a tricyclic antidepressant, the mechanism of antidepressant action is associated with the accumulation of noradrenaline and serotonin in the synaptic gap in the central nervous system (CNS) as a result of inhibiting their reuptake by presynaptic neuron membranes.
Amitriptyline is a blocker of Mi- and M2-muscarinic cholinoreceptors, H j-histamine receptors and a-adrenoreceptors. According to the so-called monoamine hypothesis, there is a correlation between emotional tone and neurotransmitter function in brain synapses. A clear correlation between the plasma concentration of amitriptyline and the clinical effect has not been shown, but the optimal clinical effect appears to be achieved at concentrations in the range of 100-260 µg/L. Clinical relief of depression is achieved later than the equilibrium
plasma concentrations, after 2-6 weeks of treatment. In addition, amitriptyline has a quinidin-like effect on the cardiac conduction system.
Indications
Depression (especially with anxiety, agitation and sleep disorders, including in childhood, endogenous, involutional, reactive, neurotic, drug-induced, with organic brain lesions, alcohol withdrawal), schizophrenic psychoses, mixed emotional disorders, behavior disorders (activity and attention), nocturnal enuresis (except for patients with bladder hypotonia), bulimia nervosa, chronic pain syndrome (chronic pain in cancer patients, migraine, rheumatic pain, atypical facial pain, postherpetic neuralgia, posttraumatic neuropathy, diabetic neuropathy, peripheral neuropathy), migraine prevention, gastric and duodenal ulcer.
Contraindications
– Hypersensitivity to amitriptyline or excipients that make up the drug;
– lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
-concomitant use of MAO inhibitors and two weeks before starting treatment (see section “Interaction with other medicinal products”).
myocardial infarction (acute and recovery period),
Atrioventricular and intraventricular conduction disorders (blockages of any degree), arrhythmias, heart failure,
bradycardia, congenital long QT interval syndrome, as well as concomitant use with drugs,
leading to prolongation of the QT interval;
– delirium disorders;
– paralytic ileus, intestinal obstruction;
-pylorostenosis;
– acute alcohol intoxication;
– acute intoxication with sleeping pills, analgesic and psychoactive drugs;
– closed-angle glaucoma;
-prostate hyperplasia with urinary retention;
– hypokalemia;
– Severe liver disease;
– Children under 6 years of age (in the treatment of nocturnal enuresis); – Age under 18 years;
Pregnancy, breast-feeding.
With caution
Cardiovascular diseases (angina, arterial hypertension), blood diseases, elevated intraocular pressure, closed-angle glaucoma, flat anterior chamber and acute angle of the eye chamber, prostatic hyperplasia without urinary retention, patients with seizures, bladder hypotension, hyperthyroidism, bipolar disorder, schizophrenia, epilepsy (amitriptyline lowers seizure threshold), liver or kidney function disorders, chronic alcoholism, concurrent use with antipsychotics and sleeping pills, advanced age.
If you have one of the above diseases, before taking the drug, be sure to consult your doctor.
Use in pregnancy and during breastfeeding
Amitriptyline is contraindicated
Amitriptyline is contraindicated in pregnancy and during breastfeeding.
Pregnancy
Animal studies have demonstrated adverse effects at doses several times the standard human dose. Clinical experience with amitriptyline in pregnant women is limited.
The use of amitriptyline in pregnancy has not been established.
Amitriptyline is not recommended for use during pregnancy, especially in the first and third trimesters, unless the anticipated benefit to the mother exceeds the potential risk to the fetus. In this case, it is necessary to warn the patient about the possible risk of developing neurological pathology in the newborn (this is especially true for the third trimester of pregnancy). The use of high doses of tricyclic antidepressants in the third trimester of pregnancy can lead to neurological disorders in the newborn.
When amitriptyline is prescribed to pregnant women, somnolence, agitation and respiratory depression have been reported in the newborn, and urinary retention has been reported when nortriptyline (the metabolite of amitriptyline) is prescribed.
Breastfeeding period
The use of amitriptyline during breastfeeding is contraindicated. Amitriptyline penetrates into breast milk. The ratio of breast milk/plasma concentrations is 0.4-1.5 in a breastfed baby. Adverse reactions may occur. If it is necessary to use the drug during lactation, breastfeeding should be stopped.
Dosage and administration
- Orally, without chewing (immediately after a meal).
Treatment of major depressive disorder in adults - Adults:
The initial daily dose of Amitriptyline is 25-50 mg (1-2 tablets), divided into two doses, or as a single
intake before bedtime. If necessary, the daily dose may be gradually increased to 150 mg. - The maximum daily dose is 225 mg; in some cases, 300 mg. The total course of treatment is usually 6 months or more to prevent relapse.
Elderly patients:
Elderly patients are more sensitive to the m-cholin-blocking unwanted effects of amitriptyline. Therefore, the recommended dose for them is 25-30 mg/day, usually once daily, at bedtime.
Further dose increases should be made gradually, every other day, reaching a dose of 50-100 mg/day, if necessary, until a therapeutic effect is achieved. Additional evaluation is necessary before a second course of treatment is prescribed. Daily doses above 100 mg should be used with caution. - Duration of treatment:
Antidepressant effects are usually evident in 2 to 4 weeks.
Treatment with antidepressants is symptomatic and therefore should be long enough, usually for 6 months or more, to prevent a relapse of depression.
Withdrawal:
The drug should be withdrawn gradually to avoid the development of withdrawal symptoms such as headaches, sleep disturbances, irritability, and general malaise. These symptoms are not a sign of drug dependence. Chronic pain syndrome (including neuropathic pain), prophylactic treatment of chronic tension headache and migraine in adults The dose should be individually titrated, to a dose that provides adequate pain relief with minimal adverse reactions. The lowest effective doses and the shortest courses of treatment should be used. Adults Recommended doses are 25-75 mg. The dose can be taken once daily, or divided into 2 doses. A single dose of 75 mg is not recommended. The initial dose should be 13 10-25 mg in the evening. Doses may be gradually increased by 10-25 mg
every 3 to 7 days, depending on tolerance.
Analgesic effect usually occurs after 2-4 weeks of taking the drug.
Elderly patients Elderly patients over 65 years of age and patients with cardiovascular disease. - The recommended starting dose is 10-25 mg in the evening. Doses above 75 mg should be used with caution. The dose may be increased depending on the individual patient’s reaction and tolerability of the drug.
Duration of treatment
Since treatment is symptomatic, therapy may take a long time. Regular reassessment of therapy is recommended to confirm that continued treatment is appropriate for the patient.
Treatment of nocturnal enuresis in children 6 years of age and older in the absence of organic pathology - Recommended doses for:
– Children aged 6 to 10 years: 10-20 mg;
– Children aged 11 years and older: 25-50 mg daily.
The dose should be increased gradually.
The drug should be administered until 1 to 114 hours before bedtime.
Before starting therapy with amitriptyline, ECG should be performed to exclude QT interval prolongation syndrome.
Duration of treatment The maximum duration of treatment should not exceed 3 months.
If repeated courses of amitriptyline are necessary, medical examinations should be performed every 3 months, including an ECG.
Withdrawal - When amitriptyline treatment is discontinued, the drug should be withdrawn gradually. The drug should be prescribed by a specialist experienced in the treatment of bedwetting.
- Special patient groups
Dosage adjustment is not required in patients with renal impairment.
Use in patients with hepatic impairment In patients with hepatic impairment, the dose of Amitriptyline should be reduced.
