Amitriptyline

Amitriptyline

Amitriptyline is a classic tricyclic antidepressant. Suppresses the reuptake of norepinephrine and serotonin by presynaptic neurons, which leads to an increase in the concentration of these mediators and the development of an antidepressant effect. With regular use, it suppresses the activity of cerebral beta-adrenergic receptors and serotonin receptors, normalizes the propagation of nerve impulses through these receptors, eliminates the imbalance of these systems caused by depression, exhibits an anxiolytic (eliminating anxiety) effect, reduces agitation (emotional overexcitation) and manifestations of depression. It has a mild analgesic effect, which, according to scientists, is due to fluctuations in the level of monoamines (primarily the neurotransmitter serotonin) in the central nervous system and the effect on the body’s own (internal) opiateergic systems. The pronounced ability to bind to m-cholinergic receptors determines the powerful anticholinergic effect of Amitriptyline, and its ability to interact with histamine H1 receptors and block alpha-adrenergic receptors causes a sedative effect. It has an antiulcer effect, reduces the severity of pain in stomach and duodenal ulcers, and ensures rapid scarring of the ulcer. The above-mentioned anticholinergic activity of Amitriptyline, which increases the elasticity of the bladder walls and their ability to stretch, makes it effective in the treatment of enuresis. This property of the drug is reinforced by direct beta-adrenergic stimulation and blocking the uptake of the transmitter serotonin by central neuronal synapses. Amitriptyline reduces bulimia nervosa both with and without comorbid depression. The antidepressant effect of the drug begins to clearly manifest itself 2-3 weeks after the start of drug therapy.

The bioavailability of Amitriptyline is about 50%, the half-life is 30-45 hours. Elimination from the body occurs through urine. The drug is available in tablet and ampoule form. Pharmacotherapy is started with a dose of 25-50 mg, the optimal time of administration is before bedtime. Gradually over the course of a week the dose is increased by 3-4 times. If there is no improvement in the condition in the second week, the daily dose is raised to 300 mg. Elimination of depressive symptoms is not a reason to refuse treatment: in this case, the dose is reduced to daily 50-100 mg and pharmacotherapy is continued for at least another three months. In elderly people with mild depression, the dose of the drug is set in the range from 30 to 100 mg per day, and when positive results are achieved, they move on to a maintenance daily dose of 250-50 mg. During treatment, it is necessary to avoid situations that require sudden standing up from a sitting or lying position. It is not recommended to abruptly interrupt treatment: in this case, withdrawal syndrome may develop. It is necessary to take the necessary precautions when using Amitriptyline in patients suffering from epilepsy, because the drug in a daily dose of over 150 mg reduces the seizure threshold. When planning treatment, one should be aware of possible suicide attempts in patients suffering from severe depression. The combined use of Amitriptyline and electroconvulsive therapy is possible only with constant medical monitoring. In patients with a complicated medical history and the elderly, taking the drug can lead to the occurrence of pharmacological psychoses (after stopping drug therapy, such phenomena quickly disappear). Long-term use of Amitriptyline can lead to the development of caries. The drug is not compatible with alcohol.

How to take Amitriptyline

Amitriptyline should be taken exactly as prescribed by your doctor. If you have any doubts, you should consult your doctor or pharmacist.

Not all dosage regimens are possible with different dosage forms and doses of the drug.

The appropriate dosage form and dose of the drug should be selected for the starting and subsequent increasing doses.

Depression

Adults:

The recommended starting dose is 25 mg twice daily. Depending on the clinical effect, the dose may be increased to 150 mg/day, divided into two doses.

Elderly patients (over 65 years of age) and patients with cardiovascular diseases

The recommended starting dose is 10-25 mg per day. Depending on the clinical effect, the dose may be increased to 100 mg/day, divided into two doses. If you take 100 mg to 150 mg of the drug, you may need to consult your doctor more often.

Use in children and adolescents

Amitriptyline is not recommended for use in children and adolescents for the treatment of depression. For more information see section 2.

tension headaches and migraine prevention

Your doctor will choose the right dose based on your symptoms and your body's response to treatment.

Adults:

The recommended starting dose is 10-25 mg in the evening.

The recommended daily dose is 25-75 mg.

Depending on the clinical effect, the dose may be gradually increased. If you take more than 100 mg/day, you may need to consult your doctor more often. Your doctor will advise you to take the drug once a day or divide the dose into two doses.

Elderly patients (over 65 years of age) and patients with cardiovascular diseases

The recommended starting dose is 10-25 mg in the evening.

Depending on the clinical effect of the drug, the dose may be gradually increased.

If you take more than 75 mg/day, you may need to consult your doctor more often.

Use in children and adolescents

Amitriptyline is not recommended for use by children and adolescents for the treatment of neuropathic pain, chronic tension-type headaches, and for the prevention of migraine. For more information, see the section What you need to know before using Amitriptyline.

Bed-wetting

Use in children and adolescents

Recommended dose for children:

• Children under 6 years of age: See section “Do not take Amitriptyline tablets”
• Children from 6 to 10 years: 10-20 mg per day. In this age group, appropriate release forms are used.
• Children 11 years and older: 25-50 mg.

The dose should be increased gradually.

You should take the drug 1 or one and a half hours before bedtime.

Before starting treatment, your doctor may perform an ECG to determine if there are signs of a heartbeat abnormality.

Your doctor will re-evaluate your condition after 3 months of treatment and perform a repeat ECG if necessary.

Do not stop taking the drug without consulting your doctor.

Special patient groups

Patients with liver disease or known to be "poor metabolizers" are usually prescribed lower doses.

Your doctor may take blood samples to determine your amitriptyline level (see What you need to know before you use Amitriptyline).

How and when to take Amitriptyline

The drug should be taken during or after meals.

The tablets should be swallowed whole with water. The tablets should not be chewed.

Treatment period

You should not change the dose of the drug or stop taking the drug without consulting your doctor.

Depression

As with other medications used to treat depression, it may take several weeks before you feel any improvement in your condition.

When treating depression, the duration of treatment is individual and is usually at least 6 months. The duration of treatment is determined by your attending physician.

Continue taking Amitriptyline for as long as prescribed by your doctor. The disease can persist for a long time. If you stop treatment too early, your symptoms may return.

tension headaches and migraine prevention

It may take several weeks for your condition to improve.

Consult your doctor about the duration of treatment and continue taking the drug until your doctor stops it.

Bed-wetting

Your doctor will determine the need to continue treatment after 3 months of taking the drug.

If you take more Amitriptyline than recommended

If you take more Amitriptyline than prescribed by your doctor, you should immediately contact your doctor or the nearest hospital emergency room, even if you do not experience any discomfort or symptoms of poisoning. Take the medicine package with you if you are going to the doctor or hospital.

Overdose symptoms include:

• dilated pupils
• fast or irregular heartbeat
• difficulty urinating
• dry mouth or tongue
• intestinal obstruction
• seizures
• fever
• anxiety
• confusion
• hallucinations
• involuntary movements
• low blood pressure, weak pulse, pallor
• difficulty breathing
• bluish skin
• decreased heart rate
• drowsiness
• loss of consciousness
• coma
• various heart diseases, such as cardiac conduction block, heart failure, hypotension, cardiogenic shock, metabolic acidosis, hypokalemia.

If you forget to take Amitriptyline

Take your next dose at your usual time. Do not take a double dose of the drug to compensate for the missed dose.

If you stop taking Amitriptyline

Your doctor will decide when and how to stop treatment to avoid unwanted symptoms that may occur if the drug is suddenly stopped (for example, headache, feeling unwell, insomnia and irritability).

If you have additional questions about the use of the drug, contact your doctor or pharmacist.

Amitriptyline

Amitriptyline enhances the inhibitory effect on the central nervous system of the following drugs: antipsychotics, sedatives and hypnotics, anticonvulsants, analgesics, anesthetics, alcohol; exhibits synergism when interacting with other antidepressants. Tricyclic antidepressants, including amitriptyline, are metabolized by the hepatic cytochrome P450 isoenzyme CYP2D6. The CYP2D6 isoenzyme in humans has several isoforms. CYP2D6 isoenzymes can inhibit various psychotropic drugs, for example, antipsychotics, selective serotonin reuptake inhibitors (SSRIs) with the exception of citalopram (a very weak inhibitor of the CYP2D6 isoenzyme), [3-blockers and the latest generation antiarrhythmics. These drugs can inhibit the metabolism of tricyclic antidepressants and significantly increase their plasma concentrations. In addition, the isoenzymes CYP2C19 and CYP3A are involved in the metabolism of amitriptyline.

MAO inhibitors

Concomitant use of amitriptyline with MAO inhibitors can cause the development of serotonin syndrome (possible agitation, confusion, anxiety, tremor, myoclonus, hyperthermia, coma) and lead to death.

The break in treatment between taking MAO inhibitors and tricyclic antidepressants should be at least 14 days!

Amitriptyline can be prescribed 14 days after discontinuation of treatment with irreversible non-selective MAO inhibitors and at least 1 day after discontinuation of therapy with the reversible MAO inhibitor moclobemide. The use of MAO inhibitors can be started 2 weeks after discontinuation of amitriptyline. In any case, both the MAO inhibitor and amitriptyline should be started at low doses and gradually increased depending on the effect.

Sympathomimetics

Amitriptyline may potentiate the effects of epinephrine, ephedrine, isoprenaline, norepinephrine, phenylephrine and phenylpropanolamine on the cardiovascular system.

Anticholinergic drugs

Tricyclic antidepressants may enhance the effects of anticholinergic drugs on the eye, central nervous system, intestines and bladder; simultaneous use of these drugs should be avoided due to an increased risk of paralytic ileus.

Drugs that reduce sympathetic activity

Tricyclic antidepressants may reduce the antihypertensive effects of guanethidine, betanidine, reserpine, clonidine and methyldopa. During therapy with tricyclic antidepressants, it is recommended to adjust antihypertensive therapy.

Indirect anticoagulants

With the simultaneous use of amitriptyline and indirect anticoagulants (coumarin or indadione derivatives), the anticoagulant activity of the latter may increase.

Acetalidehyde dehydrogenase inhibitors

Concomitant use with disulfiram and other acetaldehyde dehydrogenase inhibitors may increase the risk of developing psychotic conditions and confusion.

Glucocorticoids

Amitriptyline may enhance depression caused by glucocorticoids.

Antithyroid drugs

Concomitant use with drugs for the treatment of thyrotoxicosis increases the risk of developing agranulocytosis.

Drugs that prolong the QT interval

Drugs that prolong the QT interval, including antiarrhythmics such as quinidine, H1-blockers such as astsmizole and terfsiadine, some antipsychotics (particularly pimozide and sertindole), cisapride, halofantrine and sotalol may increase the likelihood of developing ventricular arrhythmias when concomitantly prescribed with tricyclic antidepressants.

CNS depressants

When used simultaneously with blockers of III-histamine receptors, clopidine, alcohol and barbiturates, the inhibitory effect on the central nervous system may be enhanced. Amitriptyline may enhance the effects of other drugs that depress the central nervous system.

St. John's wort

The simultaneous use of amitriptyline and drugs containing St. John's wort can lead to increased metabolism of amitriptyline and a decrease in the maximum serum concentration of amitriptyline by 20%, due to the induction of its metabolism by the liver isoenzyme CYP3A4. Theoretically, it is possible to increase the risk of serotonin syndrome.

Lithium

With the simultaneous use of lithium and tricyclic antidepressants, the risk of psychotic symptoms and toxic complications from the central nervous system may increase, even against the background of therapeutic concentrations of lithium in the blood plasma. Cases of mania, myoclonus, tremor, tonic-clonic seizures, memory disorders, confusion, disorganization of thinking, hallucinations, serotonin syndrome and neuroleptic malignant syndrome, which began a few days after the start of combination therapy, have been described; in most cases, discontinuation of therapy with either tricyclic antidepressants or lithium was required. Elderly patients are especially prone to such reactions. Tricyclic antidepressants and antipsychotics mutually inhibit each other's metabolism, which can lead to a decrease in the seizure threshold and the development of seizures. Doses of these medications may need to be adjusted.

Fluoxetine and fluvoxamine increase the concentration of tricyclic antidepressants in the blood plasma.

Cimetidia and methylphenidate, as well as blockers of “slow” calcium channels, can slow down the metabolism of amitriptyline, increase its plasma concentrations and, therefore, increase toxic effects.

Barbiturates and other inducers of microsomal liver enzymes, for example, rifampicin and carbamazepine, can increase the metabolism of tricyclic antidepressants, leading to a decrease in their plasma concentrations and a decrease in the anti-depressant effect.

Amitriptyline enhances the effect of antiparkinsonian drugs and other drugs that cause extrapyramidal reactions.

Quinine slows down the metabolism of amitriptyline.

Antifungal drugs, such as fluconazole and terbinafine, increase plasma concentrations of tricyclic antidepressants and increase their associated toxic effects.

Estrogens and oral contraceptives containing them may increase the bioavailability of amitriptyline. It may be necessary to adjust the doses of medications or discontinue one of them. Alcohol increases plasma concentrations of free amitriptyline and nortriptyline.

Pimozide and probucol may increase cardiac arrhythmias.

Phenytoin

Tricyclic antidepressants may increase serum concentrations of phenytoin and. accordingly, increase the risk of its toxic effects (ataxia, hyperreflexia, nystagmus, tremor).

Sibutramine

Prescription with sibutramine should be avoided (inhibits the reuptake of norepinephrine and serotonin), this combination increases the risk of developing central nervous system toxicity and the potentially fatal condition serotonin syndrome. Epidemiological studies conducted primarily in patients aged 50 years and older show an increased risk of bone fractures in patients receiving concomitant tricyclic antidepressants (amitriptyline) and selective serotonin reuptake inhibitors.

Antiviral drugs

The combination of amitriptyline with antiviral drugs may increase plasma concentrations of amitriptyline with the development of toxic effects, which necessitates careful monitoring of therapeutic and side effects when coadministered.

Nitrates

Decreased salivary secretion and dry mouth (blocking the action of acetylcholine) when taking amitriptyline may reduce the effect of sublingual nitrates.

Centrally acting muscle relaxants

Concomitant use with amitriptyline increases their effect.