Modern analogues of "amitriptyline", their comparison and reviews. Complications and side effects of amitriptyline Is amitriptyline a hormonal drug or not?
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 cessation of 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.
Pharmacology
An antidepressant from the group of tricyclic compounds, a derivative of dibenzocycloheptadine.
The mechanism of antidepressant action is associated with an increase in the concentration of norepinephrine in synapses and/or serotonin in the central nervous system due to inhibition of the reverse neuronal uptake of these mediators. With long-term use, it reduces the functional activity of β-adrenergic receptors and serotonin receptors in the brain, normalizes adrenergic and serotonergic transmission, and restores the balance of these systems, disturbed during depressive states. In anxiety-depressive conditions, it reduces anxiety, agitation and depressive symptoms.
It also has some analgesic effect, which is believed to be associated with changes in the concentrations of monoamines in the central nervous system, especially serotonin, and effects on endogenous opioid systems.
It has a pronounced peripheral and central anticholinergic effect due to its high affinity for m-cholinergic receptors; strong sedative effect associated with affinity for histamine H1 receptors and alpha-adrenergic blocking effect.
It has an antiulcer effect, the mechanism of which is due to the ability to block histamine H2 receptors in the parietal cells of the stomach, as well as to have a sedative and anticholinergic effect (in case of gastric and duodenal ulcers, it reduces pain and helps accelerate the healing of ulcers).
Efficacy for bedwetting appears to be due to anticholinergic activity leading to increased bladder distensibility, direct β-adrenergic stimulation, and α-adrenergic agonist activity accompanied by increased sphincter tone and central blockade of serotonin uptake.
The mechanism of therapeutic action for bulimia nervosa has not been established (possibly similar to that for depression). Amitriptyline has been shown to be clearly effective against bulimia in patients both without and with depression, while a decrease in bulimia can be observed without a concomitant decrease in depression itself.
During general anesthesia, it reduces blood pressure and body temperature. Does not inhibit MAO.
The antidepressant effect develops within 2-3 weeks after the start of use.
Pharmacokinetics
The bioavailability of amitriptyline is 30-60%. Plasma protein binding 82-96%. V d - 5-10 l/kg. Metabolized to form the active metabolite nortriptyline.
T1/2 - 31-46 hours. Excreted mainly by the kidneys.
Release form
10 pieces. - contour cell packaging (5) - cardboard packs.
50 pcs. - polymer jars (1) - cardboard packs.
Dosage
For oral administration, the initial dose is 25-50 mg at night. Then, over 5-6 days, the dose is individually increased to 150-200 mg/day (most of the dose is taken at night). If there is no improvement during the second week, the daily dose is increased to 300 mg. When signs of depression disappear, the dose is reduced to 50-100 mg/day and therapy is continued for at least 3 months. In elderly patients with mild disorders, the dose is 30-100 mg/day, usually 1 time/day at night; after achieving a therapeutic effect, they switch to the minimum effective dose - 25-50 mg/day.
For nocturnal enuresis in children aged 6-10 years - 10-20 mg/day at night, in children aged 11-16 years - 25-50 mg/day.
IM - the initial dose is 50-100 mg/day in 2-4 injections. If necessary, the dose can be gradually increased to 300 mg/day, in exceptional cases - up to 400 mg/day.
Interaction
When used simultaneously with drugs that have a depressant effect on the central nervous system, a significant increase in the inhibitory effect on the central nervous system, hypotensive effect, and respiratory depression is possible.
When used simultaneously with drugs that have anticholinergic activity, the anticholinergic effects may be enhanced.
With simultaneous use, it is possible to enhance the effect of sympathomimetic drugs on the cardiovascular system and increase the risk of developing heart rhythm disturbances, tachycardia, and severe arterial hypertension.
When used simultaneously with antipsychotics (neuroleptics), metabolism is mutually inhibited, and the threshold for convulsive readiness decreases.
When used simultaneously with antihypertensive drugs (with the exception of clonidine, guanethidine and their derivatives), the antihypertensive effect and the risk of developing orthostatic hypotension may be increased.
When used simultaneously with MAO inhibitors, a hypertensive crisis may develop; with clonidine, guanethidine - it is possible to reduce the hypotensive effect of clonidine or guanethidine; with barbiturates, carbamazepine - the effect of amitriptyline may be reduced due to an increase in its metabolism.
A case of the development of serotonin syndrome with simultaneous use with sertraline has been described.
When used simultaneously with sucralfate, the absorption of amitriptyline decreases; with fluvoxamine - the concentration of amitriptyline in the blood plasma and the risk of developing toxic effects increases; with fluoxetine - the concentration of amitriptyline in the blood plasma increases and toxic reactions develop due to inhibition of the CYP2D6 isoenzyme under the influence of fluoxetine; with quinidine - the metabolism of amitriptyline may be slowed down; with cimetidine - it is possible to slow down the metabolism of amitriptyline, increase its concentration in the blood plasma and develop toxic effects.
When used simultaneously with ethanol, the effect of ethanol is enhanced, especially during the first few days of therapy.
Side effects
From the central nervous system and peripheral nervous system: drowsiness, asthenia, fainting, anxiety, disorientation, agitation, hallucinations (especially in elderly patients and patients with Parkinson's disease), anxiety, motor restlessness, manic state, hypomanic state, aggressiveness, disturbance memory, depersonalization, increased depression, decreased ability to concentrate, insomnia, nightmares, yawning, activation of symptoms of psychosis, headache, myoclonus, dysarthria, tremor (especially of the hands, head, tongue), peripheral neuropathy (paresthesia), myasthenia gravis, myoclonus , ataxia, extrapyramidal syndrome, increased frequency and intensification of epileptic seizures, changes in the EEG.
From the cardiovascular system: orthostatic hypotension, tachycardia, conduction disturbances, dizziness, nonspecific changes on the ECG (ST interval or T wave), arrhythmia, blood pressure lability, intraventricular conduction disturbances (widening of the QRS complex, changes in the PQ interval, bundle branch block ).
From the digestive system: nausea, heartburn, vomiting, gastralgia, increased or decreased appetite (increased or decreased body weight), stomatitis, change in taste, diarrhea, darkening of the tongue; rarely - impaired liver function, cholestatic jaundice, hepatitis.
From the endocrine system: testicular swelling, gynecomastia, breast enlargement, galactorrhea, changes in libido, decreased potency, hypo- or hyperglycemia, hyponatremia (decreased vasopressin production), syndrome of inadequate ADH secretion.
From the hematopoietic system: agranulocytosis, leukopenia, thrombocytopenia, purpura, eosinophilia.
Allergic reactions: skin rash, itching, urticaria, photosensitivity, swelling of the face and tongue.
Effects due to anticholinergic activity: dry mouth, tachycardia, accommodation disturbances, blurred vision, mydriasis, increased intraocular pressure (only in individuals with a narrow anterior chamber angle), constipation, paralytic ileus, urinary retention, decreased sweating, confusion, delirium or hallucinations.
Other: hair loss, tinnitus, edema, hyperpyrexia, swollen lymph nodes, pollakiuria, hypoproteinemia.
Indications
Depression (especially with anxiety, agitation and sleep disorders, including in childhood, endogenous, involutional, reactive, neurotic, drug-induced, with organic brain damage, alcohol withdrawal), schizophrenic psychoses, mixed emotional disorders, behavioral (activity) disorders and attention), nocturnal enuresis (except for patients with bladder hypotension), bulimia nervosa, chronic pain syndrome (chronic pain in cancer patients, migraine, rheumatic pain, atypical pain in the face, post-herpetic neuralgia, post-traumatic neuropathy, diabetic neuropathy, peripheral neuropathy), migraine prevention, peptic ulcer of the stomach and duodenum.
Contraindications
Acute period and early recovery period after myocardial infarction, acute alcohol intoxication, acute intoxication with hypnotics, analgesics and psychotropic drugs, closed-angle glaucoma, severe disturbances of AV and intraventricular conduction (bundle branch block, AV block of the second degree), lactation period, children up to 6 years of age (for oral administration), children up to 12 years of age (for intramuscular and intravenous administration), simultaneous treatment with MAO inhibitors and a period of 2 weeks before the start of their use, hypersensitivity to amitriptyline.
Features of application
Use during pregnancy and breastfeeding
Amitriptyline should not be used during pregnancy, especially in the first and third trimesters, unless absolutely necessary. Adequate and strictly controlled clinical studies of the safety of amitriptyline during pregnancy have not been conducted.
Amitriptyline should be gradually discontinued at least 7 weeks before the expected birth to avoid withdrawal syndrome in the newborn.
In experimental studies, amitriptyline had a teratogenic effect.
Contraindicated during lactation. Excreted in breast milk and may cause drowsiness in nursing infants.
Use in children
Contraindication: children under 6 years of age (for oral administration), children under 12 years of age (for intramuscular and intravenous administration).special instructions
Use with caution for ischemic heart disease, arrhythmia, heart block, heart failure, myocardial infarction, arterial hypertension, stroke, chronic alcoholism, thyrotoxicosis, and during therapy with thyroid drugs.
During amitriptyline therapy, caution is required when suddenly moving to a vertical position from a lying or sitting position.
If you stop taking it abruptly, withdrawal syndrome may develop.
Amitriptyline in doses of more than 150 mg/day reduces the seizure threshold; the risk of developing epileptic seizures in predisposed patients should be taken into account, as well as in the presence of other factors that increase the risk of developing convulsive syndrome (including brain damage of any etiology, simultaneous use of antipsychotic drugs, during the period of ethanol withdrawal or drug withdrawal, having anticonvulsant activity).
It should be taken into account that patients with depression may experience suicide attempts.
Should only be used in combination with electroconvulsive therapy under close medical supervision.
In predisposed patients and elderly patients, it can provoke the development of drug-induced psychoses, mainly at night (after discontinuation of the drug, they disappear within a few days).
May cause paralytic ileus, primarily in patients with chronic constipation, the elderly, or those forced to bed rest.
Before performing general or local anesthesia, the anesthesiologist should be warned that the patient is taking amitriptyline.
With long-term use, an increase in the incidence of caries is observed. The need for riboflavin may increase.
Amitriptyline can be used no earlier than 14 days after discontinuation of MAO inhibitors.
Should not be used simultaneously with adrenergic and sympathomimetics, incl. with epinephrine, ephedrine, isoprenaline, norepinephrine, phenylephrine, phenylpropanolamine.
Use with caution simultaneously with other drugs that have anticholinergic effects.
Avoid drinking alcohol while taking amitriptyline.
Impact on the ability to drive vehicles and operate machinery
During the treatment period, you should refrain from potentially hazardous activities that require increased attention and rapid psychomotor reactions.
Formula: C20H23N, chemical name: 3-(10,11-Dihydro-5H-dibenzcyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine (as hydrochloride or embonate).
Pharmacological group: neurotropic drugs / antidepressants / tricyclic compounds, dibenzocycloheptadine derivative.
Pharmachologic effect: thymoleptic, anxiolytic, antidepressant, sedative.
Pharmacological properties
Amitriptyline inhibits the reuptake of neurotransmitters such as serotonin and norepinephrine by the presynaptic nerve endings of neurons, causing the accumulation of monoamines in the synaptic cleft and increasing postsynaptic impulses. With prolonged use, amitriptyline reduces the functional activity (causes desensitization) of serotonin and beta-adrenergic receptors in the brain, normalizes serotonergic and adrenergic transmission, and balances these systems, which are disturbed in depressive states. Blocks histamine and m-cholino receptors of the central nervous system. It is well and quickly absorbed from the gastrointestinal tract when taken orally. The bioavailability of amitriptyline depends on the route of administration and ranges from 30 to 60%, and its metabolite, nortriptyline, is 46–70%. In the blood, the maximum concentration after oral administration will be within 2.0–7.7 hours. Treatment blood levels for amitriptyline are 50-250 ng/ml, for nortriptyline - 50-150 ng/ml. Amitriptyline is 95% bound to blood proteins. Both amitriptyline and nortriptyline easily penetrate through various barriers, including placental, blood-brain, and also penetrate into breast milk. The half-life of amitriptyline is 10–26 hours; for nortriptyline it is 18–44 hours. In the liver, amitriptyline is biotransformed (hydroxylation, demethylation, N-oxidation occurs) and forms active -10-hydroxy-amitriptyline, nortriptyline and inactive metabolites. It is excreted by the kidneys (mainly in the form of metabolites) within several days. In anxiety-depressive conditions, amitriptyline reduces agitation, anxiety and depressive symptoms. Within 2 to 3 weeks from the start of treatment, an antidepressant effect will develop. If you suddenly stop taking amitriptyline after long-term therapy, withdrawal syndrome may develop.
Indications
Amitriptyline is used for depression of various origins, especially those in which there is severe anxiety and agitation (strong emotional arousal, accompanied by feelings of anxiety and fear and turning into motor restlessness, the need to move, or speech restlessness, often unconscious), including endogenous, neurotic, reactive, involutional, medicinal, with organic brain damage; schizophrenic psychoses; mixed emotional disorders; behavioral disorders; bulimia nervosa; childhood enuresis (except for children with bladder hypotension); chronic pain syndrome (neurogenic); migraine prevention.
Method of administration of amitriptyline and dose
Amitriptyline is taken orally and intramuscularly. The dosage regimen is set individually depending on tolerability and indications. Treatment should begin with the lowest effective dose and then increase over 5–6 days. Average doses for adults when taken orally: initial 25-50 mg, average daily - 150-250 mg, in 2-3 doses (the main part is prescribed at night). The maximum dose for outpatient treatment is up to 150 mg/day, in hospital - up to 300 mg/day, for elderly patients - up to 100 mg/day. Intramuscularly at a dose of 20–40 mg 4 times a day, injections are gradually replaced by oral administration. The course of treatment is no more than 6–8 months. For the treatment of nocturnal enuresis in children over 6 years of age: 12.5–25 mg at night (the dose should not exceed 2.5 mg/kg body weight). For chronic neurogenic pain (including long-term headaches) - from 12.5–25 mg to 100 mg/day.
Take amitriptyline orally during or immediately after meals, without chewing, with a small amount of water. When a stable therapeutic effect is achieved after 2 to 4 weeks, the dose can be gradually and slowly reduced to avoid withdrawal syndrome. If signs of depression reappear, the previous doses must be prescribed. When signs of depression disappear, the dose is reduced to 50-100 mg/day and this treatment is continued for at least 3 months.
If you miss your next dose of amitriptyline, you should immediately contact your doctor.
Amitriptyline should be used with caution in case of arrhythmia, coronary heart disease, heart block, myocardial infarction, heart failure, stroke, arterial hypertension, chronic alcoholism, thyrotoxicosis, and during treatment with thyroid medications. During treatment with amitriptyline, caution is required when suddenly moving from a sitting or lying position to an upright position. Withdrawal syndrome may develop if you abruptly stop taking it. Amitriptyline in doses of more than 150 mg/day lowers the seizure threshold; the possibility of developing epileptic seizures should be taken into account in patients predisposed to them, as well as in the presence of other factors that increase the possibility of developing a convulsive syndrome (including with the simultaneous use of antipsychotic drugs, brain damage of any etiology, during the period of withdrawal of drugs that have anticonvulsant activity or ethanol withdrawal). It must be remembered that patients with depression may have suicidal attempts (suicide attempts). Amitriptyline should only be used in combination with electroconvulsive therapy after close medical supervision. In predisposed patients, as well as in elderly patients, amitriptyline can provoke the development of drug-induced psychoses, which occur mainly at night (after discontinuation of the drug, they disappear within a few days). Amitriptyline can cause paralytic ileus, usually in patients who suffer from chronic constipation, as well as in elderly people or in patients who must remain in bed. Before using local or general anesthesia, it is necessary to warn the anesthesiologist that the patient is taking amitriptyline. With prolonged use of amitriptyline, an increase in the incidence of caries is observed. The need for riboflavin may increase. Amitriptyline can be used no earlier than 2 weeks after discontinuation of MAO inhibitors. Do not use together with adrenergic and sympathomimetics, including ephedrine, epinephrine, isoprenaline, phenylephrine, norepinephrine, phenylpropanolamine. Use cautiously with other drugs that have anticholinergic effects. During amitriptyline therapy, alcohol consumption should not be allowed. During treatment, you should refrain from potentially dangerous activities that require rapid psychomotor reactions and increased attention. It is not recommended to prescribe amitriptyline to patients with mania. If there is no improvement in the patient's condition within 1 month, it is necessary to reconsider the treatment tactics.
Contraindications and restrictions for use
Hypersensitivity, myocardial infarction, use of MAO inhibitors in the previous 2 weeks, decompensated heart failure, severe arterial hypertension, intracardiac conduction disorders, bladder atony, benign prostatic hyperplasia, pyloric stenosis, paralytic ileus, peptic ulcer of the stomach and duodenum in exacerbation, diseases blood, acute liver and/or kidney diseases with severe impairment of their function, children under 6 years of age (for injection forms - up to 12 years). Limit the use of amitriptyline for epilepsy, arrhythmia, coronary heart disease, heart failure, angle-closure glaucoma, intraocular hypertension, hyperthyroidism.
Use during pregnancy and breastfeeding
Amitriptyline is contraindicated during pregnancy. During treatment with amitriptyline, breastfeeding should be stopped.
Side effects of amitriptyline
Caused by blockade of peripheral m-cholinergic receptors: urinary retention, dry mouth, intestinal obstruction, constipation, blurred vision, increased intraocular pressure, accommodation paresis, increased sweating;
from the nervous system and sensory organs: headache, ataxia, dizziness, increased fatigue, irritability, weakness, drowsiness, nightmares, insomnia, tremor, motor agitation, paresthesia, EEG changes, peripheral neuropathy, dysarthria, impaired concentration, hallucinations, confusion, tinnitus;
from the cardiovascular system: orthostatic hypotension, tachycardia, arrhythmia, widening of the QRS complex on the ECG (impaired intraventricular conduction), lability of blood pressure, fainting, symptoms of heart failure, changes in the blood picture, including agranulocytosis, eosinophilia, thrombocytopenia, leukopenia, purpura;
from the digestive system: heartburn, nausea, vomiting, discomfort in the epigastrium, anorexia, increased activity of liver transaminases, gastralgia, taste disturbance, stomatitis, darkening of the tongue; from the metabolic side: changes in the secretion of ADH, galactorrhea, rarely - impaired glucose tolerance, hypo- or hyperglycemia;
from the genitourinary system: change in potency, glucosuria, libido, testicular swelling, pollakiuria;
allergic reactions: skin rash, angioedema, itching, urticaria;
others: hair loss, increased size of mammary glands in women and men, enlarged lymph nodes, increased body weight (with prolonged use), photosensitivity; withdrawal syndrome: headache, nausea, diarrhea, vomiting, irritability, increased excitability, sleep disturbance with vivid, unusual dreams (after long-term treatment, especially in high doses, if the drug is abruptly stopped).
Interaction of amitriptyline with other substances
Amitriptyline is incompatible with MAO inhibitors. Amitriptyline enhances the inhibitory effect on the central nervous system of antipsychotics, anticonvulsants, hypnotics and sedatives, anesthetics, analgesics, alcohol; interacts with other antidepressants, showing synergy. When used together with anticholinergic drugs and/or neuroleptics, the development of paralytic intestinal obstruction and febrile temperature reaction is possible. Enhances the hypertensive effects of catecholamines and other adrenergic stimulants, which increases the possibility of developing arrhythmias, tachycardia, and severe hypertension. May reduce the antihypertensive effect of guanethidine and drugs with a similar mechanism of action, and also reduce the effects of anticonvulsants. When used together with anticoagulants - derivatives of indanedione or coumarin - there is a risk of increasing the anticoagulant activity of the latter. Cimetidine increases the concentration of amitriptyline in plasma with the possible development of toxic effects, inducers of microsomal liver enzymes (carbamazepine, barbiturates) reduce it. Quinidine inhibits the metabolism of amitriptyline; estrogen-containing oral contraceptives may increase bioavailability. Concomitant use with disulfiram and other acetaldehyde dehydrogenase inhibitors may cause delirium. Probucol may increase arrhythmias. Amitriptyline may increase depression caused by glucocorticoids. When used together with drugs for the treatment of thyrotoxicosis, the possibility of developing agranulocytosis increases. Caution should be used when combining amitriptyline with baclofen and digitalis preparations.
Overdose
An overdose of amitriptyline causes convulsions, hallucinations, delirium, hypothermia, coma, extrasystole, cardiac conduction disturbances, and ventricular arrhythmia. Gastric lavage, fluid infusions, taking activated charcoal, laxatives, maintaining normal body temperature, symptomatic therapy, monitoring the functioning of the cardiovascular system for at least 5 days are necessary, since a relapse of disorders can develop after 2 days or even later. Forced diuresis and hemodialysis are ineffective.
Amitriptyline is a drug belonging to the group of non-selective monoamine uptake inhibitors, used in the presence of depression of various origins, as well as other diseases of the central nervous system and gastrointestinal tract.
Composition and release form
The active substance in this medicine is amitriptyline hydrochloride. The content of this component is: 11.32 mg, or 28.3 mg in each tablet or 1 ml of solution.
Among the auxiliary agents, it should be noted the presence of such compounds as: microcrystalline cellulose, lactose monohydrate, pregelatinized corn starch, colloidal silicon dioxide, purified medical talc, magnesium stearate.
The excipients in solutions are water for injection and dextrose. The release is carried out strictly according to the prescription of the attending physician.
Pharmacological action of Amitriptyline
This medicinal substance has a whole range of effects on the human body: antidepressant, analgesic, antihistamine, antiserotonin, and some others.
The antidepressant effect is due to the suppression of the reuptake of neurotransmitters: norepinephrine and serotonin, which leads to an increase in the concentration of these substances in the synaptic cleft. As a result of this, the process of transmission of nerve impulses from one neuron to another is normalized, which improves the functioning of the nervous system.
This effect is expressed in reducing the severity of depressive states, suppressing anxiety, improving mood and other positive effects.
The antihistamine effect is due to partial blocking of histamine receptors located in the parietal cells of the gastric mucosa. This circumstance affects the intensity of hydrochloric acid production and the acceleration of regenerative processes, which can have a positive effect in the presence of ulcers or hyperacid gastritis.
An increase in the concentration of serotonin in the synapses of the central nervous system is the reason for the onset of the analgesic effect. Perhaps there is also stimulation of the activity of internal opioid systems.
The drug can also be used in the presence of bulimia nervosa, and this disease does not necessarily have to be accompanied by depressive symptoms.
The antidepressant effect develops already after 2 or 3 weeks from the start of using Amitriptyline and lasts throughout the entire period of taking this medication.
Indications for use
Amitriptyline is prescribed if the following indications exist:
Depression of various origins, including severe anxiety, sleep pathology, and so on;
Organic lesions of the central nervous system, complicated by the presence of a depressive state;
As part of complex therapy for schizophrenia and psychosis;
Nocturnal enuresis;
Bulimia nervosa;
Chronic pain syndrome in patients with severe cancer;
Migraine conditions;
Peptic ulcer of the stomach and duodenum.
A specialist with appropriate experience should prescribe this remedy, as well as evaluate the effectiveness of its use. Uncontrolled use is fraught with negative consequences.
Contraindications for use
Amitriptyline cannot be prescribed in the presence of the following conditions:
Hypersensitivity to any component of the drug;
Simultaneous use of drugs - monoamine oxidase inhibitors;
Severe cardiac conduction disturbances;
Angle-closure glaucoma;
The patient's age is less than 6 years.
Relative contraindications are the following conditions: alcoholism, severe bronchial asthma, some forms of schizophrenia, epilepsy, severe angina, high blood pressure, intestinal obstruction, acute urinary retention in prostate adenoma and other conditions.
Treatment with Amitriptyline
Application, dosage and administration of Amitriptyline
The tablets should be taken after meals without chewing. You can drink the required amount of plain water. Adult patients with depression should be prescribed 25–50 mg once at night.
If there are positive dynamics, the dosage can be increased to 300 mg per day. It should be remembered that most of the medicine should be taken at night. The duration of therapy is determined by the attending physician and depends on the patient's response to the drug used.
In the form of solutions, Amitriptyline is used according to the following scheme: 10 – 30 mg of the drug is administered intramuscularly, up to 4 times a day. If necessary, the dose can be increased to 150 mg per day. After a couple of weeks, you should switch to using tablet forms.
Overdose
Signs of Amitriptyline poisoning: confusion up to coma, hyperthermia, drowsiness, drop in blood pressure, hallucinations, convulsions, vomiting, abnormal heart rhythm.
In this case, you need to stop using the medication, perform infusion therapy, and take all measures aimed at maintaining the functioning of vital organs.
Side effects
From the central nervous system: increased fatigue, weakness, dizziness, drowsiness, tinnitus, sleep pathology, convulsions, and so on.
From the digestive system: nausea, vomiting, heartburn, damage to the oral mucosa, discoloration of the tongue, stomach pain, liver damage.
Other side effects: allergic reactions, changes in the hemogram, abnormalities in the electrocardiogram, decreased libido and other undesirable manifestations.
Analogues
Analogs of the drug Amitriptyline are the following drugs: Amizol, Amirol, Amitriptyline hydrochloride, Apo-Amitriptyline, Saroten retard, Triptisol, Elivel.
Conclusion
When treating diseases of the central nervous system, it is extremely important to punctually follow all the doctor’s instructions, both in terms of the use of medications, and in relation to the regime of work and rest, nutrition, and so on.
Amitriptyline is a popular drug in psychiatry. It combines antidepressant, hypnotic and anti-anxiety effects and is recommended by the World Health Organization. But, in addition to the therapeutic effect, many side effects of amitriptyline have been recorded, which requires a detailed study of this drug.
Today, this tricyclic antidepressant is available in the form of pills with an amount of the active substance - amitriptyline hydrochloride - from 10 to 75 mg. The tablets are packaged in a plastic bottle, the coating is light pink. When the dragee is broken, the inner layer of a yellowish tint is visible. The drug also includes additional components - sucrose, lactose, calcium stearate, corn starch, gelatin, opadry white - the main component of the dense coating of Amitriptyline tablets.
The second possible form of release is capsules. The outer gelatinous shell is red-brown. Auxiliary components: shellac, talc, sucrose, titanium dioxide, povidone, stearic acid.
The last form, used primarily for acute manifestations of depressive disorders, is a solution (1%) in 2 ml ampoules. Externally absolutely transparent liquid without sediment or subsequent color change. Additional components: injection water, glucose. Amitriptyline injections can be administered intramuscularly, or drip therapy (intravenous) is used.
Side effects and contraindications of Amitriptyline
The principle of action of amitriptyline is the reuptake of neurotransmitters such as dopamine, norepinephrine, mainly serotonin, which are responsible for the depressive state of a person. This provides calming, anti-anxiety, sedative effects. Along with this, amitriptyline exhibits anticholinergic activity, which is the cause of a large number of side effects.
To reduce possible negative effects, at the beginning of therapy it is necessary to gradually increase the dose, and at the end, consistently discontinue the drug.
The following symptoms associated with anticholinergic effects occur:
- problems with urination, up to bladder atony;
- impaired visual function (blurry and defocused image near, photosensitivity);
- constipation, which without the necessary therapy develops into acute intestinal obstruction or paralysis;
- dilated pupils, agitation, feeling similar to intoxication, apathy (due to sedative effects, especially in large doses), lethargy;
- delirium (clouding of consciousness, attention, perception, emotions) - mainly in elderly patients;
- anticholinergic syndrome is extremely rare.
Other side effects include the following:
- impaired taste perception, dyspeptic disorders, constant hunger;
- development of allergies;
- changes in blood composition: thrombocytopenia (platelet deficiency), leukopenia (lack of leukocytes in plasma), eosinophilia (decreased concentration of eosinophils), hyponatremia (decreased number of Na ions), fluctuations in sugar levels;
- low blood pressure, tachycardia, other heart rhythm disorders, orthostatic collapse (problems with blood flow to the brain when changing body position, darkening of the eyes, dizziness or loss of consciousness);
- disturbances in liver function;
- in gynecology - decreased libido, potency, anorgasmia, gynecomastia (hypertrophic enlargement of the mammary glands), galactorrhea (spontaneous leakage of milk from the breast), ejaculation disorders;
- in neurology - extrapyramidal syndromes (spontaneous involuntary contractions of individual muscles), ataxia (inconsistency in skeletal muscle tension), neuropathy (mainly peripheral, manifested as increased sensitivity of the limbs, tingling or numbness of the hands, feet), dysarthria (pronunciation problems due to restrictions on the flow of nerve impulses to the speech organs);
- in psychiatry - mania, hypermania (typical for patients with thyroid dysfunction, affective or schizoaffective disorders), hallucinations, depersonalization.
Patients with epilepsy treated with Amitriptyline may experience seizures from taking small amounts of the antidepressant, which also applies to patients with traumatic brain injuries. In people without contraindications, seizures occur when large doses are administered intravenously.
An important side effect is the worsening of suicidal tendencies when the initial dose is increased. Because of this, it is recommended to start taking the drug in small quantities and only in the evening; gradually the dose can be increased by adding doses in the morning and afternoon. In case of acute manifestations of suicidal ideation due to depression, treatment should begin in a hospital setting.
The likelihood of suicide increases if you have the following diseases:
- astheno-depressive syndrome;
- depression with acts of self-blame;
- depersonalization.
Amitriptyline can affect the speed of reaction and perception, therefore, during therapy, it is not recommended to drive or perform complex work that requires significant concentration and poses a danger to life due to inattention.
The drug is contraindicated in the following pathologies:
- cardiovascular diseases: severe hypertension, decompensated heart disease, recovery after a heart attack;
- ulcers of the intestines and stomach, pyloric stenosis (insufficient size of the opening between the stomach and duodenum);
- glaucoma;
- atony (paralysis) of the bladder or intestines;
- pregnancy;
- manic phase;
- age up to 12 years;
- dysfunction of the prostate gland.
Drug addiction
In some countries (for example, in Ukraine) Amitriptyline is prohibited and included in the list of narcotic substances. This is due to the fact that patients, having experienced a temporary relief of symptoms of depression, can independently increase the dose to obtain a permanent effect. The effect on the central nervous system (CNS), in which a feeling of relaxation and some “inhibition” of consciousness is noted, leads to the fact that the patient can additionally drink a double or triple dose to induce a feeling of euphoria.
Some of the side effects are perceived as the first signs of drug addiction, but are not: tremors of the palms (involuntary trembling), dilated pupils, irritability, short temper, photosensitivity, intoxication.
There is also some physical dependence on the drug - when taken for more than 1 month, the body develops a persistent addiction to the antidepressant, and abrupt cessation of treatment can be reflected in the form of withdrawal syndrome. But this property is typical for many drugs, especially for drugs of a similar nature and other drugs whose course of treatment exceeds 3-5 months.
Possible consequences of consumption with alcohol
The principle of action of amitriptyline and alcohol is partially similar - “inhibition” of the central nervous system occurs. But when used together, these substances increase the degree of impact on the body. The result is severe intoxication due to severe side effects of the antidepressant or signs of overdose.
The most common symptoms are severe abdominal pain, vomiting, stool disorders, stomatitis, and changes in taste perception.
The load on the heart increases due to serious disturbances in its rhythm, which, under the influence of elevated temperature and nervous overexcitation, can lead to a stroke or heart attack.
The liver wears out quickly - the main metabolic reactions take place there, including the processing of toxins from alcohol and medications. The risk of developing toxic necrosis increases.
The kidneys excrete metabolites of Amitriptyline and ethyl alcohol, which, in turn, also increases the load on them. Therefore, disturbances in the function of the excretory system are possible, including the appearance of acute kidney injury (acute renal failure).
Other symptoms include confusion, confusion, hallucinations, irregular breathing, increased sweating, rash, redness or other allergic reactions.
In case of unintentional combination of Amitriptyline and ethyl alcohol, the patient must immediately rinse the stomach and take a detoxifier (the most common option is activated carbon). Next - carry out rehabilitation in the hospital under the guidance of an experienced specialist.
Contraindications during pregnancy and lactation
Amitriptyline is not prescribed during pregnancy due to its potential to affect fetal development, except in situations where no other alternative is available. Studies have shown that after childbirth a child may experience pathological drowsiness, irritability, tearfulness, and sometimes have problems with urination. This effect is due to the influence of one of the metabolites of the substance - nortriptyline.
This antidepressant is also not prescribed during lactation, although there is no specific data on the harmful effects on the newborn during breastfeeding. No more than 2% of the daily dose taken by the mother can enter the child’s body, which may manifest itself as drowsiness. Therefore, treatment with Amitriptyline during lactation is not prohibited, but in this case it is recommended to carefully monitor the child’s condition, especially in the first 4 weeks of life.
Amitriptyline withdrawal syndrome
Withdrawal syndrome is a pathological condition that occurs when a drug is abruptly stopped, especially with long-term use.
This is the body's reaction to a supporting substance and can cause the following symptoms:
- dizziness, headaches, photosensitivity, tinnitus;
- insomnia, nightmares;
- dyspeptic disorders, decreased salivation;
- emotional disturbances, panic;
- bradycardia (slow heart rate), tachycardia (increased heart rate).
Symptomatic treatment of withdrawal syndrome is recommended: taking sedatives, preferably herbal, cleansing the body, restoring electrolyte balance, consulting a gastroenterologist to get rid of gastrointestinal disorders, possible taking antihypertensive drugs (to equalize the heart rate), as additional strengthening procedures - physiotherapy, massage, oxygen therapy, etc. In cases of acute panic attacks or suicidal ideas, you will need to take antipsychotics.
The best preventive action for Amitriptyline withdrawal syndrome is gradual withdrawal of the drug, minimizing stress and other detrimental factors to the patient's health.
Instructions for use
The main principle on which the prescription of Amitriptyline is based is to gradually increase the daily dose of the drug to prevent the occurrence of side effects.
The initial dose is 50-75 mg of the active substance. It is recommended to add 25-50 mg every day. The standard dose at which the buildup stops is 150-250 mg (up to 300 mg if the patient has severe depression).
Vulnerable groups of patients (elderly, adolescents, people in primary care) and patients with mild depression may increase the dose less quickly, for example, adding 25 mg to the previous amount every 2-3 days.
In the presence of diseases that require quick results, it is possible to start therapy with higher levels, for example, 100 mg of the substance per day, but treatment must be carried out in a hospital setting.
If drug tolerance allows, it is possible to prescribe 400-450 mg of Amitriptyline, but only under the strict supervision of the attending physician.
In severe depressive states, injections (intramuscular) or drips (intravenously) are prescribed. Gradually replaced with tablets.
Patients over 55 and adolescents begin treatment with lower doses and increase them more slowly, with the exception of acute depressive disorders.
The effect of the drug is noticeable 2-4 weeks after reaching the “working” (150-200 mg) dose.
To avoid withdrawal syndrome, it is necessary to gradually reduce the amount of the drug taken at the same rate as the increase.
Amitriptyline is the most popular tricyclic antidepressant used to treat depressive disorders of varying severity. Despite the relatively easy absorption of the drug by the body, there is a long list of contraindications and special instructions that must be taken into account when prescribing and taking the drug. And under no circumstances should you self-medicate with this type of medication.
Apo-amitriptyline is a pharmaceutical drug that tends to suppress reverse...
This drug is produced in the form of tablets and solution for injection. In its instructions for use, the reader will be able to find all the necessary information regarding its dosages, side effects, contraindications, and so on. Let us immediately note that amitriptyline should under no circumstances be used by patients with certain malfunctions in the cardiovascular system. In this case we are talking about both myocardial infarction and hypertension, as well as decompensated heart failure. Various disorders of the normal functioning of the liver or kidneys are also considered to be a contraindication to the use of this drug. If a patient has atony of the bladder, individual intolerance to any components of this medication, diseases of the hematopoietic system, or enlargement of the prostate gland, then he should also stop taking amitriptyline. It is strictly contraindicated in case of exacerbation of a stomach or duodenal ulcer.
When using this medication, we must not forget that amitriptyline cannot be used along with all drugs. Often, when using this medication, various disorders of the central nervous system are noted, which every patient should be aware of. If the course of therapy is stopped very suddenly, this may cause withdrawal syndrome.
If we talk directly about the reviews that relate to this drug, then there are actually a lot of them. In about fifty percent of cases, people complain of side effects that occur within a day or two of treatment with this medication. Most often they express apathy and excessive drowsiness. Given the occurrence of such side effects, patients are forced to take this drug mainly before going to bed. There are also cases when patients complain about the same signs, while pointing to the fact that they continue to haunt them for more than two to three months. In such cases, the drug is most often replaced by another pharmaceutical agent. There are also reviews in which people confidently say that they did not experience a single side effect while using amitriptyline. The most common review is that this medication is not very well tolerated by the body, but it can cause completely different side effects in all people. Even if the body does not accept it, then this medicine can be replaced with another drug at any time.
When using this medication, it is recommended to be extremely careful when changing a lying position to a sitting or standing position. All movements should be performed smoothly. We also note the fact that in case of abrupt withdrawal of this medication, the occurrence of the so-called withdrawal syndrome is quite possible. Using this drug in a dosage of more than one hundred and fifty milligrams per day, there is a decrease in the threshold for convulsive readiness. It must be remembered that if a person is predisposed to convulsive conditions, then an attack of epilepsy can occur at any time. Such attacks can also occur in those patients who use certain antipsychotic medications.
We should not forget that patients suffering from depression may also experience suicide attempts. Amitriptyline can be used along with electroconvulsive treatment only under the constant supervision of a specialist. In older people, as well as citizens who are predisposed to the development of certain disorders, this medication can cause drug-induced psychoses. Most often, such psychoses occur at night. After stopping the medication, they disappear on their own within three to five days.
All those patients who have chronic constipation should be especially careful when using amitriptyline. The thing is that in this pathological condition, taking this medication can provoke the development of paralytic intestinal obstruction. The same phenomenon can also be observed in those patients who, for one reason or another, are bedridden. If a person is taking this medication and needs general or local anesthesia, he must inform the anesthesiologist of this fact. This medicine can be used no earlier than two weeks after a course of therapy with MAO inhibitors. Under no circumstances should this drug be used along with norepinephrine, epinephrine, phenylpropanolamine and other sympathomimetics.
While undergoing a course of amitriptyline therapy, it is very important that the patient leads a truly healthy lifestyle, in which, first of all, there should be no place for alcoholic beverages.
Contraindications to the use of this drug
This pharmaceutical product cannot be used by everyone, and this is because it has numerous contraindications for use. So, for example, it should never be prescribed to patients who are undergoing therapy with inhibitors
monoamine oxidases. You should also avoid using this drug if you have prostatic hypertrophy, bladder atony, paralytic ileus, or pyloric stenosis. Its use is also not recommended for glaucoma and myocardial infarction. It is very important not to use this medication during pregnancy or lactation. In childhood, it should be used only on the recommendation of a specialist. Extreme caution should be taken with this medication and all those patients who have arrhythmia, heart failure, coronary heart disease or various heart rhythm disorders.
Let us immediately draw the readers' attention to the fact that against the background of the use of apo-amitriptyline, very diverse side effects can make themselves known. This may include blurred vision, dry mouth, constipation, excessive sweating, urinary retention, dizziness, excessive drowsiness, ventricular arrhythmia, tremor, cardiac conduction disturbances, and so on. Various types of allergic reactions often make themselves known, accompanied by the appearance of not only a skin rash, but also itching. When using this pharmaceutical, it is very important to pay close attention to the available precautions for its use along with other drugs.
