Amitriptyline 25 mg (50 tablets)
Amitriptyline is used to treat mental/mood problems such as depression. It may help improve mood and feelings of well-being, relieve anxiety and tension, help you sleep better, and increase your energy level. This medication belongs to a class of medications called tricyclic antidepressants.
Common brand names: Elavil, Endep, Vanatrip
One tablet contains the active substance – amitriptyline 25 mg (in the form of amitriptyline hydrochloride 0.0283 g)
Amitriptyline is used for
– depressive phases of mild, moderate and high severity with or without psychotic signs in all types of affective disorders, such as bipolar disorder, recurrent depressive disorder and organic affective disorder
– schizoaffective disorders of the depressive type; depression associated with schizophrenia (against the background of constant treatment with antipsychotics)
– depression, previously defined as reactive and neurotic depression: dysthymia, mixed anxiety-depressive disorder, depressive disorders that have arisen as a reaction to severe stress or are a manifestation of adjustment disorder
– depression that develops during treatment with reserpine, inorganic enuresis (i.e. primary), not accompanied by a hypotonic bladder, inorganic encopresis (fecal incontinence), anorexia nervosa, and irritable bowel syndrome
– used for long-term treatment of pain in complex therapy
– for the treatment of nocturnal enuresis in cases where organic pathology is excluded and other types of drug and non-drug treatment have no effect (it is used exclusively as a third-line therapy).
The drug is intended for use in adults.
The actual dose is individualized for each patient, and this dosage should be strictly adhered to.
The initial dose is usually 25-50 mg, taken before bedtime, then the doses are gradually increased depending on tolerance over 5-6 days to 150-200 mg daily, with the maximum part of the daily dose taken before bedtime. If the patient’s condition does not improve during the second week of therapy, the dose is increased to 300 mg per day. This dose is then gradually reduced until the symptoms of depression disappear, and reduced doses of 50-100 mg per day are usually taken for 3 months.
The therapeutic effect usually appears 7-10 days after starting treatment. Amitriptyline therapy can be considered ineffective only if there is no improvement in the patient’s condition after 3 weeks of treatment.
The onset of antidepressant action can be accelerated when amitriptyline is taken together with nortriptyline. In most cases, treatment with amitriptyline for more than 6-8 months is ineffective. Lithium preparations are more suitable to prevent the expected phase of intermittent depression. For this purpose, amitriptyline can be prescribed only to those patients for whom the use of lithium preparations is contraindicated.
For the treatment of chronic pain, the recommended daily dose is 50-100 mg of amitriptyline, which must be divided into several individual doses.
Elderly patients or patients with mild depressive syndrome receiving outpatient treatment are given lower doses of 50-100 mg as one daily dose at bedtime.
Before starting primary therapy with amitriptyline, it is necessary to perform an ECG procedure in order to exclude long QT interval syndrome. The dose must be increased gradually. The duration of the primary course of treatment is 3 months, with repeated courses of amitriptyline, a medical examination must be carried out every 3 months. In case of cancellation of amitriptyline, it must be stopped gradually.
The tablets must be swallowed whole, without chewing, drinking plenty of water.
In general, amitriptyline is well tolerated. These side effects include common side effects of the tricyclic group of antidepressants. Not all of them are associated with the use of amitriptyline, some of them are indicated with a similar pharmacological group. Since the antidepressant effect of amitriptyline may not appear during the first 2-4 weeks of treatment, patients should be monitored during this period.
The incidence of adverse reactions is estimated as follows: “very often” (> 1/10), “often” (from ≥ 1/100 to <1/10), “infrequently” (from> 1/1000 to <1/100) , “Rare” (> 1/10000 to <1/1000), “very rare” (<1/10000), “frequency not known” (cannot be determined from the available data).
Blood and lymphatic system disorders: bone marrow suppression, neutropenia, leukopenia, eosinophilia, purpura, and thrombocytopenia
Immune System Disorders: Skin rash, hives, photosensitivity, swelling of the face and tongue
Endocrine system disorders: syndrome of inappropriate release of antidiuretic hormone. Hyponatremia (with lethargy, confusion, or seizures) may be associated with inappropriate antidiuretic hormone secretion, and is most common in old age
Metabolic and nutritional disorders: rising or falling blood sugar, weight loss, increased appetite and weight gain
Mental disorders: delirium (in elderly patients), hallucinations, hypomania, mania, anxiety, insomnia, suicidal thoughts (were noted during treatment with amitriptyline or immediately after stopping treatment), decreased libido
Nervous system disorders: weakness, lethargy, fatigue, headache, confusion, impaired concentration, disorientation, insomnia, nightmares, numbness, tingling and paresthesia of the extremities, peripheral neuropathy, lack of coordination, ataxia, tremor, coma, convulsions, extrapyramidal symptoms, including abnormal involuntary movements and tardive dyskinesia, dysarthria (due to high doses), and neuroleptic malignant syndrome. Anticholinergic action includes hyperpyrexia.
Visual impairment: Mydriasis. Anticholinergic action includes blurry vision, increased intracranial pressure, and habits
Hearing impairment: tinnitus.
Cardiovascular disorders: hypotension, syncope, orthostatic hypotension, dizziness, hypertension, tachycardia, rapid heartbeat, myocardial infarction, arrhythmia, heart block, sudden cardiac death, stroke, ECG changes, including non-specific ECG changes, dose-dependent (usually without consequences ,) and changes in AV conductance. Arrhythmias, including QT prolongation and bidirectional tachycardia, and hypotension occur due to high dose or overdose.
Gastrointestinal disorders: nausea, stomach discomfort, vomiting, anorexia, stomatitis, taste disturbances, diarrhea, parotid swelling, black tongue. Anticholinergic effects include dry mouth, gastric obstruction, functional intestinal obstruction.
Liver and biliary tract disorders: rarely hepatitis (including changes in liver function, cholestasis and bile spillage) and liver necrosis.
Skin and subcutaneous tissue disorders: increased sweating, baldness and pruritis.
Kidney and urinary tract disorders: frequent urination. Anticholinergic effects include urinary retention and dilatation of the urinary tract.
Reproductive system disorders: testicular tumor, gynecomastia, breast augmentation, galactorrhea, erectile dysfunction
Research: long QT electrocardiogram.
Side effects for enuresis:
Changes in the behavior of children taking tricyclic antidepressants for the treatment of bedwetting have been noted. The dose for enuresis is much lower than that for depression, so side effects are rare. The most common of these are lethargy and anticholinergic effects. Another adverse reaction that is less common is mild sweating and hiccups. This indicates that the recommended dose has been exceeded.
Symptoms associated with the withdrawal of tricyclic antidepressants, especially after long-term use, include gastrointestinal diseases such as nausea; general somatic symptoms such as malaise, chills, headache, and increased sweating; irritability, restlessness, anxiety, and agitation; sleep disorders (insomnia and realistic dreams); parkinsonism or akathisia; hypomania or obsession (such cases are rarely reported, occurs within 2-7 days after stopping long-term treatment with tricyclic antidepressants); cardiac arrhythmia. These symptoms do not indicate drug dependence. Withdrawal symptoms are more common and more severe in children. Adverse reactions such as withdrawal symptoms, respiratory distress, and agitation have been reported in newborns whose mothers were taking tricyclic antidepressants in the last trimester of pregnancy.
Epidemiological studies, conducted mainly in patients 50 years of age and older, have demonstrated an increased risk of bone fracture in patients taking SSRIs and tricyclic antidepressants. The mechanism that increases this risk is not known.
Adverse reaction reporting
It is very important to report adverse reactions after registration of a medicine. This will allow you to control the balance of benefits and risks of the drug. Healthcare professionals must report adverse reactions using the yellow card scheme
Epidemiological studies conducted mainly in patients over 50 years of age and older show an increased risk of bone fractures in patients receiving selective serotonin reuptake inhibitors and tricyclic antidepressants. The mechanism leading to this risk is not clear.
– hypersensitivity to the active and auxiliary components of the drug
– hereditary fructose intolerance
– deficiency of the enzyme lactase
– glucose-galactose malabsorption
– acute intoxication with drugs that inhibit the central nervous system
– alcohol poisoning
– acute delirium
– paralytic intestinal obstruction (due to the anticholinergic effect of amitriptyline)
– pyloric stenosis
– concomitant therapy with MAO inhibitors (MAO inhibitors must be excluded from the intake at least 14 days before starting treatment with amitriptyline)
– children and adolescents up to 18 years old
Alcohol: Amitriptyline may increase the alcohol response and the alcohol-disulfiram reaction (antabuse). Delirium has been reported in patients taking amitriptyline with disulfiram.
Alpha-2-adrenergic receptor stimulants: the simultaneous use of apraclonidine and brimonidine should be avoided.
Anesthetics: Increased risk of hypotension and cardiac arrhythmias during anesthesia.
Analgesics: Increased anticholinergic side effects with nefopam; Increased analgesia with morphine. Increased risk of CNS toxicity when using tricyclic drugs with tramadol.
Antiarrhythmics: Other drugs that prolong the QT interval, including amiodarone, disopyramide, procainamide, propafenone, and quinidine, should be avoided due to the increased risk of QT prolongation and bidirectional tachycardia.
Antibacterial drugs: plasma concentration is reduced by rifampicin (reduced antidepressant effect). Concomitant use with linezolid may lead to CNS excitation and hypertension. An increased risk of ventricular arrhythmias with tricyclic drugs with moxifloxacin is a concomitant use.
Anticholinergics: An excessive anticholinergic effect may occur if tricyclic antidepressants are taken together with anticholinergics. Functional bowel obstruction, urinary retention, or acute glaucoma may occur, especially in elderly patients. Amitriptyline in the treatment of enuresis should not be taken with anticholinergic drugs.
Anticoagulants: Amitriptyline can increase or decrease anticoagulant activity – prothrombin time must be controlled.
Antidepressants: Antidepressants with different mechanisms of action can be taken with other drugs only after studying their possible drug enhancement and pharmacology. Monoamine oxidase inhibitors can potentiate the effects of tricyclic antidepressants such as amitriptidine, and seizures, hyperthermic crisis and death can occur. There should be at least 14 days between stopping MAOIs and starting amitriptyline, which must be administered carefully, and gradually increase the dosage. Fluoxetine inhibits Cyt P450 II D6, which is involved in the metabolism of some tricyclic antidepressants. It is necessary to monitor the increase in the level of the antidepressant in the plasma and the toxic effect if fluoxetine is taken simultaneously. Antidepressant dosage adjustment may be required. Reboxetine should be used with caution.
Once you stop taking tricyclic antidepressants, you should not start taking moclobemide for one week.
Antiepileptics: Tricyclic antidepressants can counteract the anticonvulsant effects of antiepileptic drugs (the seizure threshold is lowered). Carbamazepine may decrease the antidepressant effect of amitriptyline. Sodium valproate may increase plasma levels of amitriptyline.
Antifungal drugs: Fluconazole may increase the serum concentration of amitriptyline, increase the prolongation of the QT interval and increase the risk of developing bidirectional tachycardia.
Antihistamines: Increased effects of CNS depressants. Astemizole and terfenadine should be avoided due to the increased risk of prolonged QT interval and bidirectional tachycardia.
Antihypertensives: In general, the antihypertensive effect of antihypertensive drugs is enhanced by tricyclic antidepressants, but amitriptyline may block the antihypertensive effects of guanethidine, debrisoquine, betanidine, and clonidine. A sudden failure of amitriptyline in patients stabilized on a postganglionic blocking agent can cause severe hypotension. All antihypertensive therapy should be monitored after the tricyclic antidepressant is discontinued and during treatment. There is an increased risk of hypertension when clonidine is discontinued.
Antipsychotics: an increased risk of a prolonged QT interval and bidirectional tachycardia with sertindole, pimozide and sonapax – their concomitant use should be avoided. Plasma concentrations of phenothiazines and amitriptyline can be increased with simultaneous use. Antipsychotic medications can lower the seizure threshold and increase the risk of seizures.
Antivirals: Based on the known metabolism of amitriptyline, a protease inhibitor, ritonavir, may increase serum amitriptyline levels. Therefore, careful monitoring of therapeutic and side effects when these drugs are administered concurrently is recommended. Increased risk of ventricular arrhythmias when tricyclic antidepressants are taken with saquinavir – their combined use should be avoided.
Anxiolytics and hypnotics: enhanced sedation. It is recommended to be careful if patients are taking large doses of ethylchlorinol in parallel. Transient delirium has been reported in patients treated with 1 g of ethylchlorinol and 75 mg to 150 mg of amitriptyline.
Barbiturates and other CNS depressants: increased reaction. Barbiturates may decrease the antidepressant effect of amitriptyline.
Beta blockers: Increased risk of prolonged QT interval and bidirectional tachycardia with sotalol – concomitant use should be avoided.
CNS stimulants: Methylphenidate may increase the antidepressant effect of amitriptyline.
Diuretics: increased risk of orthostatic hypotension.
Dopaminergic drugs: Selegiline may potentiate the effects of tricyclic and hyperpyretic crises, severe seizures, and deaths. Tricyclic drugs should generally not be given to patients receiving selegiline or for at least two weeks after discontinuation. One week should elapse after you stop taking tricyclic antidepressants and start taking selegiline. Combined use with entacapone should be avoided.
Muscle relaxants: tricyclic antidepressants enhance the muscle relaxant effect of baclofen.
Nitrates: Reducing the effect of sublingual nitrates (due to dry mouth).
Estrogens and progestogens: Oral contraceptives counteract the antidepressant effect (but side effects may be increased due to increased plasma amitriptyline concentration).
Smoking: May reduce plasma amitriptyline concentration.
St. John’s wort: Tricyclic antidepressants should not be used with St. John’s wort. St. John’s wort can reduce plasma amitriptyline levels.
Amitriptyline should not be co-administered with sympathomimetic agents such as epinephrine, isoprenaline, norepinephrine, phenylephrine, phenylpropanolamine, and ephedrine due to increased pressor response to these agents (hypertension, cardiac arrhythmias, etc.), but local anesthetics with epinephrine are considered safe …
Thyroid hormone: May enhance the response of the tricyclic antidepressant, but may precipitate cardiac arrhythmias.
Caustic-healing agents: Cimetidine has been reported to reduce the hepatic metabolism of some tricyclic antidepressants.
Amitriptyline enhances the anticholinergic effect of drugs used to treat Parkinson’s disease, phenothiazine derivatives, thiazide diuretics and vasodilators.
Amitriptyline enhances the effects that narcotic analgesics and barbiturates have on the central system.
Amitriptyline impairs the response to disulfiram.
Amitriptyline potentiates the effect of alcohol (mainly vegetative disorders and poor health can occur), enhances the sympathomimetic and psychostimulatory effects.
Concomitant use with other serotonergic active substances (such as selective serotonin reuptake inhibitors (SSRI), selective serotonin-norepinephrine reuptake inhibitors (SNRI), monoamine oxidase (MAO) inhibitors, lithium drugs, tryptan, tramadol, linezolid, L-tryptophan) St. John’s wort – Hypericum perforatum) can lead to the development of serotonin syndrome. Therapy with amitriptyline in combination with any of these substances must be carried out under the close supervision of a physician. In any case, the administration of irreversible monoamine oxidase inhibitors should be discontinued at least 14 days before starting amitriptyline therapy.
Amitriptyline may increase the effectiveness of some antiarrhythmic drugs (grade 1 and 3).
Substances that alkalinize urine and methylphenidate enhance the effect of amitriptyline.
Amitriptyline reduces the antihypertensive effect of reserpine and guanethidine, reduces the activity of anticonvulsants.
Urine alkalizing drugs methylphenidate increase the effectiveness of amitriptyline.
The induction of enzyme synthesis caused by the intake of barbiturates leads to a decrease in the level of amitriptyline to the level of one twentieth.
When treating enuresis, do not combine amitriptyline with an anticholinergic drug.
The use of amitriptyline is not recommended in the following conditions, or the risk-benefit ratio should be carefully weighed: first trimester of pregnancy, coronary heart disease, heart failure, prostatic hypertrophy, urinary retention, any condition associated with tachycardia or heart rhythm disturbances.
It is forbidden to drink alcoholic beverages while taking amitriptyline!
During the period of taking amitriptyline, it is recommended to periodically monitor: blood pressure control, electrocardiogram (ECG), blood test control, liver function tests, electroencephalography (EEG) may be used.
Amitriptyline in doses above 150 mg / day reduces the threshold of seizure activity, therefore, the possibility of seizures in patients who are predisposed to this due to age or injury should be considered.
Amitriptyline should be used with caution in persons suffering from alcoholism, bronchial asthma, inhibition of bone marrow hematopoiesis, hyperthyroidism, schizophrenia (although when it is taken, there is usually no exacerbation of productive symptoms).
Treatment with amitriptyline in old age should be closely monitored, using minimal doses of the drug and gradually increasing them, in order to avoid the development of delirious disorders, hypomania and other complications.
Patients with a depressive phase of manic-depressive syndrome can go into a manic stage.
Suicidal attempts / suicidal thoughts
Depression is associated with an increased risk of suicidal thoughts and suicidal attempts. The risk exists until a stable remission occurs. Improvement may not be observed during the first weeks of treatment or more, so patients should be monitored by a physician until signs of improvement appear. In accordance with general clinical experience, the risk of suicide increases during the initial phase of the recovery period.
Other mental conditions for which amitriptyline is prescribed may also be associated with an increased risk of suicide. Therefore, during the treatment of patients with other mental disorders, the same precautions should be followed as with major depressive disorders, namely, patients should be under strict medical supervision.
Patients who have attempted suicide in history, or with a high degree of probability of suicidal thoughts before starting the use of amitriptyline, should be closely monitored during treatment, as they have a greater risk of suicidal thoughts or attempts at suicide. In adult patients with mental disorders, the risk of suicidal behavior is increased with antidepressants compared with placebo in patients under 25 years of age.
Patients (and their caregivers) should be warned about the need for monitoring and possible clinical deterioration, and if they develop suicidal behavior or thoughts, or unusual changes in behavior, seek immediate medical attention.
Hyperglycemia / Diabetes
Epidemiological studies have revealed an increased risk of diabetes mellitus in depressed patients who received tricyclic antidepressants. It is necessary to carefully monitor the level of blood glucose in patients with diagnosed diabetes mellitus or with risk factors for the development of diabetes mellitus who begin therapy with amitriptyline.
Prescribe cautiously to patients with diabetes mellitus
Serotonin syndrome can develop if tricyclic antidepressants are used concomitantly with other serotonergic active substances (see the section on drug interactions). Serotonin syndrome, which is caused by excess serotonin, can be fatal and includes the following symptoms:
– neuromuscular agitation (muscle twitching, hyperreflexia, myoclonus, muscle stiffness);
– vegetative changes (hyperthermia, tachycardia, changes in blood pressure, sweating, tremor, hyperemia, dilated pupils, diarrhea);
– change in mental state (anxiety, agitation, confusion, coma).
Therapy, in which serotonergic active substances are combined with amitriptyline, must be carried out under the close supervision of a physician. In case of development of serotonin syndrome, therapy with amitriptyline should be discontinued.
Due to the presence of lactose in the composition, the drug is contraindicated in patients with hereditary lactose intolerance, Lapp-lactase enzyme deficiency, glucose-galactose malabsorption.
Amitriptyline should only be prescribed by a healthcare professional with expertise in the treatment of persistent enuresis.
– before starting the primary therapy with amitriptyline, it is necessary to carry out an ECG procedure in order to exclude the syndrome of prolonged QT interval.
– when treating enuresis, do not take amitriptyline in combination with anticholinergics.
– suicidal thoughts and behavior can also develop with early antidepressant treatment for disorders other than depression; Therefore, when treating patients with depression, the same precautions should be followed when treating patients with enuresis.
Long QT syndrome
Cases of prolonged QT interval and arrhythmias have been reported in the post-marketing period. Caution should be exercised in patients with severe bradycardia, decompensated heart failure, or patients taking concomitantly QT-prolonging drugs. It is known that electrolyte imbalance (hypokalemia, hyperkalemia, hypomagnesemia) increases the proarrhythmogenic risk.
The use of amitryptyline is not recommended during pregnancy, especially in the I-trimester. Application is possible only after a careful comparison of the benefits and risks. To date, no phenomena have been reported about the development of developmental anomalies when taking therapeutic doses of amitriptyline.
It is not recommended to use the drug during breastfeeding, since the active substance penetrates in small quantities into breast milk. If the administration of the drug is inevitable during breastfeeding, it is recommended to stop feeding.
Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms
While taking amitriptyline, it is prohibited to drive vehicles, maintain mechanisms, high-rise and other types of work that require increased concentration of attention.
Symptoms: lethargy, agitation, psychomotor agitation with pronounced antimuscarinic effects, such as dry mouth, hot dry skin, dilated pupils, strabismus, lengthening of the QRS interval, tachycardia, urinary retention, enteral hypotension, hypothermia.
With more severe intoxication, the following symptoms are observed: ataxia, loss of consciousness, convulsions, myoclonus, hyperreflexity, arterial hypotension, depression of respiratory and cardiac activity with life-threatening arrhythmias, which can recur after recovery, serotonin syndrome. Overdose can be fatal.
Treatment: Patients must be hospitalized. Symptomatic and supportive therapy is carried out. Monitoring is necessary: ECG recording and blood pressure control. Shown by tube gastric emptying, as well as preparations of activated carbon. Even in the case of acidosis, 50 mmol of sodium bicarbonate must be injected intravenously