Use of the substance Imipramine
Depressive states of various etiologies: asthenodepressive syndrome, depression (endogenous, involutional, menopausal, reactive, alcoholic), depressive states in psychopathy and neuroses, panic disorders, functional enuresis in children.
Contraindications
Hypersensitivity, hepatic-renal failure, ischemic heart disease, tachycardia, congestive heart failure, early post-infarction period, tendency to seizures, schizophrenia, epilepsy, glaucoma, prostate adenoma, bladder atony, pregnancy, children (up to 6 years).
Imipramine
Imipramine
(English
imipramine
, Latin
Imipraminum
) is a tricyclic antidepressant, used, among other things, in gastroenterology.
Imipramine is a chemical compound
The chemical name of imipramine is N-(3-dimethylaminopropyl)-iminodibenzyl hydrochloride or 5-(3-dimethyl-aminopropyl)-10,11-dihydro-5H-dibenzo-[b, f]-azepine hydrochloride. The empirical formula of imipramine is C19H24N2. Imipramine is a white crystalline powder, easily soluble in water and alcohol, soluble in acetone, insoluble in benzene and ether. The molecular weight of imipramine is 208.4 g/mol.
Imipramine is a drug
Imipramine is the international nonproprietary name (INN) of the drug. According to the pharmacological index, imipramine belongs to the group “Antidepressants”. According to ATC, imipramine is included in the group “N06 Psychoanaleptics”, subgroup “N06AA Non-selective monoamine reuptake inhibitors” and has the code N06AA02. Also, in the same subgroup there is the code “N06AA03 Imipramine oxide”.
Indications for use of imipramine
Imipramine is indicated for:
- depression (anxiety, with sleep disorders, neurotic, medicinal, with organic brain damage, with alcohol withdrawal syndrome, the depressive phase of bipolar disorder, atypical depression and others)
- panic disorders
- functional enuresis
Contraindications to the use of imipramine
Imipramine is contraindicated in:
- hypersensitivity to any component of the drug or other tricyclic antidepressants from the dibenzoazepine group
- together with MAO inhibitors and within two weeks after taking them
- initial recovery period after a heart attack
- angle-closure glaucoma
- intracardiac conduction disorders
- heart rhythm disturbances
- benign prostatic hyperplasia
- bladder atony
- paralytic ileus
- diseases of the liver and/or kidneys with severe impairment of their function
Procedure for using imipramine and dose
Imipramine (Melipramine) is available in the form of dragees, film-coated tablets for oral administration and a solution for intramuscular administration. The dose of imipramine should be individualized. The duration of therapy varies from two to eight weeks. Treatment begins with the minimum effective dose that corresponds to the specific disease. Below are the approximate doses: When taken orally
, the dose is gradually increased over 10–14 days to 150–250 mg per day and, when a clinical effect is achieved, gradually reduced to a maintenance dose of 50–150 mg. For mild depression - 75-150 mg per day, maintenance dose is 25-50 mg per day. For children over 6 years of age, doses are determined depending on age.
Intramuscularly
25 mg is administered 3 times a day along with 25 mg taken orally; the dose can be increased by 25 mg every day. After 1 week, they begin to reduce the dose to maintenance (25 mg per day) and take 50 mg orally. From the 13th day of treatment, take only 350 mg orally per day in 3 divided doses.
For enuresis, depending on age, 25-75 mg 1 time per day, an hour before bedtime.
Maximum daily doses
:
- when taken orally for adults on an outpatient basis - 200 mg
- in a hospital setting - 300 mg
- elderly patients - 100 mg
- children - 100 mg
Use of imipramine during pregnancy, breastfeeding and children
Imipramine is not recommended for pregnant women, nursing mothers and children under 6 years of age (injectable forms - up to 12 years).
Prohibited for use in the first trimester of pregnancy; in the second and third trimesters it is allowed only when absolutely necessary. Imipramine has been assigned a risk category for the fetus when used by pregnant women according to the FDA "N" (this medicine has not yet been classified by the FDA).
Use of imipramine in gastroenterology
Imipramine, like other tricyclic antidepressants, is used in gastroenterology, although somewhat less frequently than amitriptyline. Imipramine can be recommended for the following diseases and conditions of the digestive system:
- For functional heartburn and increased sensitivity of the esophagus to reflux, imipramine is recommended in doses of 50 mg per day; treatment is empirical, since there are no clinical studies (Sheptulin A.A.).
- Imipramine in low doses is used in the treatment of functional disorders of the biliary tract (Ardatskaya M.D.).
- Low doses of tricyclic antidepressants, in particular imipramine, help alleviate the painful manifestations of diabetic neuropathy - nausea, vomiting, pain. The starting dose is usually 10 mg 2 hours before bedtime; in the future, it is advisable to increase it to 25–50 mg (Shulpekova Yu.O.).
- The American Gastroenterological Association's 2020 update on functional heartburn guidelines notes that in a double-blind, placebo-controlled study of 83 patients with functional heartburn and a hypersensitive esophagus, patients were randomized to placebo or imipramine 25 mg daily at within 8 weeks. Although there was no difference in heartburn between the imipramine and placebo groups, significant improvements in quality of life were achieved with imipramine therapy (Fass R, Zerbib F, Gyawali CP)
The use of imipramine (daily dose 200 mg, course dose - 3600 mg) is provided for by the Standard of specialized medical care for irritable bowel syndrome without diarrhea (Order of the Ministry of Health of Russia dated December 24, 2012 No. 1420n).
It must be taken into account that imipramine can cause constipation (Plotnikova E.Yu.).
Trade names of drugs with the active substance imipramine
In the Russian Federation, medicines with the active substance imipramine are approved for use only* with a single brand - Melipramin (ZAO Egis Pharmaceutical Plant, Hungary).
Brands of imipramine in the USA are Tofranil, Tofranil-PM.
Information for US patients from the manufacturer (in English, pdf): Medication Guide - Tofranil-PM™ (imipramine pamoate) capsules Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions.
Note. * Based on information as of early 2022.
Imipramine has contraindications, side effects and application features; consultation with a specialist is necessary.
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Side effects of the substance Imipramine
From the nervous system and sensory organs: headache, dizziness, excessive sedation, paresthesia, tremor, convulsions, dysarthria, impaired coordination of movements, sleep disturbance, agitation, hallucinations, impaired accommodation.
From the cardiovascular system and blood (hematopoiesis, hemostasis): tachycardia, arrhythmia, orthostatic hypotension, leukocytosis or leukopenia, agranulocytosis.
From the gastrointestinal tract: dry mouth, constipation, hepatitis.
From the genitourinary system: urinary retention, gynecomastia, galactorrhea, decreased libido, impotence.
Other: weight gain, photosensitivity, hair loss, fever, hyperhidrosis
Precautions for the substance Imipramine
In the initial period of therapy, constant medical supervision of patients with suicidal tendencies is mandatory. During treatment, the consumption of alcoholic beverages is prohibited. It is recommended to monitor the cellular composition of peripheral blood and liver function. It should be prescribed 2 weeks (not earlier) after discontinuation of MAO inhibitors, starting with small doses - 25 mg/day. When used in patients with diabetes, dose adjustment of oral hypoglycemic drugs is necessary. Please be aware that the injection solution contains sulfites, which may cause or intensify reactions such as anaphylaxis.
In the initial period of therapy, it is necessary to refrain from driving vehicles and performing potentially hazardous types of work.
Imipramine
Patients with a history of suicidal behavior or patients with significant suicidal ideation before starting therapy are at increased risk of suicidal ideation or suicide attempts and therefore require careful monitoring during therapy.
A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with mental disorders found an increased risk of suicidal behavior with antidepressants compared with placebo.
Drug therapy should be accompanied by careful monitoring of patients, in particular high-risk patients, especially in the early stages of treatment and after dose changes.
Patients (and their caregivers) should be warned to monitor for any clinical worsening, suicidal behavior or thoughts, and unusual changes in behavior and to seek immediate medical attention if these symptoms occur.
The therapeutic effect can be expected no earlier than 2-4 weeks of treatment. As with other antidepressants, the delayed onset of therapeutic effect means that the patient's suicidal tendencies will not be eliminated immediately, so the patient needs careful medical monitoring until significant improvements are achieved.
Therapy with a maintenance dose of the drug should continue for at least 6 months and be discontinued gradually, since abrupt cessation of the drug can cause symptoms of “withdrawal syndrome” (nausea, headache, fatigue, restlessness, anxiety, sleep disorders, arrhythmia, extrapyramidal symptoms, especially in children). Behavioral disorders may occur in children receiving imipramine for the treatment of nocturnal enuresis.
In the case of bipolar depression, imipramine may contribute to the development of mania. The drug should not be used during manic episodes.
Like other tricyclic antidepressants, imipramine lowers the seizure threshold, so patients with epilepsy and spasmophilia or a history of epilepsy require careful medical monitoring and adequate anticonvulsant therapy.
Serotonin syndrome can occur when using drugs that inhibit the reuptake of serotonin (tricyclic and tetracyclic antidepressants, serotonin reuptake inhibitors, etc.) or block the metabolism of serotonin (MAO inhibitors). Serotonin syndrome can develop when they are combined or when combined with other drugs that enhance the effect of serotonin (L-tryptophan, pentazocine, meperidine, bromocriptine, dextromethorphan, etc.). Due to the risk of developing serotonin syndrome, caution is required when combining imipramine with such drugs, as well as when transferring a patient from antidepressants that are selective serotonin reuptake inhibitors to imipramine (or vice versa), especially in cases with fluoxetine (given the long T1/2 of this drug). Serotonin syndrome, which includes three groups of symptoms - motor, autonomic and mental disorders - develops within a few hours or days after starting treatment with a serotonin mimetic drug or increasing its dose. Treatment includes discontinuation of serotonergic agents and symptomatic measures.
Imipramine increases the risk associated with electroconvulsive therapy, therefore use of the drug during electroconvulsive therapy is not recommended.
As a paradoxical reaction, patients with panic disorders may experience increased anxiety in the first few days of therapy. Increased anxiety usually resolves spontaneously within 1-2 weeks, and benzodiazepine derivatives can be used to treat it if necessary.
In patients with psychosis, increased restlessness, anxiety and agitation may occur when starting treatment with tricyclic antidepressants.
Due to the presence of an anticholinergic effect, the use of imipramine requires careful medical supervision for glaucoma, prostatic hyperplasia and severe constipation, since treatment can lead to an increase in the severity of these symptoms. In patients who wear contact lenses, decreased tear production and accumulation of mucous discharge can lead to damage to the corneal epithelium.
Imipramine should be used with caution in patients with ischemic heart disease, impaired liver and kidney function, and diabetes mellitus (changes in blood glucose concentrations).
Treatment of patients with adrenal tumors (pheochromocytoma or neuroblastoma) requires special caution, since imipramine can provoke the development of a hypertensive crisis.
Treatment of patients with hyperthyroidism and patients using thyroid hormone preparations requires careful medical supervision, taking into account the increased risk of cardiovascular adverse reactions in these patients.
Given the increased risk of arrhythmia and decreased blood pressure during general anesthesia, the anesthesiologist should be informed before surgery that the patient is taking imipramine.
In some cases, the development of eosinophilia, leukopenia, agranulocytosis, thrombocytopenia and purpura has been reported during treatment with imipramine, so regular monitoring of blood test parameters is required.
Hyponatremia (especially in the elderly) is associated with the use of antidepressants of any type. The risk of hyponatremia should be considered if the patient experiences symptoms such as drowsiness, confusion, or convulsions.
