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Pharmacological properties

Imipramine; 5- (3-dimethylaminopropyl) -10,11-dihydro-5n-dibenzo- (b, f) azepine monohydrochloride is a derivative of dibenzoazepine. belongs to a group of drugs called tricyclic antidepressants. has a timoleptic effect, improves mood, reduces the feeling of sadness. It has a concomitant stimulating effect, reduces motor inhibition, increases the mental and general tone of the body. It has a central and peripheral m-anticholinergic, myotropic (antispasmodic), moderate antihistamine effect.

When used internally, imipramine is well absorbed in the gastrointestinal tract, bioavailability is 29–77%. It is quickly distributed in tissues, easily penetrates the BBB. Selectively accumulates in the brain, kidneys, and liver. The maximum concentration in blood plasma is achieved 1–2 hours after administration. Binding to blood plasma proteins - 76–95%.

Intensively metabolized in the liver. Within 24 hours, up to 40% of imipramine taken is excreted in the urine in the form of inactive metabolites, 1-2% is unchanged, and about 20% is excreted in the bile. The elimination half-life is 4–24 hours. The therapeutic concentration in the blood plasma is 0.05–0.16 mg / l, the toxic concentration is 0.7 mg / l, and the lethal is 2 mg / l.


In all forms of depression (with or without anxiety): deep depression, in the depressive phase of bipolar disorder, depression with an atypical course, depressive states, dysthymia;

with panic disorders;

with nocturnal enuresis (in children over 6 years of age): as a means of short-term additional therapy, if organic causes are excluded.


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Daily doses should be determined individually depending on the severity and origin of the symptoms. As with other antidepressants, to achieve an adequate therapeutic effect, a course of treatment of at least 2–4 weeks is necessary, sometimes 6–8 weeks. It is recommended to start Melipramine therapy in low doses and gradually increase the daily dose until a maintenance dose is achieved. During the treatment period, the minimum dose that has an effect should be determined; caution is required in determining the dose for elderly and adolescent patients (under 18 years of age).


Parenteral drug Melipramin is used to treat patients with depression in a state of severe excitement or when an oral route of administration is not possible. Depending on the condition of the patient, the doctor may prescribe the introduction of a solution for injection of Melipramine only for a short time, and then switch to taking the drug in the form of dragees.

Doses for adults

Depression. Outpatient treatment of patients begins on the basis of a daily dose of 25 mg in a dragee or 2 ml of injection solution (1-3 times a day) IM. The maximum daily dose for this method of administration is 100 mg. In the future, as the patients condition improves, you can switch to treatment with a tablet form of the drug.

This dose can be gradually increased to 150-200 mg / day for 1 week. The maintenance dose is 50-100 mg / day. In hospitalized patients with severe depression, a daily dose of 75 mg / day is started. This dose can be gradually increased by adding 25 mg each time to reach 200 mg / day. In exceptional cases, the daily dose may be increased to 300 mg / day.

Elderly patients (over 60 years old) and adolescents (under 18 years old). These patients are more susceptible to the drug, as a result of which they may have adverse reactions in response to standard doses for adults. Therefore, treatment of these patients should begin with the lowest dose that controls the symptoms of the disease. Further, a gradual increase in dose is possible until the daily intake is reached - 50–75 mg. It is recommended that the optimal dose be achieved within 10 days and continued treatment in the same dose.

Panic disorder.Patients with such disorders are more likely to develop side effects, so treatment should be started with the lowest possible dose. Transient attacks of greater anxiety observed at the very beginning of Melipramine therapy can be controlled with benzodiazepine derivatives. This adjuvant therapy is gradually withdrawn as symptoms of anxiety disappear. The daily dose of Melipramin is gradually increased to 75–100 mg / day (as an exception, to 200 mg / day). The course of treatment is long, at least 6 months. The course of therapy ends by gradually reducing the dose and discontinuing the drug.

Doses for children

The following treatment regimens are recommended: children aged 6–8 years (20–25 kg) - 25 mg / day; children 9–12 years old (25–35 kg) - 25–50 mg / day; older than 12 years (35 kg) - 50–75 mg / day.

Therapy in children is carried out mainly by Melipramine in the form of dragees.

If a low initial dose is ineffective, to achieve an adequate therapeutic effect, the drug is used in higher doses, but within the limits of the scheme, taking into account the age of the child. When treating children, it is necessary to ensure that the daily dose does not exceed 2.5 mg / kg body weight per day. In each scheme, the lowest effective dose from the indicated interval should be used. The daily dose can be prescribed in one dose at bedtime. If enuresis is noted in the early evening, it is recommended to divide the daily dose (one part - to the child in the afternoon in the afternoon, another - before going to bed). The duration of treatment should not exceed 3 months. The maintenance dose should be selected as the severity of symptoms decreases. Before the complete discontinuation of the drug, a gradual decrease in the daily dose is recommended.


Melipramine tablets should not be used:

during pregnancy and lactation;

with an allergy to imipramine or other ingredients of the drug;

allergies to other tricyclic antidepressants of the dibenzoazepine series;

in the treatment of MAO inhibitors;

in the presence of a history of heart attacks (myocardial infarction) or cardiac arrhythmias (arrhythmias);

severe kidney and / or liver disease;

with urinary retention (prostatic hypertrophy);

in the presence of narrow-angle glaucoma.

Melipramine Injection should not be administered to children under the age of 6 years.

Side effects

The most common side effects of the drug are drowsiness, postural hypotension, tachycardia and atropine-like symptoms: dry mouth, constipation, urinary retention, blurred vision, impaired accommodation, increased body temperature and intraocular pressure.

Other, less frequent, side effects are neurological: headache, peripheral neuropathy, tinnitus, extrapyramidal symptoms (tremor, ataxia, difficulty speaking, especially in the elderly), confusion, delirium;

epileptogenic effect: primarily in patients with epilepsy or with a tendency to seizures;

cardiovascular: rarely, mainly after administration of the drug in high doses to especially sensitive patients - arrhythmia, severe hypotension and / or vasospasm, which is manifested by blueness of the fingers of the extremities;

gastrointestinal: very rarely - hepatitis with impaired liver function, icteric skin and sclera, pain in the liver, metallic taste in the mouth, inflammation of the oral mucosa (stomatitis), nausea, vomiting and, in exceptional cases, paralytic ileus;

allergic skin reactions (after 14-60 days from the start of treatment): urticaria, angioedema, photosensitivity;

endocrine: an increase in the mammary glands, galactorrhea, complications of diabetes, a decrease in glucose tolerance, very rarely - a decrease in the production of antidiuretic hormone;

sexual disorders - decreased libido, impotence, painful ejaculation, orgasm disorder;

very rarely, mainly in the elderly, changes in peripheral blood counts during laboratory tests.

special instructions

The therapeutic effect of melipramine develops gradually - over 2-4 weeks from the start of treatment. therefore, supportive treatment should be continued for at least 3, sometimes up to 6 months, until a significant improvement in the patients condition occurs. Melipramine should be discontinued gradually - sudden withdrawal of therapy can lead to symptoms such as nausea, headache, discomfort, anxiety, sleep disturbance, arrhythmia, extrapyramidal symptoms, such as difficulty speaking, especially in children.

Before using Melipramin, it is necessary to determine the functional state of the liver, kidneys, cardiovascular system, blood glucose, blood pressure, and hemogram values. If electroshock therapy is used, Melipramine should not be administered.

When treating with MAO inhibitors, it is necessary to take a break of 3-4 weeks before using Melipramin. This prevents the occurrence of seizures, an increase in blood pressure or body temperature.

In the transition after the use of Melipramine to the use of MAO inhibitors, a break for several days should also be taken.

Throughout the course of treatment with Melipramine, you can not drink alcoholic beverages.

In the event of persistent constipation or difficulty urinating during treatment, the doctor should be informed.

It is necessary to be very careful if epileptic seizures are noted before or during treatment with Melipramine. It is possible that other drugs should be prescribed to prevent seizures.

Due to the sedative effect of Melipramin, when it is used, it is impossible to drive vehicles and work with mechanisms or engage in activities that require increased attention.


When using melipramine, it should be borne in mind that:

atropine and similar drugs increase the incidence of side effects of Melipramine;

central nervous system depressants and alcohol enhance the sedative effect of Melipramine; benzodiazepines and weak antipsychotics increase the sedative and anticholinergic effects of Melipramine;

enzyme stimulants (alcohol, nicotine, meprobamate, barbiturates, antiepileptic drugs) enhance the breakdown of imipramine, reduce its level in blood plasma and thus reduce its antidepressant effect;

cimetidine, methylphenidate, oral contraceptives, steroids, antipsychotics, selective serotonin uptake inhibitors reduce the breakdown of imipramine and therefore increase its antidepressant effect and toxicity;

tricyclic antidepressants increase the level of antipsychotic agents in blood plasma (due to competitive binding by liver enzymes);

thyroid hormones enhance the antidepressant effect of imipramine;

imipramine reduces the hypotensive effect of adrenergic blockers (e.g. guanethidine) and α agonists2adrenergic receptors (clonidine, methyldopa);

imipramine enhances the pressor effect of sympathomimetics (primarily epinephrine, norepinephrine);

anticholinergics (phenothiazine derivatives, antiparkinsonian drugs, antihistamines, atropine, biperiden): the combined use of any of these substances and imipramine can lead to the appearance of anticholinergic action, as well as to increase side effects (for example, paralytic intestinal obstruction). Patients receiving this combination therapy require constant monitoring, and doses for them should be selected carefully;

sympathomimetics (mainly epinephrine, norepinephrine, isoprenaline, ephedrine, phenylephrine): combined use with imipramine can lead to an increase in the effect on the cardiovascular system;

quinidine: the simultaneous use of this antiarrhythmic agent and tricyclic antidepressants should be avoided. During the period of combined therapy, the risk of impaired cardiac conduction and the occurrence of arrhythmia increases;

oral anticoagulants: tricyclic antidepressants can inhibit the catabolism of oral anticoagulants, which can lead to an increase in the half-life of the latter, and as a result, an increased risk of bleeding. It is recommended during treatment to monitor the concentration of prothrombin;

antidiabetic drugs: during the treatment with imipramine, changes in blood glucose concentration may occur. Regular monitoring of blood glucose levels is recommended at the beginning and at the end of treatment, as well as during the dose selection period.


Symptoms: dizziness, agitation, ataxia, convulsions, stupor, coma, mydriasis, sinus tachycardia, arrhythmia, av blockade, impaired repolarization, collapse (with high venous pressure), hypotension, respiratory depression, cyanosis, vomiting, fever.

Treatment: in case of suspicion of an overdose of imipramine, immediate hospitalization with constant monitoring for at least 72 hours is necessary. There is no specific antidote. Supportive and symptomatic therapy is indicated. Due to the anticholinergic effect, gastric emptying is delayed for ≥12 hours; therefore, first of all, it is necessary to remove the drug from the stomach. It is necessary to rinse the stomach or induce vomiting, take activated charcoal. It is necessary to monitor the indicators of the function of the cardiovascular system, as well as the gas and electrolyte composition of the blood. If necessary, anticonvulsant therapy is used (iv diazepam, phenytoin, phenobarbital, as well as inhaled anesthesia and muscle relaxants). You can use hardware breathing, an artificial pacemaker. Plasma substituting solutions are introduced, drip infusions of dopamine and dobutamine. The need for resuscitation is rare. Neither hemodialysis nor peritoneal dialysis is effective due to the low concentration of imipramine in blood plasma. Forced diuresis is also not effective due to the large volume of distribution of the drug. The use of physostigmine was associated with the occurrence of severe bradycardia, asystole and epileptic seizures; therefore, with an overdose of imipramine, the use of physostigmine is not recommended.

Storage conditions

At a temperature of 15–25 ° C.