What is Imipramine?
Imipramine is a tricyclic antidepressant.
What is Imipramine used for?
Imipramine is used to treat:
- All forms of depression (with anxiety and without it): major depression, depressive phase of bipolar disorder, atypical depression, depressive states;
- Panic disorder;
- Bed-wetting in children (aged 6 years and above).
Avoid taking Imipramine in case of:
- Hypersensitivity to any of the drug's components or other tricyclic antidepressants from the same group;
- Simultaneous intake of MAO inhibitors;
- Recent myocardial infarction;
- Violation of intracardiac conduction;
- Heart rhythm disorders;
- Manic episodes;
- Severely impaired renal function and/or liver disease;
- Urinary retention;
- Angle-closure glaucoma;
- Children up to 6 years for treatment of nocturnal enuresis, and up to 18 years for treatment of depression and panic disorder (lack of sufficient clinical experience).
Imipramine dosage and dosing frequency are determined individually depending on the nature and severity of symptoms. As with other antidepressants, it takes at least 2-4 weeks (maybe 6-8 weeks) to achieve a therapeutic effect. Treatment should start with a low dosage with gradual increase up to the lowest effective maintenance dosage.
Elderly people and children younger than 18 years should increase dosage with caution to achieve efficiency.
Imipramine dosage to treat depression
Outpatients 18-60 years:
The standard dosage is 25 mg of Imipramine 1-3 times a day. The dosage can be gradually increased up to 150-200 mg of Imipramine until the end of the first week of therapy. The standard maintenance dosage is 50-100 mg of Imipramine a day.
Hospital patients 18-60 years of age:
The starting dosage of Imipramine for hospital patients in severe cases is 75 mg a day. The dosage can be increased by 25 mg a day up to 200 mg of Imipramine a day (in exceptional cases, the daily dosage can be up to 300 mg).
People older than 60 years:
Treatment should be started with the lowest possible dosages in order to avoid possible side effects. The initial dosage may be gradually increased up to 50-75 mg of Imipramine a day. It is recommended to achieve optimal dosage for 10 days and maintain this dosage throughout the treatment period.
Imipramine dosage to treat panic disorder
Treatment should be started with the lowest possible dosages of Imipramine since people with panic disorder have an increased predisposition to side effects of the drug. Transient increase of anxiety at the beginning of treatment with antidepressants can be prevented by using benzodiazepine medications. Gradually decrease the dosage of benzodiazepine drugs with an improvement of anxiety symptoms. Imipramine dosage can be gradually increased up to 75-100 mg a day (in exceptional cases up to 200 mg). The minimum duration of treatment is 6 months. It is recommended to cancel Imipramine gradually at the end of treatment.
Imipramine dosage for children
Only children of 6 years and older should take the drug as a temporary adjuvant treatment of nocturnal enuresis with an exclusion of organic pathology.
The are following recommended dosages of Imipramine for children:
- 6-8 years old (with a body weight of 20-25 kg): 25 mg a day.
- 9-12 years (with a body weight of 25-35 kg): 25-50 mg a day.
- older than 12 years and with body weight above 35 kg: 50-75 mg a day.
Exceeding the recommended dosage is justified only in cases, where there is no satisfactory treatment effect after 1 week of treatment with lowest dosages of Imipramine.
The daily dosage for children should not exceed 2.5 mg/kg of body weight.
It is recommended to use the lowest dosage of the dosage range mentioned above. It is recommended to take a daily dosage of Imipramine after your meals at night before going to bed. If nocturnal enuresis is usually observed in the early evening hours, it is recommended to divide the daily dosage into two dosages - one for the afternoon and one at night. The duration of treatment should not exceed 3 months. The maintenance dosage can be reduced depending on a clinical effect of treatment. Imipramine should be withdrawn gradually after completion of treatment.
Most common symptoms of overdose with Imipramine are:
Nervous system: dizziness, lethargy, stupor, coma, ataxia, agitation anxiety, increased reflexes, muscle rigidity, convulsions.
Cardiovascular system: decrease in blood pressure, tachycardia, arrhythmias, conduction disorders, shock, heart failure, in very rare cases – heart failure.
Others: respiratory depression, cyanosis, vomiting, fever, sweating, mydriasis, oliguria or anuria.
Symptoms of overdosage can occur within 4-6 days. Children compared with adults are more susceptible to acute overdose, which should be considered dangerous and potentially fatal to them.
Seek immediate medical help, if you think you took too much of Imipramine or start to feel any of side effects listed above.
MAO Inhibitors: combination with MAO inhibitors should be avoided, as these two types of drugs have a synergistic effect and their peripheral noradrenergic effects can reach toxic levels (hypertensive crisis, hyperpyrexia, myoclonus, agitation, seizures, delirium, coma). For security reasons, Imipramine therapy should not be started earlier than 3 weeks after completion of therapy with MAO inhibitors (except for moclobemide – 24 hours break will be enough in this case). The period without drug therapy lasting three weeks should also be followed when transferring a patient from Imipramine to MAO inhibitors. Treatment with MAO inhibitors or Imipramine should start with small dosages with gradual increase while monitoring clinical effects.
Inhibitors of microsomal liver enzymes may lead to a decrease in metabolism of Imipramine when used in conjunction with the drug and thus lead to increased Imipramine concentrations in plasma. Inhibitors of this type include drugs that are not substrates for cytochrome P450 2D6 isoenzyme (cimetidine, methylphenidate), and drugs that are metabolized with this isoenzyme (i.e., many other antidepressants, phenothiazines, class Ic antiarrhythmics (propafenone, flecainide)). All antidepressants relating to selective serotonin reuptake inhibitors are inhibitors of cytochrome P450 2D6 isoenzyme of different power. That is why, be cautious combining Imipramine with these medications as well as to switch from selective serotonin reuptake inhibitors to Imipramine (and vice versa), particularly in cases with Fluoxetine (given the long half-life of the drug).
Tricyclic antidepressants may lead to an increase of antipsychotic medications concentration in blood.
Oral contraceptives, estrogens: decrease of antidepressants effectiveness and development of toxic effects of antidepressants is sporadically observed in women taking oral contraceptives or estrogen drugs together with tricyclic antidepressants. Thus, take this kind of drugs with Imipramine with caution. Lower the dosage of any of the drugs in case of toxic side effects.
Inductors of microsomal liver enzymes (alcohol, nicotine, meprobamate, barbiturates, antiepileptic drugs, etc.) increase metabolism of Imipramine and reduce its concentration in blood plasma and antidepressive effects.
Drugs with anticholinergic properties (eg, phenothiazines, drugs for the treatment of Parkinson's disease, blockers of H1-histamine receptors, atropine, biperiden) may increase side effects of Imipramine (eg, paralytic ileus). Combination therapy with these drugs requires medical supervision careful dosages adjustment.
Drugs suppressing the central nervous system: a combination of Imipramine with drugs that cause central nervous system depression (eg, opioids, benzodiazepines, barbiturates, drugs for general anesthesia) and alcohol leads to the substantial strengthening of the effects and side effects of these drugs.
Antipsychotic drugs may increase tricyclic antidepressants concentration in blood plasma, thereby increasing the risk of possible side effects. The dosage reduction may be required. The combined use of thioridazine and Imipramine can cause severe arrhythmia.
Thyroid hormones may increase the antidepressant effect of Imipramine and its side effects connected with a heart. Therefore, their combined use requires special care.
Cardiovascular sympathomimetic effects (mainly epinephrine, norepinephrine, isoprenaline, ephedrine, phenylephrine) increased under the influence of Imipramine.
Phenytoin: Imipramine reduces anticonvulsant effects of phenytoin.
Quinidine: in order to avoid the risk of arrhythmias and conduction disorders, tricyclic antidepressants should not be used in combination with Quinidine.
Indirect anticoagulants: tricyclic antidepressants inhibit the metabolism of anticoagulants and increase their half-life. It leads to an increased risk of bleeding.
Hypoglycemic agents: glucose concentration in blood plasma during treatment with Imipramine may vary. However, it is recommended to control glucose concentration in blood at the beginning and at the end of treatment.
Imipramine during pregnancy and lactation
Since there have been possible connections discovered between the use of tricyclic antidepressants and impaired fetal development, avoid using Imipramine during pregnancy.
Imipramine is excreted in breast milk, that is why it is not recommended to use the drug during breastfeeding.
Imipramine side effects
The following undesirable effects are not necessarily observed in all people. Some of the side effects depend on the drug's quantity when you decrease or increase Imipramine dosage. A number of side effects are difficult to distinguish from symptoms of depression (eg, fatigue, sleep disorders, agitation, anxiety, dry mouth).
Suspend Imipramine intake in case severe neurological or psychiatric reactions.
Elderly people are rather sensitive to the anticholinergic, neurological, psychiatric or cardiovascular effects. The ability to eliminate the drug from the body can be reduced, leading to a risk of increased concentration in blood.
Cardiovascular system: sinus tachycardia and ECG changes with no clinical significance (modifications of the T wave and ST segment) in patients with normal heart activity, orthostatic hypotension, arrhythmias, conduction abnormalities, palpitations, cardiac decompensation, increased blood pressure, peripheral vasospastic reactions.
Hematopoietic system: agranulocytosis, leukopenia, thrombocytopenia, purpura, eosinophilia.
Central nervous system: tremor, paresthesia, headache, dizziness, delirious confusion (especially in elderly patients with Parkinson's disease), disorientation and hallucinations, transition from depression to hypomania or mania, agitation, anxiety, increased anxiety, fatigue, insomnia, sleep disorders, libido and potency disorders, seizures, activation of psychotic symptoms, extrapyramidal symptoms, ataxia, aggression, myoclonus, speech disorder.
Sight and hearing: violation of accommodation, blurred vision, glaucoma, mydriasis, ringing in ears.
Digestive system: constipation, dry mouth, vomiting, nausea, paralytic ileus, stomach disorders, stomatitis, tongue damage, hepatitis.
Urinary system: urinary disorders.
Skin: increased sweating, allergic skin reactions (rash, urticaria), edema, photosensitivity, pruritus, petechiae, hair loss.
Endocrine system: breast enlargement, syndrome of inappropriate secretion of antidiuretic hormone, increase or decrease of glucose concentration in blood.
Metabolism and nutrition disorders: weight gain, anorexia, weight loss.
Other: hyperpyrexia, weakness, systemic anaphylactic reactions, including reduced blood pressure, allergic alveolitis (pneumonitis) with or without eosinophilia. There is an increased risk of bone fractures for people over 50 years old taking antidepressants.
There were reports of cases of suicidal thoughts and suicidal behavior after canceling the drug.
Keep out of reach of children at a temperature above 25 ° C (77 F).
There is a high risk of suicidal thoughts, self-harm, and suicide during a depression. People taking antidepressants should be under constant medical supervision until improvements are achieved because health improvement may be noted only after 1 or 2 weeks of treatment. According to general clinical experience, the suicide risk may be increased during early stages of treatment. Suicide rate increases among children and young persons under 24 years old.
Imipramine can be prescribed for other psychiatric conditions, which are also may be connected to an increased risk of suicides. Moreover, all these conditions can be accompanied by major depressive disorder.
People with suicide attempts in history or people with suicidal ideas before treatment have a higher risk of suicidal thoughts or suicide attempts during treatment with Imipramine. Therefore, such people required increased medical attention during treatment.
The therapeutic effect can be expected no earlier than 2-4 weeks after the beginning of treatment. As with other antidepressants, later onset of therapeutic effect means that the patient's suicidal aspirations will not be eliminated immediately, so the patient needs careful medical supervision to achieve significant improvements.
Maintenance dosage therapy should be continued for at least 6 months.
Imipramine intake should be withdrawn gradually, as abrupt discontinuation may cause withdrawal symptoms, such as nausea, headache, fatigue, restlessness, anxiety, sleep disorders, arrhythmia, extrapyramidal symptoms.
In the case of bipolar depression, Imipramine may contribute mania. The drug should not be used during manic episodes.
Like other tricyclic antidepressants, Imipramine reduces the seizure threshold. That is why people with epilepsy and seizure disorders in history require careful medical supervision and adequate anticonvulsant therapy.
Imipramine increases the risk associated with electroconvulsive therapy. Therefore, the drug is not recommended to be used for electroconvulsive therapy.
People with panic disorder may experience increased anxiety in the first few days of therapy. Increased anxiety usually passes spontaneously within 1-2 weeks of treatment. Benzodiazepine derivatives may be used if it is necessary to reduce anxiety.
People with psychosis may experience increased anxiety and agitation at the beginning of treatment with tricyclic antidepressants.
People with glaucoma, prostatic hyperplasia, and severe constipation require medical supervision during Imipramine therapy, as the treatment may lead to increased severity of these symptoms. Reduced tear fluid and accumulation of mucus discharge can lead to damage of the corneal epithelium in people using contact lenses.
Imipramine should be used with caution in case of ischemic heart disorder, abnormal liver and kidney function and diabetes mellitus (changes in blood glucose concentrations).
Treatment of patients with adrenal tumors (pheochromocytoma or neuroblastoma) requires special care, as Imipramine may trigger the development of the hypertensive crisis.
Treatment of patients with hyperthyroidism and patients treated with thyroid hormone drugs requires careful medical supervision, taking into account the increased risk of possible cardiovascular adverse reactions.
Given the increased risk of arrhythmias and lower blood pressure during general anesthesia, the anesthesiologist should be informed before the surgery that the patient is taking Imipramine.
Long-term treatment with antidepressants may increase a risk of dental caries. Regular dental checkups are recommended in this case.
Side effects may be more severe in nature in elderly and younger people, especially at the beginning of treatment. Lower Imipramine dosage if you experience unpleasant side effects.
Imipramine causes photosensitivity, that is why try to avoid exposure to direct sunlight during treatment.
Imipramine tablets, film-coated, contain lactose monohydrate. Avoid drinking alcoholic beverages during treatment with Imipramine.
It is recommended to monitor the following indicators before and during Imipramine treatment:
- Arterial pressure (especially in patients with unstable circulation or hypotension);
- Liver function (especially in patients with liver disease);
- Peripheral blood indicators (immediately after increase in body temperature or in case of laryngitis, since they may be a symptom of leukopenia and agranulocytosis );
- ECG (in elderly patients and patients with heart disease).
Avoid driving a car or working with potentially dangerous equipment at the beginning of treatment with Imipramine, when your body reaction to the drug is not yet known.
These restrictions are determined individually by your doctor later during treatment.
Use of Imipramine for elderly people.
Imipramine may cause the anticholinergic (delirious) syndrome in people of advanced age, which passes in a few days after canceling the drug.
Side effects may be more severe in nature in elderly people. Therefore, lower dosages should be used especially at the beginning of treatment.
Imipramine for children
Children until 6 years old should avoid taking the drug to treat nocturnal enuresis. Children until 18 years old should avoid taking the drug to treat depression and panic disorder.