Imipramine is a drug indicated for the treatment of depression. It is available as 10 mg, 25 mg, and 50 mg oral tablets and 75 mg, 100 mg, 125 mg, and 150 mg oral capsules. Imipramine is a tricyclic antidepressant (TCA) and elicits a positive effect on mood by preventing the reuptake of neurotransmitters serotonin and norepinephrine. The US Food and Drug Administration (FDA) approved Imipramine to treat depression in 1959.
Imipramine is also indicated to treat nocturnal enuresis (bed-wetting) in children. The non-FDA indications include neuropathic pain in diabetic patients, panic disorder, and urinary incontinence. The drug may increase sun sensitivity in some individuals. Hence, protective clothing and sunscreens are advised for patients taking the drug. Avoid sudden discontinuation of drug use as it may lead to withdrawal symptoms.
How Does Imipramine Work?
Imipramine acts by preventing the reuptake of neurotransmitters serotonin and norepinephrine. Lack of norepinephrine and serotonin activation of the postsynaptic neuron has been associated with depression. The concentration of these neurotransmitters in the synaptic cleft rises when the reuptake of these molecules is slowed. This has a knock-on effect on protein kinase signaling, which is thought to be a factor in the altered neurotransmission and brain physiology that alleviates the symptoms of depression.
What Is the Dosage of Imipramine?
The therapy dose with Imipramine starts at one 25 mg tablet up to three times daily. The dose of the medication will be adjusted based on the response to the treatment.
The dose of the medication will be altered based on considerations of age and weight in children and patients above the age of 65 years.
Imipramine administration should be as advised by the physician. The drug should not be suddenly discontinued. The doctor determines the duration of the therapy. It is important to adhere to the instructions carefully.
1. Suicidal Ideation: An increased incidence of suicidal ideation, self-injury, and suicide is linked to depression (suicide-related events). The first few weeks or more of treatment may not see improvement. Thus, patients should be cautiously watched until this happens. In the early phases of recovery, the risk of suicide may rise, according to common clinical experience.
Drug therapy should be accompanied by close patient monitoring, especially in the early stages of treatment and after dose adjustments. Patients (and their carers) should be informed that it is important to watch for any signs of clinical deterioration, suicidal behavior or thoughts, and odd changes in behavior and that they should seek medical attention immediately if any of these symptoms appear.
Patients' families and caregivers should be instructed to watch for the onset of sudden or severe mood change symptoms daily because changes may come suddenly. If such symptoms are severe, suddenly appear, or are not among the patient's presenting symptoms, they should be reported to the prescriber or healthcare provider.
2. Serotonin Syndrome: Serotonin syndrome, a potentially fatal condition, may arise from taking Imipramine and Buprenorphine/opioids together. Serotonin syndrome symptoms can include gastrointestinal issues, neuromuscular abnormalities, changes in mental status, and autonomic instability. Depending on the severity of the symptoms, therapy reduction or withdrawal should be considered if serotonin syndrome is suspected.
3. Pregnancy and Lactation: There is no proof that the medication is safe during pregnancy in humans. Tricyclic antidepressant use and negative consequences (developmental abnormalities) on the fetus have been linked to sporadic occurrences. When pregnant, treatment with Imipramine should be avoided unless the possible advantages outweigh the risks to the fetus. Imipramine is excreted in breast milk. It should not be given to nursing mothers unless necessary, in which case the mother should be counseled to stop breastfeeding.
What Is Depression?
Depression is a mood disorder that can cause a person to feel persistently sad or low and interfere with their daily life. There are many possible causes of depression, including genetic factors, brain chemistry, and stressful life events. It is not always clear what causes depression, but it is often a combination of these factors. Signs and symptoms of depression can vary from person to person. Still, they may include persistent feelings of sadness or low mood, loss of interest in activities that were once enjoyed, changes in appetite or weight, insomnia or excessive sleeping, fatigue, difficulty concentrating, feelings of worthlessness or guilt, and thoughts of death or suicide. Depression is treatable with medication, therapy, and lifestyle changes. Depending on the severity of the depression, treatment may involve a combination of these methods.
Learn More About Imipramine:
Before Starting Imipramine:
When and Why to Take Imipramine?
Imipramine is a member of the tricyclic antidepressant pharmacological class of medications. It is a prescription drug used to treat the symptoms of depression. It helps with symptoms of these mood changes.
Things to Inform The Doctor Before Taking Prescribe Imipramine:
Inform the doctor if any of the following conditions are present:
If hypersensitive to tricyclic antidepressants, Imipramine, or any other component of this medication.
Have severe liver disease.
Suffer from porphyria (a genetic condition of the red blood cells hemoglobin causing skin blisters, abdominal pain, and brain/nervous system disorders).
Have irregular heartbeats, heart blocks, or a recent heart attack.
Experience periods of increased and exaggerated behavior (mania).
Difficulty in passing urine.
Is taking medications to treat psychiatric conditions like Buprenorphine. If taken along with Imipramine, this medication can result in a condition called serotonin syndrome (symptoms include hallucinations, agitation, profuse sweating, increased body temperature, tremor, etc.), which requires medical attention.
Have increased pressure in the eye (glaucoma).
Has been on therapy with drugs belonging to the monoamine oxidase inhibitor (MAOI) class in the last 14 days. Examples include Phenelzine, Selegiline, Tranylcypromine, etc.
Have a history of epilepsy or brain damage.
Have low blood pressure or poor circulation.
Have severe kidney illness.
Have an overactive thyroid gland and are taking medications to treat thyroid conditions.
How Is Imipramine Given?
Imipramine is started with 25 mg dosing in adults, which will be further adjusted by the doctor based on the response to the medication. The tablet is usually taken at bedtime. Take the drug at around the same time every day, making it easier to remember the time of drug administration. Avoid consuming alcohol while taking this medication.
Things to Do After Starting Imipramine:
After Imipramine therapy is started, the doctor will monitor the blood levels and liver functions periodically. It is important to appear for the consultation at the scheduled appointment to assess the patient's response to the therapy and if any side effects are experienced.
What Are the Side Effects of Imipramine?
Some individuals may experience side effects after taking the medication. If these adverse effects appear, notify the doctor immediately. The list of side effects of Imipramine is as follows:
Dilation of pupils.
Changes in blood pressure.
Loss of appetite.
Ringing in the ears.
Liver damage (symptoms include yellowing skin or eyes, dark urine, severe abdominal discomfort, etc.).
The sudden discontinuation of Imipramine can lead to withdrawal symptoms. The symptoms include nervousness, anxiety, headache, irritability, etc. It is advised not to suddenly discontinue the drug use. Always talk to the doctor about any changes in the dose and follow the instructions carefully.
What Should Be Done if a Dose Is Missed?
Do not take a double dose to make up for a missed dose. If a dose is missed, take it as soon as it is recalled, followed by the next dose at the scheduled time.
What Should Be Done to Treat Imipramine Overdose?
If the patient or anyone else swallows many tablets at once, or you suspect a kid may have done so, call the casualty department of the local hospital or notify the doctor immediately.
Fast or irregular heartbeat, low blood pressure, lethargy, fits, coma, agitation, muscle rigidity, illness, or fever are all signs of an overdose.
How to Store Imipramine?
Keep the medication away from infants, pets, and children.
Store in a dry area at or below 25°C.
After the expiration date shown on the label, carton, or bottle, do not use this medication. The last day of that month is referred to as the expiry date.
Never dispose of medications in wastewater or household garbage. Find out from the pharmacist how to dispose of expired medications. These actions will aid in environmental protection.
Imipramine is indicated for the treatment of depression. Compared to other depressive states, endogenous depression has a higher chance of recovery. Before the best therapeutic results are seen, one to three weeks of treatment may be necessary.
Mechanism of Action:
Imipramine belongs to the dibenzazepine group of medications class. The exact mechanism of action is unknown. However, the drug is thought to block norepinephrine uptake at the nerve endings.
Hospitalized Patients: 100 mg orally per day in divided doses.
Maximum Dose: 300 mg/day.
Outpatients: 75 mg orally per day.
Maximum Dose: 200 mg/day.
Maintenance Dose: 50 to 150 mg/day.
Renal and Hepatic: Dosing adjustments may be required.
Geriatric (Major Depression): 30 to 40 mg orally in divided doses or at bedtime; the usual maximum dose is 100 mg/day. Doses greater than 75 mg/day are not appropriate for the elderly.
Imipramine increases serotonin- and norepinephrine-based neurotransmission, comparable to other monoamine-targeted antidepressants. The serotonin reuptake transporter has a far higher affinity for Imipramine than the norepinephrine reuptake transporter, despite inhibiting both.
Along with reducing depressive symptoms, this regulation of neurotransmission causes a wide range of changes in the structure and function of the brain. Increases in hippocampus neurogenesis and a decreased downregulation of this process in response to stress are two modifications. These suggest that brain-derived neurotrophic factor signaling is a crucial component of the antidepressant effect, albeit it is unclear how this is connected to the increase in monoamine neurotransmission. The brain's adrenergic receptors may also be down-regulated by serotonin reuptake-targeting drugs like Imipramine.
The pharmacokinetics of the drug are discussed below:
About 95 % of the orally administered drug is absorbed and reaches systemic circulation. Due to the substantial inter-individual variability, the bioavailability of the drug ranges from 29 to 77 %. Normal peak plasma concentration occurs two to six hours after oral treatment. The presence of food does not affect absorption.
Imipramine shows 60 to 96 % protein binding with lipoproteins, albumin, and -1-acid glycoprotein. The drug's apparent volume of distribution is considerable, ranging from 10 to 20 L/kg. The medication builds up in the brain at concentrations 30 to 40 times higher than in the bloodstream.
The liver primarily metabolizes Imipramine. Desipramine, an active metabolite of the drug, is formed by the enzymes CYP1A2, CYP3A4, and CYP2C19. Imipramine taken orally is eliminated unaltered in less than 5 % of cases.
Imipramine is excreted in the urine, with around five percent of the drug as the parent compound.
The active ingredient in Imipramine tablets is Imipramine hydrochloride or Imipramine Pamoate.
The inactive ingredients include carnauba wax, gelatin, colloidal silica, maize starch, lactose, magnesium stearate, polyvidone, stearic acid, and sucrose.
Warnings and Precautions:
Beers Criteria: Due to its strong anticholinergic and sedative effects, Imipramine should not be used in elderly patients, especially those with a history of fractures or falls (unless safer alternatives are not available), dementia, cognitive impairment, delirium or a high risk of developing delirium, patients at risk for syncope, and men with lower urinary tract symptoms or benign prostatic hyperplasia. There could be various adverse CNS effects, such as ataxia, bradycardia, syncope, orthostatic hypotension, falls, reduced psychomotor function, or a worsening of preexisting illness conditions. Avoid using three or more CNS-active medications simultaneously in any combination due to the increased risk of falling. If taken, caution is advised, and monitoring is suggested because SIADH or hyponatremia could develop or worsen.
Cardiovascular: Patients with cardiovascular disorders or a history of cardiac disease; monitoring arrhythmia and conduction delay may occur. Myocardial infarction, tachycardia, and cardiovascular toxicity are probable.
Concurrent Use: Avoid using products that include sympathomimetic amines (such as Epinephrine and Norepinephrine) (e.g., decongestants, local anesthetics)
Dermatologic: Photosensitization has been reported in some patients.
Endocrine: Cardiovascular toxicity may happen in hyperthyroid patients or those receiving thyroid medication. Blood sugar levels have been noted to rise or fall.
Hematologic: There may be pathological neutropenia; discontinue treatment in such cases.
Neurologic: A stroke could happen. Patients with a history of seizures should use it cautiously since the medicine may lower their seizure threshold.
Ophthalmic: Patients with anatomically narrow angles who do not have a patent iridectomy may have worsening of their angle-closure glaucoma.
Psychiatric: Patients with cyclic disorders are more likely to experience manic or hypomanic episodes; discontinuation may be required. Schizophrenia patients may experience psychotic activation; dosage adjustment may be necessary.
Special Populations: Elderly patients are at increased risk of developing cardiac abnormalities
Surgery: Stop the medication before any surgical procedures.
Imipramine is contraindicated in the following conditions:
Hypersensitivity to Imipramine or any other drug belonging to the dibenzazepine class.
Concurrent administration with an MAOI (monoamine oxidase inhibitor) or use within 14 days of discontinuing an MAOI.
During the acute recovery phase of myocardial infarction.
Overdosage may result in death for drugs in this class of medications. Intentional tricyclic overdose is often accompanied by the consumption of many drugs, including alcohol. It is advised that the doctor contact a poison control center for the most up-to-date information on treatment because the management is complicated and constantly changing. After a tricyclic overdose, toxicity symptoms and signs start to appear quickly. So, as quickly as feasible, hospital supervision is needed.
Adults are reportedly less vulnerable to an acute overdose of Imipramine than children. Acute overdoses should always be taken seriously and may be lethal, especially in infants and young children.
Clinical Studies for Imipramine:
A controlled study to assess the effect of Imipramine was conducted in which all of the subjects involved in the trial were outpatients, and anyone displaying severe agitation or extensive retardation, as well as those who had a high risk of suicide, were immediately eliminated because they had been admitted for inpatient care.
Four 25 mg tablets were administered on the first and second days of treatment; by the fifth day, the dosage had been raised to six, eight, and ten tablets per day. Weekly visits were made to the patients, and this dosage was continued for four weeks.
Of the treatment of the 55 endogenous depression cases, 27 received Imipramine, and 28 received a placebo. Of subjects administered Imipramine, 20 showed a positive response, whereas seven responded poorly. In contrast, six people did well, and 22 did poorly on the placebo.
Twenty of the 42 cases of reactive depression received a placebo, and 22 received Imipramine. Among those who received Imipramine, 13 exhibited improvement, and nine did not; among the 20 controls, four did so, and 16 had subpar results.
Twenty of the 27 cases of endogenous depression treated with Imipramine involved women and seven involved men. Six of the seven men and fourteen of the twenty women had successful outcomes. 9 out of 14 (women) of the 22 reactive depression cases receiving Imipramine responded well, as opposed to 4 out of 8 cases (men) in the control group.
Lower doses than those typically recommended for either the tricyclic antidepressant or the other medication may be necessary when using tricyclic antidepressants concurrently with medications that can inhibit cytochrome P450 2D6.
An increased tricyclic antidepressant (TCA) dose is necessary if any other medications are removed from co-therapy. When a TCA is taken along with a medication known to be a P450 2D6 inhibitor, it is preferable to monitor the TCA plasma levels.
The plasma concentration of Imipramine may rise when the medication is given concurrently with hepatic enzyme inhibitors such as Cimetidine and Fluoxetine, and fall when the medication is given concurrently with hepatic enzyme inducers (such as barbiturates and Phenytoin). Adjusting the dosage of Imipramine may therefore be necessary.
The atropine-like effects could intensify in vulnerable patients or those on anticholinergic medications (such as anti-parkinsonism therapies) in conditions like paralytic ileus. When Imipramine is used with anticholinergic medications, careful monitoring and dosage adjustment are necessary.
To prevent tricyclic antidepressants from amplifying the effects of catecholamines, avoid concurrent use of medications like decongestants and local anesthetics that include any sympathomimetic amine (e.g., Epinephrine, Norepinephrine).
Monitoring of blood pressure is required in patients taking Imipramine in hypertensive patients.
Imipramine can potentiate the action of CNS depressant drugs. Caution is required in such patients.
Imipramine in Pregnant Women:
The effect of Imipramine has not been thoroughly studied in pregnant women to see its impact on the developing fetus. However, clinical reports of congenital abnormalities connected to the drug's use have been made.
The use of Imipramine by pregnant women may pose a risk to the fetus, even though a link between these side effects and the medication could not be proven. As a result, women who are or may become pregnant should only use Imipramine if the clinical condition justifies any potential danger to the fetus.
Imipramine in Lactating Women:
Some studies suggest that Imipramine is excreted in breast milk. Hence, nursing mothers taking the medication should be advised to avoid breastfeeding because there is a chance that the drug will be secreted in the breast milk and could harm the unborn child.
Imipramine in Geriatrics:
There are no discernible changes in reactions between geriatric and adult patients according to post-marketing clinical experience. The dose selection for senior patients should be cautious, beginning at the low end of the dosing range, reflecting a higher incidence of reduced hepatic, renal, or cardiac function and concurrent disease or other pharmacological therapy.