Imipramine 

Inhibiting the reuptake of serotonin and, to a lesser degree, norepinephrine, two significant neurotransmitters in the central nervous system, Imipramine increases neurotransmission and has an antidepressant effect. There are other pharmacological effects of Imipramine that are connected with its adverse consequences. Low levels of certain neurotransmitters in the brain may be the cause of depression and other mental illnesses. Affected parts of the brain may undergo alterations as a result of this condition leading to psychological problems like anxiety or sadness. It is likely that Imipramine works as an antidepressant via increasing serotonin and norepinephrine levels. 

 A three-to-four-week time lag is typical for medicines to have the best possible impact, which might be the amount of time required for the brain to return to normal before the illness’s symptoms are lessened.
The U.S. Food and Drug Administration (FDA) authorized Imipramine for the treatment of depression and enuresis, or bedwetting, in children older than six. Utilizing a drug to treat its labeled usage refers to authorized indications. However, in actual practice, doctors often prescribe medications for unlabeled (or “off-label”) applications when the safety and effectiveness of such therapies are supported by published clinical studies, case reports, or their own clinical experiences.

 Imipramine is used unlabeled for the treatment of chronic Insomnia, panic disorder, premenstrual dysphoric disorder, posttraumatic stress disorder, migraine headaches, diabetic neuropathy, cancer pain, eating problems (bulimia nervosa), and assistance with cocaine withdrawal are examples of pain syndromes. Moreover, Imipramine may be used by doctors in conjunction with another antidepressant, such as an SSRI, to increase its antidepressant effects.  When there is insufficient response to a single antidepressant, this method is often effective in treating resistant depression.

Information about Dosing 

75 mg per day is the suggested beginning dose, which is best taken just before bed. In week 2, the dosage is raised to 150 mg/day, if necessary, and may be given as split doses or as a single dose at bedtime. The doctor may decide to change the patient’s antidepressant prescription or raise the dose to a maximum of 300 mg per day if the patient’s depression symptoms don’t go away. Lower doses of 25–100 mg per day is often needed for seniors and teenagers; dosages more than 100 mg per day are not advised for these people.
The simplicity of taking a single daily dose of Tofranil-PM sustained-release capsules, ideally in the night or just before bed. 

Conveniently, taking one dosage at night will reduce sleepiness throughout the day and the unpleasant side effects of anticholinergic medications. A single dose of standard Imipramine yields a high peak at higher doses, blood levels that most individuals may experience greater adverse consequences from. Tofranil-PMs sustained-release formulation, however, could make a single daily dosage more tolerable.

Typical Side Effects

Tricyclic antidepressants (TCAs) often elicit a group of symptoms known as anticholinergic side effects, which include dry mouth and skin, since they suppress cholinergic neurons in the nervous system, constipation, difficulties urinating, and impaired vision. Most people become used to these side effects, but if not, severe anticholinergic effects may cause disorientation and delirium, a mental illness.
In some cases, the doctor may recommend a different drug to offset the anticholinergic effects of the antidepressant. For instance, a doctor could recommend a 1% pilocarpine eyedrop to treat impaired eyesight and bethanechol, a cholinergic medication used to treat urinary problems (e.g., Urecholine). An over-the-counter stool softener like (docusate) is often beneficial for constipation.
TCAs may cause dizziness in certain people. The medications’ ability to temporarily lower blood pressure may contribute to dizziness because they prevent the body’s natural reaction to keep blood pressure steady when a person shifts from a laying down to a sitting or standing posture. Orthostatic hypotension is the medical name for this response. Orthostatic hypotension caused by these antidepressants may be more common in elderly people and those on other blood pressure-lowering drugs. 

• Gaining weight is another prevalent issue. The majority of people gain several pounds while using TCAs, such as Tofranil. Should the patient’s weight not stabilize, the doctor can consider changing the patient’s prescription. 
• In addition, Imipramine may cause reduced sexual desire in both men and women, as well as impotence and difficulty ejaculating in males. If this continues to be an issue, the doctor may decide to replace the patient’s prescription with an antidepressant that doesn’t affect sexual function, such bupropion.

Adverse Events and Safety Measures

Some individuals may have severe sleepiness and impaired vision while using Tofranil. Before doing any potentially dangerous duties, such as operating equipment or driving, patients should make sure that their eyesight, attentiveness, and other the medicine has no effect on or coordination. Imipramine should not be administered to patients who have a known allergy to it or who have had a serious response to it.

Imipramine may have an impact on cardiac conduction by delaying the electrical impulses that pass through cardiac tissues, which may cause an arrhythmia, or irregular heartbeat. Seniors and those with a history of arrhythmias or cardiovascular disease are more likely to have this adverse effect. Therefore, pretreatment electrocardiograms and frequent examinations (at least yearly) are recommended for individuals over 65 and those with a history of cardiac disease. Seniors may also be unable to handle single daily dosages due to the higher risk of cardiovascular problems and adverse effects.

As mentioned before, elderly people and those on blood pressure-lowering drugs may be vulnerable to orthostatic hypotension caused by Tofranil. In these vulnerable people, the abrupt decrease in blood pressure or sudden increase in blood pressure might result in fainting. The person should get up gently to avoid this, allowing their blood pressure to regulate gradually.

 
Utilization during pregnancy and lactation: Category D Pregnancy
Imipramine is categorized as higher risk due to reports of congenital abnormalities linked to the medication. However, it was not shown that these women’s prenatal exposure to Imipramine had a clear correlation with the flaw. During pregnancy, particularly in the first three months, TCAs are not advised. Fetal anticholinergic syndrome is the term for the anticholinergic adverse effects that TCAs may cause. These symptoms can also impact the unborn child. Use during pregnancy must thus be carefully considered in relation to the possible danger to the growing embryo. Women who are or may become pregnant should talk to their physician about this. When they stop taking their antidepressant, some women may have a relapse of depression. In these situations, it can be essential to resume taking the medicine or look for a different kind of drug or therapy.

Imipramine should not be used by nursing women since tiny quantities may enter the breast milk and be ingested by the unborn child. Breastfeeding should not begin if quitting the antidepressant is not an option.

Potential Interactions with Drugs

When Imipramine is used together with other drugs, there might be negative drug interactions as a consequence of one medication changing the other’s blood levels. Below is a summary of the major medication interactions that exist with Tofranil.

• When Imipramine and an SSRI are used together, the amount of Imipramine in the body may rise noticeably, which might have harmful or hazardous effects.

• Carbamazepine, When Imipramine and Carbamazepine are combined, Imipramine levels may drop and its beneficial pharmacological effects may be diminished; Carbamazepine levels may rise and cause additional adverse effects and higher toxicity. 
• Warfarin, Imipramine may raise the anticoagulant effects of Warfarin and its levels causing hemorrhage as a consequence. 
• Clonidine, When Imipramine and Clonidine are combined, they might cause harmful increase in blood pressure and need to be stayed away from. 
• Quinidine Avoid using quinidine, an antiarrhythmic medication, in conjunction with Imipramine since this may raise the risk of arrhythmias. 

Name: Depakene, Depakote, or Depakote ER, Imipramine levels may rise as a result of Depakene use, thus increasing the likelihood of negative effects.

• Combining Imipramine may result in an increase in anticholinergic adverse effects with a drug that has anticholinergic adverse effects or an anticholinergic agent.

• Disulfiram and TCAs together have been known to create organic brain syndrome, an uncommon but possibly dangerous response that impairs mental function. 

Monoamine oxidase inhibitors (MAOIs), a class of antidepressants, should not be used with Tofranil, since the combination can possibly result in a hazardous response characterized by increased blood pressure, raised temperature, and excessive excitement and agitation. Patients need to speak with their doctor or see your pharmacist before starting any new prescription regimen that includes Tofranil, including over-the-counter drugs and herbal supplements. 

• Alcohol should be avoided or used in moderation by patients on Imipramine since the combination may make depression worse. 

Overdosing

Similar to other tricyclic antidepressants (TCAs), Imipramine may be fatally overdosed in an acute manner, particularly in young children. Overdosing may be fatal, particularly if the antidepressant is used with additional drugs. 

 Heart rhythm disturbance is often the primary cause of mortality.
Treating any suspected overdose as an emergency is imperative. The individual has to be brought to the emergency space for care and observation. It is advisable to include both the prescription bottle of medicine and any other medication suspected in the overdose, since the information on the label may be useful in helping the treating physician figure out how many tablets the patient has taken.

 
Precautions Points to Remember

Major depressive disorder may often be effectively treated with medication, psychotherapy, or both. For the treatment of moderate to severe depression, the combination of psychotherapy and antidepressants is particularly successful. Medication enhances mood, energy, sleep, and appetite, while therapy helps people develop coping mechanisms, addresses any potential underlying problems and enhances behavior and mental habits.

 
60% to 70% of those who take antidepressants on their own report feeling better overall. The majority of people do not see noticeable advantages from their antidepressants until after 3–4 weeks, and it may sometimes take up to 8 weeks for the medicine to have its full effects. A small percentage of people may notice some improvement before the end of the first week. Therefore, it is crucial that patients take their antidepressant for the whole recommended amount of time and that they do not give up and stop taking it too soon if they do not start feeling better right away.
Antidepressants have been shown in short-term trials to raise the likelihood of suicidal thoughts and actions in kids and teenagers suffering from severe depressive illness and other mental health issues. When beginning antidepressant treatment in children and adolescents, the FDA mandates that the prescriber disclose this risk to the patient.

According to FDA research, there is an age-related risk of suicide thoughts and actions while using antidepressants. This occurrence is more likely to happen early in the course of therapy and is more common in younger populations.
Antidepressant use did not seem to be associated with a higher incidence of suicidality in people over the age of 24, as compared to placebo use. The results demonstrated that antidepressants had a “protective” effect in people over 65.

• According to other research, suicide rates are lower in communities where a larger proportion of the population takes antidepressants. 
• Suicide risk is a part of depression and may not go away until the patient responds to therapy. Upon initiating or modifying antidepressant treatment, the individual particularly if they are a child or adolescent should have continuously monitored for increasing symptoms of depression, and any concerns should be reported to the doctor by the family or caregiver. 
•  Caution: If you are experiencing suicidal thoughts, please notify your doctor or a family member right away. Whenever your depressed symptoms increase or you feel like you can’t manage suicide thoughts or desires, see a psychiatrist or your family doctor. 
• It is important to speak with your doctor before stopping Tofranil. It is advisable to go off Imipramine gradually rather than stopping it entirely at once. Stopping Imipramine suddenly might result in headaches, nausea, and malaise. 
•  Take the missed dosage as soon as you remember. If your next planned dosage is approaching, skip the missed one and go on with your usual dosing regimen. 
• Avoid taking two doses at once. 
• Imipramine may make you feel very sleepy. You should refrain from using equipment and driving until you are assured that your medicine is not interfering with your alertness and coordination. 
• You shouldn’t drive, operate equipment, or carry out other potentially dangerous duties if your eyesight is blurry. Should you notice blurriness in your vision, speak with your doctor. 
• If you have ever had a serious response to Imipramine or have a known allergy to it, avoid using it. 
• Keep the medicine out of direct sunlight and dampness, in the light-resistant container that came with it. Your drug may break down more quickly in hot and humid environments, losing its therapeutic benefits. 

Make sure kids can’t get to your medicine. TCA overdose in young toddlers may be quite harmful.