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Imipramine

Brands and Forms

  • Tofranil
    • tablet: 10mg, 25mg, 50mg.
  • Tofranil PM
    • capsule: 75mg, 100mg, 125mg, 150mg.

Uses of Imipramine

Imipramine can be used for treating Major Depressive Disorder and Dysthymia, Anxiety Disorders, ADHD, and it is also used at times for alleviating neuropathic pain, enuresis (bed wetting), and cataplexy syndrome.

How Imipramine Works

Imipramine is a Tricyclic Antidepressant. It blocks serotonin and norepinephrine reuptake in the central nervous system and thus boosts serotonin and norepinephrine neurotransmission, and also increases dopamine activity. Its anticholinergic and antihistimine properties account for some of the side-effects of this medication.

Cautions when Using Imipramine

Imipramine can induce Manic or Mixed Episodes and Rapid Cycling in people with Bipolar Disorder.

Children and adolescents who use antidepressants like Imipramine may develop self-injurious or suicidal behaviors (for more information, see here).

Use caution in people with a known seizure disorder, heart disease (can increase QTc interval), urinary retention, glaucoma, or hyperthyroidism.

Tricyclic Antidepressants such as Imipramine have been shown to increase the risk of cardiovascular disease [ref]. Furthermore, because of the risk of cardiac arrhythmias and other cardiovascular side-effects, the risk/benefit ratio may not justify the use of this medication in individuals with heart disease.

Long-term use of Imipramine may increase the risk of osteoporosis and bone fractures.

Imipramine should not be used during or within 14 days following the administration of an MAOI, because a hypertensive crisis may result.

Dosing of Imipramine

The usual therapeutic range of Imipramine is 100-300mg/day. It is given once daily at bedtime, as it tends to be sedating, but it can also be given twice a day.

Initial dose is usually 25mg/day, and it can be increased by 25mg no quicker than every 3 days. Once at 75-100mg/day, it is generally recommended to wait at least 4 weeks to see if therapeutic effects occur before increasing the dose further.

When wanting to stop this medication, the dose should be decreased gradually over a period of 6-8 weeks. A sudden cessation of the medication can result in a discontinuation syndrome.

Onset of action

Therapeutic effects are not expected before 2-4 weeks at a dose of 75-100mg/day. If no significant effects are seen after 6-8 weeks of use, including at least 2 weeks at a dose above 100mg/day, then the medication may not work at all.

Kidney impairment

Use with caution. May need to lower dose.

Liver impairment

Use with caution. May need to lower dose.

Elderly

May be more sensitive to the anticholinergic, cardiovascular, hypotensive and sedative effects. Initial dose 30-40mg/day, and maximum dose 100mg/day.

Side-effects of Imipramine

Below is a list of most of the reported side-effects of Imipramine. Most of these side-effects occur in only a minority of individuals, and many also resolve with time while the medication is continued.

Cardiovascular: orthostatic hypotension; hypertension; tachycardia; palpitations; arrhythmias; QTc prolongation; heartblock; congestive heart failure (rare); stroke (rare).

Central Nervous System: drowsiness; dizziness; weakness; numbness; headache; nightmares; confusion; extrapyramidal symptoms (rare); seizures (rare); serotonin syndrome (rare).

Dermatologic: rash; pruritus; photosensitivity reaction; dry skin; acne; itching; hair loss.

Endocrine/Metabolic: elevation or depression of blood glucose levels; weight gain; abnormal breast milk secretion; breast enlargement in men and women; breast pain.

Eyes, Ears, Nose and Throat: nasal congestion; tinnitus; conjunctivitis; dilated pupils; blurred vision; increased IOP.

Gastrointestinal: nausea; vomiting; anorexia; upset stomach; diarrhea; flatulence; peculiar taste in mouth; dry mouth; constipation; paralytic ileus (rare); hepatitis (rare).

Genitourinary: impotence; sexual dysfunction; nocturia; urinary frequency; urinary tract infection; vaginitis; cystitis; dysmenorrhea; amenorrhea; urinary retention and hesitancy.

Hematologic: bone marrow depression, including agranulocytosis; eosinophilia; purpura; thrombocytopenia.

Muskuloskeletal: risk of osteoporosis and bone fractures with long-term use.

Psychiatric: anxiety; agitation; apathy; irritability; worsening depression; depersonalization; suicidal thoughts; self-injurious behaviors among children and adolescents; can induce Manic or Mixed Episodes and Rapid Cycling in people with Bipolar Disorder.

Respiratory: pharyngitis; rhinitis; sinusitis; laryngitis; coughing.

Common side-effects of Imipramine

Dizziness, sedation/fatigue, tremor, headache, blurred vision, constipation, urinary retention, ejaculation failure; impotence; increased appetite, weight gain, dry mouth, nausea, diarrhea, heartburn, unusual taste in mouth, weakness, anxiety, restlessness, sweating, sexual dysfunction.

Rare but serious side-effects of note of Imipramine

  • Children and adolescents who use antidepressants like Imipramine may develop self-injurious or suicidal behaviors (for more information, see here).
  • Seizures
  • QTc prolongation, which can lead to serious heart arrhythmias
  • Heart attack and stroke
  • Acute angle glaucoma
  • Paralytic ileus
  • Liver failure
  • Bone marrow depression

Imipramine discontinuation syndrome

Individuals who suddenly stop using Imipramine after taking the medication at moderate or high doses over a significant period of time are at risk of developing a discontinuation syndrome, which can include the following symptoms: dizziness, electric shock-like sensations, sweating, nausea, insomnia, tremor, anxiety, restlessness, agitation, depressed mood, irritability, confusion, lethargy, and vertigo. These symptoms usually start anywhere from one day to one week after the medication was stopped, and can persists for days or even weeks.

This syndrome can be treated by restarting the medication at its prior dose. It can be prevented by decreasing the dose gradually over a period of 6-8 weeks when wanting to stop the medication. In rare cases, individuals may experience the discontinuation syndrome even when the medication is being tapered gradually; in such cases, an extremely slow and gradual taper will be necessary.

Imipramine overdose

Convulsions, heart arrhythmias, severe hypotension, CNS depression, coma. Death may occur.

Imipramine and pregnancy

Category D: human studies have shown evidence of risk to fetus. For further information, see the section on treating Depression in pregnancy.

Medical Monitoring for Imipramine

Monitor blood counts (CBC with differential), body mass index; blood sugars (in patients with diabetes), electrocardiogram, and liver function tests as needed.

Drug Interactions with Imipramine

  • Combining Imipramine with other anticholinergic drugs can increase the risk of paralytic ileus or hyperthermia.
  • Combining Imipramine with Pimozide, Thioridazine, selected antiarrhythmics, Moxifloxacin and Sparfloxacin can increase the risk of life-threatening cardiac arrhythmias resulting from QTc prolongation.
  • Imipramine blood concentrations can be decreased by Carbamazepine.
  • Imipramine blood concentrations can be increased by Bupropion, Cimetidine, Duloxetine, Fluoxetine, Fluvoxamine, Haloperidol, Paroxetine.
  • Imipramine should not be used during or within 14 days following the administration of an MAOI, because a hypertensive crisis may result.