Norpramin (desipramine), a tricyclic antidepressant, belongs to a class of drugs used to treat major depression. Major depression refers to a persistent episode of a depressed mood that usually alters and interferes with daily activities. In some cases, this medication may also be prescribed to treat panic attacks and has been used in “off-label” (prescribed for a purpose not listed on the product’s FDA label) treatment for insomnia, neuropathic pain, and attention-deficit hyperactivity. The structure of this medication is similar to that of phenothiazines.

How Does Norpramin Work?

Norpramin inhibits the recycling of serotonin and norepinephrine—two important neurotransmitters. Serotonin, which is an inhibitory neurotransmitter, maintains a balance between the inhibition and excitement of the brain. It is necessary to maintain mood, sleep cycle, digestion, and the immune system. Norepinephrine is an excitatory (meaning it stimulates the brain) neurotransmitter that also functions to regulate mood, sleep, and digestion. By blocking the reuptake of serotonin and norepinephrine, this medication relieves symptoms associated with depression. Norpramin also inhibits Histamine-1 and Alpha-1 adrenergic and muscarinic receptors, which sometimes causes a sedative and hypnotic effect.

Dosage FAQs

  • What is a normal dose of this medication?
    For the treatment of depression, the prescription is started at a low dose of 75 to 150 mg daily depending on the condition of the patient or severity of the condition. Dose can be increased to 300 mg daily. Doses higher than 300 mg are not recommended although some hospitalized individuals may receive a higher dose. Individuals 65 years of age or older are typically given a low dose of 25 mg to 50 mg to start. Due to postural hypotension, care must be taken with this age group. Additional monitoring of kidney and liver functioning should be performed while treating geriatric individuals with this drug.
  • How does my body process this drug?
    Norpramin is soluble in water and is very well absorbed from the gastrointestinal tract. It will reach a peak blood plasma concentration in four to six hours. It is metabolized in the liver to an active metabolite, 2-hydroxydesipramin, which retains this drug’s ability to block the reuptake of serotonin and norepinephrine. This active metabolite has some cardiac depressant effects too. The half-life of this drug ranges from 7 to 65 hours and it is mainly excreted from the body in the urine.
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    Is it safe to use this drug if I am pregnant or become pregnant while being treated?
    Although there is no data on the effects of Norpramin during human pregnancy, the class of drugs that Norpramin belongs to (tricyclic antidepressants) did cause abnormalities in animal studies. These abnormalities included embryotoxic effects, intrauterine deaths, still births, and underweight births. Tricyclic antidepressants may also cause limb deformities and developmental delays. This drug may be secreted in the mother’s milk. All benefits and risks should be thoroughly weighed before prescribing this drug to someone who is pregnant or continuing treatment if someone becomes pregnant.
  • How can I get the most out of my treatment with this drug?
    Norpramin is prescribed for several conditions that also show positive results when treated with psychotherapy. If you are prescribed this drug for depression or panic attacks, consider finding a qualified therapist or counselor to help you better understand what you are experiencing, work on a self-care routine, and help you develop strategies for a better, longer-lasting mental health outcome than you might experience with medication alone.

Possible Side Effects

Norpramin has several adverse effects of which to be aware. These include the following:

  • Anticholinergic effects: Dry mucous due to sublingual inflammation, blurred vision due to the dilation of the pupil (mydriasis), paralysis of the ciliary muscles which may reduce the eye’s ability to focus, and ocular hypertension occur. Dilation of the urinary tract, constipation, delayed micturition, and urinary retention have also been experienced.
  • Nervous system effects: Effects include drowsiness, weakness, fatigue, lethargy, nightmares, restlessness, and insomnia. These may precipitate depression. Suicidal ideation may also increase. In some cases, increased paranoia and exacerbation of psychosis in schizophrenia have been reported.
  • Cardiovascular effects: Postural hypotension may occur. Make sure to stand up slowly as this is a common side effect of many antidepressant medications. This drug can also cause palpitations, increased heart rate (tachycardia), sudden death, stroke, and congestive heart failure.
  • Hepatic (liver) effects: Norpramin may disrupt the liver function test of those being treated with it. It can cause an increase in transaminase concentration, changes in serum alkaline phosphatase concentration, obstructive jaundice, and hepatitis, which is allergic in nature.
  • Gastrointestinal effects: This drug may lead to nausea, vomiting, diarrhea, and abdominal cramps. Black tongue and a specific and peculiar taste are also experienced by some in treatment with this drug.

Precautions for Norpramin

Norpramin may worsen depression and suicidal ideation for some individuals in treatment. Please inform your doctor if you experience sudden episodes of agitation or drastic changes in mood while taking this drug.

This drug may lower the threshold for seizures and the use of this drug should be monitored for people with a background of seizures.

In the acute withdrawal phase of alcoholism, the use of this medication may be limited and should be monitored as it may predispose the patient to extreme withdrawal symptoms.

This drug is contraindicated for people who are in the recovery phase of myocardial infarction. Additionally, people with a family history of sudden death and cardiac arrhythmias should use this drug with extreme caution.

The use of Norpramin should be discontinued several days before surgery.

Drug Interactions of Norpramin

Norpramin may have an interaction with the following agents:

Be sure to discuss your entire health history, medications, and any supplements you regularly take with your doctor and/or pharmacist before using this drug.

How to Safely Withdraw

If you stop taking this drug abruptly, you may experience nausea, persistent headaches, fatigue, and general malaise. To minimize the severity and occurrence of withdrawal symptoms, develop a safe plan with your health care provider to slowly taper off your dose of this medication.


  1. Cassano, P. and Fava, M. (2004). Tolerability issues during long-term treatment with antidepressants. Annals of Clinical Psychiatry, 16, 15–25.
  2. Cohen, L.S., Nonacs, R., Viguera, A.C., and Reminick, A. (2004). Diagnosis and treatment of depression during pregnancy. CNS Spectrums, 9, 209–216.
  3. Gillman, P.K. (2007). Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. British Journal of Pharmacology, 151(6), 737.
  4. Hirschfeld, R.M. (2000). Antidepressants in long-term therapy: A review of tricyclic antidepressants and selective serotonin reuptake inhibitors. Acta Psychiatrica Scandanavia, 403, 35.

Page content reviewed by James Pendleton, ND.