Desipramine Hydrochloride – Norpramin®

Brand name

  • Norpramin®

Drug Class

  • Tricyclic Anti Depressants


  • Desipramine Hydrochloride Tablets (United States Pharmacopeia): 10, 25, 50, 75, 100 and 150 mg


  1. Depressed phase of bipolar manic-depressive illness
  2. Melancholic Depression
  3. Psychotic depression
  4. Depressive neurosis



  • Mechanisem of action: Norepinephrine & Serotonine reuptake inhibitors. Down regulate beta adrenergic receptors and serotonin receptors



  1. Absorption: Gastrointestinal tract following oral administration
  2. Distribution: plasma proteins in the order of 90 – 95% >>> full effect: 2-3 weeks.
  3. Metabolism: Cytochrome P2D6 in liver.
  4. Excretion: largely in the urine >>> approximately 70% and partly in the bile.


1. Usual Adult Dose: 100 to 200 mg per day >>> in severely ill patients: gradual increase to 300 mg/day >>> Maximum dose: 300 mg/day

  • Treatment of patients requiring as much as 300 mg should generally be initiated in hospitals

2. Elderly and Debilitated Patient Dose: 25 to 100 mg/day >>> Maximum dose: 100 mg/day >>> in severely ill patients: 150 mg/day

Drug Interactions

1. Monoamine oxidase inhibitors

2. Alcohol

3. CNS depressants

4. Guanethidine

5. Medications which are/ has or cause:

  • CYP2C19 substrate
  • CYP2D6 substrate
  • Anticholinergic effects
  • CNS depression
  • Hyperprolactinemic effects, weak
  • Hypertensive effects
  • Hypernatremia
  • Hypotensive effects
  • Lowers seizure threshold
  • Prolongs QT interval (known)
  • Serotonergic effects, strong

Adverse Effects



  • Dry mouth,
  • Disturbances of visual accommodation,
  • Constipation
  • Mild urinary retention.
  • Light headedness, drowsiness,
  • Increased perspiration
  • Mild tremors
  • Insomnia

Less Frequent:


  • Cardio-Vascular: Hypotension, hypertension, tachycardia, palpitation, arrhythmias, heart block, myocardial infarction, stroke, premature ventricular contractions, ventricular tachycardia, ventricular fibrillation, sudden death.
  • Psychiatric: Confusional states (especially in the elderly) with hallucinations, disorientation, delusions; anxiety, restlessness, agitation; insomnia and nightmares; hypomania; exacerbation of psychosis.
  • Neurologic: Numbness, tingling, paresthesias of extremities, incoordination, ataxia, tremors; peripheral neuropathy; extrapyramidal symptoms; seizures; alteration in EEG patterns; tinnitus.
  • Allergic: Skin rash, petechiae, urticaria, itching, photo-sensitization (excessive exposure to sunlight should be avoided), edema (of face and tongue or general), drug fever, cross sensitivity with other tricyclic drugs.
  • Hematologic: Bone marrow depressions including agranulocytosis, eosinophilia, purpura, thrombocytopenia.
  • Gastrointestinal: Anorexia, nausea and vomiting, epigastric distress, peculiar taste, abdominal cramps, diarrhea, stomatitis, black tongue, hepatitis, jaundice (simulating obstructive), altered liver function, elevated liver function tests, increased pancreatic enzyme levels.
  • Endocrine: Gynecomastia in the male, breast enlargement and galactorrhoea in the female; increased or decreased libido, impotence, painful ejaculation, testicular swelling; elevation or depression of blood sugar levels; syndrome of inappropriate antidiuretic hormone secretion (SIADH).


1.Monoamine oxidase inhibitors

2. Acute recovery period following myocardial infarction

3. In poorly controlled cardiac decompensation

4. Prior hypersensitivity to the drug

5. Alcohol

6. CNS depressants

 7. Guanethidine

Pregnancy and Breastfeeding

Pregnancy: Category C

Lactation: Do not use in nursing mothers


1. Caution for developing suicidality (Suicial ideation) or unusual behavior changes during treatment : Close observation and communication with physician.

2. Desipramine hydrochloride increases the percentage of Stage 4 sleep (deep sleep) and decreases the percentage of REM sleep. A partial recovery of REM sleep is seen after 3 to 5 weeks of drug administration. However, in spite of this recovery, a REM rebound occurs following rapid drug withdrawal, which is experienced as an increase in dreaming.

3. Desipramine should not be given in conjunction with, or within 2 weeks of, treatment with Monoamine oxidase inhibitors. >>> Caution for Serotonin syndrome! >>> Hyperpyretic crises, severe convulsions and death may occur! At least two weeks should elapse between treatments.

4. Caution in In patients with cardiovascular disease >>> possibility of conduction defects, arrhythmias, tachycardias, strokes and acute myocardial infarction.

5. Caution in In patients with a history of urinary retention / glaucoma.

6. Caution in In patients with thyroid disease or those taking thyroid medication, >>> possibility of cardiovascular toxicity.

7. Caution in in patients with a history of seizure disorder, >>> lower the seizure threshold.

8. Desipramine hydrochloride may impair the mental / physical abilities required for the performance Caution in driving / operating machinery.

9. Desipramine is not recommended for use in children.

10. Desipramine may cause exacerbation of psychosis in schizophrenic patients.

11. Desipramine should be discontinued if there is evidence of pathologic neutrophil depression. >>> CBC with differential should be performed in case of developing fever and sore throat during therapy.

12. Caution in concomitant use with alcoholic beverages or other CNS depressants >>> Sedative effect may be exaggerated.

13. Caution in concomitant use with Guanethidine >>> blocking the antihypertensive effect.

14. Do NOT do abrupt discontinuation of the medication >>> Withdrawal Symptoms: nausea, headache, malaise and abdominal cramping.

15. Over-dosage: Symptoms >>> peripheral atropine effects, agitation and cardiac arrhythmias, pressure of speech, agitation, hallucinations, hyperacusia, choreoathetoid movements and myoclonus which may be mistaken for seizures, increased tendon reflexes, Babinski reflex, grand mal seizures and hyperactive coma progressing to flaccid coma >>> Injectable physostigmine salicylate (over a period of about 2 minutes 1 mg to 2 mg intravenously) is presently considered the treatment of choice in the reversal of the more severe CNS and cardiovascular complications of poisoning from tricyclic antidepressants >>> No universal antidote >>> do supportive therapy:

  • The best available evidence of impending toxicity of desipramine hydrochloride is prolongation of the QRS or QT intervals on the ECG.

16. Lower dosages are recommended for elderly and debilitated patients >>> initiate at a low level and increased according to clinical response


This document is prepared by the “Mental Health for All” team. This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.

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