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HomeHealth articlesprotriptylineWhat Are the Uses of Protriptyline?

Protriptyline - Uses, Indications, Contraindications, and Adverse Effects

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Protriptyline hydrochloride is used to improve mood in people with depression. To know more, read the article.

Medically reviewed by

Dr. Kaushal Bhavsar

Published At November 15, 2022
Reviewed AtApril 26, 2023


Protriptyline is a potent tricyclic antidepressant used to elevate mood in people with depression and also used to treat anxiety. It has fewer sedative and tranquilizing effects than other tricyclic antidepressants. Protriptyline has both Food and Drug Administration (FDA) approved and non-approved indications. It was first patented in 1962. Protriptyline is also used to treat brain-injured adults with attention and behavioral difficulties. Protriptyline also improves drowsiness, snoring, acne episodes, and cataplexy (loss of muscle tone resulting in weakness and loss of muscle control) related to narcolepsy (excessive uncontrolled daytime sleep).

Protriptyline is a secondary tricyclic amine- structurally similar to Nortriptyline. It undergoes first-pass hepatic metabolism and crosses the blood-brain barrier. It has a half-life of 80 to 200 hours which is more than three days.

What Are the FDA Approved Indications?

  • Mental depression.

  • Narcolepsy.

  • Headaches.

  • Attention deficit hyperactivity disorder.

What Are the FDA Non-approved Indications?

  • Treatment-resistant depression.

  • Local anesthetic.

  • Cocaine dependence.

  • Smoking cessation.

  • Apnea.

What Is the Mechanism of Action?

Serotonin and norepinephrine are the two important chemicals that are related to mood. These chemicals are reduced in depressed people and are the main targets for antidepressants. This drug has the fastest onset of action among other antidepressants, and clinical effects occur within the first week of use.

  • Protriptyline increases norepinephrine neurotransmission by blocking the norepinephrine reuptake pump.

  • In the frontal cortex, neurotransmission by dopamine increases secondary to reuptake.

  • At high doses, Protriptyline increases serotonin neurotransmission.

  • Protriptyline also causes calcium-independent cell death.

For Patients:

What Are the Uses of Protriptyline?

How to Administer?

  • Protriptyline is available in 5 and 10 mg tablets.

  • It can be initiated at 15 to 40 mg daily as a morning dose, and the maximum dose should be 60 mg daily, if necessary.

  • Doses need to be administered in three or four doses and not to be taken all at one time.

  • Should begin the doses at a lower level and can increase gradually depending on the individual's response and side effects as the dose increases.

What Are the Common Adverse Effects?

  • Central nervous system depression.

  • Seizures.

  • Cardiac toxicity.

  • Weight gain.

  • Coma.

  • Anxiety.

  • Nausea.

  • Headache.

  • Diarrhea.

  • Constipation.

  • Itching.

  • Rash.

  • Blurred vision.

  • Suicidal thoughts and attempts.

What Are the Serious Adverse Effects of Protriptyline?

  • Liver failure.

  • Increased intraocular pressure.

  • Myocardial infarction.

  • Stroke.

  • Seizures.

  • Coma.

  • Sudden death.

What Are the Contraindications?

  • Heart problems - Uncompensated heart failure, heart block, palpitations, increased blood pressure, decreased blood pressure, and recent myocardial infarction.

  • Use of drugs that inhibit tricyclic antidepressant metabolism.

  • The use of Tramadol increases the risk of seizure disorder.

  • Pregnancy and breastfeeding women.

  • Age younger than twelve due to increased risk of suicidal thoughts.

  • History of hypersensitivity to Protriptyline.

  • Hyperthyroidism and urinary retention.

  • Renal impairment.

  • Alcohol consumption.

What Is the Information to the Patient?

  • The patient should read the medication guide of the antidepressant medication.

  • Should inform the family members and healthcare provider about the following:

    • The risks and benefits of treatment associated with antidepressant medicines.

    • The treatment choices for depression and other serious mental illnesses.

What Is the Most Important Information the Patient Should Know About Antidepressant Medicines?

  • Initially, antidepressant medicines may increase suicidal thoughts in children, teenagers, and young adults.

  • The causes of suicidal thoughts and behavior are depression and mental status.

  • Some people may have a high risk of having suicidal thoughts. These people will have a family history of bipolar illness and suicidal thoughts or actions.

How Can the Patient Watch for and Try to Prevent Suicidal Thoughts and Actions Among a Family Member or Themselves?

  • The patient should pay attention to sudden changes in behaviors, moods, feelings, and thoughts.

  • This is important during the start of antidepressant medicine and when the dose is changed.

  • Call the healthcare provider right away to report sudden changes in mood, behavior, thoughts, and feelings.

  • Should regularly follow the visits with the healthcare provider as per schedule.

  • Call the healthcare provider between visits if needed.

  • Call a healthcare provider if the individual experience any of the following symptoms:

    • Thoughts about suicide or dying.

    • New or worse irritability.

    • Attempts to commit suicide.

    • Acting aggressively, being angry, or being violent.

    • New or worse depression.

    • Acting on dangerous impulses.

    • New or worse anxiety.

    • An extreme increase in activity and talking.

    • Feeling very agitated or restless.

    • Other unusual changes in behavior or mood.

    • Panic attacks.

    • Visual problems - Eye pain, swelling or redness in and around the eye, and changes in vision.

    • Trouble sleeping.

What Else Should the Patient Need to Know About Antidepressant Medicines?

  • Never stop an antidepressant medicine without talking to a healthcare provider.

  • Suddenly stopping an antidepressant medicine can lead to other symptoms.

  • Patients, their families, and caregivers should discuss the treatment choices with the healthcare providers.

  • Inform the healthcare providers about the side effects of the drug prescribed.

  • Antidepressant medicines can interact with other medicines.

  • It should show the list of all medicines that one's family member usually takes.

  • Check with the healthcare provider before starting new medicines.

For Doctors:

What Is Protriptyline?

Protriptyline hydrochloride, a dibenzo cycloheptene derivative, is a whitish-yellow powder that is freely soluble in water. It is supplied as 5 mg or 10 mg film-coated tablets.

Inactive Ingredients: Corn starch, anhydrous lactose, carnauba wax, dibasic calcium phosphate, hypromellose, hydroxypropyl cellulose, magnesium stearate, polyethylene glycol, microcrystalline cellulose, polysorbate 80, sodium starch glycolate, propylene glycol, and titanium dioxide.

What Is the Clinical Pharmacology of Protriptyline?

  • It is an antidepressant agent.

  • It is not a monoamine oxidase inhibitor.

  • It does not act by stimulation of the central nervous system primarily.

What Is the Mechanism of Action?

  • Protriptyline increases norepinephrine neurotransmission by blocking the norepinephrine reuptake pump.

  • In the frontal cortex, neurotransmission by dopamine increases secondary to reuptake.

  • At high doses, Protriptyline increases serotonin neurotransmission.

  • Protriptyline also causes calcium-independent cell death.

What Are the Indications and Usage?

  • Mental depression.

  • Narcolepsy.

  • Headaches.

  • Attention deficit hyperactivity disorder.

What Are the Contraindications?

  • Heart problems- Uncompensated heart failure, prolonged QT interval, arrhythmias, heart block, palpitations, increased blood pressure, decreased blood pressure, and recent myocardial infarction.

  • The use of drugs that inhibit tricyclic antidepressant metabolism inhibits CYP450 2D6 or prolongs QTc interval.

  • Use of anticholinergic drugs.

  • The use of Tramadol increases the risk of seizure disorder.

  • Pregnancy and breastfeeding women.

  • Age younger than twelve due to increased risk of suicidal thoughts.

  • History of hypersensitivity to Protriptyline.

  • Hyperthyroidism, angle closure glaucoma, and urinary retention.

  • Renal impairment.

  • Alcohol consumption.

  • Psychosis due to tricyclic antidepressants aggravating psychotic symptoms.

What Are the Warnings?

  • Clinical Worsening and Suicidal Risk: Patients with the major depressive disorder may experience worsening depression, the emergence of suicidal thoughts, and unusual changes in behavior.

  • Screening Patients for Bipolar Disorder: A major depressive episode is the initial clinical presentation of bipolar disorder. Treating bipolar disorder with an antidepressant alone may increase the precipitation of a manic episode. However, before starting treatment with Protriptyline, patients with the depressive disorder should be screened to determine whether they are at risk for bipolar disorder. This screening involves a detailed psychiatric history and family history of suicide, depression, and bipolar disorder. Hence, Protriptyline is not an approved drug to use for treating bipolar disorder.

  • Hypertension: Protriptyline blocks the antihypertensive effects of Guanethidine and similarly acting compounds.

  • Seizures: Protriptyline should be used with caution with seizure patients. Because of its autonomic activity, it causes urinary retention and increased intraocular tension.

  • Cardiovascular Disorders: Antidepressants should be used with caution in patients having cardiovascular disorders such as tachycardia, hypotension, arrhythmias, and prolongation of the conduction time. The use of Protriptyline also causes myocardial infarction and stroke.

  • Hypothyroidism: Patients taking thyroid medications may develop arrhythmias while taking Protriptyline.

  • Alcohol Consumption: Patients who take excessive alcohol along with Protriptyline had increased suicidal thoughts.

  • Angle-Closure Glaucoma: The use of Protriptyline increases the chances of angle closure glaucoma in patients with anatomically narrow angles.

  • Usage in Pregnancy: There is no evidence of safe usage in pregnancy.

What Are the Precautions?

  • The use of Protriptyline to treat schizophrenia may aggravate the psychotic symptoms.

  • Likewise, the use of Protriptyline in manic-depressive psychosis patients causes a shift toward the manic phase.

  • Paranoid delusions may be exaggerated with the use of Protriptyline.

  • In any of the above conditions, reducing the dose of Protriptyline is advisable.

  • Administration of Protriptyline and electroshock therapy together may increase the hazards, and it should be limited to patients for whom it is essential.

  • Should discontinue the drug several days before elective surgery.

  • It is reported that there is both an increase and decrease in blood sugar levels with the usage of Protriptyline.

What Are the Adverse Reactions?

  • Cardiovascular: Myocardial infarction, heart block, arrhythmias, stroke, hypotension, hypertension, particularly orthostatic hypotension, tachycardia, and palpitation.

  • Psychiatric: Confusional states with delusions, hallucinations, disorientation, anxiety, restlessness, agitation, exacerbation of psychosis, insomnia, hypomania, panic, and nightmares.

  • Neurological: Seizures, incoordination, ataxia, tremors, peripheral neuropathy, tingling, numbness, paresthesias of extremities, extrapyramidal symptoms, dizziness, weakness, fatigue, drowsiness, headache, syndrome of inappropriate antidiuretic hormone secretion (SIADH), tinnitus, and alteration in electroencephalogram patterns.

  • Anticholinergic: Paralytic ileus, hyperpyrexia, delayed micturition, urinary retention, constipation, dilatation of the urinary tract, blurred vision, disturbance of accommodation, mydriasis, increased intraocular pressure, dry mouth, and rare sublingual adenitis.

  • Allergic: Drug fever, petechiae, urticaria, itching, skin rash, photosensitization, and edema (general, face, and tongue).

  • Hematologic: Agranulocytosis, bone marrow depression, leukopenia, thrombocytopenia, purpura, and eosinophilia.

  • Gastrointestinal: Nausea and vomiting, anorexia, diarrhea, peculiar taste, stomatitis, epigastric distress, abdominal cramps, and black tongue.

  • Endocrine: Impotence, increased or decreased libido, testicular swelling, gynecomastia in the male, galactorrhea and breast enlargement in the female, and elevation or depression of blood sugar levels.

  • Other: Jaundice, altered liver function, parotid swelling, flushing, nocturia, alopecia, weight gain or loss, urinary frequency, and perspiration.

What Are the Withdrawal Symptoms?

Abrupt cessation of treatment after prolonged therapy with Protriptyline may produce nausea, headache, and malaise.

What Happens in Case of Overdosage?

  • Deaths may occur from overdosage with Protriptyline.

  • Multiple drug ingestion is common in tricyclic antidepressant overdose.

  • Since the management of overdose is complex and challenging, it is advised that the physician should contact a poison control center in order to know the current information on treatment.

  • The signs and symptoms of Protriptyline toxicity develop rapidly after a Protriptyline overdose, and hospital monitoring is required as soon as possible.

Clinical Manifestations:

  • Cardiac dysrhythmias.

  • Severe hypotension.

  • Convulsions.

  • Central nervous system depression.

  • Coma.

  • Changes in the electrocardiogram, particularly in QRS width.

  • Confusion.

  • Disturbed concentration.

  • Transient visual hallucinations.

  • Dilated pupils.

  • Agitation.

  • Hyperactive reflexes.

  • Stupor.

  • Drowsiness.

  • Muscle rigidity.

  • Vomiting.

  • Hypothermia.

  • Hyperpyrexia.



  • Should take an ECG (electrocardiogram) immediately and start with cardiac monitoring.

  • Protect the airway first and then establish an intravenous line.

  • Then gastric decontamination is initiated.

  • And therefore, six hours of observation with cardiac monitoring is necessary.

  • Then observe for signs of the central nervous system or respiratory depression, hypotension, cardiac dysrhythmias, conduction blocks, and seizures.

  • If signs of toxicity occur during this period, extended monitoring is required.

  • Monitoring plasma drug levels will not help in guiding the management of the patient.

-Gastrointestinal Decontamination:

  • All patients suspected of a Protriptyline overdose should receive gastrointestinal decontamination.

  • This includes large gastric lavage followed by activated charcoal.

  • In case of impaired consciousness, the airway should be secured prior to lavage.

  • Emesis is usually contraindicated in overdose.


  • The QRS duration of ≥ 0.10 seconds indicates the severity of the overdose.

  • Intravenous sodium bicarbonate is then used to maintain the serum pH between 7.45 to 7.55.

  • In case of inadequate pH, hyperventilation may also be used.

  • Use of hyperventilation and sodium bicarbonate concomitantly should be done with extreme caution, along with pH monitoring.

  • A pH > 7.60 and a pCO2 < 20 mmHg are undesirable.

  • Dysrhythmias that are not responsive to sodium bicarbonate therapy and hyperventilation may respond to Lidocaine, Bretylium, or Phenytoin.

  • In rare situations, hemoperfusion may be useful in treating acute refractory cardiovascular instability in patients with acute toxicity.

  • However, hemodialysis, exchange transfusions, peritoneal dialysis, and forced diuresis are generally ineffective in Protriptyline poisoning.

-Central Nervous System:

  • Early intubation is advised in patients with central nervous system disorder due to the risk of abrupt deterioration.
  • Seizures should be controlled with Benzodiazepines or other anticonvulsants like Phenobarbital and Phenytoin.

  • Psychiatric Follow-up:

  • Overdosage is often deliberate; hence patients may attempt suicide during the recovery phase.

  • Psychiatric referral may be appropriate in these conditions.

  • Pediatric Management: It is strongly recommended that physicians should contact the local poison control center for specific treatment.

What Are Dosages and Administration?

Antidepressant dosages should be started at a low level and then increased gradually, noting the clinical response and intolerance carefully.

1. Adult Dosage:

  • 15 to 40 mg a day- divided into three or four doses, and a maximum of 60 mg a day can be taken if required.

  • Dosages above 60 mg are not recommended.

  • An increase in dosage should be made in the morning dose.

2. Adolescent and Elderly Patients’ Dosage:

  • In general, lower doses are recommended for these patients.

  • 5 mg Protriptyline initial dosage can be given three times a day and then increased gradually.

  • If the dose exceeds 20 mg, then elderly patients should be closely monitored for cardiovascular symptoms.

  • Once satisfactory improvement is reached, dosage should be maintained to relieve the symptoms.

How Is the Drug Supplied?

  • 5 mg: Orange, oval, film-coated, unscored tablets. Debossed OP 701. They are available in bottles having 100 tablets.

  • 10 mg: Yellow, oval, film-coated, unscored tablets. Debossed OP 702. They are available in bottles having 100 tablets.

  • Store at 20° to 25°C.

  • It should dispense in a tight, light-resistant container with a child-resistant closure.

  • Keep the container tightly closed.

How Is the Drug Metabolized?

  • Studies on the disposition of radioactive Protriptyline show an increase in plasma levels within two hours, more at eight to 12 hours, and then declining gradually.

  • Urinary excretion studies show significant amounts of radioactivity within two hours.

  • The excretion rate is slow.

  • Cumulative urinary excretion during 16 days accounts for approximately 50 % of the drug.

What Are the Clinical Inferences Obtained?

  • Pooled analyses of short-term placebo-controlled trials of Protriptyline showed that It increases the risk of suicidal thoughts and behavioral changes in children, adolescents, and young adults of 18 to 24 years with psychiatric disorders and major depressive disorders.

  • Short-term studies do not show any increase in the risk of suicide attempts with tricyclic antidepressants compared to placebo in adults beyond 24 years.

  • There was a reduction in suicidal thoughts with Protriptyline antidepressants compared to placebo in adults aged 65 years and older.

Dr. Kaushal Bhavsar
Dr. Kaushal Bhavsar

Pulmonology (Asthma Doctors)


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