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Tricyclic Antidepressant

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Brand Name (Manufacturer)

Vivactil (Merck)

Type of Drug

Psychoactive-tricyclic antidepressant

Used For

Protriptyline is used for the relief of symptoms of mental depression.

General Information

Protriptyline belongs to a class of drugs known as tricyclic antidepressants. It is chemically unrelated to other classes of antidepressants, including monoamine oxidase (MAO) inhibitors. It is thought to work by increasing the concentrations of neurotransmitters called serotonin and norepinephrine in the brain.

Tricyclic antidepressants are usually taken over long periods. It takes weeks for steady levels of protriptyline to build up in the blood, and it may take up to a month for the drug to have an effect on depression.

Protriptyline is available as tablets for oral administration.


To prevent side effects, the dosage of the drug should initially be low and increased as necessary until improvement, as long as there are no serious side effects.

The recommended initial dosage for treatment of depression in adults is 15 to 40 mg a day, divided into three or four doses. When satisfactory improvement has been reached, the dosage should be reduced to the smallest amount that will maintain relief of the symptoms. Lower doses (15 mg per day to start) are recommended for elderly adults.

Cautions and Warnings

Protriptyline should not be used by anyone with a known allergy to it. It should also not be used by people recovering from heart attacks. Because of the risk of serious side effects, protriptyline should not be used in combination with antidepressants of the monoamine oxidase (MAO) inhibitor class.

When protriptyline replaces an MAO inhibitor for treatment of depression, a minimum of fourteen days should elapse after stopping the MAO inhibitor before starting therapy with protriptyline. Protriptyline should be started cautiously with a gradual increase in dose until a response is achieved.

Protriptyline should be used with caution in people with a history of seizures, difficulty urinating, or glaucoma. People with thyroid disease or those receiving thyroid medication should not use protriptyline because of the risk of heart toxicity.

Protriptyline may increase the hazards of concurrent electroshock therapy. Similarly, when possible, the drug should be discontinued several days before surgery.

Protriptyline may impair the mental and physical abilities necessary to drive an automobile or operate dangerous machinery.

Rapidly stopping protriptyline may cause withdrawal symptoms, including nausea, headache, and a sickly feeling.

Side Effects

The most common side effects of protriptyline include rapid heartbeat, fainting when getting up quickly, sedation, blurred vision, disorientation, confusion, hallucinations, muscle spasms, seizures, dry mouth, constipation, difficulty urinating, and sensitivity to bright light or sunlight.

Other potential side effects include heart attack, stroke, changes in blood pressure, palpitations, delusions, anxiety, restlessness, agitation, panic, nightmares, numbness, tingling or pain in the extremities, weakness, fatigue, headache, allergic reactions, bone-marrow toxicity, nausea, vomiting, loss of appetite, stomach upset, diarrhea, peculiar taste, blackened tongue, impotence, changes in sex drive, jaundice, hair loss, weight change, frequent urinating, altered blood-sugar levels, and increased perspiration.


Protriptyline has not been formally studied in pregnant women. Protriptyline crosses the placenta. There have been reports of birth defects when the drug was taken during the first three months of pregnancy and severe side effects in newborns whose mothers took the drug during delivery. Pregnant women are encouraged to discuss the benefits and potential risks of protriptyline with their physician before deciding to use the drug.

HIV can be passed from a woman to her child through breast milk. In areas where nutritional alternatives are readily available, breast-feeding is discouraged for HIV-positive women. Protriptyline is excreted in human milk. Because of the potential toxicity of the drug for newborns, women are encouraged to consider alternatives to breast-feeding while taking it.

Use In Children

Protriptyline is not recommended for children because its safety and efficacy has not been formally established for them in clinical trials.

Use in the Elderly

Older adults may be more susceptible to the side effects of protriptyline. If they use the drug, it is usually at reduced dosages, as described above.

Drug Interactions

Protriptyline may interfere with the effect of blood-pressure medications such as guanethidine or clonidine. Taking protriptyline and thyroid drugs together may intensify the effects of both drugs.

Oral contraceptives and cigarette smoking may decrease the effect of protriptyline. Estrogens can increase or decrease the effect of protriptyline.

Bicarbonate of soda, acetazolamide, quinidine, and procainamide may increase the effect of protriptyline. Methylphenidate, cimetidine, and phenothiazines (perphenazine, prochlorperazine, etc.) may increase blood levels of protriptyline, potentially increasing the risk of its side effects.

Protriptyline may increase the effect of other central nervous system depressants including alcohol, sleeping pills, narcotic pain relievers, tranquilizers, barbiturates, and antihistamines.

Food Interactions

Protriptyline may be taken with or without food.

Other Drugs Used for Similar Conditions

For treatment of depression, there are many options, including other tricyclic antidepressants (desipramine, amitriptyline, nortriptyline, amoxapine, maprotiline, imipramine, trimipramine, doxepin), MAO inhibitors (tranylcypromine, phenelzine, isocarboxazid), serotonin reuptake inhibitors (fluoxetine, paroxetine, and sertraline), and stimulants such as methylphenidate. The appropriate choice varies from person to person and depends on age, physical health and condition, and other drugs being concurrently used.

Desipramine is often the first choice among tricyclic antidepressants because it is effective and has relatively few side effects in most people. Protriptyline is more likely to cause abnormal heart rhythms or low blood pressure and to aggravate agitation and anxiety than other antidepressants.

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