Protriptyline is an oral tricyclic antidepressant. It is sold in the United States under the brand name Vivactil and is also available under its generic name.


Protriptyline is used primarily to treat depression and to treat the combination of symptoms of anxiety and depression. Like most antidepressants of this chemical and pharmacological class, protriptyline has also been used in limited numbers of patients to treat panic disorder , obsessive-compulsive disorder , attention-deficit/hyperactivity disorder , enuresis (bed-wetting), eating disorders such as bulimia nervosa , cocaine dependency, and the depressive phase of bipolar disorder (manic-depressive) disorder. It has also been used to support smoking cessation programs.


Tricyclic antidepressants act to change the balance of naturally occurring chemicals in the brain that regulate the transmission of nerve impulses between cells. Protriptyline acts primarily to increase the concentration of norepinephrine and serotonin (both chemicals that stimulate nerve cells) and, to a lesser extent, to block the action of another brain chemical, acetylcholine. Protriptyline shares most of the properties of other tricyclic antidepressants, such as amitriptyline , clomipramine , desipramine , imipramine , nortriptyline , and trimipramine . Studies comparing protriptyline with these other drugs have shown that protriptyline is no more or less effective than other antidepressants of its type. Its choice for treatment is as much a function of physician preference as any other factor.

The therapeutic effects of protriptyline, like other antidepressants, appear slowly. Maximum benefit is often not evident for at least two weeks after starting the drug. People taking protriptyline should be aware of this and continue taking the drug as directed even if they do not see immediate improvement.

Recommended dosage

As with any antidepressant, protriptyline must be carefully adjusted by the physician to produce the desired therapeutic effect. Protriptyline is available as 5-mg and 10-mg tablets. Doses range from 15 to 40 mg per day and can be taken in one daily dose or divided into up to four doses daily. Some people with severe depression may require up to 60 mg per day.

In adolescents and people over age 60, therapy should be initiated at a dose of 5 mg three times a day and increased under supervision of a physician as needed. Patients over age 60 who are taking daily doses of 20 mg or more should be closely monitored for side effects such as rapid heart rate and urinary retention.


Like all tricyclic antidepressants, protriptyline should be used cautiously and with close physician supervision in people, especially the elderly, who have benign prostatic hypertrophy (enlarged prostate gland), urinary retention, and glaucoma, especially angle-closure glaucoma (the most severe form). Before starting treatment, people with these conditions should discuss the relative risks and benefits of treatment with their doctors to help determine if protriptyline is the right antidepressant for them.

A common problem with tricyclic antidepressants is sedation (drowsiness, lack of physical and mental alertness). This side effect is especially noticeable early in therapy. In most people, sedation decreases or disappears entirely with time, but, until then, patients taking protriptyline should not perform hazardous activities requiring mental alertness or coordination. The sedative effect is increased when protriptyline is taken with other central nervous system depressants, such as alcoholic beverages, sleeping medications, other sedatives, or antihistamines. It may be dangerous to take protriptyline in combination with these substances. Protriptyline may increase the possibility of having seizures . Patients should tell their physician if they have a history of seizures, including seizures brought on by the abuse of drugs or alcohol. These people should use protriptyline only with caution and should be closely monitored by their physician.

Protriptyline may increase heart rate and stress on the heart. It may be dangerous for people with cardiovascular disease, especially those who have recently had a heart attack, to take this drug or other antidepressants in the same pharmacological class. In rare cases in which patients with cardiovascular disease must take protriptyline, they should be monitored closely for cardiac rhythm disturbances and signs of cardiac stress or damage.

Side effects

Protriptyline shares side effects common to all tricyclic antidepressants. The most frequent of these are dry mouth, constipation, urinary retention, increased heart rate, sedation, irritability, dizziness, and decreased coordination. As with most side effects associated with tricyclic antidepressants, the intensity is highest at the beginning of therapy and tends to decrease with continued use.

Dry mouth, if severe to the point of causing difficulty speaking or swallowing, may be managed by dosage reduction or temporary discontinuation of the drug. Patients may also chew sugarless gum or suck on sugarless candy in order to increase the flow of saliva. Some artificial saliva products may give temporary relief.

Men with prostate enlargement who take protriptyline may be especially likely to have problems with urinary retention. Symptoms include having difficulty starting a urine flow and more difficulty than usual passing urine. In most cases, urinary retention is managed with dose reduction or by switching to another type of antidepressant. In extreme cases, patients may require treatment with bethanechol, a drug that reverses this particular side effect. People who think they may be experiencing any side effects from this or any other medication should tell their physicians.


Dangerously high blood pressure has resulted from the combination of tricyclic antidepressants, such as protriptyline, and members of another class of antidepressants known as monoamine oxidase (MAO) inhibitors. Because of this, protriptyline should never be taken in combination with MAO inhibitors. Patient taking any MAO inhibitors, for example Nardil ( phenelzine sulfate) or Parmate ( tranylcypromine sulfate), should stop the MAO inhibitor then wait at least 14 days before starting protriptyline or any other tricyclic antidepressant. The same holds true when discontinuing protriptyline and starting an MAO inhibitor.

Protriptyline may decrease the blood pressure–lowering effects of clonidine . Patients who take both drugs should be monitored for loss of blood-pressure control and the dose of clonidine increased as needed.

The sedative effects of protriptyline are increased by other central nervous system depressants such as alcohol, sedatives, sleeping medications, or medications used for other mental disorders such as schizophrenia . The anticholinergic effects of protriptyline are additive with other anticholinergic drugs such as benztropine , biperiden , trihexyphenidyl , and antihistamines.

See also



American Society of Health-System Pharmacists. AHFS Drug Information 2002. Bethesda: American Society of Health-System Pharmacists, 2002.

DeVane, C. Lindsay, Pharm.D. "Drug Therapy for Mood Disorders." In Fundamentals of Monitoring Psychoactive Drug Therapy. Baltimore: Williams and Wilkins, 1990.

Jack Raber, Pharm.D.

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