VA Class:CN601

AHFS Class:

• Tricyclics and Other Norepinephrine-reuptake Inhibitors 28:16.04.28

Generic Name(s):

• Protriptyline Hydrochloride

Protriptyline hydrochloride is a dibenzocycloheptene-derivative tricyclic antidepressant.

Administration

Protriptyline hydrochloride is administered orally. Although protriptyline has been administered in up to 4 divided doses throughout the day, it is long-acting and the entire daily dose may be administered at one time.

Dosage

There is a wide range of dosage requirements, and dosage of protriptyline hydrochloride must be carefully individualized. Initial dosages should be low and generally range from 15-40 mg daily, depending on the severity of the condition being treated. Dosage may be gradually adjusted to the level which produces maximal therapeutic effect with minimal toxicity; increases should be made to the morning dose.100 Dosages may range up to 60 mg daily. Geriatric and adolescent patients should usually be given lower than average dosages. The manufacturers state that therapy should be initiated with 5 mg 3 times daily in these patients. Dosage may be gradually increased if necessary, but geriatric patients receiving more than 20 mg daily should be carefully monitored for cardiac abnormalities. Maximum antidepressant effects may not occur for 2 or more weeks after therapy is begun.

After symptoms are controlled, dosage should be gradually reduced to the lowest level which will maintain relief of symptoms. To avoid the possibility of precipitating withdrawal symptoms, protriptyline should not be terminated abruptly in patients who have received high dosage for prolonged periods.

Patients should be monitored for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustment.101,102,103 (See Cautions: Precautions and Contraindications, in the Tricyclic Antidepressants General Statement 28:16.04.28.)

Protriptyline shares the pharmacologic actions, uses, and toxic potentials of the tricyclic antidepressants, and the usual precautions of tricyclic antidepressant administration should be observed. Patients should be fully advised about the risks, especiallysuicidal thinking and behavior (suicidality), associated with tricyclic antidepressant therapy.102,103 For a complete discussion, see Cautions: Precautions and Contraindications and Cautions: Pediatric Precautions, in the Tricyclic Antidepressants General Statement 28:16.04.28.

Pediatric Precautions

Safety and efficacy of protriptyline in pediatric patients have not been established.100

The US Food and Drug Administration (FDA) has determined that antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder and other psychiatric disorders.102 However, FDA also states that depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.102 Anyone considering the use of protriptyline in a child or adolescent for any clinical use must therefore balance the potential risk of therapy with the clinical need.102,103,104 (See Cautions: Precautions and Contraindications and Cautions: Pediatric Precautions, in the Tricyclic Antidepressants General Statement 28:16.04.28.)

Pharmacokinetics

Protriptyline is completely absorbed from the GI tract. Peak plasma concentrations occur within 24-30 hours. Protriptyline is metabolized via the same pathways as are other tricyclic antidepressants. The drug is eliminated slowly; 50% of a dose is excreted in the urine as metabolites within approximately 16 days. Very little drug is excreted in the feces via the bile.

Chemistry and Stability

Chemistry

Protriptyline hydrochloride is a dibenzocycloheptene-derivative tricyclic antidepressant. The drug occurs as a white to yellowish powder and is freely soluble in water and in alcohol.

Stability

Commercially available protriptyline hydrochloride tablets have an expiration date of 5 years following the date of manufacture. Protriptyline hydrochloride tablets should be stored in tight containers at 15-30°C.100

Additional Information

For further information on chemistry, pharmacology, pharmacokinetics, uses, cautions, acute toxicity, drug interactions, and dosage and administration of protriptyline, see the Tricyclic Antidepressants General Statement 28:16.04.28.

Only references cited for selected revisions after 1984 are available electronically.

100. Odyssey Pharmaceuticals, Inc. Vivactil^® (protriptyline hydrochloride) tablet prescribing information. East Hanover, NJ; 2003 Jan.

101. Food and Drug Administration. FDA news: FDA proposes new warnings about suicidal thinking, behavior in young adults who take antidepressant medications. Rockville, MD; 2007 May 2. From the FDA web site. [Web]

102. Food and Drug Administration. Antidepressant use in children, adolescents, and adults: class revisions to product labeling. Rockville, MD; 2007 May 2. From the FDA web site. [Web]

103. Food and Drug Administration. Revisions to medication guide: antidepressant medicines, depression and other serious mental illnesses and suicidal thoughts or actions. Rockville, MD; 2007 May 2. From the FDA web site. [Web]

104. Bridge JA, Iyengar S, Salary CB. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA . 2007; 297:1683-96. [PubMed 17440145]