perphenazine and amitriptyline hydrochloride (Etrafon - brand no longer available in the US)

  • Pharmacy Author:
    Omudhome Ogbru, PharmD

    Dr. Ogbru received his Doctorate in Pharmacy from the University of the Pacific School of Pharmacy in 1995. He completed a Pharmacy Practice Residency at the University of Arizona/University Medical Center in 1996. He was a Professor of Pharmacy Practice and a Regional Clerkship Coordinator for the University of the Pacific School of Pharmacy from 1996-99.

  • Medical and Pharmacy Editor: Charles Patrick Davis, MD, PhD
    Charles Patrick Davis, MD, PhD

    Charles Patrick Davis, MD, PhD

    Dr. Charles "Pat" Davis, MD, PhD, is a board certified Emergency Medicine doctor who currently practices as a consultant and staff member for hospitals. He has a PhD in Microbiology (UT at Austin), and the MD (Univ. Texas Medical Branch, Galveston). He is a Clinical Professor (retired) in the Division of Emergency Medicine, UT Health Science Center at San Antonio, and has been the Chief of Emergency Medicine at UT Medical Branch and at UTHSCSA with over 250 publications.

GENERIC NAME: perphenazine and amitriptyline hydrochloride

BRAND NAME: Etrafon (no longer available in the US)

DRUG CLASS AND MECHANISM: Perphenazine/amitriptyline is a combination of an antipsychotic and an antidepressant. Perphenazine is an antipsychotic that works in the brain and nervous system. Its exact mechanism of action is unknown. Amitriptyline is a tricyclic antidepressant. It is believed that in some patients with depression, abnormal levels of neurotransmitters (chemicals that nerves use to communicate with each other) may be related to their depression. Amitriptyline elevates mood by raising the level of neurotransmitters in nerves in the brain. The FDA approved perphenazine/amitriptyline in September 1969.



PREPARATIONS: Tablets: 2/10, 2/25, 4/10, 4/25, and 4/50 mg

STORAGE: Store Perphenazine/amitriptyline tablets at room temperature between 20 C to 25 C (68 F to 77 F). Protect the drug from light.

PRESCRIBED FOR: Perphenazine/amitriptyline tablets are used in patients with moderate to severe anxiety and/or agitation and depressed mood, in patients with depression in whom anxiety and/or agitation are severe and in patients with depression and anxiety in association with chronic physical disease. Patients with schizophrenia with depressive symptoms can be considered for therapy with perphenazine/amitriptyline.


  • Anxiety or agitation with depression: Initial dose is one tablet of 2/25 mg or 4/25 mg by mouth three to four times a day OR take one tablet of 4/50 mg by mouth twice a day.
  • Depression with schizophrenia: Initial dose is two tablets of 4/25 mg by mouth twice or three times a day, a fourth dose may be given at bedtime.
  • Maintenance dose for all patients: Take one tablet of 2/25 mg or 4/25 mg by mouth two to four times a day OR take one tablet of 4/50 mg by mouth twice a day. 2/10 mg and 4/10 mg doses can be used to increase flexibility in adjusting maintenance dosage to the lowest amount consistent with relief of symptoms.
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