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

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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.

The maximum dose is 16/200 mg per day.

DRUG INTERACTIONS: Perphenazine/amitriptyline should be used with caution with medications like paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft) because these medications also increase the concentration of neurotransmitters in the body leading to severe and deadly reactions.

Perphenazine/amitriptyline should be avoided with medications like quinidine, disopyramide (Norpace), procainamide (Pronestyl), propafenone (Rhythmol), and flecainide (Tambocor) because they may also affect heart rhythm and increase the risk of an irregular heart rate and rhythm.

Perphenazine/amitriptyline should be used with caution with medications like epinephrine due to increased risk of irregular heart rates and rhythms.

PREGNANCY: Newborn babies may be at risk for withdrawal or extrapyramidal symptoms. Perphenazine/amitriptyline is not recommended for use in pregnant women.

NURSING MOTHERS: Perphenazine/amitriptyline enters breast milk and is not recommended during breastfeeding.

SIDE EFFECTS: Side effects of Perphenazine/amitriptyline are abnormal muscle contractions, difficulty breathing and swallowing, neck spasms, and movement abnormalities on face, arms, and legs. This medication also causes dizziness, drowsiness, sedation, irregular heart rate and rhythm, increase or decrease in blood pressure, and blurred vision.

Antidepressants increased the risk of suicidal thinking and behavior in short-term studies in children and adolescents with depression and other psychiatric disorders. Anyone considering the use of antidepressants in a child or adolescent must balance this risk of suicide with the clinical need. Patients who are started on therapy should be closely observed for clinical worsening, suicidal thoughts, or unusual changes in behavior.

Elderly patients with dementia related psychosis treated with antipsychotics are at an increased risk of death.


FDA Prescribing Information.

Medscape. amitriptyline/perphenazine.

Medically Reviewed by a Doctor on 8/11/2014

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