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Medication Guide — Perphenazine And Amitriptyline Hydrochloride

Patient-friendly FDA guidance and safety information.

Last updated · May 12, 2026Source: DailyMed ↗
Boxed Warning

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Perphenazine and amitriptyline hydrochloride is not approved for the treatment of patients with dementia-related psychosis (see WARNINGS).

Poison Help

If you suspect an overdose or accidental ingestion, call Poison Control: 1-800-222-1222 (free, 24/7, U.S.). For life-threatening symptoms, call 911.

Medication Guide

This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.

Revised: 8/2025

Antidepressant Medicines, Depression and Other Serious Mental Illnesses,
and Suicidal Thoughts or Actions

Read the Medication Guide that comes with your or your family member’s antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines. Talk to your, or your family member’s, healthcare provider about:

  • •all risks and benefits of treatment with antidepressant medicines
  • •all treatment choices for depression or other serious mental illness

What is the most important information I should know about antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions?

  1. 1. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment.
  2. 2. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions.
  3. 3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?
    1. •Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.
    2. •Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
    3. •Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.

Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:

  • •thoughts about suicide or dying
  • •attempts to commit suicide
  • •new or worse depression
  • •new or worse anxiety
  • •feeling very agitated or restless
  • •panic attacks
  • •trouble sleeping (insomnia)
  • •new or worse irritability
  • •acting aggressive, being angry, or violent
  • •acting on dangerous impulses
  • •an extreme increase in activity and talking (mania)
  • •other unusual changes in behavior or mood
  • • Low salt (sodium) levels in the blood. Elderly people may be at greater risk for this. Symptoms may include:
  • •headache
  • •weakness or feeling unsteady
  • •confusion, problems concentrating or thinking or memory problems
  • • Visual problems: eye pain, changes in vision, swelling or redness in or around the eye
  • ▪ Serotonin Syndrome. This condition can be life-threatening and symptoms may include:
  • •agitation, hallucinations, coma, or other changes in mental status
  • •racing heartbeat, high or low blood pressure
  • •coordination problems or muscle twitching (overactive reflexes)
  • •nausea, vomiting, or diarrhea
  • •sweating or fever
  • •muscle rigidity

What else do I need to know about antidepressant medicines?

  • • Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
  • • Visual problems: Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are.
  • • Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.
  • • Antidepressant medicines have other side effects. Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member.
  • • Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider. 
  • • Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child’s healthcare provider for more information.
  • •Tell your healthcare provider if have low sodium levels in your blood during treatment with perphenazine and amitriptyline hydrochloride tablets.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Manufactured for:
Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.

Manufactured by:
Mylan Laboratories Limited
Hyderabad — 500 096, India

75110210

MXA:PRAT:R4m

Sources

RxCUI: 856706

NDC: 0378-0042

Last fetched: May 12, 2026

Source: DailyMed ↗

⚠️ Disclaimer

This information is for educational purposes only and is not medical advice. Always consult your doctor, pharmacist, or other licensed healthcare professional before starting, stopping, or changing any medicine. Read full medical disclaimer.