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Drug Profile

Do NOT stop taking this or any drug without the advice of your physician. Some drugs can cause severe adverse effects when they are stopped suddenly.

Do Not Use [what does this mean?]
Generic drug name: amitriptyline and perphenazine (a mee TRIP ti line and per FEN a zeen)
Brand name(s): TRIAVIL
GENERIC: not available FAMILIES: Traditional or Typical Antipsychotics, Tricyclics
Find the drug label by searching at DailyMed.

Alternative Treatment [top]

For Depression, see desipramine and nortriptyline.

Safety Warnings For This Drug [top]

FDA BLACK BOX WARNING

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Elderly patients with dementia-related psychosis who are treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials, largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients that was 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 percent, compared with a rate of about 2.6 percent in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (for example, heart failure or sudden death) or infectious (for example, 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. Combination amitriptyline-perphenazine is not approved for the treatment of patients with dementia-related psychosis.

Suicidality and Antidepressant Drugs

Compared with placebo, antidepressants increased the risk of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder and other psychiatric disorders. Anyone considering the use of combination amitriptyline-perphenazine or any other antidepressant in a child, adolescent or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults beyond age 24; there was a reduction in the risk with antidepressants compared with placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber.

Combination amitriptyline-perphenazine is not approved for use in pediatric patients.

Anticholinergic Effects

Warning: Special Mental and Physical Adverse Effects

Older adults are especially sensitive to the harmful anticholinergic effects of these drugs. Drugs in this family should not be used unless absolutely necessary.

Mental Effects: confusion, delirium, short-term memory problems, disorientation and impaired attention

Physical Effects: dry mouth, constipation, difficulty urinating (especially for a man with an enlarged prostate), blurred vision, decreased sweating with increased body temperature, sexual dysfunction and worsening of glaucoma

If you use this drug, ask your doctor about switching to another antidepressant. Do not stop taking this drug suddenly. Your doctor must give you a schedule to lower your dose gradually, to prevent withdrawal symptoms such as headache, mood change, nausea, vomiting, diarrhea, or trouble sleeping and vivid dreams.

Facts About This Drug [top]

The brand-name product TRIAVIL contains two active ingredients: a tricyclic antidepressant, amitriptyline, and an antipsychotic, perphenazine. It is used to treat moderate to severe anxiety, agitation, and depression. Public Citizen recommends against using TRIAVIL for four major reasons. 

  1. Although TRIAVIL is available in different strengths, the dose of each of its two ingredients is fixed and may not exactly fit your needs. 
  2. Combining an antipsychotic with an antidepressant...

The brand-name product TRIAVIL contains two active ingredients: a tricyclic antidepressant, amitriptyline, and an antipsychotic, perphenazine. It is used to treat moderate to severe anxiety, agitation, and depression. Public Citizen recommends against using TRIAVIL for four major reasons. 

  1. Although TRIAVIL is available in different strengths, the dose of each of its two ingredients is fixed and may not exactly fit your needs. 
  2. Combining an antipsychotic with an antidepressant has not been shown to produce a more effective drug.[1]
  3. Using this combination raises the risk of harmful side effects, since it may cause any of the side effects of either of its ingredients, including severe drowsiness and other anticholinergic effects (see box). 
  4. The antidepressant ingredient in this combination, amitriptyline, has more side effects than any other drug in its family (see Adverse Effects of Antidepressants table in Depression: When are Drugs Called For And Which Ones Should You Use?) and should not be used by older adults either alone or in combinations such as this one.

A group of highly regarded drug safety experts maintains a list of drugs they consider inappropriate for use in patients over 65. This irrational combination product is among the 48 medications or classes of medication on that list.[2] 

For patients who need an antidepressant drug, we recommend trying one of the newer selective serotonin reuptake inhibitors (SSRIs) (for example, fluoxetine [PROZAC, SARAFEM, SELFEMRA]) first, as these are the safest antidepressants. If symptoms do not improve sufficiently with use of an SSRI and remain severe, further treatment with other antidepressants is warranted.

In 2015, a study published in JAMA Internal Medicine showed that strong anticholinergic drugs were associated with an increased risk of dementia in older adults. The study also showed that higher doses and longer use of these drugs are associated with higher risk of dementia.[3]

Refer to the August 2015 issue of Worst Pills, Best Pills News for examples of strong anticholinergic drugs.

Regulatory actions surrounding amitryptyline and perphenazine

2004: In October 2004 the Food and Drug Administration (FDA) issued a public health advisory requiring manufacturers to add a black-box warning to its professional product labeling (package insert) of all antidepressants. A black-box warning is the strongest type of warning that the FDA can require. The FDA also requires that a Patient Medication Guide be given to patients receiving this drug advising them of the risk and precautions that can be taken.  

2007: The FDA announced in May 2007 that it will require new warnings concerning the increased risk of suicidal thoughts and behavior in young adults ages 18 to 24 during the first one to two months of treatment with antidepressants. The agency wants the new warnings to be black-box warnings printed on the professional product labels for all antidepressants sold in the US. The warning is an amendment to an existing black-box warning for children and adolescents.[4]

last reviewed January 31, 2024