Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, studies have shown that a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. It is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition. Tell the doctor right away if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms when a new antidepressant is started or when the dose is changed.
There may be a slightly increased risk of serious, possibly fatal side effects (such as stroke, heart failure, fast/irregular heartbeat, pneumonia) when this medication is used by older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication, as well as other effective and possibly safer treatments for dementia-related behavior problems, with the doctor.
See also Warning section.
Before taking amitriptyline with perphenazine, tell your doctor or pharmacist if you are allergic to it; or to other tricyclic antidepressants (such as nortriptyline); or to other phenothiazines (such as chlorpromazine, fluphenazine); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.
Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding problems, decreased bone marrow function, breathing problems (such as asthma, emphysema), liver problems, low blood pressure, recent heart attack, breast cancer, problems urinating (such as due to enlarged prostate), overactive thyroid (hyperthyroidism), personal or family history of glaucoma (angle-closure type), personal or family history of bipolar disorder, alcohol/substance abuse, family history of suicide, seizures, diabetes, conditions that may increase your risk of seizures (such as head injury, drug/alcohol withdrawal), a certain severe reaction to other medications (neuroleptic malignant syndrome), a certain adrenal gland tumor (pheochromocytoma), restless legs syndrome, Parkinson's disease.
Perphenazine/amitriptyline may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.
The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using perphenazine/amitriptyline, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).
Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, vomiting, or eating disorders (such as bulimia). Talk to your doctor about using perphenazine/amitriptyline safely.
This drug may make you dizzy or drowsy or blur your vision. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).
Before having any surgery, procedure, or imaging (such as X-ray, CT-scan), tell your doctor or dentist about this medication and all the products you use (including prescription drugs, nonprescription drugs, and herbal products).
This medication may make you more sensitive to the sun. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors. Tell your doctor right away if you get sunburned or have skin blisters/redness.
Caution is advised during hot weather because the perphenazine in this product can reduce sweating, increasing your risk for a severe reaction to too much heat (heatstroke). Drink plenty of fluids. Avoid strenuous exercise in hot weather. If you become overheated, promptly seek cooler shelter and/or stop exercising. Get medical help right away if your body temperature is above normal or if you have mental/mood changes, headache, or dizziness.
Avoid exposure to certain chemicals used in gardening (organic phosphate insecticides). Get medical help right away if you are exposed to garden chemicals and have an unusual headache, heavy sweating, or difficulty breathing.
If you have diabetes, this drug may increase your blood sugar. Check your blood sugar regularly as directed and share the results with your doctor. Tell your doctor right away if you have symptoms such as increased thirst/urination. Your doctor may need to adjust your diabetes medication, exercise program, or diet.
Children may be more sensitive to the side effects of this drug, especially uncontrolled movements.
Older adults may be more sensitive to the side effects of this drug, especially dizziness, lightheadedness, drowsiness, confusion, bleeding, constipation, difficulty urinating, uncontrolled movements, and QT prolongation (see above). Dizziness, lightheadedness, drowsiness, and confusion can increase the risk of falling.
During pregnancy, this medication should be used only when clearly needed. Babies born to mothers who have used this drug during the last 3 months of pregnancy may rarely develop symptoms including muscle stiffness or shakiness, drowsiness, feeding/breathing difficulties, or constant crying. If you notice any of these symptoms in your newborn especially during their first month, tell the doctor right away.
Since untreated mental/mood problems (such as depression, schizophrenia) can be a serious condition, do not stop taking this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately discuss with your doctor the benefits and risks of using this medication during pregnancy.
This medication passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breastfeeding.
See also Warning section.
Drowsiness, dizziness, lightheadedness, dry mouth, blurred vision, constipation, tiredness, weight gain, or trouble urinating may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.
Dizziness and lightheadedness can increase the risk of falling. Get up slowly when rising from a sitting or lying position.
To relieve dry mouth, suck on hard candy or ice chips, chew gum, drink water, or use a saliva substitute.
Tell your doctor right away if any of these side effects occur: muscle spasm/stiffness, shaking (tremor), restlessness, mask-like expression of the face, drooling/trouble swallowing, or shuffling walk. Your doctor may prescribe another medication to decrease these side effects.
Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
Tell your doctor right away if you have any serious side effects, including: nausea/vomiting that doesn't stop, heartburn that doesn't go away, easy bleeding/bruising, signs of infection (such as sore throat that doesn't go away, fever), stomach/abdominal pain, yellowing eyes/skin.
Perphenazine may cause a condition known as tardive dyskinesia. In some cases, this condition may be permanent. Tell your doctor right away if you develop any uncontrollable movements such as lip smacking, mouth puckering, tongue thrusting, chewing, or unusual arm/leg movements.
In rare cases, perphenazine may increase your level of a certain substance made by the body (prolactin). For females, this increase in prolactin may result in unwanted breast milk, missed/stopped periods, or difficulty becoming pregnant. For males, it may result in decreased sexual ability, inability to produce sperm, or enlarged breasts. If you develop any of these symptoms, tell your doctor right away.
This medication may rarely cause a very serious condition called neuroleptic malignant syndrome (NMS). Get medical help right away if you have any of the following symptoms: fever, muscle stiffness/pain/tenderness/weakness, severe tiredness, severe confusion, sweating, fast/irregular heartbeat, dark urine, signs of kidney problems (such as change in the amount of urine).
Get medical help right away if you have any very serious side effects, including: signs of stroke (such as weakness on one side of the body, trouble speaking, confusion), eye pain/swelling/redness, widened pupils, vision changes (such as seeing rainbows around lights at night), chest/jaw/left arm pain, severe dizziness/fainting, black stools, vomit that looks like coffee grounds, seizures.
A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
In the US -
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.
In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
Copyright © 2025 TraceGains, Inc. All rights reserved.
RxAnswers™ is a copyrighted combined product from TraceGains and First DataBank, Inc.
Drug information is selected from data included with permission and copyrighted by First DataBank, Inc. This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your healthcare professional. Always seek the advice of your healthcare professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your healthcare professional. This information does not contain any assurances that this product is safe, effective or appropriate for you.
This information is intended only for residents of the United States. Products sold under the same brand names in other countries may contain different ingredients.
Learn more about First DataBank
There are some limitations on the information provided in “Nutrient Interactions.” Do NOT rely solely on the information in this article. Please read the disclaimer.
Learn more about TraceGains, the company.
TraceGains and/or its suppliers make no warranties or representations as to the accuracy or completeness of this content herein or that of any organization referred or linked to within this content and will not be liable for any damages arising out of your access to or use of any information found herein or that of any organization referred to within this content.
Information expires December 2025.