Table of contents


16 min read

Doxepin vs. Protriptyline

Written by Klarity Editorial Team

Published: May 5, 2023

Medically Reviewed by Dr. Zoe Russell

Table of contents

Finding the right treatment for your depression symptoms can take time as you and your healthcare provider work to adjust your doses and navigate side effects. 

While doxepin and protriptyline are tricyclic antidepressants that may not work for everyone, they could be good alternatives for you if your current medications aren’t working. In this post, we’ll compare doxepin vs. protriptyline, including their side effects, warnings, and interactions so that you can have an informed discussion with your care provider. 

Discover the right medication for your depression symptoms with a trusted care provider from the comfort of your own home. Schedule an appointment, and Klarity will connect you with a licensed medical provider within 48 hours so that you can get the care you need to find relief.

This article discusses suicide, suicidal ideation, and self-harm. If you or someone you know is experiencing suicidal thoughts or is in crisis, contact the Suicide Prevention Lifeline immediately at 800-273-8255.

Protriptyline and Doxepin Are the Same Class of Drugs (Tricyclics)

Protriptyline and doxepin are both tricyclic antidepressants prescribed to treat depression. While they belong to the same class of drugs, they have different uses, doses, and side effects.

What are Tricyclics?

Tricyclic antidepressants impact the chemical messengers (neurotransmitters) in the brain and work to ease symptoms of depression. These neurotransmitters block the reabsorption of serotonin and norepinephrine, which help regulate mood. With more serotonin and norepinephrine in your system, you’re more likely to experience boosts in mood and alertness.

Protriptyline and Doxepin Are Both Used to Treat Major Depressive Disorder

Protriptyline and doxepin are prescribed to treat major depressive disorder, but they have a number of possible side effects. 

What Else Does Protriptyline Treat?

Protriptyline is FDA-approved to treat depression, but it can also be prescribed to treat other issues on an off-label basis. 

Off-Label Uses for Protriptyline

Off-label use means that your healthcare provider is prescribing a medication that’s been approved by the FDA to treat a particular condition you do not have. For example, protriptyline is primarily FDA-approved to treat depression, but it can be prescribed off-label for anxiety, ADHD, narcolepsy, and headaches as well. 

Additionally, a medication may be used in an off-label capacity if your healthcare provider prescribes it in a different form or dose than what’s been FDA-approved. So, if your medication typically comes as a capsule, but your healthcare provider deems an oral solution to be the better choice for you, that would be considered an off-label prescription. 

Ultimately, off-label use means that the medication hasn’t been through the same tests as FDA-approved medications. Off-label prescriptions are not uncommon, and your healthcare provider can offer you the best guidance as to what’s right for you. 

What Else Does Doxepin Treat?

Doxepin is FDA-approved to treat depression and anxiety, but like protriptyline, it also has off-label uses.

Off-Label Uses for Doxepin

If you experience trouble sleeping, your healthcare provider may prescribe doxepin to help alleviate insomnia symptoms. This medication can make you drowsy and allow you to fall asleep more easily and stay asleep longer.

Doses, Dosage Form, and Side Effects of Doxepin

Depending on the severity of your symptoms and your doctor’s recommendation, the form, and dosage you take will vary. 

Common Doxepin Doses and Forms

Doxepin can be taken as a liquid, tablet, or capsule. For those experiencing mild symptoms, your healthcare provider may prescribe a lower dose, like 25-50 mg, to be taken once a day. If your symptoms are more severe, the typical adult dosage is 75-150 mg daily, with a maximum dose of 300 mg.

Once you begin taking doxepin, it may take two to three weeks for the antidepressant to take effect. If you’re prescribed doxepin for anxiety, you’ll likely see results soon after you begin using it. 

Common Doxepin Side Effects

Doxepin has several side effects, including:

  • Dizziness
  • Dilated pupils
  • Mouth sores
  • Sensitivity to sunlight on your skin
  • Flushing
  • Digestive problems
  • Difficulty urinating
  • Changes in sex drive
  • Excessive sweating
  • Chills
  • Headache
  • Hair loss
  • Increased breast size 
  • Swollen testes 
  • Milky discharge from the nipple (in females)
  • Nausea
  • Vomiting
  • Weakness
  • Weight gain or weight loss
  • Loss of appetite
  • Dry mouth

If you have more serious side effects like increased heart rate, yellowing skin or eyes, unusual bleeding or bruising, and skin irritation or swelling, contact your healthcare provider immediately.

Common Doxepin Drug Interactions

Doxepin has varying interactions with 20 commonly prescribed medications. Major interactions include Cymbalta, Flexeril, Lexapro, Topamax, and Zoloft. 

Moderate interactions can occur with the following medications:

  • Abilify
  • Adderall
  • Ambien
  • Benadryl
  • Klonopin
  • Lamictal
  • Lyrica
  • Norco
  • Seroquel
  • Synthroid
  • Xanax
  • Zyrtec

Doxepin also interacts with 27 diseases, including cardiovascular diseases, seizure disorders, depression, and others. Talk with your care provider about your medical history before taking any new medication. 

Taking doxepin while drinking alcohol can change or increase its effects, and you should always discuss it with your healthcare provider before mixing the two. 

How Much Does Doxepin Cost?

How much you pay for doxepin depends on your pharmacy and the dosage your healthcare provider prescribes. If you’re paying cash, you can expect your prescription to cost anywhere from $17 to $292. That said, you may be able to find more affordable monthly options if you have insurance.

Doses, Dosage Form, and Side Effects of Protriptyline

Everyone experiences protriptyline differently depending on their current symptoms and medical history. Always discuss new medications with your healthcare provider beforehand.

Common Protriptyline Doses and Forms

Protriptyline comes in tablet form, and the adult dose typically starts between 15 to 40 mg daily. If your healthcare provider recommends a higher amount to treat your symptoms, they may increase it to a maximum of 60 mg per day. The dosage can be lower for teenagers and older adults, starting at 5 mg daily. 

Common Side Effects of Protriptyline

Like doxepin, protriptyline also has the following side effects:

  • Changes in urination
  • Excessive sweating
  • Dizziness
  • Chills
  • Weakness
  • Weight gain or loss

Beyond those side effects, you can also experience:

  • Stomach pain
  • Irritability
  • Vision issues
  • Clay-colored stool
  • Chest pain
  • Confusion
  • Ringing in the ears
  • Difficulty speaking
  • Irregular heartbeat
  • Fever
  • Hallucinations
  • Hearing issues
  • Lower back pain
  • Sores or ulcers in the mouth
  • Difficulty sleeping
  • Tics in the face, neck, and back
  • Yellow eyes or skin

If you experience symptoms of overdose, like a change in consciousness, disorientation, dilated pupils, excessive drowsiness, or trouble breathing, contact emergency medical services immediately. 

Common Protriptyline Drug Interactions

Protriptyline interacts with 20 most frequently checked medications. Major interactions include Cymbalta, Trintellix, and Zoloft. 

Protriptyline has moderate interactions with the following:

  • Abilify
  • Adderall
  • Benadryl
  • Bentyl
  • Klonopin
  • Lyrica
  • Nuvigil
  • Synthroid
  • Zyrtec

Additionally, there are several diseases that interact with protriptyline, including cardiovascular diseases, depression, seizure disorders, and certain psychiatric disorders. 

Like doxepin, drinking alcohol while taking protriptyline can alter its effects, so it’s important to talk with a healthcare professional before doing so. 

How Much Does Protriptyline Cost?

Your costs will vary depending on your prescription, the pharmacy you use, and your insurance coverage plan. If you’re paying cash, protriptyline can start at $55 per month for 30 tablets of 10 mg.

Do I Need a Prescription for Protriptyline or Doxepin?

Yes, you need a prescription from a trusted medical provider for protriptyline and doxepin.

Other Tricyclic Side Effects

Tricyclic antidepressants are not the first-line choice for treating depression, as they have many possible side effects, including serotonin syndrome, pregnancy or breastfeeding issues, risk of abnormal bleeding, and they come with a black box warning.

Serotonin Syndrome

Serotonin syndrome can be fatal and is brought on by using medications that boost your serotonin levels, like tricyclic antidepressants. You can experience mild symptoms of serotonin syndrome, including diarrhea or nausea, to severe symptoms like high fever and seizures. You must take your tricyclic antidepressants exactly as prescribed to avoid this.  

Pregnancy and Breastfeeding on Tricyclics

Talk with your healthcare provider before taking tricyclics while pregnant or breastfeeding. In some cases, tricyclic antidepressants can result in birth abnormalities, fetal withdrawal symptoms, and excessive drowsiness while breastfeeding. 

Increased Bleeding Risk with Tricyclics

Tricyclics impact blood levels, which can lead to an increased risk of internal bleeding. This is especially true if you’re taking tricyclic antidepressants with blood thinners. 

Black Box Warning with Antidepressants

Both doxepin and protriptyline are tricyclic antidepressants that come with black box warnings. This warning, the highest warning issued by the U.S. Food and Drug Administration, indicates that antidepressants like doxepin and protriptyline have an increased risk of suicidal thoughts and behaviors. 

Licensed providers on Klarity provide personalized treatment. Find a provider that matches your needs and preferences.

Doxepin and Protriptyline Frequently Asked Questions

What is doxepin?

Doxepin is a tricyclic antidepressant used to treat MDD and anxiety.

What is protriptyline?

Protriptyline is a medication primarily prescribed to treat depression.

Are doxepin and protriptyline the same drug?

While doxepin and protriptyline are tricyclic antidepressants and treat similar symptoms, they are administered in different forms and doses and have different side effects. 

Why is doxepin an off-label treatment for anxiety?

Doxepin is FDA-approved to treat MDD, but medical providers may prescribe it off-label to treat other mental health issues because it can be an effective way to manage symptoms.

What’s better for anxiety? Doxepin or protriptyline?

Both doxepin and protriptyline can help alleviate symptoms of anxiety. Doxepin can make you drowsy, which may not work for your schedule. On the other hand, protriptyline can lower your sex drive and exacerbate heart issues. You should discuss your anxiety symptoms with your healthcare provider to determine which medication is right for you.

What’s better for depression? Doxepin or protriptyline?

Which medication is better to treat your depression depends on your health history and the recommendation of your healthcare provider. Protriptyline is part of the first-line medications prescribed to treat depression, while doxepin is a second-line treatment due to its many side effects. 

Can I drive on antidepressants like doxepin or protriptyline?

Doxepin and protriptyline can make you drowsy, and you should not operate a vehicle or any machinery until you know how they impact your body and behavior.

Can I drink alcohol on doxepin or protriptyline?

Drinking alcohol with doxepin or protriptyline can alter its intended impact and result in adverse side effects. Talk with your doctor before mixing alcohol and tricyclic antidepressants. 

Does it matter what time of day I take doxepin or protriptyline?

You should take doxepin about 30 minutes before going to sleep at night. Protriptyline should be taken exactly as instructed, ideally at the same time each day. 

How Klarity Gets You Access to Depression Treatment

When you’re ready to speak with a healthcare provider about your depression treatment options, you shouldn’t have to endure long wait times or inconvenient travel to your nearest clinic. 

Schedule an appointment, and we’ll match you with a board-certified care provider within 48 hours who will thoroughly discuss your symptoms and prescribe the right medication for you and your needs. 


“Compare Vivactil vs. Doxepin.” Iodine

Mayo Clinic Staff. “Tricyclic Antidepressants and Tetracyclic Antidepressants.” Mayo Clinic

“Protriptyline” National Library of Medicine

David N. Neubauer. “Pharmacotherapeutic Approach to Insomnia in AdultsScienceDirect

“Doxepin Interactions.”

“Doxepin Prices, Coupons, and Patient Assistance Programs.”

IBM Micromedex. “Protriptyline (Oral Route) Proper Use.” Mayo Clinic

IBM Micromedex. “Protriptyline (Oral Route) Side Effects.” Mayo Clinic

“Protriptyline Interactions Checker.”

“Serotonin Syndrome: What it is, Causes, Symptoms & Treatment.” Cleveland Clinic

“The use of antidepressants in pregnancy.” Medsafe

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