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Depression
16 min read
Written by Klarity Editorial Team
Published: May 5, 2023
Medically Reviewed by Dr. Zoe Russell
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 both tricyclic antidepressants prescribed to treat depression. While they belong to the same class of drugs, they have different uses, doses, and side effects.
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 prescribed to treat major depressive disorder, but they have a number of possible side effects.
Protriptyline is FDA-approved to treat depression, but it can also be prescribed to treat other issues on an off-label basis.
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.
Doxepin is FDA-approved to treat depression and anxiety, but like protriptyline, it also has off-label uses.
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.
Depending on the severity of your symptoms and your doctor’s recommendation, the form, and dosage you take will vary.
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.
Doxepin has several side effects, including:
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.
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:
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 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.
Everyone experiences protriptyline differently depending on their current symptoms and medical history. Always discuss new medications with your healthcare provider beforehand.
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.
Like doxepin, protriptyline also has the following side effects:
Beyond those side effects, you can also experience:
If you experience symptoms of overdose, like a change in consciousness, disorientation, dilated pupils, excessive drowsiness, or trouble breathing, contact emergency medical services immediately.
Protriptyline interacts with 20 most frequently checked medications. Major interactions include Cymbalta, Trintellix, and Zoloft.
Protriptyline has moderate interactions with the following:
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.
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.
Yes, you need a prescription from a trusted medical provider for protriptyline and doxepin.
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 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.
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.
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.
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.
Doxepin is a tricyclic antidepressant used to treat MDD and anxiety.
Protriptyline is a medication primarily prescribed to treat depression.
While doxepin and protriptyline are tricyclic antidepressants and treat similar symptoms, they are administered in different forms and doses and have different side effects.
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.
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.
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.
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.
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.
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.
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.
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