Table of contents


21 min read

Doxepin vs. Trimipramine: Which Should I Take?

Written by Klarity Editorial Team

Published: Jan 13, 2023

Medically Reviewed by Dr. Zoe Russell

Table of contents

With so many different depression medications on the market, it can be challenging to navigate them and understand which one is best for you. Living with symptoms of depression can be difficult, but finding the right medication doesn’t have to be. 

In this article, we will compare two medications used in the treatment of depression, Doxepin and Trimipramine, so that you can be better informed when discussing treatment options with your healthcare provider. 

If you are looking to treat your depression with medications like Doxepin or Trimipramine, Klarity may be able to help. We’ll match you with a licensed healthcare provider in your state for simple and affordable online depression treatment. 

Find a provider today and be seen in just 48 hours for your first telehealth appointment. After a brief evaluation, your provider can determine if antidepressants are right for you, and send them directly to your local pharmacy as part of your personalized treatment plan. 

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.

Drug ClassTricyclic antidepressantTricyclic antidepressant

Brand / Generic StatusGeneric (Brand name: Surmontil)Generic (Brand name: Silenor)

Form(s) of the Drug• Immediate-release capsules• Immediate-release capsules
• Immediate-release tablets
• Clear, blueberry-mint flavored liquid suspension
• Topical cream (for itching)
Standard DosageImmediate-release capsules:
• 25 mg
• 50 mg
• 100 mg
Immediate-release capsule:
• 10mg
• 25mg
• 50mg
• 75mg
• 100mg
• 150mg

Immediate-release tablets:
• 3mg
• 6mg

Liquid suspension:
• 10mg per dose

Topical cream:
• 5% formula
Conditions TreatedFDA-approved:
• Major depressive disorder

Off-label uses:
• Difficulty sleeping
FDA-approved uses:
• Major depressive disorder
• Anxiety disorder

Off-label uses:
• Itchiness due to atopic dermatitis, pruritus, or lichen simplex chronicus
• Topical neuropathic pain
CostGeneric (trimipramine):
• $30 to $78 for a 30-day supply

Brand name:
• $160 to $171 for a 30-day supply

Brand name (Silenor):
• $32 to $525 for a 30-day supply

Generic form (doxepin)
• $36 to $90 for a 30-day supply
• $8 for a 30-day supply with coupons/discounts
Side-EffectsCommon side effects:
• Drowsiness, fatigue
• Nausea, vomiting, abdominal cramping, or constipation
• Dry mouth
• Changes in blood pressure
• Blurred vision
• Changes of sensation, such as feeling “pins and needles” in your extremities
• Loss of appetite
• Decreased sex drive
• Headache
• Skin rash

Serious side effects:
• Suicidal thoughts or self-harm behaviors
• Serotonin syndrome
• Signs of heart attack
• Signs of stroke

Common side effects:
• Agitation, confusion
• Black, tarry stools, bleeding gums, blood in urine or stool
• Blurred vision
• A sensation of burning, itching, or “pins and needles” on the skin
• Chest pain or tightness, fast or irregular heartbeat
• Chills, cold sweats
• Urinary retention
• Dizziness upon standing, loss of consciousness
• Headache
• Hearing loss
• Muscle spasms, stiffness, twitching
• Seizures
Warnings For UseDrug interactions
• Anticholinergic medications
• Certain medications for high blood pressure
• Drugs that may increase the level of the medication
• Protease inhibitors
• Drugs that affect heart rhythm
• Motion sickness medication
• St. John’s wort
• Thyroid medications
Drug interactions:
• Thyroid supplements
• Anticholinergic drugs
• Some blood pressure medications: clonidine
• MAO inhibitors: isocarboxazid, linezolid, metaxalone, methylene blue
• St. John's Wort
• Cimetidine
• Terbinafine
• Drugs to treat irregular heart rate

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

Trimipramine and Doxepin are two medications that belong to the same class of drugs called tricyclic antidepressants (TCAs). These medications are both primarily used to treat depression but have different properties that make each drug unique. 

What Are Tricyclics?

Serotonin and norepinephrine are two important neurotransmitters, or chemical messengers, that are involved in several bodily functions, such as mood, appetite, sleep, and sex drive. 

TCAs work by blocking the reuptake of serotonin and norepinephrine in the brain, which results in increased levels of these neurotransmitters and improvement in depressive symptoms. 

Tricyclics are some of the oldest forms of medication used to treat depression, but they have been phased out in recent years in favor of other drugs, like SSRIs and SNRIs. Due to the way tricyclics work, they target other parts of the brain in addition to serotonin and norepinephrine. Because of this, they have a much larger side effect profile than selective drugs. 

While tricyclics aren’t prescribed as often as they once were, they are still useful in certain patients, including those who feel that SSRIs and SNRIs are ineffective in treating their depression.

Trimipramine and Doxepin Are Both Used To Treat Major Depressive Disorder

Tricyclic antidepressants, including Trimipramine and Doxepin, are used to treat depressive disorders, the most common of which is Major Depressive Disorder (MDD). 

MDD is characterized by:

  • Loss of interest in pleasurable activities 
  • Feelings of sadness, emptiness, or hopelessness
  • Irritability 
  • Sleep disturbances, including insomnia or increased need for sleep
  • Changes in appetite, resulting in weight loss or gain

What Else Does Trimipramine Treat?

Trimipramine, sometimes called Surmontil, is a unique tricyclic medication. Thanks to its weak antipsychotic properties, it can be useful in treating depression with delusions or psychotic features. 

Off-label Uses for Trimipramine 

The term off-label refers to any use of a medication that has not been FDA-approved, which requires a lengthy and extensive research process. Like most TCA medications, Trimipramine has sedative effects and is also useful in the treatment of insomnia and other sleep disorders. 

What Else Does Doxepin Treat?

Doxepin, also known as Silenor, is primarily used in the treatment of depression and anxiety. In 2010, 3mg and 6mg Doxepin tablets were FDA-approved for the treatment of insomnia.

Other Uses for Doxepin  

Doxepin is also available as a topical cream to treat itching associated with certain dermatological conditions, such as eczema. Additionally, it is often prescribed off-label to treat diabetic neuropathy pain.

What is Doxepin?

Doxepin, also known as Silenor in its brand-name form, is a tricyclic medication that is commonly used in the treatment of anxiety and depression. It is also commonly prescribed to treat primary insomnia, otherwise known as sleep onset insomnia, in which patients have difficulty falling asleep. 

Doses, Dosage Form, and Side Effects of Doxepin  

Common Doxepin Doses and Forms

Doxepin is available in capsules, tablets, an oral solution, and topical creams. Doxepin capsules are available in a large range from 10 mg to 150 mg, while tablets are only available in 3 mg and 6 mg.  

Doxepin is typically started at a low dose of 75 mg once daily and can then be titrated up weekly to a maximum dose of 150 mg per day. 

Common Doxepin Side Effects

There are several potential side effects associated with Doxepin, ranging in severity from mild to serious and even life-threatening. It is important to contact your healthcare provider or seek immediate medical attention if you begin to experience any of the serious side effects listed below. 

Common side effects associated with Doxepin include: 

  • Agitation or confusion 
  • Chills, increased sweating 
  • Headache 
  • A sensation of burning, itching, or “pins and needles” on the skin 
  • Dizziness upon standing 
  • Muscle spasms, stiffness, twitching 

Serious side effects of Doxepin include: 

  • Signs of easy bruising or bleeding
  • Chest pain or tightness
  • Fast or irregular heartbeat 
  • Blurred vision 
  • Hearing loss 
  • Seizures
  • Loss of consciousness

Common Drug Interactions with Doxepin

The majority of TCAs interact with several other commonly prescribed medications. As always, it is important to discuss all medications, including over-the-counter medications and supplements, with your healthcare provider before starting a new medication.

Common drug interactions with Doxepin include: 

  • Anticholinergic drugs 
  • MAOI medications, including isocarboxazid, linezolid, or methylene blue 
  • SSRIs
  • Thyroid supplements 
  • Certain antihypertensive medications, such as clonidine
  • Antifungal medications, like Terbinafine 
  • Antiarrhythmic medications or drugs that treat irregular heart rate
  • St. John’s Wort

How Much Does Doxepin Cost?

Doxepin is typically covered by most insurance plans and is a relatively affordable medication for those who are uninsured. The use of coupon codes that are found at large name-brand pharmacies can lower the cost of your 30-day supply from the average retail price of $50 to less than $10 per month. 

What is Trimipramine?

Trimipramine, also known as Surmontil, is another tricyclic medication that is also commonly used to treat anxiety and depression. This medication is a unique TCA, as it has mild antipsychotic properties and can be used for the treatment of depression with psychotic features. 

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

Doses, Dosage Form, and Side Effects of Trimipramine  

Common Trimipramine Doses and Forms

Trimipramine is available in 25 mg, 50 mg, and 100 mg capsules. The initial recommended dose is 25 mg at bedtime, but this can vary based on the severity of symptoms. For example, the starting dose in hospitalized patients can be as high as 100 mg but requires close monitoring. 

The daily dose of Trimipramine can be slowly increased weekly with a maximum dose of 200 mg per day. This medication can be prescribed as a single dose at bedtime or divided into multiple doses throughout the day. 

Common Trimipramine Side Effects

As with any medication, there are associated risks, such as side effects, that should be considered before starting a medication. The most common side effects associated with Trimipramine are mild, but there are a few serious adverse effects that require immediate medical attention. 

The most common side effects of Trimipramine include: 

  • Fatigue 
  • Drowsiness 
  • GI upset, including nausea, vomiting, abdominal pain, or constipation 
  • Changes in blood pressure 
  • Loss of appetite
  • Headache 
  • Dry mouth 
  • A sensation of “pins and needles” on the skin of your extremities
  • Rash 
  • Decreased libido or changes in sex drive 

Rare but serious side effects of Trimipramine that require immediate medical attention: 

  • New or worsening suicidal thoughts or self-harm behaviors 
  • Signs of a heart attack – chest pain, fast or irregular heartbeat, sweating, or dizziness
  • Signs of a stroke – weakness, difficulty speaking, headache, imbalance or loss of coordination, changes in mental status, or paralysis of one side of your body
  • Serotonin syndrome – fever, high blood pressure, fast heart rate, changes in mental status, irregular movements 

Common Trimipramine Drug Interactions

Like other tricyclic antidepressants, there are several drug interactions with Trimipramine. As always, you must disclose all current medications you are currently taking with your healthcare provider, including all over-the-counter medications and supplements. 

The most common drug interactions with Trimipramine include: 

  • MAO inhibitors 
  • Anticholinergic medications
  • Certain antihypertensive medications: clonidine, guanethidine
  • Protease inhibitors 
  • Medicines that affect heart rhythm: flecainide, quinidine, propafenone
  • Thyroid supplements 
  • Haloperidol 
  • Motion sickness medications 
  • Other drugs that increase levels of serotonin: SSRIs, St. John’s Wort, MDMA, or ecstasy 

How Much Does Trimipramine Cost?

Trimipramine, or name-brand Surmontil, is covered by the majority of health insurance plans, and coupon codes significantly reduce the cost of the medication for those who are uninsured. Coupons can be found at large retail pharmacies and lower the retail price down from $130 to $35 for a 30-day supply. 

Do I Need A Prescription for Trimipramine or Doxepin?

Yes. Like with all other antidepressant drugs, a prescription from a licensed healthcare provider is necessary for both Trimipramine and Doxepin. These medications are not available over the counter because, as described above, there are several drug interactions and side effects that need to be taken into account before starting a TCA medication. 

A healthcare provider on Klarity can determine if a TCA medication, such as Trimipramine or Doxepin, is right for you. 

Other Tricyclic Side Effects

There are a couple of uncommon but serious side effects that are associated with the use of tricyclic medications. It is important to be closely monitored when starting a TCA medication, and if you begin to experience any of the following adverse effects, contact your healthcare provider or seek out immediate medical attention. 

What is Serotonin Syndrome?

Serotonin syndrome is a rare but serious and potentially life-threatening condition that occurs when there are high levels of serotonin in the body. This is most common in those who are taking multiple medications that increase serotonin levels. 

Several medications cause serotonin levels to increase in the body, including other antidepressants, ADHD medicines, opioids, and non-prescription drugs like St. John’s Wort or MDMA. 

The signs and symptoms of serotonin syndrome include: 

  • High fever
  • Rapid heart rate and high blood pressure 
  • Nausea, vomiting, or diarrhea 
  • Dilated pupils 
  • Insomnia 
  • Agitation or restlessness
  • Muscle twitching or rigidity 
  • Altered mental status or confusion 

Severe complications of serotonin syndrome: 

  • Seizures 
  • Arrhythmias or irregular heartbeat 
  • Unconsciousness 

It is important to seek immediate medical attention if you begin to experience these symptoms after starting a TCA medication, as this condition can be fatal if left untreated. 

Pregnancy and Breastfeeding on Tricyclics

Tricyclics are generally avoided in pregnancy because of the following complications: 

  • Spontaneous loss of pregnancy 
  • High blood pressure, preeclampsia, or eclampsia 
  • Preterm birth 
  • Postpartum hemorrhage 
  • Postnatal effects: withdrawal symptoms, hypoglycemia, jaundice, or lack of respiratory drive

Taking a TCA medication while breastfeeding is typically viewed to be safe for the infant because there are relatively low levels of the drug within breast milk. 

Black Box Warning With Antidepressants

As with most antidepressant medications, there is a risk of worsening depression and suicidal ideation or self-harm behavior. This is a rare occurrence but is most commonly seen in those who are under the age of 24.    

Access Depression Treatment Today with Klarity

With so many different treatment options available for depression, finding the medication that is best for you can seem overwhelming. Let the providers on Klarity help. 

At Klarity, we connect patients with licensed healthcare providers for straightforward and affordable online depression treatment. If you are looking to treat your depression with medication, an experienced provider can evaluate your symptoms and medical history to determine which antidepressant, if any, is right for you. 

With Klarity, no insurance or subscriptions are necessary, and there are no hidden fees. Schedule an appointment today, and in 48 hours, we’ll connect you with a licensed medical professional to get started on your online personalized treatment plan. 

Doxepin and Trimipramine Frequently Asked Questions

When comparing two medications from the same class of drugs, things can get confusing. We went over a lot of information, and it is common to have additional questions. Below we have answered some of the most frequently asked questions about Doxepin and Trimipramine:

Are Doxepin and Trimipramine the same drug?

No, although both Doxepin and Trimipramine belong to the same class of drugs called tricyclics, they are two separate medications, and each has unique properties. 

Why is Doxepin an off-label treatment for anxiety?

Doxepin is considered to be an off-label treatment for anxiety because there are newer medications that are more effective in treating anxiety with fewer side effects. 

There are several reasons one of these newer drugs may be ineffective for some, including drug interactions, certain health conditions, and the inability to tolerate the medication. In these cases, TCA medications like Doxepin remain to be a good alternative when treating anxiety. Your healthcare provider will help determine which anti-anxiety medication is best for you. 

What’s better for anxiety? Doxepin or Trimipramine?

Doxepin appears to be a better choice for the treatment of anxiety over Trimipramine, but it is also important to note that this is still considered off-label use for the medication. 

What’s better for depression? Doxepin or Trimipramine?

Although both medications are used to treat depression, Trimipramine is slightly more effective than Doxepin and can be used for more serious forms of depression due to its mild antipsychotic effects. 

Can I drive on antidepressants like Doxepin or Trimipramine?

Driving or operating heavy machinery should generally be avoided when initially starting any TCA medication because of the potential to cause sedative effects. 

Can I drink alcohol on Doxepin or Trimipramine?

You should avoid drinking alcohol while taking any TCA medication, including Doxepin or Trimipramine, because of an increased risk of adverse effects. Drinking alcohol and TCA medications both cause sedation and can be dangerous when taken together. 

Does it matter what time of day I take Doxepin or Trimipramine?

Due to the sedating effects of TCA medications, Doxepin and Trimipramine are typically prescribed to be taken at night before bedtime. Your healthcare provider will instruct you on how to take your medication, and it is important to follow these instructions. 

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