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Doxepin vs. Amitriptyline


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Are you dissatisfied with your current anxiety medication, or would you like to know more about your different treatment options? There are a number of different medications available, which can make this process feel overwhelming. 

In this article, we will discuss the major differences between two commonly prescribed tricyclic medications: Doxepin and Amitriptyline. Although these two medications are a part of the same family of drugs, there are a number of key differences between them that we’ll outline. We’ll cover the basics, including how they work, common side effects, and some warnings associated with each medication. 

It is important to understand these differences in order to figure out which medication is best for you. A healthcare professional on Klarity can help navigate this process with you and find which medication is best for you, if applicable. Start by making an online appointment with a licensed and certified provider in your state who can help you with medication management.

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

Doxepin and Amitriptyline belong to the class of medications called tricyclic antidepressants (TCAs) and are commonly prescribed to treat depression and anxiety disorders. This class of medications is among some of the oldest forms of antidepressant medications that were developed, but due to their side effect profile, they have become less popular among the general population. However, this type of medication remains to be a good treatment option for some. 

What Are Tricyclics?

Tricyclic antidepressants are a class of drugs that work by acting on a number of different chemical neurotransmitter pathways or messaging systems in the brain to improve mood. TCAs block the reuptake of serotonin and norepinephrine, leading to increased levels of these chemicals. They work in the brain to elevate mood, slow down activity, as well as relieve itching. 

Below are different types of Tricyclics.


Tofranil (imipramine hydrochloride) is commonly prescribed to treat depression, as well as nighttime bed wetting in children. 


Pamelor (nortriptyline) is used to treat depression. It is inexpensive but remains to be slightly less popular compared to other tricyclic medications. 


Asendin (amoxapine) is used to treat depression and anxiety disorders. This drug is typically taken once before bedtime due to drowsiness. 


Elavil (amitriptyline) is a commonly prescribed drug used to treat migraine headaches and major depressive disorder. It is one of the most commonly prescribed tricyclic medications. Amitriptyline is only available as a generic drug, and in addition to Elavil, generic names include Amitid, Amitril, and Endep. 


Surmontil (trimipramine) is another tricyclic medication used to treat depression. This medication is available as a capsule and is taken one to three times a day. 


Vivactil (protriptyline) is used to treat depression. This medication is less popular because it is more expensive than other tricyclics and is typically prescribed for multiple doses per day. 


Silenor (doxepin) is primarily used to treat insomnia and helps you sleep throughout the night. There are currently no available generic alternatives for this medication, and it remains to be less popular than other comparable medications. 

Zonalong or Prudoxin (doxepin) is another form of this medication and is prescribed to reduce itching that is caused by various skin conditions, such as eczema. 


Norpramin (desipramine) is used to treat depression. It is less commonly prescribed than comparable drugs due to increased side effects in the elderly and those who have heart conditions. 

Amitriptyline and Doxepin Are Both Used To Treat Major Depressive Disorder

Amitriptyline and Doxepin are two common medications used in the treatment of major depressive disorder and various anxiety disorders. Despite having the same mechanism of action, there are a number of differences between these medications. 

What Else Does Amitriptyline Treat?

In addition to anxiety and depression, Amitriptyline is used to treat and prevent migraines and can be used to treat schizophrenia with depression.

Off-label Uses for Amitriptyline:

  • Chronic pain – fibromyalgia 
  • Nerve pain, including postherpetic neuralgia 
  • Irritable Chronic fatigue syndrome-related sleep disorders 
  • Bladder pain 
  • Irritable bowel syndrome

What Else Does Doxepin Treat?

In addition to anxiety and depression, Doxepin is used to treat insomnia. 

Off-label Uses for Doxepin

  • Itchiness caused by atopic dermatitis, pruritus, or lichen simplex chronicus
  • Topical neuropathic pain

Doses, Dosage Form and Side Effects of Doxepin

Common Doxepin Doses and Forms

Doxepin is available in capsule, tablet, and solution forms. Capsules come in 10, 25, 50, 75, 100, and 150 mg dosing, tablets are available in 3 and 6 mg dosing, and solutions are 10 mg/mL dosing only. In addition, there is a topical cream 5% used when prescribed for itching. 

The initial dose of Doxepin typically starts at 75 mg once daily for the treatment of anxiety. This dose can then be slowly titrated up to a maximum dose of 150 mg/day. Your healthcare provider will help determine which dose is best for you based on your clinical symptoms and ability to tolerate the medication. 

Common Doxepin Side Effects

Like any medication, there are some common side effects to keep in mind when starting a new medication. 

Some of the most common side effects associated with Doxepin include:

  • Agitation, confusion 
  • Black, tarry stools, bleeding gums, blood in urine or stool
  • Blurred vision 
  • A sensation of burning, itching, “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 spasm, stiffness, twitching 
  • Seizures 

Common Doxepin Drug Interactions

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. 

Some common drug interactions with Doxepin include:

  • Thyroid supplements 
  • Anticholinergic drugs 
  • Some blood pressure medications: clonidine
  • MAO inhibitors: isocarboxazid, linezolid, metaxalone, methylene blue
  • SSRIs 
  • St. John’s Wort
  • Cimetidine
  • Terbinafine
  • Drugs to treat irregular heart rate

How Much Does Doxepin Cost?

Doxepin is relatively affordable with the use of coupon cards and is covered by the majority of insurance providers. A 30-day supply of capsules ranges from $36 – $90 based on dosing and is significantly reduced with coupon cards—around $8.  

Doses, Dosage Form and Side Effects of Amitriptyline

Common Amitriptyline Doses and Forms

Amitriptyline is available as a tablet or solution. Tablets come in 10, 25, 50, 75, 100, 150 mg dosing and the solution as 10 mg/mL. The average dose for anxiety is 75 mg and is taken at bedtime. 

The typical maximum dose on an outpatient basis is 150 mg per day, although when used in an acute hospitalized setting, patients may require up to 300 mg per day. 

Common Amitriptyline Side Effects

As with other medications, Amitriptyline is commonly associated with side effects. Everyone reacts to medication differently when initially starting a new medication and with different doses. 

Some common side effects of Amitriptyline include:

  • Drowsiness, blurred vision
  • Dry mouth, constipation 
  • Weight gain
  • Difficulty urinating 
  • Persistent heartburn
  • Easy bruising or bleeding: black stools, vomit that looks like coffee grounds  
  • Muscle spasms, shaking
  • Severe abdominal pain 
  • Decreased libido
  • Enlarged or painful breasts 
  • Severe dizziness, fainting, seizures, confusion 
  • Eye pain, redness or swelling, vision changes 
  • Sweating 

Common Amitriptyline Drug Interactions

There are a number of drug interactions associated with Amitriptyline, and it is important that you disclose all medications that you are currently taking with your healthcare provider, including over-the-counter medications and supplements. 

Some common drug interactions with Amitriptyline include:

  • Quinidine
  • Cimetidine 
  • Many other antidepressants: SSRIs
  • Type 1C antiarrhythmics 
  • MAO inhibitors 
  • Thyroid medication 
  • Alcohol, barbiturates & other CNS depressants 
  • Anticholinergic drugs  

How Much Does Amitriptyline Cost?

Amitriptyline ranges from $140 – $300 for a 30-day supply, based on dose and frequency. This medication is covered by most insurances, and the price is significantly reduced with the use of coupon cards—around $4 for a 30-day supply. 

Do I Need A Prescription for Amitriptyline or Doxepin?

Yes, you need a prescription from a healthcare provider for both medications. 

Schedule an appointment with one of Klarity’s expert healthcare providers to discuss your current symptoms and find out which medication may work best for you. 

Other Side Effects of Tricyclics:

What is Serotonin Syndrome?

Serotonin Syndrome is a serious and potentially life-threatening condition that occurs from high levels of serotonin accumulated in the body. Signs and symptoms include:

  • Altered mental status: agitation, confusion, anxiety, delirium, coma 
  • Autonomic dysfunction: high blood pressure, fast heart rate, sweating, overheating, nausea, vomiting, diarrhea
  • Neuromuscular abnormalities: tremor, exaggerated reflexes, muscle rigidity, involuntary movements
  • Serious complications: breakdown of muscle, metabolic acidosis, kidney or respiratory failure, seizures, and even death 

Pregnancy and Breastfeeding on Tricyclics

TCAs are typically avoided during pregnancy due to the following complications: 

  • Spontaneous abortion 
  • High blood pressure, preeclampsia 
  • Postpartum hemorrhage 
  • Preterm birth 
  • Postnatal effects: withdrawal symptoms, hypoglycemia, respiratory illness, jaundice

Breastfeeding while on TCAs is viewed as generally safe for the infant due to relatively low drug levels found in breast milk. 

  • Nortriptyline is the preferred medication for lactating women starting treatment with a TCA postpartum 
  • Doxepin is avoided due to its long half-life

Increased Bleeding Risk With Tricyclics

TCAs do not appear to increase bleeding risk when used alone. This is unlike other antidepressants, such as SSRIs, which have a significantly increased bleeding risk, especially when used with over-the-counter pain relievers.  

TCAs prevent Warfarin metabolism and breakdown in the body. When taking both medications simultaneously, there could potentially be an increased risk of bleeding due to increased levels of Warfarin. 

Signs and symptoms include: 

  • Black, tarry stools
  • Severe abdominal pain
  • Easy bruising 
  • Bleeding gums 

Doxepin and Amitriptyline Frequently Asked Questions

What is Doxepin?

Doxepin is a tricyclic antidepressant that is used to treat anxiety, depression, and hives. It acts on the neurochemistry of your brain by increasing serotonin and norepinephrine. 

What is Amitriptyline?

Amitriptyline is a tricyclic antidepressant that is used to improve mood and treat nerve pain and insomnia. It acts on the neurochemistry of your brain by increasing serotonin and norepinephrine.  

Are Doxepin, Amitriptyline, and other Tricyclics the same drug?

No, they are all different medications but belong to the same class of medications that act in similar ways on your brain’s neurotransmitters. They have similar side effects and drug interactions but are not identical. 

Why is Doxepin an off-label treatment for anxiety?

Doxepin is considered an off-label treatment for anxiety because there are other medications that are safer and more effective in treating anxiety, like SSRIs for example. 

What’s better for anxiety? Doxepin or Amitriptyline?

Of the two medications, Doxepin is a better medication to treat anxiety. Although, due to the safety and efficacy of other medications, TCAs are rarely used to treat anxiety alone. 

What’s better for depression? Doxepin or Amitriptyline?

Amitriptyline is a better medication to treat depression when compared to Doxepin. Yet, due to the side effect profiles of both medications, they are no longer considered first-line medications to treat anxiety or depression. 

Can I drive on antidepressants like Doxepin or Amitriptyline?

Due to the sedative effects of TCAs, they are typically prescribed to take at night before bedtime. People taking Doxepin or Amitriptyline should be instructed by their prescribing physician not to drive or operate machinery after taking the medication. 

Can I drink alcohol on Doxepin or Amitriptyline?

No, you should avoid alcohol consumption while taking TCAs due to the sedating effects of both substances. When taken together, there is a greater risk for safety and health concerns, such as falls and depression of the central nervous system, which can be lethal. 

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

Yes, these medications should be taken at night before bed due to their sedating effects. 

Find the Right Medication for Your Anxiety with Healthcare Providers on Klarity

There are a large number of medications and different treatment modalities, such as therapy and exercise, that are used to treat anxiety. With so many options, finding the right medication may seem like a challenge to some people. 

Let Klarity help you find the right, individualized treatment plan for your mental health needs. Klarity offers affordable care at your convenience, with no insurance, subscriptions, or hidden fees. Schedule an appointment today or take a free self-evaluation to be seen in as little as 48 hours by a licensed healthcare provider in your area. 


Start today, and discuss your symptoms with a specialist who can help.

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