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Doxepin vs. Tofranil – What Is the Difference and Which One Should I Take?


Doxepin vs. Tofranil - What Is the Difference and Which One Should I Take?

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Navigating depression can feel overwhelming, especially when first-line depression treatment hasn’t worked. Searching for effective antidepressant medicine takes some time, but… 

You’re not alone, and you deserve to get the treatment you need when you need it! Not weeks later. 

In this article, we’ll review doxepin and Tofranil, two antidepressant drugs that can be prescribed to treat major depressive disorder when first-line antidepressants like selective serotonin reuptake inhibitors (SSRIs) are not effective in reducing depression symptoms.

We’ll discuss—

  • What class of antidepressants these two drugs belong to
  • What symptoms each antidepressant is designed to treat
  • Potential side effects of each antidepressant treatment
  • Potential drug interactions for each antidepressant treatment
  • The costs, doses, and formulations for each antidepressant
  • Drug warnings for each antidepressant
  • Plus, some frequently asked questions our mental health providers often receive!

Klarity connects people with board-certified mental health providers who can diagnose and prescribe treatment for a variety of mental health issues, including depression.

If you want to talk to a medical provider about your treatment-resistant depression and are exploring different antidepressants, then schedule an appointment, and we’ll match you with a licensed provider in your state within 48 hours

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: Silenor)

Generic (Brand name: Silenor)

Form(s) of the DrugImmediate-release tablets
• Shapes indicate dosage
• Immediate-release capsules
• Immediate-release tablets
• Clear, blueberry-mint flavored liquid suspension
• Topical cream (for itching)
Standard DosageImmediate-release tablets:
• 10mg triangular tablet
• 25mg small round tablet
• 50mg large round tablet
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 uses:
• Major depressive disorder

Off-label uses:
• Bulimia
• Nerve Pain
• Panic Disorder
• Irritable bowel syndrome (IBS)
• Enuresis in children

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 form (imipramine):
• $10 for a 30-day supply

Brand name:
• $430 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:
• Mood/behavior changes
• Anxiety
• Difficulty sleeping
• Agitation, hostility, and aggression
• Increased depression and suicidal thoughts
• Blurred vision
• Lightheadedness
• Fever
• Hallucinations
• Confusion
• Pain or difficulty urinating
• Seizures
• Difficulties with sex
• Constipation
• Nausea and vomiting
• Diarrhea
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:
• Blood pressure medication
• Anticholinergics
• Digoxin
• Disopyramide
• Valproic acid
• Thyroid supplements

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

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

Tofranil (Imipramine) and doxepin (Silenor) are tricyclics, a class of antidepressants developed in the 1950s. These medications are primarily prescribed to treat major depressive disorder (MDD) but also have other off-label uses, such as treating anxiety disorders or managing chronic pain.

Tricyclics are nonselective antidepressants meaning they affect much more serotonin receptors than other antidepressants like SSRIs or SNRIs, which are newer antidepressants that are selective.

What Are Tricyclics?

Tricyclics work by blocking the reuptake of certain neurotransmitters in the brain, which can help improve mood and reduce symptoms of depression. Tricyclics don’t work for everyone, but they can be an effective means of treatment for some people based on their health history and current diagnosis, such as treatment-resistant depression.

Tofranil and Doxepin Are Both Used To Treat Major Depressive Disorder

Tofranil and doxepin are prescription medications used to treat major depressive disorder. Each drug has its own forms, doses, and side effects, and you should always consult your mental health provider before taking a new medication.  

Though Tofranil and Doxepin are in the same class of medication, it’s important to understand that they are different antidepressants and each will affect your mind and body differently.

Let’s compare these two antidepressant medications—

What Else Does Tofranil Treat?

Tofranil is primarily used to treat symptoms of MDD, but it may also be used off-label to treat other conditions. The FDA has an approval system where a series of tests determines whether or not a medication will be an effective treatment for a particular issue. Off-label use is when a medication isn’t approved for a certain issue, but it’s proven to be an effective treatment. 

Off-label Uses for Tofranil

Tofranil is FDA-approved to treat major depressive disorder. Off-label uses may include:

  1. Anxiety disorders: Some healthcare providers might prescribe Tofranil for generalized anxiety disorder, panic disorder, or social anxiety disorder.
  2. Neuropathic pain: Tofranil has been used to manage chronic neuropathic pain, such as diabetic neuropathy or post-herpetic neuralgia.
  3. Fibromyalgia: Tofranil may help manage pain and improve sleep in fibromyalgia patients.
  4. Migraine prophylaxis: Tofranil has been used as a preventive treatment for migraine headaches.
  5. Irritable bowel syndrome (IBS): Tricyclic antidepressants like Tofranil may help manage abdominal pain and other IBS symptoms.
  6. Chronic fatigue syndrome: Some healthcare providers might prescribe Tofranil to help alleviate symptoms of chronic fatigue syndrome.
  7. Insomnia: Tofranil may be prescribed at low doses for patients who struggle with sleep.

What Else Does Doxepin Treat?

Doxepin is also primarily prescribed to treat MDD and anxiety. Since it increases the levels of certain chemicals in the brain responsible for regulating mood, it’s also used off-label to treat other conditions. 

Off-label Uses for Doxepin

Off-label uses for doxepin may include:

  1. Chronic urticaria: Doxepin has antihistamine properties, so it has been used to treat chronic urticaria (hives) in some cases.
  2. Neuropathic pain: Like other tricyclic antidepressants, doxepin may be prescribed for the management of neuropathic pain, such as diabetic neuropathy or post-herpetic neuralgia.
  3. Migraine prophylaxis: Like Tofranil, doxepin has been used as a preventive treatment for migraine headaches.
  4. Fibromyalgia: Some evidence suggests that doxepin may help manage pain and improve sleep for people with fibromyalgia.
  5. Irritable bowel syndrome (IBS): Tricyclic antidepressants like doxepin can help manage IBS symptoms.
  6. Pruritus: Doxepin’s antihistamine properties may also make it useful for treating pruritus (itching) related to various skin conditions.
  7. Chronic pain: Doxepin may be prescribed for managing chronic pain conditions, such as chronic low back pain or chronic tension-type headaches.

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Doses, Dosage Form, and Side Effects of Doxepin

Doxepin comes in different doses and forms that contribute to the overall cost of the medication. Depending on your recommended dose, you may experience common side effects, and it’s important to know how your body might respond. Additionally, doxepin interacts with several drugs, so you should tell your care provider about any other medications you take.

Common Doxepin Doses and Forms

Doxepin is available in oral capsule, oral solution, and topical form. The recommended starting dose for adults is 75 mg daily, divided into three smaller doses and taken at bedtime. Your dose may increase gradually, up to a maximum of 300 mg per day. 

Common Doxepin Side Effects

Doxepin can cause several common side effects. These side effects are usually mild and may disappear as your body adjusts to the medication.

Common doxepin side effects include:

  • Drowsiness
  • Dizziness
  • Dry mouth
  • Blurred vision
  • Constipation
  • Difficulty urinating
  • Nausea and vomiting
  • Stomach pain
  • Weight gain
  • Changes in taste

However, if these side effects persist or if you experience any severe side effects, such as worsening depression, suicidal ideation, difficulty breathing, or swelling of the face, lips, tongue, or throat, you should contact your care provider right away.

Common Doxepin Drug Interactions

Doxepin can interact with other medications and substances, such as alcohol and certain herbal supplements. There are also 661 drugs that doxepin interacts with, including 134 major interactions, 502 moderate interactions, and 25 minor interactions. 

Of the most frequently checked medications, doxepin has major interactions with Cymbalta, Flexeril, Lexapro, Topamax, and Zoloft. 

Moderate interactions include:

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

How Much Does Doxepin Cost?

The cost of doxepin depends on the pharmacy you use, your recommended dose, and if you have insurance. You can expect to pay anywhere from $4.26 to $42.15 monthly for 30 capsules of 75 mg. Talk to your provider about using the generic form Silenor to save money.

Doses, Dosage Form, and Side Effects of Tofranil

Like doxepin, Tofranil also comes in several doses and forms and has its own set of side effects. It also interacts with a series of other medications, so you must tell your care provider about any other medicines you’re taking.

Common Tofranil Doses and Forms

There are several doses and forms of Tofranil available, including tablets, capsules, and a liquid form. Common doses are between 10 and 200 mg daily, with the typical dose starting at 75 mg. Your care provider will determine the right dose based on your symptoms and other factors, like your health history. 

Common Tofranil Side Effects

Tofranil can cause some side effects. You must contact your mental health provider if these side effects persist or become severe.

Common side effects include:

  • Weight gain or loss
  • Dry mouth
  • Vision issues
  • Headache
  • Drowsiness
  • Constipation
  • Nausea and vomiting
  • Loss of appetite
  • Diarrhea
  • Stomach cramps
  • Tingly feeling
  • Weakness
  • Lack of coordination
  • Ringing in your ears
  • Breast swelling
  • Decreased sex drive
  • Impotence
  • Difficulty orgasming

If you experience any of the following serious side effects, contact your healthcare provider immediately.

  • Easy bruising or bleeding
  • Fever
  • Sore throat
  • Dark urine
  • Yellowing eyes or skin
  • New or worsening chest pain
  • Irregular heartbeat
  • Sudden numbness
  • Purple or red spots under the skin
  • Confusion
  • New or worsening depression
  • Suicidal ideation
  • Seizures

Common Tofranil Drug Interactions

Tofranil interacts with 690 drugs, with 134 major interactions, 529 moderate interactions, and 27 minor interactions. Major interactions occur with 

  • Cymbalta
  • Celexa
  • Lexapro
  • Paxil
  • Prozac
  • Trazodone
  • Zoloft

Moderate interactions include:

  • Adderall
  • Ambien
  • Ativan
  • Elavil
  • Gabapentin
  • Klonopin
  • Lamictal
  • Levothyroxine 
  • Lisinopril
  • Seroquel
  • Synthroid
  • Xanax

How Much Does Tofranil Cost?

The cost of Tofranil varies depending on your dose, pharmacy, and insurance coverage. The price ranges from $12.22 to $53.60 for 90 tablets at 25 mg. You should also consider asking about Imipramine, the generic form of Tofranil, as it’s often less expensive. 

Other Tricyclic Side Effects

While they can be effective for many people, tricyclic antidepressants can have other potentially harmful side effects. These adverse effects could include serotonin syndrome, pregnancy and breastfeeding complications, and an increased risk of bleeding. 

What is Serotonin Syndrome?

One potential side effect of tricyclic antidepressants is serotonin syndrome, which occurs when there’s too much serotonin in the body. Symptoms of serotonin syndrome include agitation, hallucinations, and rapid heartbeat. If you experience these symptoms, contact your care provider immediately.

Pregnancy and Breastfeeding on Tricyclics

Another potential concern with tricyclic antidepressants is using them during pregnancy and breastfeeding. Taking tricyclics while pregnant can lead to preterm birth, respiratory distress, neonatal convulsions, or low birth weight. It’s important to talk to your healthcare provider about the potential risks and benefits of taking a tricyclic antidepressant during pregnancy.

Increased Bleeding Risk With Tricyclics

Tricyclic antidepressants can also increase the risk of bleeding. If you are taking a tricyclic antidepressant and planning surgery or dental work, let your care provider know beforehand. You may need to stop taking the medication for a period of time before and after the procedure.

Black Box Warning With Antidepressants

The Food and Drug Administration (FDA) requires a black box warning on all antidepressants, including tricyclic antidepressants. This warning states that antidepressants may increase the risk of suicidal thoughts and behaviors in children, teenagers, and young adults. Monitor any changes in mood or behavior while taking a tricyclic antidepressant.

Doxepin and Tofranil Frequently Asked Questions

What is Doxepin?

Doxepin is a tricyclic antidepressant prescription medication commonly used to treat symptoms of depression and anxiety. 

What is Tofranil?

Tofranil is another tricyclic antidepressant medication that treats symptoms of depression. 

Are Doxepin and Tofranil the same class of drug?

Yes, doxepin and Tofranil are tricyclic antidepressants, meaning they belong to the same class of drugs. While they are within the same drug class, they have their own unique side effects and warnings, and you should consult with a licensed professional before taking either one. 

What’s better for anxiety? Doxepin or Tofranil?

Doxepin is FDA-approved to treat anxiety, while Tofranil is not. Tofranil is used to treat some panic disorders in an off-label capacity, but that’s not its primary intended use. The right medication depends on your current symptoms and your care provider’s recommendations. 

What’s better for depression? Doxepin or Tofranil?

Both doxepin and Tofranil are tricyclic antidepressant medications commonly used to treat MDD. Tofranil is a first-choice medication when it comes to treating symptoms of depression, while doxepin is a second-choice medication due to its many side effects. Your mental health provider will recommend the best option for you.

Can I drive on antidepressants like Doxepin or Tofranil?

It is generally safe to drive while taking doxepin or Tofranil as long as you do not experience any side effects that could impair your ability to operate a vehicle. Before getting behind the wheel, you should wait until you’ve taken a few doses to understand how your body responds. 

Can I drink alcohol on Doxepin or Tofranil?

You should not drink alcohol while taking doxepin or Tofranil. Alcohol can interact with these medications, increasing the risk of adverse side effects and worsening symptoms of depression and anxiety. If you do choose to drink while taking doxepin or Tofranil, only do so in moderation and talk to your healthcare provider about any potential risks.

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

It is generally recommended that you take doxepin or Tofranil at the same time each day to help maintain a consistent level of the medication in your body. Both drugs can make you tired, so it’s best to take them before bed. 

Klarity Can Help You Access Depression Treatment Online

If you have treatment-resistant depression and are looking to try new antidepressants like doxepin and Tofranil, Klarity can help. We make accessing online depression treatment easy!

Get started with online depression treatment in as little as 48 hours when you book an appointment on Klarity. 


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