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Doxepin vs. Trazodone for Sleep—Which Drug Should You Use?

Doxepin vs. Trazodone for Sleep—Which Drug Should You Use?

Doxepin and trazodone are commonly prescribed to individuals with sleep issues. While the tablet form of doxepin is FDA-approved for insomnia, trazodone is used off-label but can be effective for sleep when used as instructed by your healthcare provider.

Learn more about these drugs, including their efficacy and effects, in this doxepin vs. trazodone for sleep comparison.

Doxepin vs. Trazodone—Basic Information

Doxepin and trazodone are prescription-only medications primarily indicated for major depressive disorders, anxiety, and tension. Doxepin is a tricyclic antidepressant, while trazodone is a phenylpiperazine antidepressant.

Doxepin is sold under several brand names, including Silenor and Sinequan. Trazodone is also available under different brand names, such as:

  • Trazodone D
  • Oleptro
  • Molipaxin
  • Desyrel
  • Desyrel Dividose

Trazodone and doxepin work by increasing the concentration of serotonin in the brain. Serotonin is a neurotransmitter that regulates your mood, hunger, body temperature, and sexual behavior. It also increases the level of melatonin—a hormone that regulates your sleep-wake cycle.

The medications also inhibit the production of hormones that promote wakefulness, such as histamine. According to clinical studies, low-dose doxepin can provide relief from sleep-maintenance insomnia. Research also shows that trazodone is effective in the treatment of primary and secondary insomnia, particularly sleep issues caused by depression. However, while both medications are FDA-approved, only doxepin is approved for insomnia—trazodone is used off-label in this case.

Trazodone and doxepin aren’t controlled substances, but you can only get them with your doctor’s prescription. Even though these drugs don’t carry the risk of addiction, misusing them or continuing to take them after your doctor has stopped treatment can cause psychological dependence.

Trazodone vs. Doxepin for Sleep—Dosage and Administration

Source: Kampus Production

Doxepin is available in four forms:

  1. Tablet—FDA-approved for insomnia
  2. Capsule
  3. Solution
  4. Topical cream

Check out a breakdown of the available doses for each form in the table below:


Available Doses


  1. 3 mg

  2. 6 mg


  1. 10 mg

  2. 25 mg

  3. 50 mg

  4. 75 mg

  5. 100 mg


10 mg/mL

Topical cream

5% cream

Doctors typically prescribe the 6 mg tablet for patients with insomnia, but your healthcare provider might recommend starting with 3 mg depending on your specific sleep issues and response to the medication. Doxepin typically kicks in within 30 minutes and reaches peak concentration in the body after two hours. 

Meanwhile, trazodone comes in three forms:

  1. Capsule
  2. Tablet
  3. Liquid

Check out the available doses for each form in the table below:


Available Doses


  1. 50 mg

  2. 100 mg


  1. 50 mg

  2. 100 mg

  3. 150 mg

  4. 300 mg–extended-release only


  1. 10 mg

  2. 20 mg

The typical starting dose for adults with insomnia is 25 mg in tablet form, but your doctor will review your health status before prescribing the appropriate dosage.

You should take doxepin or trazodone an hour before bedtime and set aside seven hours for sleep to let the drug’s sedative effects kick in and wear off naturally.

Duration of Effects

Doxepin’s sedative effects typically subside eight hours after administration, while trazodone’s effects last for 5–9 hours.

Doxepin has an average half-life of 15 hours. Half-life is the period your body needs to metabolize 50% of a drug, and it takes an average of 5.5 half-lives for a drug to be eliminated from your system. You can expect to feel the effects of doxepin up to 3–4 days after treatment discontinuation. If you take the drug as recommended, you should get better sleep within seven days of starting treatment.

Trazodone has a shorter average half-life of about 5–13 hours, so your body should metabolize it 2–3 days after stopping treatment.

Which Is Better for Sleep—Trazodone or Doxepin?

Both doxepin and trazodone can alleviate sleep problems, but their effectiveness depends on your specific sleep issue and response to these medications. Insomnia typically stems from several complex factors, so medications alone may not produce sustainable results. To reach a lasting solution, you should consult a sleep expert. 

Getting an appointment with a specialist isn’t as simple as it sounds. With less than 1% of doctors trained in sleep medicine and about 50–70 million adults in the U.S. grappling with some form of insomnia, meeting with a sleep expert can be complicated.

The fantastic development is that you can use telemedicine platforms like Kick to connect with sleep medicine specialists within a day. Designed by Dr. Alex Dimitriu, a Stanford sleep expert, Kick’s sleep program lets you consult a specialist within 15 minutes and begin treatment almost immediately.

Kick—Healthy Sleep, Healthy You

Source: Kampus Production

Kick’s sleep program is tailored to your specific sleep problems and health status. The program combines cognitive behavioral therapy for insomnia (CBT-i) coaching with gentle sleep drugs to help you reach an all-encompassing solution. Kick’s medications include:

  1. Doxepin
  2. Trazodone 
  3. Cyclobenzaprine
  4. Hydroxyzine
  5. Gabapentin
  6. Ramelteon

Our drugs are fast-acting, helping you achieve the desired results as soon as possible. Your doctor will prescribe two trial prescriptions that you’ll rotate in the first two weeks to prevent developing psychological dependence on one drug. Our specialist will also monitor your progress regularly and adjust the dosage if necessary to quickly optimize the treatment.

How To Join Kick

Our sleep program has been receiving rave reviews on Trustpilot, demonstrating Kick’s commitment to helping patients achieve restorative sleep. To benefit from the program, follow these three simple steps:

  1. Go to the signup page to start your brief sleep visit
  2. Fill out the form with your medical history and specific sleep issues 
  3. Provide your payment and delivery details

Your medication will be delivered to your doorstep or local pharmacy, making the process discreet and convenient. If our team decides you’re not the best candidate for the program, you won’t pay for the initial consultations as per our Doctor Guarantee. 

Doxepin and Trazodone for Sleep—Potential Side Effects

Source: Andrea Piacquadio

Doxepin and trazodone carry the risk of similar side effects, but patients who stick to their doctor’s instructions rarely experience them.

Common Side Effects

The common unwanted reactions to doxepin or trazodone include:

  • Dry mouth—Drink plenty of water and chew gum to alleviate this side effect
  • Drowsiness—Avoid driving or operating heavy machinery until the drowsiness subsides
  • Dizziness—Get up slowly from lying or sitting positions to avoid feeling lightheaded
  • Headache—Consult your doctor about safe pain relievers to alleviate headaches
  • Nausea—Stay in a well-ventilated place and eat foods containing ginger to prevent feeling nauseous
  • Blurred vision—Avoid tasks that require sharp focus until your vision clears

Rare Side Effects

The rare side effects of doxepin and trazodone differ in specific cases. Check out the table below for more details about the severe unwanted reactions to these medications:

Rare but Severe Side Effects of Doxepin

Rare but Severe Side Effects of Trazodone

  • Seizures

  • Rapid heartbeat

  • Eye pain, swelling, or redness

  • Widened pupils

  • Mood swings

  • Allergic reactions

  • Constipation

  • Bruising or bleeding easily

  • Unexplained increase in infections, such as skin infections or sore throat

  • Irregular heartbeat

  • Allergic reactions

Patients who experience unexplained body changes or persistent adverse reactions to trazodone or doxepin should contact their doctors immediately.

Doxepin vs. Trazodone—Who Should and Shouldn’t Use These Drugs?

Source: Kampus Production

Adults (18+) experiencing sleeplessness caused by depression, anxiety, or tension can take doxepin or trazodone. Doctors also prescribe these drugs to patients with primary insomnia, depending on their health status.

Check out the table below for more details on who shouldn’t use these medications.

Who Shouldn’t Use Doxepin or Trazodone? 


Individuals with glaucoma

Doxepin or trazodone can increase interocular pressure, worsening glaucoma

People with heart conditions

These medications can contribute to heart problems, including irregular heart rhythm

Individuals with liver disease

Doxepin or trazodone can raise the risk of liver injury

Patients with epilepsy

These drugs can lower the seizure threshold, raising the risk of convulsions

People with urinary retention issues

Doxepin and trazodone carry the risk of urinary incontinence

Patients with a history of hypotension

These drugs can contribute to low blood pressure

This list isn’t exhaustive, so you should inform your doctor about any medical conditions you have to help them determine whether these medications are safe for you.

Trazodone vs. Doxepin for Insomnia—Potential Interactions With Other Substances

Check out the potential interactions between doxepin and trazodone with food and other drugs in the table below:


Interaction With Doxepin

Interaction With Trazodone


Can contribute to drowsiness

Can enhance the risk of drowsiness


Can reduce doxepin’s potency for sleep

Can contribute to alertness and anxiety


Can contribute to dizziness and drowsiness

Can raise the risk of dizziness and drowsiness

Anti-HIV medication

Consult your healthcare provider for personalized guidance

Can contribute to trazodone overdose in some cases

Anti-seizure medication

Can increase the risk of seizures

Can enhance the risk of convulsions

Blood pressure medication

Can raise the risk of low blood pressure

Can contribute to low blood pressure

Dietary supplements 

Supplements like melatonin can contribute to drowsiness, but you should consult your doctor for personalized advice

Melatonin can enhance the risk of dizziness and drowsiness

Heart medications

Can enhance the risk of irregular heartbeat

Can contribute to the risk of irregular heart rhythm

Infection medications

Can raise the risk of irregular heart rhythm

Can increase the risk of irregular heart rhythm

Muscle relaxants

Can raise the risk of serotonin syndrome in some cases

Can contribute to the sedative effects

Non-steroidal anti-inflammatory drugs (NSAIDs)

Consult your healthcare provider for personalized advice

NSAIDs and trazodone affect blood coagulation, raising the risk of bruising and bleeding, even from minor injuries

Sleep or anxiety medications

Can contribute to drowsiness and dizziness

Can enhance the sedative effects


No known interactions, but risks can’t be disregarded

Can raise the risk of side effects


Can enhance the risk of sedation

Can add to the risk of drowsiness, dizziness, and confusion

Opioids and CNS depressants

Can add to drowsiness

Can enhance the CNS depressant effects

Before taking doxepin or trazodone, inform your healthcare provider about the substances you use. Your doctor will evaluate the potential interactions and only prescribe doxepin or trazodone if the benefits outweigh the risks in your case.

Doxepin and Trazodone Alternatives

Depending on your health status and the underlying causes of your sleep issues, your doctor may recommend doxepin and trazodone alternatives, such as:

Trazodone vs. Doxepin—Quick Overview

Check out the basic facts about doxepin and trazodone in the table below:




Active substance

Doxepin hydrochloride

Trazodone hydrochloride

Drug class



FDA approval date



FDA-approved uses

  • Depression

  • Anxiety

  • Insomnia

  • Itchy skin

  • Major depressive disorders

  • Anxiety disorders

Off-label uses

As deemed necessary by your doctor


Controlled substance



Prescription or OTC



Form used for insomnia



Typical doses for sleeplessness

  1. 3 mg

  2. 6 mg

  1. 25 mg

  2. 50 mg

  3. 100 mg

Pregnancy category

C (risks can’t be disregarded)

C (risks can’t be ruled out)

Suitable for children


Not recommended for patients under 12

You should only use doxepin and trazodone in the short term. If your sleep issues persist after discontinuing doxepin or trazodone, contact your doctor for personalized guidance.

Featured image source: Karolina Grabowska