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Trazodone Versus Mirtazapine for Sleeplessness

Trazodone Versus Mirtazapine for Sleeplessness

Trazodone and mirtazapine may not be the drugs that first come to mind when considering sleep medications. However, even though they’re commonly associated with the treatment of depression, these medicines have found an off-label use in addressing sleep issues.

This comprehensive trazodone versus mirtazapine comparison will describe their mechanisms of action, efficacy for sleep, and side effects to help you determine whether they may work for you.

Trazodone vs. Mirtazapine—A Brief Overview

Trazodone and mirtazapine are both antidepressants primarily used in the treatment of major depressive disorder. Trazodone belongs to the group of antidepressants known as serotonin antagonists and reuptake inhibitors (SARIs), while mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA).

Trazodone is sold under several brand names, such as:

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

Mirtazapine is also available under different brand names, including:

  • Remeron
  • Remeron SolTab
  • Remeron RD

Trazodone works by increasing serotonin levels in the nerve synapse. The drug also blocks chemicals that interact with serotonin and other neurotransmitters and receptors that affect your sleep-wake cycle, such as 5-HT2A, alpha-1 adrenergic receptors, and histamine H1 receptors. The combined effects help reduce the period it takes to fall asleep, extend sleeping time, and enhance the rapid eye movement (REM) phase, improving sleep quality.

Meanwhile, mirtazapine increases serotonin and norepinephrine levels in the brain while blocking histamine receptors, which helps induce a sedative effect. According to clinical studies, the drug decreases sleep latency and increases deep sleep, making it effective for treating insomnia.

Both drugs are FDA-approved as antidepressants, so their use in treating sleep problems is off-label. Trazodone and mirtazapine aren’t controlled substances since they don’t carry the risk of physical addiction. Still, misuse may cause tolerance and psychological dependence, so you can only get these medications with your doctor’s prescription.

Trazodone vs. Mirtazapine for Sleep—Dosing Guidelines

Trazodone is available in six doses:

  1. 10 mg
  2. 20 mg
  3. 50 mg
  4. 100 mg
  5. 150 mg
  6. 300 mg

The average starting dose for adults with sleep problems is 25 mg in tablet form, but it may increase up to 100 mg depending on your specific condition.

As for mirtazapine, it comes in three doses:

  1. 15 mg
  2. 30 mg
  3. 45 mg

When taken for sleeplessness, the typical starting dose is 7.5 mg–15 mg, but patients with mild insomnia may find even the 3.75 mg dose effective.

You should take trazodone and mirtazapine at least an hour before going to bed. Follow your doctor’s guidelines and don’t combine doses—if you miss one, take it as soon as you remember unless it’s close to the time for the next dose.

Duration of Effects

Trazodone kicks in within 30 minutes, and its effects typically last for 5–9 hours. You should take the medication as prescribed to benefit from it. The drug can take a few days to start working, depending on your health status.

Mirtazapine also produces sedative effects 30 minutes after administration. The drug is rapidly absorbed, and the sleep-improving effects can appear within 1–2 days. Some patients may need to wait up to two weeks to feel the full effect of mirtazapine.

Whether you’re taking trazodone or mirtazapine, you should dedicate seven hours to sleep to let their effects wear off naturally. If you experience sleep problems after treatment discontinuation, inform your doctor immediately.

Which Is Better for Sleep—Trazodone or Mirtazapine?

Both trazodone and mirtazapine can be effective for sleep, but individual experiences vary. According to user testimonials, trazodone has an average rating of 6.3 out of 10 from 1,393 reviews, while mirtazapine has an average 6.8 rating out of 10 from 1,962 reviews. The varied reviews show that each drug’s efficacy for sleep depends on the patient’s health history and the specific conditions being treated.

Insomnia can stem from several behavioral, environmental, and physiological factors, so medications alone may not offer a comprehensive solution. To get lasting results, you should consult a sleep medicine expert.

With a patient-to-sleep-medicine-specialist ratio of 43,000:1 in the U.S., securing an appointment with an expert can be challenging. On the bright side, telemedicine platforms can connect you with specialists within a day, allowing you to begin treatment almost immediately. Kick, an online performance medicine clinic, allows you to consult experts within a record-breaking 15 minutes. 

Source: Andrea Piacquadio

Kick—Sleep Well, Live Well

Designed by Dr. Alex Dimitriu, a Stanford sleep expert, Kick’s sleep program has earned numerous positive reviews from patients, which serves as a testament to our effectiveness in addressing various sleep issues.

Kick’s program entails personalized treatment. When you join Kick, your designated doctor will prescribe two trial medications tailored to your health history and sleep patterns. Our expert will schedule routine online consultations and adjust the treatment if the initial plan doesn’t yield the desired results after the first two weeks.

Your doctor will also offer practical tips on healthy sleep hygiene, helping you address the environmental and behavioral factors contributing to your sleep problems. Kick’s sleep program is grounded in the latest scientific research and uses gentle but fast-acting medications, including:

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

How Kick Works

To join Kick, follow three straightforward steps:

  1. Navigate to the Sleep Visit page to start your brief consultation
  2. Fill out the medical questionnaire to help us understand your health status and sleep history
  3. Provide your delivery address and payment method

Our team will review your details and prescribe your medications, which will be delivered directly to your doorstep or nearest local pharmacy. If your doctor decides you’re not the best candidate for the program, you won’t pay for the initial consultation, according to our Doctor Guarantee.

Source: Andrea Piacquadio

Mirtazapine vs. Trazodone—Side Effects

Trazodone and mirtazapine carry the risk of unwanted reactions, though they rarely occur when patients follow their doctors’ instructions.

The Side Effects of Trazodone

Common side effects of trazodone include:

  • Dry mouth
  • Dizziness
  • Drowsiness
  • Lightheadedness

Rare but severe unwanted reactions to the drug include:

  • Fainting
  • Confusion
  • Lack of focus
  • Poor coordination
  • Shortness of breath
  • Swelling
  • Skin rash

These lists aren’t exhaustive—you should consult your doctor for comprehensive information on how to take the drug safely and avoid undesirable reactions.

The Side Effects of Mirtazapine

Common unwanted reactions to mirtazapine are:

  • Dizziness
  • Drowsiness
  • Dry mouth
  • Increased appetite
  • Weight gain

Less common but concerning side effects of mirtazapine include:

  • Dizziness or fainting
  • Back pain
  • Chills
  • Intense menstrual pain
  • Changes in menstrual cycles
  • Decreased sexual ability
  • Mood changes

Inform your doctor if you experience unusual changes while on either trazodone or mirtazapine. Your healthcare provider will adjust the dose or recommend other sleep aids, depending on your health status.

Source: Andrea Piacquadio

Mirtazapine vs. Trazodone for Sleep—Who Should and Shouldn’t Use These Drugs?

Trazodone and mirtazapine are generally safe for adults (18+) experiencing sleep problems. Patients over 65 can use these medications, but they should inform their healthcare providers if they have medical conditions that may contribute to or exacerbate the side effects. 

Pregnant women should consult their doctors before using either trazodone or mirtazapine while breastfeeding women should approach both medications with caution because these drugs can pass through breast milk.

Check out the table below for more details on who shouldn’t take these sleep medications:

Who Shouldn’t Use Trazodone?

Who Shouldn’t Use Mirtazapine?

  • People who are allergic to trazodone or its components

  • Individuals who’ve recently had a heart attack or have a history of heart disease

  • Patients with kidney or liver problems

  • People with epilepsy or a history of seizures

  • Individuals with low sodium levels in the blood

  • Individuals with glaucoma

  • Patients with heart problems

  • People with a history of low blood pressure

  • Individuals who are allergic to mirtazapine or its ingredients

The lists above aren’t comprehensive—you should tell your doctor about your complete medical history. They’ll weigh the benefits and risks of each option and recommend the safest drug.

Mirtazapine vs. Trazodone—Interactions With Other Substances


Trazodone and mirtazapine can interact with other medications, food, or drinks, potentially raising the risk of side effects or altering the effectiveness of the drugs. You can find a detailed breakdown of the interactions between trazodone and mirtazapine with other substances in the table below:


Interaction With Trazodone

Interaction With Mirtazapine

Anti-seizure medication

Interactions vary depending on the specific anticonvulsants, so you should consult your healthcare provider for specific guidance

Can reduce the effectiveness of some anti-seizure medication

Anti-HIV drugs

May cause reduced trazodone metabolism, raising the risk of an overdose

The potential for interaction is low, but risks can’t be disregarded


Can increase the risk of side effects like dizziness and drowsiness

Can enhance the risk of side effects


Can intensify the risk of drowsiness and headaches

Can contribute to severe drowsiness

Blood pressure medication

Can enhance the risk of irregular heart rhythm

Can contribute to QT prolongation

Herbal supplements

There’s not enough information to claim that it’s safe to take trazodone with herbal supplements

Herbal supplements like St. John’s wort can contribute to sedation

Infection medications

Can interact with some antibiotics, potentially changing heart rhythm

May interact with some antibiotics, raising the risk of side effects

Muscle relaxants

Can enhance the sedative effects

Can cause increased sedation

Opioids and CNS depressants

May contribute to the sedative effects, raising the risk of drowsiness and accidental falls

Can intensify the sedative effects, causing drowsiness

Sleep or anxiety medications

Can enhance the risk of sedation

Can contribute to the sedative effects

Trazodone and Mirtazapine Alternatives

If your doctor decides that the risks of undesirable reactions to trazodone and mirtazapine are high in your case, they may recommend safer and more effective alternatives for you, including:

These medications are typically used in the short term. If you have chronic insomnia, your healthcare provider may recommend stronger sleep aids.

Featured image source: Andrea Piacquadio