Is trazodone an SSRI?

In this article:

• Is trazodone an SSRI?
• How it works
• History of trazodone
• Common uses
• Dosage guidelines
• Trazodone vs. other treatments

In this article

• Is trazodone an SSRI?
• How it works
• History of trazodone
• Common uses
• Dosage guidelines
• Trazodone vs. other treatments

Trazodone hydrochloride is a generic prescription medication used to treat depression in adults. It is also sometimes prescribed off-label for insomnia and anxiety. Some people assume that trazodone belongs to a common class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). That’s not quite accurate, however. Learn what makes trazodone different from typical SSRIs, how it works, and how it compares to other sleep aids and antidepressants.  

Is trazodone actually an SSRI? 

No, trazodone is not a true SSRI. It is an atypical antidepressant that is classified as a serotonin antagonist and reuptake inhibitor (SARI). There is a good reason trazodone is often confused for an SSRI. It has a similar effect, which is increasing levels of a neurotransmitter called serotonin. 

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Understanding trazodone’s unique mechanism of action

Like SSRIs, trazodone works by inhibiting the reuptake, or reabsorption, of serotonin that has already been used to carry nerve signals in the brain. This eases symptoms of depression because more serotonin is available to facilitate communication between brain cells. But trazodone stands apart because it also has other serotonin-boosting effects. For instance, it directly blocks certain serotonin receptors and alpha-1 receptors, triggering a cascade of antidepressant, anti-anxiety, and sleep-promoting effects, according to Heather Gosnell, MD, a healthcare provider based in Phoenix, Arizona.

“Think of trazodone as a light switch panel with many switches,” says Oluwatosin Ajao, MD, a board-certified internal medicine provider in Houston, Texas. “It can turn on and off different switches in the brain. This effect makes serotonin stay longer in the brain and can help with sleep, mood, and anxiety.”

Ultimately, trazodone offers a multi-pronged approach to boosting mood, calming anxiety, and easing sleeplessness. According to Dr. Gosnell, trazodone’s multiple effects make it ideal for patients with depression and insomnia, even though it’s a less potent antidepressant than typical SSRIs, such as Prozac and Zoloft. 

The history of trazodone

Trazodone was developed in 1966 and FDA-approved as an antidepressant in 1981. That said, Dr. Ajao says it is no longer common to prescribe trazodone as a standalone depression treatment because newer antidepressants are more effective. “Doctors often give trazodone along with other antidepressants, especially SSRIs, because it can help with trouble sleeping caused by SSRIs and may also help reduce sexual side effects from SSRIs,” she adds.

These days, the most common use for trazodone is insomnia, especially in patients who are also diagnosed with depression or anxiety, according to Dr. Gosnell. Trazodone is still not FDA-approved for sleep problems, but some healthcare providers prefer to prescribe it because it is well-tolerated, available at a low price, and has a lower risk of addiction than some other sleep aids.

Common uses for trazodone

Trazodone is still only approved by the U.S. Food and Drug Administration for one purpose: The treatment of major depressive disorder (MDD) in adults. 

However, trazodone is prescribed off-label (for something other than its FDA-approved purpose) for the following:

• Insomnia
• Anxiety-based conditions, including generalized anxiety disorder (GAD), panic disorder and obsessive-compulsive disorder
• Post-traumatic stress disorder (PTSD)
• Dementia agitation

Trazodone for depression

As mentioned above, trazodone helps boost serotonin levels. It is an effective and well-tolerated depression treatment. It is also known to have a calming, even sleep-inducing, effect, which makes it one of the few antidepressants more likely to promote than disrupt sleep. 

Trazodone dosage for depression starts at 25–50 milligrams (mg) two to three times daily. Once the body adjusts to the medication, healthcare professionals typically prescribe a dose of 50–100 mg two to three times daily.

Trazodone for insomnia

Trazodone is frequently prescribed to treat short-term insomnia, which is trouble falling or staying asleep. That’s because trazodone has a sedative-like effect. A systematic review on trazodone for sleep found that low doses could be safe and effective for short-term insomnia. However, the American Academy of Sleep Medicine (AASM) recommends against trazodone for chronic insomnia.

Trazodone dosage for insomnia typically starts at 50 mg to 100 mg before bedtime, though the dosage may increase depending on individual response. 

Trazodone for anxiety and PTSD

Trazodone is sometimes prescribed off-label for anxiety, especially anxiety accompanied by insomnia. Older studies have found that trazodone can improve symptoms of anxiety and panic disorder, and post-traumatic stress disorder. However, this medication is not considered a first-line treatment for either mental health condition. 

Trazodone dosage for anxiety or PTSD is best determined by your healthcare provider. In some cases, it may follow the standard dosage for depression, which is 50–100 mg two to three times daily.

Trazodone for dementia agitation

In rare cases, trazodone is prescribed for dementia agitation, sometimes called “sundowning.” However, trazodone is not FDA-approved for dementia agitation. One study found that, compared with haloperidol, verbally aggressive and oppositional behaviors responded better to trazodone, while symptoms of excessive motor activity and unwarranted accusations responded better to haloperidol. The study also found that trazodone and haloperidol were equally effective in treating overall agitated behaviors in patients with dementia. Ultimately, caregivers and healthcare professionals must make a shared decision about trazodone for dementia on a case-by-case basis. 

There is no FDA-approved trazodone dose for dementia agitation. Dosage is determined by the healthcare team and should be adjusted based on patient and caregiver feedback.

Dosage guidelines

Trazodone doses range from 150 mg to 400 mg per day in divided doses for MDD, per DailyMed. 

The medication label also offers the following dosage guidelines:

• Start low, go slow. Trazodone dosage should be started at 150 mg (in divided doses) per day. Prescribers then increase it gradually by 50 mg, with a maximum dose of 400 mg per day (again, in divided doses).
• Take your dose of trazodone with food. Trazodone is intended to be taken immediately after a meal or snack. This is important for proper absorption.
• Take tablets whole or broken in half. Trazodone tablets have a score line to allow the medication to be broken in half for easier swallowing. Tablets should not be crushed or chewed.
• Discontinue only with medical guidance. Trazodone dosage should be gradually reduced rather than abruptly discontinued, per the medication label. 

Trazodone vs. other sleep aids and antidepressants

Trazodone is considered safe and effective. However, it’s not the best choice for everyone in need of depression or insomnia treatment.

Trazodone vs. other sleep aids

The sedating effects of trazodone are clear, but there are several FDA-approved insomnia medications. These include benzodiazepines, non-benzodiazepine sedatives, and some antidepressants. One study found that trazodone is just as effective as doxepin, a non-benzodiazepine sedative approved for insomnia. However, Dr. Gosnell says trazodone’s effectiveness for insomnia is “less consistent” than FDA-approved sleep medications.

“I still prefer to give trazodone over other sleep medications due to its lower risk of addiction and the fact that it can treat sleep problems and depression at the same time,” Dr. Ajao says. “It is usually well tolerated at low doses, costs very little and it is easy to get.”

Trazodone vs. other antidepressants

Trazodone is older than many other antidepressants. Its safety and effectiveness are well-established, but that doesn’t mean it’s the best antidepressant for everyone. 

“Studies show trazodone is less effective as an antidepressant compared to SSRIs,” Dr.Gosnell says. “But it has a more favorable side effect profile, particularly around sexual dysfunction, weight gain, and sleep disruption, which are common complaints with SSRIs.” Ajao agrees, explaining that she sometimes chooses trazodone over other SSRIs since it also helps with sleep. However, she says trazodone is a bad choice for patients who struggle with dizziness or daytime sleepiness.

How to talk to your healthcare provider about trazodone

Only a healthcare provider familiar with your complete medical and psychiatric history, other medical conditions, and current medications can help you determine if trazodone is the best treatment option for you. 

Your medical and psychiatric history, along with a list of all current health conditions and symptoms, is important because it helps prescribers pinpoint exactly which symptoms need to be treated—and, potentially, which ones are bothering you most. Talk to your healthcare provider about the severity and frequency of low mood, irritability, anxiousness, and sleep problems.

It’s also important to discuss your individual tolerance for some of trazodone’s common side effects, such as:

• Dizziness
• Dry mouth
• Blurred vision
• Drowsiness
• Constipation
• Weight gain

And serious side effects of trazodone, such as: 

• Heart rate changes
• Glaucoma
• Low blood pressure (hypotension)
• Sexual dysfunction (including priapism)
• Urinary incontinence 
• Suicidal thoughts

Trazodone is considered generally safe and effective, but there are drug interactions to consider. Let your healthcare provider know if you are taking any of the following:

• Monoamine oxidase inhibitors (MAO inhibitors or MAOIs), such as Zyvox (linezolid), Marplan (isocarboxazid), Nardil (phenelzine), Eldepryl (selegiline), Parnate (tranylcypromine), or methylene blue
• Other serotonin-modulators and antidepressant medication, such as tricyclic antidepressants, some antipsychotics, triptans, anxiolytics, opioids, L-Tryptophan or the over-the-counter supplement St. John’s wort 
• Blood thinners such as Coumadin (warfarin) or Eliquis (apixaban)
• Strong CYP3A4 inhibitors such as erythromycin or Nizoral (ketoconazole)

Remember, a clear disclosure of your health increases the likelihood of finding the best treatment option for you in the shortest time.