Taking Nefazodone as an Antidepressant

FDA's Information on Possible Side Effects and Dosages

Man taking medicine

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Nefazodone is an antidepressant that may help those who have not responded well to other antidepressants. It does carry a rare, but serious, risk of liver damage so it must be used carefully. 


Let's learn more about nefazodone, including its black box warnings, side effects, and dosages based on information from the U.Sf. Food and Drug Administration (FDA). 

It's important to note that the sale of Serzone, the brand medication of Nefazodone, was discontinued in 2003 in the United States due to the rare occurrence of severe liver damage. But generic formulations of nefazodone are still available.

Liver Failure Warning

In rare cases, people taking nefazodone have developed liver failure. If you notice any of the following symptoms, call your doctor immediately:

  • Yellowing of the skin or whites of eyes (jaundice)
  • Unusually dark urine
  • Loss of appetite that lasts several days or longer
  • Nausea
  • Abdominal (lower stomach) pain
  • Feeling unwell

People who already have any liver problems should not take this medication.

Doctors will regularly check your liver blood tests while taking nefazodone. 

Suicide Black Box Warning

As with all antidepressants, in the United States, nefazodone carries the black box warning regarding suicidality. Doctors prescribing this medication are advised to closely watch their patients for worsening of their depression or suicidal thoughts, especially at the start of the medication, or whenever there is a change in the dose. 

If you are having suicidal thoughts, contact the National Suicide Prevention Lifeline at 988 for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.

For more mental health resources, see our National Helpline Database.


According to the FDA, the manufacturer's recommended starting dose is 200 mg/day in two doses, morning and evening. Dosage may be gradually increased, waiting for side effects to subside before going up to a new level. In clinical trials, the effective dose range was generally 300 to 600 mg/day. 

Some improvement, especially in anxiety and sleeplessness (if present), should be felt by the patient within the first week or two. But it can several weeks to a few months for the full benefits of nefazodone to be experienced.

Drug Interactions

Consult your doctor before taking nefazodone if you are also taking any of the following medications, because serious interactions may occur:

  • Tegretol (carbamazepine) - Often prescribed as a mood stabilizer for bipolar disorder
  • Any MAOI antidepressant
  • Xanax (alprazolam) - An anti-anxiety medication
  • Orap (pimozide) - A rarely prescribed antipsychotic medication
  • Halcion (triazolam) - A rarely prescribed anti-anxiety medication

Allow two weeks between stopping any MAOI and starting nefazodone, and one week between discontinuing nefazodone and starting treatment with any MAOI.

There are many other drug interactions with nefazodone, so read the patient information accompanying your prescription completely. Notify your doctor if you discover any potential problems.

Also, the manufacturer recommends that patients notify their doctor if they become pregnant or are planning a pregnancy while on the medication.

Patients should also contact their doctor if they are breastfeeding. 

Side Effects

Nefazodone is a serotonin antagonist and reuptake inhibitor (SARI) that potently and selectively blocks postsynaptic serotonin (5-hydroxytryptamine; 5-HT) 5-HT2A receptors and moderately inhibits serotonin and noradrenaline (norepinephrine) reuptake. Unlike the SSRI antidepressants, nefazodone associated with minimal weight gain and minimal sexual side effects.

In addition, the reported activation of mania/hypomania may be lower with nefazodone than with some other antidepressants in bipolar patients. That being said, some risk remains, so patients should be monitored by their doctor for the onset of mania or hypomania when taking this or any antidepressant.

Most common side effects include:

  • Sleepiness
  • Dry mouth
  • Nausea
  • Constipation
  • Weakness
  • Dizziness
  • Problems with vision
  • Lightheadedness
  • Confusion

What Should I Do?

If your doctor is considering nefazodone for your depression, be sure you follow up with him closely. 

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By Marcia Purse
Marcia Purse is a mental health writer and bipolar disorder advocate who brings strong research skills and personal experiences to her writing.