Nefazodone (Serzone)

Nefazodone is a newer antidepressant that has a different structure and means of action than most others. It is not a monamine oxidase inhibitor (MAOI), a tricyclic antidepressant (TCA) or a serotonin selective uptake inhibitor (SSRI). Bristol-Meyers-Squibb received FDA approval to market Serzone for the treatment of depression in 1994.

During post-approval use, it became apparent that liver damage and failure is a rare side effect of nefazodone and it can require liver transplant or can result in death. Because there is no way to determine who will or will not have liver damage when taking the medication, nefazodone was banned in Canada, Europe and some other places in 2002-2003.

Nefazodone is still available in the USA as a generic medication. Bristol-Meyers-Squibb stopped manufacturing and selling Serzone in 2004 because of declining sales.

The Bottom Line: What You Really Need to Know


Nefazodone is used to treat depression.

Dosage and instructions

Most people begin taking nefazodone with 100 mg twice a day. The dose is slowly increased as tolerated to a maximum of 600 mg/day.

How nefazodone works

Depression is thought to be at least partially due to abnormalities in the chemicals that are found between nerve cells. These chemicals are always present, and they are always being excreted and absorbed by the nerve cells. Nefazodone seems to increase serotonin levels by preventing uptake and reuptake, and to inhibit norepinephrine reuptake.

Side Effects

Some of the side effects that nefazodone produces are:


MAOI antidepressants: If nefazodone and MAOI antidepressants are taken concurrently, a serious and severe interaction can result. The symptoms can include extremely high fever, muscle rigidity, convulsions, coma and death. MAOI antidepressants should be stopped at least two weeks before starting nefazodone. Nefazodone has a relatively short half-life (a measure that indicates how long the drug is effective) so MAOI's can be started a week after stopping it.

Terfenedine (Seldane) and astemizole (Hismanol): These medications must not be taken with nefazodone. The interaction between them can cause fatal heart dysrhythmias.

Triazolam (Halcion) and alprazolam (Xanax): These medications must be taken in very low doses, if at all, when you are taking nefazodone.

Other medications that interact with nefazodone and should be avoided are:


Although no one knows if discontinuation symptoms will occur when nefazodone is abruptly withdrawn, we assume that they will. Most other antidepressants require gradual withdrawal, so nefazodone probably does, too.

Precautions, warnings and contraindications

Suicide risk: There is an increased risk of suicide with all antidepressants, especially when you first start taking them. Close monitoring and frequent follow-up is important. Be sure to report any unusual thoughts, feelings or behaviors to your physician.

Liver damage: Liver damage, sometimes requiring liver transplant and sometimes ending in death, has occurred rarely in patients who are taking nefazodone. There is no way to predict who will have liver damage when taking nefazodone; signs and symptoms can appear after two weeks of treatment or not for six months of more. Your doctor will draw blood at frequent intervals to evaluate your liver function.

MAOIs: Nefazodone should not be taken less than two weeks after discontinuing monamine oxidase inhibiting antidepressants.

Seizures: Nefazodone lowers the seizure threshold; people who are susceptible to seizures may experience them after starting this medication.

Mania and psychosis: People with bipolar disorder can experience manic episodes while taking nefazodone unless they are also taking a mood stabilizer. People who are schizophrenic may experience psychotic episodes while taking nefazodone.

Nefazodone should not be taken if you have recently had a heart attack or stroke.

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