Nefazodone, previously branded as Serzone, is a serotonin modulator used to treat depression symptoms in adults. Medical advice and supervision is necessary while taking this medication due to side effects and adverse reactions that occur for some people.

Nefazodone brand names

Serzone was the brand name for nefazodone. Unfortunately, the pharmaceutical manufacturer of Serzone discontinued its production for business-related reasons in 2003 [1].

Nefazodone is currently only available in generic form. 

What is nefazodone prescribed for?

Nefazodone is an approved treatment for treating depressive disorders, including major depressive disorder, in adults. This medication is not recommended for children or teens. 

Using nefazodone has been linked to major, although rare, side effects affecting the liver, particularly in people with previous medical conditions or identified risk factors. Nevertheless, nefazodone is recommended as a treatment option when alternative antidepressant medications have not helped. 

How does nefazodone work?

Nefazodone is structurally different from other, more commonly prescribed medications to treat major depression. Therefore, it is considered an atypical antidepressant medication.

Nefazodone inhibits the reuptake of serotonin and norepinephrine while antagonizing other neurotransmitter receptors. The resulting chemical changes in the brain cause nefazodone's clinical effects [1]

Despite its demonstrated effectiveness, the exact mechanisms of how or why this medication reduces depression symptoms are not yet fully understood. 

How is nefazodone usually taken?

Nefazodone is taken orally as a tablet. Therefore, people taking nefazodone should be consistent with the times of day they take it and whether they take it with food or on an empty stomach [4].  

This medication is only available by prescription and should be taken as their healthcare professional prescribes. Do not take more or less of this medication without approval.

This medication is usually taken twice daily due to its short half-life of 2-4 hours. 

Take missed doses as soon as possible unless it is time or nearly time for the next dose. If you forget to take a dose, do not double up.

Nefazodone is recommended to be prescribed at a lower dose and gradually titrated up until reaching clinical effects. If adverse effects occur at higher dosages, lowering the dose may alleviate them [4].

How long does nefazodone stay in your system?

Nefazodone's half-life is 2-4 hours. This means that 50 percent of the medication will be metabolized and excreted from the body, primarily through urine, within four hours of taking it [6].

Biological factors affect how the body metabolizes the medication. Overall health and bodily function determine how long nefazodone remains detectable by urine, blood, or hair screenings. 

Nefazodone should be undetectable a few days after use by urine or blood tests. Hair follicle testing, however, has the longest timeframe for positive screenings. It may take several months for nefazodone to be undetectable in a hair follicle test. 

Nefazodone side effects

Nefazodone side effects range from mild to life-threatening. Report any serious side effects to the prescribing doctor as a change in dosage or medication may be required. 

The Public Citizen Health Research Group (PCHRG) petitioned the U.S. Food and Drug Administration (FDA) in 2003 to remove Serzone from the market due to the risk of liver toxicity. However, the FDA determined that it could be safely used as a treatment for depression when alternative options have failed [5]

Nefazodone carries a boxed warning due to the dangers of hepatotoxicity or liver damage while taking it. The doctor may recommend ongoing monitoring of liver functioning through lab work while taking this medication [2]

Signs of liver damage include [3]:

  • Loss of appetite
  • Stomach pain
  • Increased tiredness
  • Dark urine or problems urinating
  • Stool discoloration
  • Jaundice

Speak with the doctor right away if warning signs of liver problems occur. Failing to do so may result in permanent damage to bodily systems. 

During clinical trials, approximately 16% of participants stopped treatment due to side effects. The most common side effects of nefazodone during clinical trials were [2]

  • Nausea
  • Dizziness, lightheadedness
  • Insomnia
  • Agitation
  • Physical weakness (asthenia) 
  • Dry mouth
  • Constipation
  • Blurred vision or abnormal vision 
  • Confusion
  • Sleepiness

Serious nefazodone side effects include:

  • Vision changes
  • Seizures
  • Liver problems
  • Glaucoma

Some people, especially children, teenagers, and young adults, who begin taking an antidepressant medication such as nefazodone experience thoughts of suicide or sudden mood changes. 

Nefazodone may trigger a manic episode in people with bipolar disorder or who are predisposed to bipolar disorder through family history [2].

Additionally, nefazodone has caused rare side effects, such as significant drops in blood pressure and prolonged erections requiring medical intervention [2].

As with many medications, allergic reactions to nefazodone may occur. 

Warning signs of an allergic reaction to nefazodone include:

  • Hives
  • Respiratory difficulty
  • Swelling in the face, throat, or mouth
  • Difficulty swallowing
  • Itching

Seek medical attention if an allergic reaction occurs.

Nefazodone precautions

You should share preexisting conditions, current medications, familial medical history, and alcohol or substance use with your doctor before taking this medication. People with certain medical conditions should not take nefazodone.  

The doctor may request bloodwork before prescribing nefazodone to ensure no underlying conditions, such as liver problems. Continued monitoring of liver functioning may be recommended while taking nefazodone due to the chance of liver problems. 

People who have had an allergic reaction to trazodone should not take nefazodone [4]

This medication can lead to sleepiness or drowsiness during the day. Avoid operating heavy machinery, including driving a vehicle, until the effects of nefazodone are known.

Avoid consuming alcohol while taking nefazodone. 

Some people experience dizziness or lightheadedness when standing too quickly while taking nefazodone. Therefore, move slowly when standing up, particularly from a laying position [4] 

Medical conditions found to have poor outcomes with nefazodone include [3]:

Nefazodone is not approved for anyone under the age of 18. 

Nefazodone may not be safe for use during pregnancy or breastfeeding. If pregnancy occurs while taking this medication, speak with the doctor before stopping the medication. 

Nefazodone interactions

Nefazodone can cause serious adverse interactions when used concurrently with certain other medications, so it is vital to discuss all medications being taken with the doctor.

Nefazodone should not be taken with a monoamine oxidase inhibitor (MAOI) or within 14 days of taking an MAOI [2].

During clinical trials, the following medications were found to be contraindicated with nefazodone [2]:

  • Immunosuppressive agents
  • Triazolam (brand name: Halcion)
  • Terfenadine (brand name: Seldane)
  • Astemizole (brand name: Hismanal)
  • Cisapride (brand name: Propulsid)
  • Pimozide (brand name: Orap)
  • Carbamazepine (brand name: Tegretol) 

Additionally, taking the following medications at the same time as nefazodone should be closely monitored [3][2]:

Other medications that cause drowsiness, such as opioids, sleeping pills, and anxiety medications, can worsen the drowsiness caused by nefazodone [3]

Avoid drinking alcohol while taking nefazodone.

Due to the potential for liver problems, other medications that affect the liver should not be taken with nefazodone. This includes vitamins, herbal supplements, and over-the-counter medicines metabolized by the liver. 

Nefazodone storage

Nefazodone should be stored at room temperature in a tightly closed container away from moisture. 

Store all prescription medications away from the reach of children, teenagers, and pets, to prevent accidental overdose or misuse of the medicine. Always use child safety caps to prevent younger children from accidentally accessing medications.

Avoid flushing this medication down the toilet. To determine the best way to dispose of unused nefazodone medication, speak with a medical provider. 

What to do if you overdose on nefazodone

An overdose of this medication should be considered a serious medical emergency. 

Symptoms of a nefazodone overdose include:

  • Seizure
  • Unconsciousness
  • Respiratory difficulty
  • Nausea
  • Vomiting
  • Drowsiness

Seek immediate medical assistance if an overdose on nefazodone has occurred. 

Frequently asked questions about nefazodone

Is nefazodone addictive?

Nefazodone is considered to be a non-habit-forming medication for the treatment of depression symptoms. In addition, studies suggest it is nonaddictive.

However, using nefazodone while taking illicit substances can cause serious medical complications. If there are concerns about addiction or misuse, it is essential to have an honest conversation with a medical provider. 

What are the alternatives to nefazodone?

Alternative antidepressant medications are available if nefazodone is not the right treatment choice. 

These include selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and other atypical antidepressant medications.

Resources:

  1. Choi S. (2003). Nefazodone (Serzone) withdrawn because of hepatotoxicity. CMAJ : Canadian  Medical Association journal = journal de l'Association medicale canadienne, 169(11), 1187. Retrieved October 26, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC264962/
  2. DailyMed - NEFAZODONE HYDROCHLORIDE tablet. (n.d.). Retrieved October 26, 2022, from https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=51ff7db5-aaf9-4c3c-86e6-958ebf16b60f
  3. Nefazodone. (n.d.). Drugs.com. Retrieved October 26, 2022, from https://www.drugs.com/mtm/nefazodone.html
  4. Nefazodone: MedlinePlus Drug Information. (n.d.). Retrieved October 26, 2022, from https://medlineplus.gov/druginfo/meds/a695005.html
  5. Shuren, J. (2004, October 15). Determination That SERZONE (Nefazodone Hydrochloride) Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness. Federal Register: The Daily Journal of the United States Government.https://www.federalregister.gov/documents/2004/10/26/04-23857/determination-that-serzone-nefazodone-hydrochloride-was-not-withdrawn-from-sale-for-reasons-of
  6. Nefazodone. (n.d.). Go.drugbank.com. https://go.drugbank.com/drugs/DB01149