Paroxetine with Nefazodone Interaction Details

Brand Names Associated with Paroxetine

Brand Names Associated with Nefazodone

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 13, 2023

Interaction Effect

An increased risk of serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)

Interaction Summary

One case report describes the development of serotonin syndrome in a female who had stopped nefazodone after a two-week tapering period and started PARoxetine therapy one day after the complete discontinuation of nefazodone. A repeat challenge with PARoxetine seven days later did not result in the recurrence of symptoms. Coadministration of PARoxetine and other serotonergic drugs like nefazodone increases the risk of serotonin syndrome, which may be life-threatening. If used concomitantly, monitor patients for signs and symptoms of serotonin syndrome (eg, mental status changes [agitation, hallucinations, delirium, coma], autonomic instability [tachycardia, labile blood pressure, dizziness, diaphoreses, flushing, hyperthermia], neuromuscular symptoms [tremor, rigidity, myoclonus, hyperreflexia, incoordination], seizures, and gastrointestinal symptoms [nausea, vomiting, diarrhea]), particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of PARoxetine and/or nefazodone and initiate symptomatic treatment .

Severity

Major

Onset

Rapid

Evidence

Probable

How To Manage Interaction

Coadministration of PARoxetine and other serotonergic drugs like nefazodone increases the risk of serotonin syndrome, which may be life-threatening. If used concomitantly, monitor patients for signs and symptoms of serotonin syndrome (eg, mental status changes [agitation, hallucinations, delirium, coma], autonomic instability [tachycardia, labile blood pressure, dizziness, diaphoreses, flushing, hyperthermia], neuromuscular symptoms [tremor, rigidity, myoclonus, hyperreflexia, incoordination], seizures, and gastrointestinal symptoms [nausea, vomiting, diarrhea]), particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of PARoxetine and/or nefazodone and initiate symptomatic treatment.

Mechanism Of Interaction

Additive serotonergic effects

Literature Reports

A) A 51-year old female with bipolar affective disorder had received nefazodone for six months and had tapered the dose to 75 mg every twelve hours over two weeks. One day after stopping nefazodone therapy, she started PARoxetine 20 mg daily and valproic acid 250 mg three times daily. She was agitated and incoherent and then became unresponsive, with shaking movements in her arms and legs. Upon admission to the emergency department, she was diaphoretic, with uncoordinated body tremors, flailing arms, twitching legs, and dilated pupils. Her body temperature rose to 102.2 F, and her creatine kinase (CK) values reached 25,520 U/L by day 3. She became afebrile, and muscle rigidity dissipated by day 4. A repeat challenge with PARoxetine seven days later did not result in the recurrence of symptoms. Nefazodone has a half-life of 1.9 to 2.9 hours, but several active metabolites exist, with half-lives of 18 to 33 hours. The authors postulated that in this patient, nefazodone metabolites caused serotonin syndrome when the patient ingested PARoxetine. A seven day washout period is recommended after the discontinuation of nefazodone before the administration of any selective serotonin reuptake inhibitor is started .

B) Serotonin syndrome is a condition of serotonergic hyperstimulation and manifests as restlessness, myoclonus, changes in mental status, hyperreflexia, diaphoresis, shivering, and tremor. If the syndrome is not recognized and correctly treated, fatality can result .

Paroxetine Overview

• Paroxetine tablets, suspension (liquid), and extended-release (long-acting) tablets are used to treat depression, panic disorder (sudden, unexpected attacks of extreme fear and worry about these attacks), and social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life). Paroxetine tablets and suspension are also used to treat obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), generalized anxiety disorder (GAD; excessive worrying that is difficult to control), and posttraumatic stress disorder (disturbing psychological symptoms that develop after a frightening experience). Paroxetine extended-release tablets are also used to treat premenstrual dysphoric disorder (PMDD, physical and psychological symptoms that occur before the onset of the menstrual period each month). Paroxetine capsules (Brisdelle) are used to treat hot flashes (sudden feelings of warmth, especially in the face, neck, and chest) in women who are experiencing menopause (stage of life when menstrual periods become less frequent and stop and women may experience other symptoms and body changes). Paroxetine is in a class of medications called selective serotonin-reuptake inhibitors (SSRIs). It treats depression and other mental illnesses by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance. There is not enough information available at this time to know how paroxetine works to treat hot flashes.

Nefazodone Overview

• Nefazodone is used to treat depression. Nefazodone is in a class of medications called serotonin modulators. It works by increasing the amounts of certain natural substances in the brain that are needed to maintain mental balance.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.