Venlafaxine with St John's Wort Interaction Details
Brand Names Associated with Venlafaxine
- Effexor®
- Effexor® XR
- Venlafaxine
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 12, 2023
Interaction Effect
An increased risk of serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)
Interaction Summary
One case of serotonin syndrome likely resulting from concomitant use of St. John's Wort and venlafaxine has been reported. Several case reports describe the onset of serotonin syndrome-like symptoms following the addition of St. John's Wort to sertraline or nefazodone therapy . St. John's Wort is thought to inhibit serotonin reuptake and may have mild monoamine oxidase inhibitory activity , which when added to selective serotonin reuptake inhibitors may result in serotonin syndrome. Serotonin syndrome is a condition of serotonergic hyperstimulation and manifests as restlessness, myoclonus, changes in mental status, hyperreflexia, diaphoresis, shivering, and tremor. Although St. John's Wort was initially characterized as a monoamine oxidase inhibitor (MAOI), it is now believed that insufficient MAO inhibition occurs to explain the clinical activity of St. John's Wort as an antidepressant . It remains possible that the mild MAOI property of St. John's Wort may contribute to an interaction with drugs which inhibit serotonin reuptake leading to serotonin syndrome . Concomitant administration of monoamine oxidase inhibitors (MAOIs) with SSRIs has been considered an absolute contraindication in the past and still is listed as such by the manufacturers. This contraindication may be extended to venlafaxine which, though not an SSRI, inhibits serotonin and norepinephrine reuptake. A two-week washout period is suggested after discontinuing St. John's Wort before starting a SSRI , and may be applied to venlafaxine as well.
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Avoid concomitant use. Given the half-life of venlafaxine of up to 11 hours, St. John's Wort should be avoided for at least 5 half-lives (one to two days) following venlafaxine discontinuation. A two-week washout period is suggested after discontinuing St. John's Wort before starting a SSRI, and may be applied to venlafaxine as well.
Mechanism Of Interaction
Additive serotonergic effect
Literature Reports
A) A 32-year-old male experienced symptoms of serotonin syndrome (malaise, anxiety, diaphoresis, tremor, tachycardia) after 3 days of comedication with venlafaxine 250 milligrams (mg) daily and St. John's Wort tincture 200 drops three times daily (usual dose stated as 160 drops daily). The patient had been taking venlafaxine for several months for depression and self-medicated with St. John's Wort after hearing of its benefits. St. John's Wort was discontinued on day 4 while venlafaxine was continued, and symptoms improved over 3 days .
Venlafaxine Overview
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Venlafaxine is used to treat depression. Venlafaxine extended-release (long-acting) capsules are also used to treat generalized anxiety disorder (GAD; excessive worrying that is difficult to control), social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life), and panic disorder (sudden, unexpected attacks of extreme fear and worry about these attacks). Venlafaxine is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SNRIs). It works by increasing the amounts of serotonin and norepinephrine, natural substances in the brain that help 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.
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Information for our drug interactions is compiled from several drug compendia, including:
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.