Citalopram with St John's Wort Interaction Details

Brand Names Associated with Citalopram

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 11, 2023

Interaction Effect

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

Interaction Summary

Case reports describe the onset of serotonin syndrome-like symptoms, mania, and hypomania following the addition of St. John's Wort to sertraline, FLUoxetine, and PARoxetine therapy. A patient exhibited a syndrome resembling sedative/hypnotic intoxication after adding St. John's Wort to PARoxetine 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.

Severity

Major

Onset

Rapid

Evidence

Probable

How To Manage Interaction

Patients should be advised to wait two weeks after stopping St. John's Wort before restarting selective serotonin reuptake inhibitor therapy. If a patient plans to replace selective serotonin reuptake inhibitor (SSRI) therapy with St. John's Wort, the half-life of the specific SSRI should be taken into consideration, waiting at least 5 half-lives for the SSRI to be metabolized out of the body.

Mechanism Of Interaction

Additive serotonergic effects

Literature Reports

A) Five cases have been reported of serotonin syndrome in the elderly after combining prescription antidepressants and St. John's Wort. Case 1 developed dizziness, nausea, vomiting and a headache 4 days after starting St. John's Wort 300 milligrams (mg) three times daily combined with sertraline 50 mg daily. Her symptoms resolved 2 to 3 days after stopping all medications. Case 2 developed nausea, epigastric pain and anxiety 3 days after starting St. John's Wort 300 mg twice daily combined with sertraline 75 mg daily. His symptoms resolved in one week after discontinuing both medications, and he resumed sertraline use without complications. The third case developed nausea, vomiting, anxiety, and confusion 2 days after starting St. John's Wort 300 mg twice daily combined with sertraline 50 mg daily. His symptoms improved in 4 to 5 days after stopping both medications and taking cyproheptadine 4 mg three times daily. Case 4 developed nausea, anxiety, restless, and irritability 2 days after starting St. John's Wort 300 mg three times daily combined with sertraline 50 mg daily. Cyproheptadine 4 mg twice daily was administered for seven days, and his symptoms improved in 1 week after stopping the medication. Cases 1 through 4 resumed their prescriptive sertraline after symptoms subsided and had no further problems. Case 5 developed nausea, vomiting and restlessness 3 days after starting St. John's Wort 300 mg three times daily combined with nefazodone 100 mg twice daily. She continued to take St. John's Wort but discontinued the nefazodone and over 1 week her symptoms Improved. She refused to resume therapy with nefazodone, but continued therapy with St. John's Wort and mild to moderate symptoms of depression and anxiety returned .

B) A 50-year-old female taking St. John's Wort 600 mg daily experienced symptoms of sedative intoxication when she ingested a single dose of PARoxetine 20 mg. She was incoherent, groggy, slow-moving, and complained of nausea and weakness. Prior to starting St. John's Wort, she had been receiving PARoxetine 40 mg daily for eight months without adverse effects. After a night of sleep, she returned to her baseline mental status .

C) A 61-year-old female experienced restlessness and involuntary movements of her extremities after beginning PARoxetine 20 milligrams (mg) two days after discontinuing St. John's Wort 600 mg daily. The patient reported agitation and akathisia 8 hours after taking the first dose of PARoxetine. She presented with diaphoresis and involuntary movement of all extremities with hyperreflexia and rigidity. Blood pressure, heart rate, and temperature were normal. After admission, blood pressure increased to 200/116 mmHg and heart rate increased to 145 beats per minute. Creatine kinase increased from 212 units/liter (U/L) initially to 1024 U/L. The patient was managed with supportive care and LORazepam and discharged after two days .

D) A 28-year-old male developed a manic syndrome following comedication with St. John's Wort and sertraline. The patient was also on testosterone replacement therapy following bilateral orchidectomy 2 years earlier, but testosterone levels were subtherapeutic. The patient was prescribed sertraline 50 milligrams daily for depression following a 2 week trial of St. John's Wort per patient preference (dose not specified). Before sertraline was started, the patient was instructed to discontinue St. John's Wort, but continued it despite this advice. The patient experienced improved mood so did not see his physician, believing that he did not need further treatment. Over 2 months, the patient had elated mood, was irritable, and overspent, buying a car he could not afford, and was ultimately arrested for stealing fuel for the car. On arrest, he was referred to psychiatric services due to irritability and disinhibition. He was observed to be over-aroused, distractible, have flight of ideas, and grandiose delusions, leading to a diagnosis of a manic episode. The authors state the possibility of the manic state resulting from sertraline therapy alone, and that St. John's Wort may have increased the risk as a result of monoamine oxidase inhibition. Since the patient's testosterone level was subnormal, the possibility of its contribution to the manic state was considered low. However, the patient had elevated gonadotropin levels (luteinizing hormone and follicle-stimulating hormone) which may have predisposed the patient to mania .

E) A 42-year-old female experienced symptoms consistent with a mixed hypomanic episode following concomitant use of FLUoxetine, busPIRone, Ginkgo biloba, and St. John's Wort. The symptoms resolved following discontinuation of Ginkgo and St. John's Wort. The patient was being treated for depression following a mild traumatic brain injury with FLUoxetine 20 milligrams (mg) twice daily and busPIRone 15 mg twice daily. Several weeks prior to presentation, busPIRone was increased to 20 mg twice daily for persistent anxiety and the patient began taking Ginkgo biloba, melatonin, and St. John's Wort in unspecified doses. Melatonin was considered unlikely to have contributed to her symptoms. Ginkgo and St. John's Wort were considered possible contributors since they may potentiate antidepressants, and considering the temporal relationship between the use of the herbs and onset of symptoms and discontinuation of the herbs and resolution of symptoms. However, the brain injury was considered a possible contributor .

Citalopram Overview

• Citalopram is used to treat depression. Citalopram is in a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps 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.