What medications cannot be taken with sertraline? A comprehensive guide

October 11, 2025 •

4 min read

Sertraline, a widely prescribed selective serotonin reuptake inhibitor (SSRI), is associated with many potential drug interactions that can lead to significant health complications. Understanding what medications cannot be taken with sertraline is crucial for patient safety, as some combinations can trigger serious conditions like the potentially life-threatening serotonin syndrome.

Quick Summary

Sertraline has serious interactions with certain drugs, including MAOIs, specific antipsychotics, and medications that prolong the QT interval. It also increases the risk of bleeding with blood thinners and NSAIDs, and can cause serotonin syndrome when combined with other serotonergic agents or St. John's Wort.

Key Points

Contraindicated Medications: Do not take sertraline with MAOIs, pimozide, or disulfiram (with the oral solution) under any circumstances to avoid severe, dangerous reactions.
Serotonin Syndrome Risk: Combining sertraline with other serotonergic drugs like certain opioids, triptans, or St. John's Wort can cause a life-threatening serotonin syndrome.
Increased Bleeding: The risk of bleeding is heightened when taking sertraline with anticoagulants (warfarin) and NSAIDs (ibuprofen), and patients should be monitored closely.
Cardiac Concerns: Be cautious when combining sertraline with medications that can prolong the QT interval, as this can lead to irregular and dangerous heart rhythms.
Alcohol and Supplements: Avoid alcohol, St. John's Wort, and tryptophan/5-HTP supplements, as they can exacerbate sertraline's side effects or increase serotonin levels dangerously.
Full Disclosure is Key: Always inform your healthcare provider and pharmacist of all medications and supplements you are taking to properly manage or avoid potential interactions.

The Serious Threat of Serotonin Syndrome

Serotonin syndrome is a potentially life-threatening condition caused by too much serotonin in the brain. While the condition is rare, combining sertraline with other medications that increase serotonin levels can significantly elevate this risk. Signs and symptoms can range from mild (tremors, sweating) to severe (high fever, rigid muscles, seizures) and require immediate medical attention.

Medications with Absolute Contraindications

Certain medications are completely forbidden to be taken with sertraline due to severe, high-risk interactions. These are non-negotiable prohibitions to prevent dangerous health outcomes.

Monoamine Oxidase Inhibitors (MAOIs)

The combination of sertraline and MAOIs is strictly contraindicated due to a high risk of developing serotonin syndrome. MAOIs are an older class of antidepressants and are also used for Parkinson's disease. A "washout" period of at least 14 days is required between stopping an MAOI and starting sertraline, and vice-versa. Examples of MAOIs include phenelzine (Nardil), isocarboxazid (Marplan), tranylcypromine (Parnate), and selegiline (Eldepryl, Zelapar). Additionally, the antibiotic linezolid (Zyvox) and intravenous methylene blue are considered MAOIs and should not be used with sertraline.

Pimozide

Pimozide (Orap), an antipsychotic medication, should not be taken with sertraline because the combination can lead to dangerous heart rhythm problems, specifically QT prolongation.

Disulfiram and Sertraline Oral Solution

Sertraline oral solution contains alcohol and should not be used by patients taking disulfiram (Antabuse), a medication to treat alcohol use disorder. This combination can cause a severe disulfiram-alcohol reaction.

Medications Requiring Caution and Close Monitoring

For other classes of medication, concomitant use with sertraline is not absolutely contraindicated but requires careful consideration, monitoring, and in some cases, dosage adjustments.

Other Serotonergic Drugs

Combining sertraline with other drugs that affect serotonin levels increases the risk of serotonin syndrome. This includes other antidepressants like SSRIs and SNRIs, opioid pain medications such as tramadol and fentanyl, triptans for migraines (e.g., sumatriptan), lithium, amphetamines, and the cough suppressant dextromethorphan.

Drugs that Increase Bleeding Risk

Sertraline can increase the risk of bleeding or bruising. This risk is higher when combined with other agents that also affect blood clotting. These include anticoagulants like warfarin, apixaban, and heparin, antiplatelet agents such as aspirin and clopidogrel, and NSAIDs like ibuprofen and naproxen.

Medications Affecting Heart Rhythm

Combining sertraline with other drugs that can prolong the QT interval can increase the risk of dangerous arrhythmias. Examples include certain antibiotics (ciprofloxacin, azithromycin), some antiarrhythmics (amiodarone), and specific antipsychotics (ziprasidone).

Medications with Narrow Therapeutic Indexes

Sertraline can affect the metabolism of other drugs, potentially increasing their levels in the body. An example is phenytoin, an anti-seizure medication, whose level may increase when taken with sertraline, requiring monitoring.

Herbal Supplements and Lifestyle Factors

Beyond prescription drugs, certain herbal remedies and lifestyle choices also pose significant risks when combined with sertraline.

St. John's Wort

This herbal supplement should not be taken with sertraline due to the risk of serotonin syndrome from increased serotonin levels.

Tryptophan and 5-HTP Supplements

These supplements are precursors to serotonin, and taking them with sertraline can lead to excessively high serotonin levels and increase the risk of serotonin syndrome.

Alcohol

Combining sertraline with alcohol is generally discouraged as it can worsen side effects and potentially negate the antidepressant's effects.

Table: Summary of Sertraline Interactions


Interaction Type	Examples of Medications	Potential Risk	Monitoring/Management	Action
Serotonin Syndrome	MAOIs (linezolid, phenelzine), other SSRIs, SNRIs, opioids (tramadol, fentanyl), triptans, lithium, St. John's Wort	Agitation, confusion, rapid heartbeat, high fever, rigid muscles	Discontinue one or both medications; supportive care	AVOID
Increased Bleeding Risk	Warfarin, aspirin, NSAIDs (ibuprofen, naproxen)	Gastrointestinal bleeding, bruising	Regular blood work (INR monitoring for warfarin), watch for signs of bleeding	CAUTION / CONSULT DOCTOR
QT Prolongation	Pimozide, certain antibiotics (azithromycin), antiarrhythmics (amiodarone)	Irregular heartbeat (arrhythmias), fainting, potential sudden cardiac death	Baseline and follow-up ECGs for high-risk patients; use lower-risk alternatives	AVOID or CAUTION
Altered Drug Levels	Phenytoin, metoprolol, tolterodine	Increased side effects or reduced efficacy of the interacting drug	Monitor drug levels, adjust dosage as needed	CAUTION / MONITORING
Exacerbated CNS Effects	Alcohol, other depressants	Increased drowsiness, dizziness, impaired judgment, worsening depression	Avoid alcohol and other CNS depressants; monitor closely	AVOID

Why Full Disclosure to Your Doctor is Critical

Before starting sertraline or any new medication, provide your healthcare provider with a complete list of all drugs, over-the-counter medications, herbal supplements, and recreational substances you use. This allows your medical team to assess risks and ensure your treatment is safe and effective.

Conclusion

Sertraline is an effective medication, but it has potential drug interactions ranging from uncomfortable to life-threatening. Critical interactions involve serotonin-elevating drugs like MAOIs and St. John's Wort, risking serotonin syndrome. Increased bleeding with blood thinners and NSAIDs and heart rhythm abnormalities with certain other medications are also serious concerns. Always communicate openly with your healthcare provider and pharmacist about all substances you are taking to prevent harmful combinations.

Frequently Asked Questions

Combining NSAIDs with sertraline can increase the risk of bleeding, particularly gastrointestinal bleeding. While occasional low-dose use might be acceptable for some, you should always consult your doctor before combining them, and they may recommend monitoring for signs of bleeding.

The combination of sertraline with Monoamine Oxidase Inhibitors (MAOIs) is dangerous because both significantly increase serotonin levels in the brain, leading to a high risk of serotonin syndrome. Serotonin syndrome is a potentially fatal condition characterized by symptoms such as high fever, agitation, and rigid muscles.

No, it is generally not recommended to drink alcohol while taking sertraline. Alcohol can worsen side effects like dizziness and drowsiness and can also interfere with the medication's effectiveness, potentially worsening depression or anxiety.

Combining sertraline and the herbal supplement St. John's Wort is highly risky as both increase serotonin levels, which can lead to serotonin syndrome. This combination should be avoided entirely.

Yes, some common cold and flu medications containing dextromethorphan (a cough suppressant) can raise serotonin levels. You should check with your doctor or pharmacist before using these products with sertraline to avoid serotonin syndrome.

Certain migraine medications called triptans (e.g., sumatriptan) increase serotonin levels and, when combined with sertraline, can raise the risk of serotonin syndrome. Always consult your doctor before combining these medications.

Yes, sertraline can increase the risk of bleeding, and this effect is compounded when taken with blood thinners such as warfarin. For this reason, close monitoring of the international normalized ratio (INR) is necessary.