Who Should Avoid Sertraline? A Comprehensive Guide to Contraindications and Warnings

October 7, 2025 •

4 min read

Over 40 million prescriptions are filled for sertraline (Zoloft) each year in the US, but it is not a suitable treatment option for everyone. A number of critical interactions and underlying health conditions mean specific individuals should avoid sertraline entirely or use it with extreme caution and under strict medical supervision.

Quick Summary

Sertraline is contraindicated for patients with hypersensitivity, those taking MAOIs or pimozide, and requires caution for individuals with liver disease, bleeding disorders, or certain heart conditions. It can cause serious drug interactions and poses risks for specific populations.

Key Points

MAOIs and Pimozide: The use of sertraline is strictly contraindicated with Monoamine Oxidase Inhibitors (MAOIs) and the antipsychotic drug pimozide due to severe, potentially fatal, interactions.
Pre-existing Conditions: Individuals with liver disease, certain heart conditions, a history of bipolar disorder or seizures, and untreated angle-closure glaucoma should be cautious or avoid sertraline.
Increased Bleeding Risk: Sertraline increases the risk of bleeding, especially when combined with NSAIDs, aspirin, or blood-thinning medications.
Serotonin Syndrome: Taking sertraline with other serotonergic agents, like certain opioids, triptans, or St. John's Wort, can trigger a dangerous condition called serotonin syndrome.
Specific Populations: Caution is required for pregnant women, breastfeeding women, and young adults (due to increased suicidal ideation risk), necessitating a careful risk-benefit analysis with a doctor.
Liquid Concentrate Warning: The oral liquid concentrate form of sertraline should not be taken by anyone on disulfiram (Antabuse) due to its alcohol content.

Absolute Contraindications: Medications You Cannot Mix with Sertraline

Some interactions with sertraline are so dangerous that they are absolute contraindications. Combining these substances can lead to life-threatening conditions and must be strictly avoided.

Monoamine Oxidase Inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) are an older class of antidepressants that, when combined with sertraline, can cause a severe and potentially fatal reaction known as serotonin syndrome. The risk also applies if a patient has taken an MAOI within the last 14 days or plans to start one within 14 days of stopping sertraline. Examples of MAOIs include phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan), and the antibiotic linezolid (Zyvox).

Pimozide (Orap)

Another absolute contraindication is the antipsychotic medication pimozide. Co-administration with sertraline can lead to serious heart rhythm problems, including QT prolongation and irregular heartbeats. This combination should never be used.

Disulfiram (Antabuse)

For patients prescribed the liquid oral concentrate form of sertraline, co-administration with disulfiram (Antabuse) is prohibited. The liquid concentrate contains alcohol, and taking it with disulfiram can lead to a severe reaction.

Medical Conditions Requiring Caution

Certain health conditions can increase the risk of serious side effects while taking sertraline. Your doctor must be aware of your full medical history before prescribing this medication.

Liver Disease

Sertraline is extensively metabolized by the liver. Individuals with moderate to severe liver impairment should generally avoid sertraline, while those with mild impairment may need a reduced or less frequent dose. Regular monitoring of liver function tests is necessary for these patients. Rare cases of clinically significant liver injury (hepatotoxicity) have been reported, emphasizing the need for vigilance.

Heart Problems

Sertraline can cause changes to heart rhythm. Individuals with pre-existing heart conditions, a history of irregular heartbeat, high blood pressure, or a family history of long QT syndrome should be evaluated carefully. Those taking other medications known to prolong the QT interval may have an increased risk.

Bleeding Disorders

Sertraline can inhibit platelet aggregation, which increases the risk of bleeding. This risk is heightened when combined with other agents that affect clotting, such as nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or naproxen, aspirin, or blood thinners like warfarin (Coumadin).

Bipolar Disorder and Seizures

For individuals with a history of bipolar disorder, there is a risk of activating mania or hypomania when taking an antidepressant like sertraline. In patients with epilepsy or a history of seizures, sertraline may increase the risk of seizures.

Angle-Closure Glaucoma

Sertraline may increase pressure in the eye and should be avoided by patients with untreated anatomically narrow angles. Patients experiencing eye pain, changes in vision, or swelling around the eye should seek immediate medical attention.

Interacting Drugs and Supplements

Many common medications and supplements interact with sertraline, increasing the risk of side effects or reducing the effectiveness of treatment. Always inform your doctor and pharmacist of all substances you are taking.

Serotonergic Agents

Combining sertraline with other substances that increase serotonin can trigger serotonin syndrome. This includes other antidepressants (SSRIs, SNRIs), certain opioids (tramadol), migraine medications (triptans), and the herbal supplement St. John’s Wort.

NSAIDs and Blood Thinners

The combination of sertraline with NSAIDs, aspirin, or anticoagulant medications like warfarin or apixaban significantly increases the risk of abnormal bleeding.

Alcohol

Patients are advised to avoid or limit alcohol consumption while taking sertraline, as it can increase the risk of side effects like drowsiness.

Herbal Supplements

Aside from St. John's Wort, other supplements like tryptophan can also increase serotonin levels and interact adversely with sertraline.

Comparison of Sertraline vs. Other SSRIs and Risks


Feature	Sertraline (Zoloft)	Citalopram (Celexa)	Paroxetine (Paxil)	Fluoxetine (Prozac)
Hepatotoxicity Risk	Low, but requires caution with liver disease; mild enzyme elevations possible.	Very low, considered one of the safest for liver concerns.	Low to moderate risk.	Low risk.
QTc Prolongation	Generally low risk at standard doses, but possible with overdose or in at-risk individuals.	Highest risk among SSRIs, especially at high doses.	Lower risk compared to citalopram.	Lower risk compared to citalopram.
Bleeding Risk	Moderate; inhibits platelet aggregation.	Moderate risk, similar to sertraline.	Moderate risk.	Moderate risk.
Drug Interactions	Significant interactions with MAOIs, pimozide, triptans, NSAIDs, etc..	Fewer interactions, but still significant with MAOIs and caution with QTc-prolonging drugs.	Significant interactions, including with MAOIs.	Significant interactions, including with MAOIs and higher risk for serotonin syndrome.

Conclusion

Sertraline is an effective treatment for many mental health conditions, but it is not appropriate for everyone. Individuals with absolute contraindications, such as concurrent MAOI or pimozide use, must avoid it entirely. Those with pre-existing conditions like liver disease, certain heart problems, bleeding disorders, or a history of seizures or mania should exercise caution and be closely monitored. It is imperative to have a thorough discussion with a healthcare provider about all medical conditions and other medications, including over-the-counter and herbal supplements, to ensure patient safety. Never stop or start this medication without medical advice. For further information on mental health medications, resources like the National Alliance on Mental Illness (NAMI) are highly valuable and authoritative.

Frequently Asked Questions

You are at risk for serotonin syndrome if you take sertraline with other medications that increase serotonin levels, such as MAOIs, other antidepressants, certain opioids (like tramadol), triptans (for migraines), and herbal supplements like St. John's Wort. Symptoms can include agitation, rapid heart rate, hallucinations, fever, and muscle stiffness.

Sertraline is extensively metabolized by the liver, and patients with moderate to severe liver impairment should avoid it. For those with mild liver issues, a doctor may prescribe a lower dose and require regular monitoring of liver function.

Individuals with heart disease, high blood pressure, a history of irregular heartbeat, or a family history of prolonged QT interval should discuss these issues with a doctor. Sertraline can affect heart rhythm, especially when combined with other heart-affecting drugs or in overdose.

For children and young adults (under 25), there is an increased risk of suicidal thoughts and behaviors, especially when starting the medication or changing the dosage. Patients, families, and caregivers should watch for new or worsening symptoms, anxiety, agitation, and unusual changes in behavior.

Yes, sertraline can increase the risk of bleeding because it inhibits platelet aggregation. This risk is higher if you also take NSAIDs, aspirin, or anticoagulant medications like warfarin.

Combining sertraline with Monoamine Oxidase Inhibitors (MAOIs) is extremely dangerous and can cause fatal serotonin syndrome. There must be a 14-day washout period between discontinuing an MAOI and starting sertraline, and vice versa.

While sertraline is considered one of the preferred antidepressants during breastfeeding, it should be taken with caution and only after a doctor evaluates the risks and benefits. Taking it in the third trimester of pregnancy can cause complications for the newborn, and monitoring is necessary.