Sertraline, commonly known by its brand name Zoloft, is a selective serotonin reuptake inhibitor (SSRI) used to treat depression, anxiety disorders, and other mental health conditions [1.7.2]. It works by increasing the levels of serotonin, a natural substance in the brain that helps maintain mental balance [1.3.2]. While effective for many, its safety depends heavily on avoiding harmful interactions with other substances. Always provide your healthcare provider with a complete list of your medications, including over-the-counter drugs and supplements, before starting treatment [1.2.1].
Absolute Contraindications: The Most Dangerous Combinations
Certain medications are considered absolute contraindications, meaning they should never be taken with sertraline due to the risk of severe, life-threatening reactions [1.3.1].
Monoamine Oxidase Inhibitors (MAOIs)
The most critical interaction to avoid is with Monoamine Oxidase Inhibitors (MAOIs). Combining sertraline with an MAOI can lead to serotonin syndrome, a condition caused by excessive serotonin in the brain [1.3.2]. Symptoms can range from mild (tremors, sweating) to severe (high fever, seizures, and even death) [1.8.2]. A washout period of at least 14 days is required when switching between sertraline and an MAOI [1.3.2, 1.3.4].
Examples of MAOIs include [1.3.3]:
- Isocarboxazid (Marplan)
- Phenelzine (Nardil)
- Selegiline (Emsam, Zelapar)
- Tranylcypromine (Parnate)
- Linezolid (Zyvox), an antibiotic with MAOI properties [1.3.2]
Pimozide (Orap)
Taking the antipsychotic medication pimozide with sertraline is contraindicated [1.2.5]. This combination can significantly increase the risk of serious cardiac side effects, particularly a heart rhythm issue known as QT interval prolongation, which can be fatal [1.2.4].
Disulfiram (Antabuse) and Sertraline Liquid
The liquid concentrate form of sertraline contains 12% alcohol [1.2.3]. Therefore, it must not be taken with disulfiram, a medication used to treat alcohol use disorder. The combination can trigger a severe reaction with symptoms like vomiting, flushing, and heart palpitations [1.2.3].
High-Risk Interactions to Approach with Caution
Beyond absolute contraindications, several other drug classes pose significant risks when taken with sertraline. These combinations require close monitoring and dosage adjustments by a healthcare professional.
Other Serotonergic Drugs
Many medications besides MAOIs also increase serotonin levels. Combining them with sertraline heightens the risk of serotonin syndrome [1.2.3].
- Other Antidepressants: This includes other SSRIs (e.g., fluoxetine, citalopram), SNRIs (e.g., duloxetine, venlafaxine), and tricyclic antidepressants (TCAs) (e.g., amitriptyline) [1.2.4].
- Triptans: These migraine medications, such as sumatriptan and rizatriptan, can interact with sertraline [1.2.6]. While the overall risk is considered low, caution and monitoring for symptoms of serotonin syndrome are advised [1.5.1, 1.5.3].
- Certain Pain Relievers: Opioids like tramadol and fentanyl can increase serotonin levels and lead to adverse reactions when combined with sertraline [1.2.7].
- Herbal Supplements: St. John's Wort is a popular supplement for depression but should be avoided with sertraline as it also increases serotonin and the risk of serotonin syndrome [1.2.1, 1.2.7].
Drugs That Increase Bleeding Risk
Sertraline can impair the blood's ability to clot [1.2.5]. When combined with other drugs that have a similar effect, the risk of bleeding—particularly in the gastrointestinal tract—is significantly increased [1.2.7, 1.4.1].
- Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Commonly used pain relievers like ibuprofen (Advil, Motrin) and naproxen (Aleve) fall into this category [1.2.3]. Occasional, low-dose use may be safe for some, but routine use increases the bleeding risk substantially [1.4.3].
- Anticoagulants (Blood Thinners): Medications like warfarin (Coumadin), apixaban (Eliquis), and rivaroxaban (Xarelto) require careful management when used with sertraline [1.2.3, 1.4.1].
- Antiplatelet Drugs: This includes aspirin and clopidogrel (Plavix) [1.2.3].
Comparison Table: Key Sertraline Interaction Risks
| Drug Class | Example(s) | Primary Risk | Management Advice |
|---|---|---|---|
| MAOIs | Phenelzine, Isocarboxazid | Serotonin Syndrome | Contraindicated. A 14-day washout period is required [1.3.1]. |
| Pimozide | Orap | Heart Rhythm Problems (QT Prolongation) | Contraindicated [1.2.5]. |
| Other Serotonergic Drugs | Triptans, Other SSRIs, St. John's Wort | Serotonin Syndrome | Use with caution; monitor for symptoms like agitation, confusion, and rapid heart rate [1.2.3, 1.5.2]. |
| NSAIDs | Ibuprofen, Naproxen, Aspirin | Increased Bleeding Risk | Avoid routine use. Consult a doctor for pain relief alternatives like acetaminophen [1.4.3, 1.4.2]. |
| Blood Thinners | Warfarin, Apixaban, Clopidogrel | Increased Bleeding Risk | Requires close monitoring by a healthcare provider for any signs of unusual bleeding or bruising [1.2.3]. |
Conclusion: Prioritize Safety Through Communication
Managing your health while taking sertraline requires a proactive approach to medication safety. The most dangerous interactions involve MAOIs and pimozide, which are strictly contraindicated. Other common medications, including certain pain relievers, other antidepressants, and even herbal supplements like St. John's Wort, can also pose significant risks. The key to avoiding adverse effects is open and continuous communication with your doctor and pharmacist. Always disclose every medication and supplement you are taking to ensure your treatment plan is both effective and safe. Never start or stop any medication without professional medical advice [1.2.1].
