Sertraline, a selective serotonin reuptake inhibitor (SSRI), is a widely prescribed medication for depression, anxiety, and other mental health conditions [1.2.2]. It works by increasing the levels of serotonin in the brain [1.8.1]. While effective, sertraline can interact with numerous other medications, which can lead to serious and sometimes life-threatening side effects. It is vital for patients to provide their healthcare providers with a complete list of all medications, including over-the-counter drugs and herbal supplements, to prevent dangerous combinations [1.2.2].
Absolutely Contraindicated Medications
Certain medications should never be taken with sertraline due to the high risk of severe adverse reactions. The combination is considered absolutely contraindicated.
Monoamine Oxidase Inhibitors (MAOIs)
This is one of the most dangerous drug interactions in psychiatry [1.4.4]. Both SSRIs like sertraline and MAOIs increase serotonin levels. Taking them together can cause a massive accumulation of serotonin, leading to serotonin syndrome, a potentially fatal condition [1.4.1, 1.4.2]. Symptoms range from mild (tremors, sweating, agitation) to severe (high fever, rigid muscles, seizures, and death) [1.2.2, 1.4.4].
A washout period of at least 14 days is required when switching between sertraline and an MAOI [1.2.2, 1.4.3].
Examples of MAOIs include:
- Phenelzine (Nardil) [1.4.3]
- Tranylcypromine (Parnate) [1.4.3]
- Isocarboxazid (Marplan) [1.4.3]
- Selegiline (Emsam) [1.4.3]
- Linezolid (Zyvox), an antibiotic with MAOI properties [1.2.2]
Pimozide (Orap)
The antipsychotic medication pimozide is also contraindicated. Combining it with sertraline can significantly increase pimozide levels in the body, leading to a serious heart problem known as QT prolongation, which can cause fatal abnormal heart rhythms [1.2.3, 1.2.7].
Disulfiram (Antabuse)
The liquid formulation of sertraline contains 12% alcohol. Taking it with disulfiram, a medication for alcohol use disorder, can cause a severe reaction with symptoms like vomiting, flushing, and heart palpitations [1.2.2, 1.2.4]. This interaction does not apply to sertraline tablets [1.2.2].
High-Risk Interactions
These medications can be used with sertraline but require close monitoring and possible dose adjustments by a doctor due to significant risks.
Other Serotonergic Drugs
Many other medications also increase serotonin levels. Combining them with sertraline increases the risk of serotonin syndrome [1.2.2]. While the risk may be lower than with MAOIs, it remains a serious concern.
- Other SSRIs and SNRIs: Examples include fluoxetine (Prozac), duloxetine (Cymbalta), and venlafaxine (Effexor XR) [1.3.1, 1.3.4].
- Tricyclic Antidepressants (TCAs): Such as amitriptyline and nortriptyline [1.2.2].
- Triptans: Migraine medications like sumatriptan (Imitrex) can increase serotonin syndrome risk, though some studies suggest the actual risk is very low [1.6.2, 1.6.3]. Patients should be monitored closely, especially when starting treatment or increasing doses [1.6.1].
- Certain Opioids: Tramadol and fentanyl can contribute to serotonin syndrome [1.2.2, 1.3.2].
- Herbal Supplements: St. John's Wort is a notable example that should be avoided [1.2.2].
Blood Thinners and NSAIDs
Sertraline can interfere with platelet function, increasing the risk of bleeding [1.2.4]. This risk is significantly amplified when combined with other medications that affect blood clotting.
- Anticoagulants (Blood Thinners): Warfarin (Coumadin), apixaban (Eliquis), and rivaroxaban (Xarelto) fall into this category [1.2.2, 1.3.4]. The combination can lead to a higher risk of serious bleeding events [1.5.3].
- Antiplatelet Drugs: Clopidogrel (Plavix) and aspirin increase this risk [1.3.1].
- Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Common pain relievers like ibuprofen (Advil, Motrin) and naproxen (Aleve) also raise the risk of gastrointestinal bleeding when taken with sertraline [1.2.2, 1.5.5]. One study found that combining SSRIs and NSAIDs increased the relative risk of upper GI bleeding to 15.6 compared to control subjects [1.5.1].
Medications Affecting Heart Rhythm
Sertraline itself carries a low risk of causing QT interval prolongation. This risk increases when combined with other drugs that have the same effect [1.3.1].
- Antiarrhythmics: Amiodarone (Pacerone) and sotalol (Betapace) [1.3.1].
- Antipsychotics: Ziprasidone (Geodon) and thioridazine [1.2.1, 1.3.1].
- Certain Antibiotics: Azithromycin (Zithromax) and ciprofloxacin (Cipro) [1.3.1].
Comparison of Major Drug Interactions
| Drug Class | Examples | Primary Risk | Management |
|---|---|---|---|
| MAOIs | Phenelzine, Selegiline, Linezolid | Life-threatening Serotonin Syndrome [1.4.1] | Absolutely contraindicated. Requires a 14-day washout period [1.4.3]. |
| Pimozide | Orap | Severe cardiac arrhythmias (QT prolongation) [1.2.3] | Absolutely contraindicated [1.2.7]. |
| Blood Thinners & NSAIDs | Warfarin, Ibuprofen, Aspirin | Increased risk of serious bleeding, especially GI bleeding [1.5.3, 1.5.5] | Use with caution; requires close monitoring by a healthcare provider. Consider alternatives to NSAIDs [1.2.2]. |
| Other Serotonergic Drugs | Other SSRIs, Triptans, Tramadol | Increased risk of Serotonin Syndrome [1.2.2] | Avoid co-administration where possible. Requires careful monitoring and starting with low doses [1.6.1]. |
| Drugs Affecting Heart Rhythm | Amiodarone, Ziprasidone | Increased risk of QT prolongation and dangerous heart rhythms [1.3.1] | Use with caution and under medical supervision; may require heart monitoring [1.8.2]. |
Other Notable Interactions
- Phenytoin: Sertraline can increase the levels of this anti-seizure medication, heightening the risk of side effects. Blood level monitoring is often required [1.2.2].
- Grapefruit Juice: This can increase the amount of sertraline in your bloodstream, raising the risk of side effects [1.8.1, 1.8.3]. It is recommended to avoid or limit grapefruit products [1.8.6].
- Alcohol: Combining alcohol with sertraline can increase drowsiness and dizziness and may worsen depression symptoms [1.8.3, 1.8.6]. It's best to avoid alcohol until you know how the medication affects you [1.8.1].
Conclusion
Managing treatment with sertraline requires careful consideration of all other medications and substances being consumed. The most severe interactions, particularly with MAOIs and pimozide, are absolutely contraindicated and can be fatal [1.4.4, 1.2.7]. Other high-risk combinations, such as with NSAIDs, blood thinners, and other serotonergic drugs, demand close supervision by a healthcare professional to mitigate risks like bleeding and serotonin syndrome [1.2.2]. Always maintain open communication with your doctor and pharmacist about your full medication list to ensure safety and treatment effectiveness.
For more information, consult the National Alliance on Mental Illness (NAMI) page on sertraline: https://www.nami.org/about-mental-illness/treatments/mental-health-medications/types-of-medication/sertraline-zoloft/
