Sertraline, a selective serotonin reuptake inhibitor (SSRI), works by increasing the levels of serotonin in the brain to help manage mood disorders such as depression, anxiety, and obsessive-compulsive disorder. While effective for many, its mechanism of action makes it prone to significant drug interactions, some of which are strictly contraindicated and can pose serious health risks. A comprehensive understanding of these medication pitfalls is essential for both patients and healthcare providers.
Life-Threatening Combinations: Contraindicated Drugs
Certain medications should never be combined with sertraline due to the high risk of severe, and potentially fatal, adverse effects. These combinations are known as contraindications.
Monoamine Oxidase Inhibitors (MAOIs)
This is one of the most critical interactions to be aware of. Combining sertraline with MAOIs can lead to serotonin syndrome, a life-threatening condition caused by excessive serotonin levels in the central nervous system. A mandatory "washout period" of at least 14 days is required when switching between these medications to allow the body to clear one drug before starting the other.
Examples of MAOIs include:
- Isocarboxazid (Marplan)
- Phenelzine (Nardil)
- Selegiline (Emsam, Zelapar)
- Tranylcypromine (Parnate)
Other MAOI-like Substances
Some drugs and substances also function as MAOIs and must be avoided with sertraline, including:
- Linezolid (Zyvox), an antibiotic
- Methylene blue injection
Specific Antipsychotics
The antipsychotic medication pimozide (Orap) is another drug that is strictly contraindicated with sertraline due to an increased risk of severe heart rhythm problems, known as QT interval prolongation, which can be fatal.
The Risk of Serotonin Syndrome
Even with drugs not strictly contraindicated, combining sertraline with other serotonergic agents raises the risk of developing serotonin syndrome. While often manageable, severe cases can require emergency medical care. Symptoms range from mild (tremors, sweating, agitation) to severe (high fever, rigid muscles, severe agitation).
Medications that increase serotonin levels include:
- Other Antidepressants: Taking multiple antidepressants, especially other SSRIs (like fluoxetine) or SNRIs (like duloxetine), can boost serotonin to dangerous levels. Tricyclic antidepressants (TCAs) also pose a risk.
- Opioids: Certain opioid pain medications, like tramadol and fentanyl, can increase serotonin levels.
- Migraine Medications: Triptans, used for migraines (e.g., sumatriptan), can increase the risk of serotonin syndrome when combined with sertraline.
- Herbal Supplements: The herbal supplement St. John's Wort should never be taken with sertraline as it can significantly increase serotonin levels.
- Over-the-Counter Cough Medicine: Dextromethorphan, found in many OTC cough suppressants (like Delsym), can raise serotonin levels.
Increased Bleeding Risk
Sertraline can have a blood-thinning effect. When combined with other medications that also increase the risk of bleeding, the danger of bruising, nosebleeds, and gastrointestinal or intracranial bleeding is significantly heightened.
- Blood Thinners (Anticoagulants and Antiplatelets): This includes warfarin (Coumadin), heparin, apixaban (Eliquis), and clopidogrel (Plavix). Close monitoring by a healthcare provider is necessary if this combination cannot be avoided.
- Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Common NSAIDs like ibuprofen (Advil) and naproxen (Aleve) should be used with caution, especially at higher doses or for prolonged periods. Patients should consult a doctor before using these with sertraline.
Cardiac Concerns and QT Prolongation
Sertraline, while having a low risk on its own, can increase the risk of a prolonged QT interval (an irregularity in heart rhythm) when combined with other drugs that have this effect. This can be a very serious condition leading to irregular heartbeats and, in severe cases, cardiac arrest.
Examples of interacting medications include:
- Certain antibiotics (e.g., azithromycin, ciprofloxacin)
- Antiarrhythmic heart medications (e.g., amiodarone, sotalol)
- Other antidepressants (e.g., citalopram)
- Some antipsychotics (e.g., ziprasidone, pimozide)
- Oral antifungal medications (e.g., fluconazole)
Other Significant Drug Interactions
- Alcohol: Consumption of alcohol is not recommended while taking sertraline as it can worsen side effects like dizziness, drowsiness, and impaired judgment.
- Disulfiram (Antabuse): The liquid oral concentrate of sertraline contains alcohol and is contraindicated in patients taking disulfiram, a medication for alcohol use disorder.
- Phenytoin (Dilantin): This anti-seizure medication has a narrow therapeutic index, and sertraline can increase its levels in the body, requiring careful monitoring and potential dose adjustments.
- CYP450 Enzyme Inhibitors: Sertraline metabolism can be affected by other drugs that inhibit the CYP enzyme system in the liver, leading to higher sertraline levels and increased side effects. Examples include certain antifungals like fluconazole and some medications for irregular heartbeats.
Comparison of Sertraline Drug Interaction Risks
| Drug Class / Substance | Primary Risk | Specific Examples | Recommendation |
|---|---|---|---|
| Monoamine Oxidase Inhibitors (MAOIs) | Life-threatening serotonin syndrome | Phenelzine (Nardil), Selegiline (Emsam), Linezolid (Zyvox) | Absolutely contraindicated; requires 14-day washout period. |
| Blood Thinners | Increased risk of bleeding | Warfarin, Apixaban (Eliquis), NSAIDs like Ibuprofen | Requires dose adjustment and close monitoring by a doctor. |
| Serotonergic Agents | Serotonin syndrome | Triptans (migraine), other SSRIs/SNRIs, Tramadol, St. John's Wort | Use with extreme caution; close medical supervision necessary. |
| Pimozide & Thioridazine | Severe cardiac issues (QT prolongation) | Orap (pimozide) | Completely contraindicated; never combine. |
| Alcohol | Worsened side effects and impaired judgment | Any alcoholic beverages | Avoid use; can increase drowsiness and dizziness. |
| Phenytoin (Dilantin) | Elevated phenytoin levels | Dilantin, Cerebyx | Monitor blood levels closely; dose adjustment likely needed. |
Conclusion
Given the wide range of potential and serious drug interactions, anyone prescribed sertraline must provide their healthcare provider with a complete list of all medications, supplements, and herbal products they use. Never start or stop any medication without consulting your doctor first, and be vigilant for any unusual symptoms that could indicate an adverse interaction. Open communication and diligent monitoring are the most effective strategies for ensuring your safety while taking sertraline. For more authoritative information, consult the National Alliance on Mental Illness (NAMI) or speak with your prescribing physician.
