Is it safe to take tramadol (ultra pain reliever) with sertraline (selective serotonin reuptake inhibitor, SSRI)?

From the Guidelines

Taking tramadol with sertraline is potentially dangerous and should be avoided unless specifically approved and monitored by your healthcare provider. These medications can interact to cause serotonin syndrome, a potentially life-threatening condition characterized by agitation, hallucinations, rapid heart rate, fever, excessive sweating, shivering, tremors, muscle stiffness, coordination problems, nausea, vomiting, and diarrhea. This interaction occurs because tramadol has serotonergic properties, and when combined with an SSRI like sertraline (which increases serotonin levels), it can lead to excessive serotonin in the brain 1. According to the NCCN clinical practice guidelines in oncology, tramadol and tapentadol should be used with caution or avoided in patients taking other serotonergic or monoamine oxidase inhibitors (MAOI)-like medications, such as SSRIs, due to the risk of serotonin syndrome 1.

The symptoms of serotonin syndrome can arise within 24 to 48 hours after combining medications and are characterized by mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity 1. Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness, which can lead to fatalities. Treatment is hospital-based and includes discontinuation of all serotonergic agents and supportive care with continuous cardiac monitoring 1.

If you're currently taking sertraline and need pain management, consult your doctor about safer alternatives to tramadol. Some alternatives may include other pain medications that do not have serotonergic properties, such as acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs). However, it's essential to discuss the potential risks and benefits of any medication with your healthcare provider.

If you're already taking both medications and experience any symptoms of serotonin syndrome, seek immediate medical attention. Never adjust medication dosages or stop taking prescribed medications without consulting your healthcare provider first, as sudden discontinuation can cause withdrawal symptoms.

Key points to consider:

• Tramadol has serotonergic properties and can interact with SSRIs like sertraline to cause serotonin syndrome 1.
• Serotonin syndrome is a potentially life-threatening condition that requires immediate medical attention 1.
• Safer alternatives to tramadol may be available for pain management, and patients should consult their healthcare provider to discuss options.
• Patients taking tramadol and sertraline should be closely monitored for symptoms of serotonin syndrome and seek immediate medical attention if they occur.

From the FDA Drug Label

Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including Sertraline hydrochloride, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). If concomitant use of sertraline hydrochloride with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John’s Wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases

Taking tramadol with sertraline is not safe due to the increased risk of serotonin syndrome, a potentially life-threatening condition. Patients should be monitored for the emergence of serotonin syndrome symptoms, such as mental status changes, autonomic instability, neuromuscular symptoms, seizures, and/or gastrointestinal symptoms, when taking these medications together 2.

From the Research

Safety of Tramadol with Sertraline

• The combination of tramadol and sertraline can increase the risk of serotonin syndrome, a potentially life-threatening condition 3, 4, 5.
• Serotonin syndrome is characterized by symptoms such as agitation, confusion, severe shivering, diaphoresis, myoclonus, hyperreflexia, mydriasis, tachycardia, and fever 4, 5.
• The risk of serotonin syndrome is higher in patients who are taking higher doses of tramadol or sertraline, or who are also taking other medications that increase serotonin levels 3, 6.
• However, the incidence of serotonin syndrome with the combination of tramadol and sertraline is low, and the syndrome is generally mild or moderate in form 6.
• Clinicians should be aware of the potential for serotonin syndrome when prescribing tramadol to patients who are taking sertraline, and should monitor patients closely for signs of the syndrome 3, 6.

Factors that Increase the Risk of Serotonin Syndrome

• Increased age 3
• Higher dosages of tramadol or sertraline 3, 6
• Use of concomitant potent cytochrome P450 2D6 inhibitors 3
• Medical comorbidities 7
• Use or abuse of supratherapeutic doses of tramadol 7

Management of Serotonin Syndrome

• Discontinuation of tramadol and other contributing agents 7
• Administration of benzodiazepines and supportive care 7
• Administration of cyproheptadine in moderate to severe cases 7