In a patient developing serotonin syndrome, which medication would you discontinue first: sertraline (Selective Serotonin Reuptake Inhibitor - SSRI) or tapentadol (opioid analgesic)?

From the Guidelines

In the case of potential serotonin syndrome risk with concurrent sertraline and tapentadol, tapentadol should be discontinued first. This decision is based on the fact that tapentadol has weak serotonin reuptake inhibition properties that can contribute to serotonin syndrome when combined with sertraline, an SSRI 1. Abruptly stopping sertraline can cause significant withdrawal symptoms, including dizziness, nausea, headache, and mood disturbances, as it has been associated with discontinuation syndrome 1. On the other hand, tapentadol can generally be discontinued more safely, especially if alternative pain management is provided. When discontinuing tapentadol, patients should be monitored for opioid withdrawal symptoms and given appropriate pain management alternatives. The decision to stop tapentadol first is based on the principle of maintaining psychiatric stability while reducing the risk of serotonin syndrome, which can manifest as agitation, confusion, high fever, muscle rigidity, and autonomic instability. Some key considerations include:

• The potential for drug-drug interactions with SSRIs, such as sertraline, and the need for caution when starting or stopping other serotonergic medications 1.
• The importance of monitoring for symptoms of serotonin syndrome, especially in the first 24 to 48 hours after dosage changes 1.
• The need for medical education, training, and experience to safely and effectively prescribe antidepressant medications and manage potential interactions 1.

From the FDA Drug Label

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including sertraline, 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 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 Treatment with sertraline and any concomitant serotonergic agents should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated

Serotonin Syndrome Risk: Both sertraline and tapentadol can increase the risk of serotonin syndrome.

• Key Consideration: Tapentadol is a weaker serotonin reuptake inhibitor compared to sertraline.
• Clinical Decision: In the event of serotonin syndrome, it would be more appropriate to cease tapentadol first due to its weaker serotonergic activity, while also considering the clinical context and the potential risks and benefits of discontinuing either medication 2.

From the Research

Serotonin Syndrome and Medication Management

When managing serotonin syndrome induced by the combined use of sertraline and tapentadol, it is crucial to consider the potential risks and benefits of each medication.

• Sertraline is a selective serotonin reuptake inhibitor (SSRI) that can increase serotonergic activity in the body, potentially leading to serotonin syndrome 3, 4, 5.
• Tapentadol, on the other hand, is an opioid analgesic that also has serotonergic properties, which may contribute to the development of serotonin syndrome, although the current literature has limitations in characterizing this potential association 6.

Medication Cessation

In the event of serotonin syndrome, it is essential to discontinue the offending medications.

• Given the direct evidence of sertraline's role in serotonin syndrome 3, 4, 5, it would be reasonable to cease sertraline first.
• Tapentadol's contribution to serotonin syndrome is less well-characterized, but its potential serotonergic effects should not be ignored 6.
• The decision to cease tapentadol should be based on individual patient factors and the clinical presentation of serotonin syndrome, as outlined in general guidelines for managing the condition 7.