In the evaluation of serotonin toxicity or serotonin syndrome, the most commonly used and more recent criteria is the Hunter Serotonin Toxicity Criteria. In comparison to its predecessor, Sternbach’s criteria, Hunter’s Criteria is used due to its simplicity, sensitivity and specificity, and the use of well-defined clinical manifestations including clonus, tremor, and hyperthermia. This report describes a case of serotonin toxicity triggered by an increasing dose of tramadol with concurrent bupropion and sertraline treatment. Based on our knowledge, this is the first case report reviewing the drug interaction between tramadol and bupropion with outcomes of decreased hypoalgesia and increased serotonergic activity in relation to increasing doses
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In one randomized, double-blind, placebo-controlled, 4-way crossover study in healthy volunteers known to be extensive CYP2D6 metabolizers, the authors studied the effects of paroxetine, a strong CYP2D6 inhibitor, on the stereo-selective and hypoalgesic effects of tramadol. The authors demonstrated the use of paroxetine significantly inhibited the metabolism of tramadol to its active metabolite, M1, and reduced, but did not abolish the hypoalgesic effect of tramadol, particularly in opioid-sensitive tests. This study further supports previous studies on the role of M1 in tramadol’s analgesic properties, as well as the idea that other mechanisms are responsible for some of the hypoalgesia, indicating the effect of drug-drug interactions on tramadol’s analgesic effect. This study also showed higher plasma levels of the parent compounds (-) and (+) tramadol with concurrent paroxetine administration. Bupropion strongly inhibits CYP2D6 and therefore, could reduce the metabolism of medications cleared through this enzyme, such as …show more content…
This provides us with evidence to support that increased plasma levels of (+) tramadol with concurrent CYP2D6 inhibition may further decrease serotonin reuptake and increase basal serotonin release. Therefore, the increase in serotonergic activity of tramadol with CYP2D6 inhibitors would be further enhanced by an increasing dose of tramadol and subsequent increases in plasma (+) tramadol levels. The Drug Interaction Probability Scale (DIPS), a tool that has been developed for guiding a thorough evaluation of the strength of causality in ADR attributed to drug-drug interactions, is a widely used and modified version of the Naranjo Adverse Drug Reaction Probability Scale. Applying DIPS in our patient’s case, a score of 5 was obtained, indicating the drug interaction was a probable cause of her serotonin toxicity. The causality of the drug-drug interaction in our patient is further supported by the patient’s increased dose of tramadol above the recommended maximum
In one randomized, double-blind, placebo-controlled, 4-way crossover study in healthy volunteers known to be extensive CYP2D6 metabolizers, the authors studied the effects of paroxetine, a strong CYP2D6 inhibitor, on the stereo-selective and hypoalgesic effects of tramadol. The authors demonstrated the use of paroxetine significantly inhibited the metabolism of tramadol to its active metabolite, M1, and reduced, but did not abolish the hypoalgesic effect of tramadol, particularly in opioid-sensitive tests. This study further supports previous studies on the role of M1 in tramadol’s analgesic properties, as well as the idea that other mechanisms are responsible for some of the hypoalgesia, indicating the effect of drug-drug interactions on tramadol’s analgesic effect. This study also showed higher plasma levels of the parent compounds (-) and (+) tramadol with concurrent paroxetine administration. Bupropion strongly inhibits CYP2D6 and therefore, could reduce the metabolism of medications cleared through this enzyme, such as …show more content…
This provides us with evidence to support that increased plasma levels of (+) tramadol with concurrent CYP2D6 inhibition may further decrease serotonin reuptake and increase basal serotonin release. Therefore, the increase in serotonergic activity of tramadol with CYP2D6 inhibitors would be further enhanced by an increasing dose of tramadol and subsequent increases in plasma (+) tramadol levels. The Drug Interaction Probability Scale (DIPS), a tool that has been developed for guiding a thorough evaluation of the strength of causality in ADR attributed to drug-drug interactions, is a widely used and modified version of the Naranjo Adverse Drug Reaction Probability Scale. Applying DIPS in our patient’s case, a score of 5 was obtained, indicating the drug interaction was a probable cause of her serotonin toxicity. The causality of the drug-drug interaction in our patient is further supported by the patient’s increased dose of tramadol above the recommended maximum