Interactions between Medications and Supplements

Introduction to Risks

• Sertraline can cause side effects including dizziness and headache, and certain supplements, such as ceremonial cacao, may compound these effects due to their stimulant properties, according to the American Journal of Kidney Diseases 1
• The combination of certain medications, such as linezolid and tramadol, can increase the risk of serotonin syndrome, a potentially life-threatening condition, due to tramadol's serotonin reuptake inhibitory activity and linezolid's monoamine oxidase inhibitor (MAOI) properties 2, 3, 4

Mechanisms of Interaction

• Certain opioids, such as tramadol, levorphanol, meperidine, fentanyl, methadone, and tapentadol, have serotonergic activity, increasing the risk of serotonin syndrome when combined with MAO inhibitors like linezolid 2
• The following table summarizes the serotonergic activity of various opioids:

3, 4, 2

Management and Treatment

• The American College of Physicians and other medical societies recommend avoiding the combination of linezolid and tramadol whenever possible to minimize the risk of serotonin syndrome, and if antimicrobial therapy is urgently needed, choosing an alternative antibiotic if clinically appropriate 2
• If pain management is needed while on linezolid, selecting opioids without serotonergic activity, such as morphine, codeine, oxycodone, or buprenorphine, is recommended to reduce the risk of serotonin syndrome 5, 4, 2, 3
• Linezolid should be used with extreme caution or avoided in patients taking antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), Tricyclic Antidepressants (TCAs), and other antidepressants with serotonergic properties, as recommended by the Food and Drug Administration (FDA) 4, 6
• The American Thorax Society recommends screening for contraindications before prescribing linezolid, including uncontrolled hypertension, pheochromocytoma, carcinoid tumor, thyrotoxicosis, bipolar depression, schizophrenia, and acute confusional states 7

Symptoms and Diagnosis

• Monitor closely for signs of serotonin syndrome, including mental status changes, neuromuscular abnormalities, autonomic instability, and gastrointestinal symptoms, if linezolid is administered despite recent tramadol use 3
• Serotonin syndrome typically presents within 24-48 hours after starting linezolid with symptoms including mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity, according to the National Institutes of Health (NIH) 4

Treatment of Serotonin Syndrome

• If serotonin syndrome occurs, all precipitating agents should be discontinued immediately, and supportive care should be provided, including benzodiazepines for agitation, management of hyperthermia, and IV fluids for autonomic instability, and serotonin2A antagonists such as cyproheptadine may be used, as recommended by the Pediatrics society 8

General Guidance

• The Mayo Clinic Proceedings recommends avoiding concurrent use of SAM-e with MAOIs, SSRIs, and SNRIs due to risk of serotonin syndrome, and watching for early signs of serotonin syndrome in patients who may be taking SAM-e with other serotonergic medications 5
• The American Academy of Child and Adolescent Psychiatry recommends that combination therapy should only be used when there is a clear justification, such as the treatment of multiple disorders or symptoms that do not respond to monotherapy, with a strength of evidence supporting this recommendation 9