What medications, including Temgesic (buprenorphine), gabapentin, and topiramate, can cause Serotonin Syndrome, and what are its clinical manifestations?

From the Guidelines

Serotonin syndrome is a potentially life-threatening condition that can be caused by medications such as opioids with serotonin reuptake inhibitory activity, including tramadol, meperidine, and fentanyl, as well as other medications that increase serotonin levels, and temgesic, gabapentin, and topiramate are not typically associated with serotonin syndrome when used alone, but the risk may increase when combined with other serotonergic drugs. The medications that can cause serotonin syndrome include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and some over-the-counter supplements like St. John's Wort 1.

Regarding the specific medications mentioned, temgesic (buprenorphine) has a very low risk of causing serotonin syndrome as it doesn't significantly affect serotonin levels, gabapentin and topiramate also have minimal effects on serotonin and are not typically associated with serotonin syndrome when used alone, however, when these medications are combined with other serotonergic drugs, the risk may increase 1.

Some key points to consider when evaluating the risk of serotonin syndrome include:

• The use of one or more medications that affect serotonin levels, such as monoamine oxidase inhibitors, SSRIs, SNRIs, tertiary amine tricyclic antidepressants, trazodone, dextromethorphan, linezolid, ritonavir, sibutramine, ondansetron, granisetron, metoclopramide, triptans, tryptophan, St. John’s wort, and ginsing 1
• The timing and dosage of medication administration, as well as the patient's individual tolerance and medical history 1
• The potential for drug interactions and the need for careful monitoring and adjustment of medication regimens as needed 1

The signs of serotonin syndrome include a triad of symptoms: mental status changes (agitation, confusion, hallucinations), autonomic instability (high fever, sweating, rapid heart rate, high blood pressure), and neuromuscular abnormalities (tremor, muscle rigidity, hyperreflexia, clonus). Symptoms typically develop rapidly, often within hours of starting a new medication or increasing a dose 1. If you suspect serotonin syndrome, seek immediate medical attention as severe cases can be life-threatening. Treatment often involves discontinuing the precipitating agent and providing supportive care, which may include treatment of agitation, amelioration of hyperthermia, and management of autonomic instability 1.

In severe cases, emergency sedation, neuromuscular paralysis, and intubation may be considered, and physical restraints may be detrimental as they can exacerbate isometric contractions, worsen hyperthermia and lactic acidosis, and increase mortality 1. The mortality rate for serotonin syndrome is approximately 11%, with significant morbidity and mortality associated with the condition 1.

From the Research

Drugs that Cause Serotonin Syndrome

• Serotonergic agents alone or in combination with monoamine oxidase inhibitors can cause serotonin syndrome 2, 3
• The combination of a monoamine oxidase inhibitor (MAOI) with serotonergic drugs is especially dangerous and may lead to severe serotonin syndrome 3
• Bupropion, which inhibits noradrenaline and dopamine reuptake with milder effects on serotonergic activity, can also cause serotonin syndrome when combined with selective serotonin reuptake inhibitors (SSRIs) 4
• Many commonly used medications have proven to be the culprits of serotonin syndrome, and proper education and awareness about serotonin syndrome can improve the accuracy of diagnosis and promote the institution of the appropriate treatment 5

Specific Drugs Mentioned

• Temgesic (buprenorphine) is not typically associated with serotonin syndrome, but it can be used in combination with other medications that may increase the risk of serotonin syndrome
• Gabapentin is not typically associated with serotonin syndrome, but it can be used in combination with other medications that may increase the risk of serotonin syndrome
• Topiramate is not typically associated with serotonin syndrome, but it can be used in combination with other medications that may increase the risk of serotonin syndrome

Signs of Serotonin Syndrome

• Alteration of mental status, abnormalities of neuromuscular tone, and autonomic hyperactivity are the classic signs of serotonin syndrome 2
• Clinical manifestations are diverse and nonspecific, which may lead to misdiagnosis 2
• Fever, seizure, and tremors are common symptoms of serotonin syndrome, and the presence of high-grade fever, seizures, and high creatine kinase activities may be associated with severe serotonin syndrome 6
• Symptoms can evolve rapidly, within 24 hours after the administration of serotonergic drugs, and can range in severity from mild to life-threatening 2, 6