Serotonin syndrome associated with methadone and milk thistle seeds: a case report

Andreja Celofiga,Tomo Brus Hladen

doi:10.1590/0101-60830000000238

Andreja Celofiga, Tomo Brus Hladen

Open Access

https://doi.org/10.1590/0101-60830000000238

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Abstract

Background Serotonin syndrome is rarely, potentially life threatening condition, associated with use of serotonin acting medications and psychoactive drugs. In the majority of cases the symptoms occur soon after the initiation of a new drug or a change in the dose. Objective To present a case report and to describe the possible mechanism of development of serotonin syndrome during the interactions between milk thistle seeds and methadone on hepatic cytochrome enzyme system P450. Methods A case report of a young man on regular therapy with methadone, who develop a serotonin syndrome after ingestion a high dose of milk thistle seeds. Results Commercial preparations of milk thistle include the extract silibinin, which exhibits no beneficial or harmful drug interactions at normal doses, but at higher concentrations it can lead to dose-dependent effects on methadone metabolism, through inhibition of CYP3A4 and P-glycoprotein. As a result, it may lead to enhanced serotonin re-uptake inhibition and increased serotonin activity. Discussion Milk thistle is widely used and recommended for detoxification, but it may have serious and life threatening interactions with psychotropic drugs and psychoactive substances when used in high doses.

Highlights

Serotonin syndrome (SS) is a rare, potentially life threatening, condition, associated with the use of serotonin-acting medications and psychoactive drugs
A possible mechanism of the development of SS was through interaction on the hepatic drug-metabolizing enzyme system cytochrome P450
In vitro studies of methadone show a greater tendency toward serotonin reuptake inhibition compared with other opiates, which may explain methadone-mediated precipitation of SS4

Summary

Introduction

Serotonin syndrome (SS) is a rare, potentially life threatening, condition, associated with the use of serotonin-acting medications and psychoactive drugs. Objective: To present a case report and to describe the possible mechanism of development of serotonin syndrome during the interactions between milk thistle seeds and methadone on hepatic cytochrome enzyme system P450. Methods: A case report of a young man on regular therapy with methadone, who develop a serotonin syndrome after ingestion a high dose of milk thistle seeds. Results: Commercial preparations of milk thistle include the extract silibinin, which exhibits no beneficial or harmful drug interactions at normal doses, but at higher concentrations it can lead to dose-dependent effects on methadone metabolism, through inhibition of CYP3A4 and P-glycoprotein. Discussion: Milk thistle is widely used and recommended for detoxification, but it may have serious and life threatening interactions with psychotropic drugs and psychoactive substances when used in high doses

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