Serotonin-toxicity risk rises

Published March 13, 2007 at midnight

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The death of Libby Zion, an 18-year-old college student, in a New York hospital on March 5, 1984, led to a highly publicized court battle and created a cause celebre over the lack of supervision of overworked young doctors.

But only much later did experts zero in on the preventable disorder that apparently led to Zion's death: a form of drug poisoning called serotonin syndrome.

Zion, who went to the hospital with a fever of 103.5, had been taking an antidepressant, phenelzine (Nardil). The combination of that and the narcotic painkiller meperidine (Demerol) given to her at the hospital could raise the circulating serotonin to dangerous levels.

When she became agitated, a symptom of serotonin toxicity, and tried to pull out her intravenous tubes, she was restrained, and the resulting muscular tension is believed to have sent her fever soaring to lethal heights.

Now, with the enormous rise in the use of serotonin-enhancing antidepressants, often taken in combination with other drugs that also raise serotonin levels, emergency-medicine specialists are trying to educate doctors and patients about this not-so-rare and potentially life-threatening disorder.

In March 2005, two such specialists, Dr. Edward W. Boyer and Dr. Michael Shannon of Children's Hospital Boston, noted that more than 85 percent of doctors were "unaware of the serotonin syndrome as a clinical diagnosis." In their review in The New England Journal of Medicine, Boyer and Shannon cited a report based on calls to poison-control centers around the country in 2002 showing 7,349 cases of serotonin toxicity and 93 deaths. (In 2005, the last year for which statistics are available, 118 deaths were reported.)

The experts fear that failure to recognize serotonin syndrome in its mild or early stages can result in improper treatment and an abrupt worsening of the condition, leading to severe illness or death. They want doctors and patients to know just what drugs and drug combinations can cause serotonin poisoning.

Although serotonin poisoning can be caused by an antidepressant overdose, it more often results from a combination of an SSRI or MAOI (monoamine oxidase inhibitors) with another serotonin-raising substance. Patients at particular risk, some experts say, are those taking combinations of antidepressant and antipsychotic drugs sometimes prescribed to treat resistant depression. All it may take is a small dose of another serotonin-inducing drug to cause the syndrome.

Most important to preventing the syndrome is for patients to give their doctors a complete list of drugs they regularly take - including prescriptions, over-the- counter medication, dietary supplements and recreational drugs - before a doctor prescribes something new.

The triggers

Adding to the challenge of diagnosing serotonin syndrome is the fact that a huge number of drugs can trigger it, including:

• tricyclic antidepressants and MAOIs (for monoamine oxidase inhibitors)

• narcotic painkillers like fentanyl and tramadol

• over-the-counter cough and cold remedies containing dextromethorphan

• triptans like Imitrex used to treat and prevent migraines

• the antibiotic Zyvox (linezolide)

• anti-nausea drugs

• the weight-loss drug Meridia (sibutramine)

• lithium

• St. John's wort and ginseng

• several abused drugs, including ecstasy, LSD and amphetamines