Doctors Fail to Recognize Life-Threatening Serotonin Syndrome

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Serotonergic receptors are found throughout the central nervous system and are involved in the regulation of the sleep-wake cycle, behavior, appetite, temperature and muscle tone, and serotonin neurotransmission is involved with the regulation of gastrointestinal motility and vascular tone. Serotonin syndrome results from excessive stimulation or agonism at postsynaptic serotonin receptors.

According to the FDA, symptoms of the syndrome may include restlessness, hallucinations, loss of coordination, fast heart beat, rapid changes in blood pressure, increased body temperature, overactive reflexes, nausea, vomiting and diarrhea.

The patients often have changes in mental status, including agitation, hypervigilance and pressured speech, and in severe cases, may present with profound hypertension and tachycardia, and proceed rapidly to shock.

In severe cases, patients may exhibit delirium, seizures, muscular rigidity and hypertonicity. A core temperature may exceed 40º C (104 F), and may be accompanied by metabolic acidosis, rhabdomyolysis, renal failure and disseminated intravascular coagulation.

Experts say the most important information for doctors to know when dealing with a possible case of serotonin syndrome is what drugs have been ingested, because in addition to SSRIs, there are other classes of drugs with different mechanisms that can also increase serotonin levels to differing degrees.

A greater awareness of the combinations that trigger the syndrome could lead to prevention, but a diagnostic challenge exists due to the fact that the list not only includes prescription drugs, but also over-the-counter medications and herbal supplements. The following are some of the products known to be associated with serotonin syndrome:

Monoamine oxidase inhibitors (MAOIs)
Tricyclic antidepressants (TCAs)
Selective serotonin reuptake inhibitors (Zoloft, Prozac, Paxil, Lexapro, Celexa)
Venlafaxine (Effexor)
Trazodone (Desyrel)
Nefazodone (Serzone)
Meperidine (Demerol)
Dextromethorphan (Cold Remedies)
Chlorpheniramine
Sumatriptan (Imitrex)
Atypical antipsychotic (Zyprexa, Risperdal, Seroquel)
L-dopa
Meridia
Lithium
Valproic acid (Depakene)
Linezolid (Zyvox)
St John's Wort
Ginkgo Biloba

Many experts blame the rise in cases of serotonin syndrome on the fact that so many different drugs are being prescribed to patients at the same time in combinations, or "drug cocktails," which have never been approved as safe and effective by the FDA for any use and without considering the over-the-counter medications that patients may be taking.

The syndrome has become more prevalent in children as the off-label use of drug cocktails with children has increased. Some experts suspect serotonin syndrome in the death of 4-year-old, Rebecca Riley in Massachusetts, on December 13, 2006.

Critics say the Riley case highlights the need to put an end to the rampant off-label prescribing of adult psychiatric drugs to children. "The general public is unaware that almost no psychiatric drugs have ever truly been tested for children," according to David Oaks, director of MindFreedom, an international human rights organization.

"All psychiatric drugging of children," he says, "is essentially 'off label' in the sense that doctors have an enormous range of discretion when prescribing psychiatric drugs to young people."

"It's time for society to get hands-on with the mental health system," Mr Oaks warns, "and rein in the immense tyrannical power that doctors now have."

The State Police investigator's report in this case said psychiatrist Dr Kayoko Kifuji, at the Tufts-New England Medical Center, prescribed 3 medications for Rebecca: 750 milligrams a day of Depakote; 200 milligrams a day of Seroquel; and .35 milligrams a day of clonidine.

Rebecca was given Seroquel, for bipolar disorder, a drug only approved to treat adults with schizophrenia or bipolar, Clonidine, for attention deficit disorder, a drug approved only to treat adults with high blood pressure, and Depakote, an anti-convulsant drug approved to treat epilepsy in adults.

She was kept on this 3-drug cocktail since she was 2 and a-half-years-old, until she was found dead on the floor of her parent's home on December 13, 2006. At the time of her death, there were also over-the-counter cold medications in her system including Children's Tylenol Cough and Runny Nose, which contain acetaminophen, dextromethorphan and chlorpheniramine.

According to a report by investigators, Rebecca's teachers and a school nurse repeatedly complained about the child's extreme lethargy and how she seemed better when the drugs wore off, and the nurse also pointed out that Rebecca did not exhibit the kind of behavior that might justify prescribing these types of drugs.

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