Doctors Fail to Recognize Life-Threatening Serotonin Syndrome

by Evelyn Pringle

In addition to recent reports that the drugs work no better than sugar pills, the latest warnings added to the long list of adverse events linked to selective serotonin reuptake inhibitor antidepressants have focused on birth defects, suicide risks and violence.

However, the massive over-prescribing of SSRIs, including Prozac, Paxil, Zoloft, Celexa and Lexapro in combination with many other drugs now has medical experts scrambling to educate doctors about a life-threatening condition known as "serotonin syndrome."

According to the report, "A Mix of Medicines That Can Be Lethal," by Jane Brody, in the February 27, 2007 New York Times, "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."

According to the Times, patients at particular risk, some experts say, are those taking a combination of antidepressants and antipsychotic drugs prescribed to treat resistant depression.

Ms Brody notes that in the March 2005 New England Journal of Medicine, two specialists, Dr Edward Boyer of the University of Massachusetts Medical School and Dr Michael Shannon of Children's Hospital Boston, found that more than 85% of doctors were "unaware of the serotonin syndrome as a clinical diagnosis."

In a report based on calls made to poison control centers in the US in 2002, the doctors found 7,349 cases of serotonin toxicity and a total of 93 deaths. In 2004, the Toxic Exposure Surveillance System identified 48,204 exposures to SSRIs that resulted in moderate or major outcomes in 8,187 patients and death in 103 patients, according to the September 2005 American Journal of Emergency Medicine.

In 2005, the last year for which statistics are available, a total of 118 deaths were reported, according to the New York Times.

The true incidence of serotonin syndrome, experts say, may be under-reported in these figures because the syndrome may be wrongly attributed to another cause, mild cases may be dismissed or medical professionals may not suspect the condition.

Studies have shown that when an expectant mother takes an SSRI, her system is flooded with extra serotonin, which then passes across the placenta into the womb, soaking the developing fetus in serotonin, according to Houston Attorney Robert Kwok.

"It is this prolonged and unanticipated exposure to serotonin," he says, "that our experts believe leads to the baby's birth defects. "

Studies indicate," he explains, "that mothers who take an SSRI during pregnancy have 1.5 to 2 times the risk of giving birth to a baby with a heart defect such as an atrial septal defect or ventricular septal defect, and are 6 times more likely to give birth to a baby with a severe and life-threatening lung disorder known as persistent pulmonary hypertension (PPHN).

And the cases of birth defects are on the rise. "Our group has over 100 SSRI baby birth defect cases in medical review," Mr Kwok states, "with most babies bearing strikingly similar heart and lung defects."

Mr Kwok is representing the family of Chase Steele, a baby born with severe heart defects after his mother took an SSRI during her pregnancy and the family of Gavin Shore, an infant also with severe heart defects to a mother who took the SSRI Celexa during her pregnancy.

"You would think by now," Mr Kwok says, "that the FDA would ban SSRIs for children, since the same logic applies to developing adolescents and developing babies in the womb during pregnancy."

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.