May 4, 2007
Doctors Fail to Recognize Life-Threatening Serotonin Syndrome
Doctors Fail to Recognize Life-Threatening Serotonin Syndrome
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.
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."
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
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
In 2005, the last year for which statistics are
available, a total of 118 deaths were reported, according to the New
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.
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. "
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
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
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
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.
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
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
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.
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)
Dextromethorphan (Cold Remedies)
Atypical antipsychotic (Zyprexa, Risperdal, Seroquel)
Valproic acid (Depakene)
St John's Wort
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
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.
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."
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.
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.
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.
A therapist who treated the
children also told investigators she was concerned about the
medications prescribed to Rebecca because she never noticed symptoms of
attention deficit or bipolar disorder.
A state trooper's
affidavit said a Walgreen's pharmacy filled a number of clonidine
prescriptions for the Riley's when they should have had an ample supply
and that several times, Dr Kifuji approved extra pills because Carolyn
Riley said she had run out or lost her supply.
told investigators that Dr Kifuji had authorized the extra doses to
help Rebecca get to sleep, the affidavit said. The trooper also
reported that Dr Kifuji received calls from a therapist and a nurse at
Elden Johnson Early Childhood Center, where Rebecca was a student,
saying they were concerned about her medication.
shows that no testing was conducted on Rebecca in making the diagnosis
of attention deficit or bipolar disorder and that Dr Kifuji said she
diagnosed Rebecca based on the parents' statements and "brief visits"
in her office as frequently as twice a month and as seldom as once
every two months.
In July 2006, a social worker treating
Rebecca filed a complaint with the agency reporting that Carolyn Riley
was "neglecting her children" and "appeared heavily drugged and unable
to respond" on one of her visits to the family home.
social worker said that during one visit, Carolyn told her that urine
on the floor was from when Rebecca had taken a nap on the floor,
according to an affidavit from investigators, and the social worker
said she had to tell Carolyn to clean the floor.
out the social worker's complaint, the DSS Commissioner said all the
doctors and a psychiatric hospital caring for one of the children in
July 2006 said the medications were appropriate and there was no one
else to consult, so the department did not substantiate the complaint.
medical examiner's office determined that Rebecca died from
"intoxication due to the combined effects" of the drugs clonidine,
Depakote, dextromethorphan, and chlorpheniramine, the district
attorney's office said in a statement.
The official autopsy
report states that Rebecca died of the "combined effects" of the drugs
and that her lungs and heart were damaged by "prolonged abuse of these
prescription drugs, rather than one incident."
have some experts wondering whether the medical examiner may be a
member of the 85% of doctors identified by the New England Journal of
Medicine study who are unaware of the serotonin syndrome as a clinical
The statement released by the DA states, "This
occurred as a result of the intentional overdose of Rebecca with
clonidine," and the manner of death "was determined to be homicide."
Rebecca's parents have both been charged with murdering their daughter.
psychiatrist Dr Grace Jackson, a leading authority on psychotropic
drugs, takes issue with the claim of the manner of death being
"I'd put my money on serotonin syndrome as the cause
of death," she says, "a potentially lethal condition of serotonin
excess, leading to signs and symptoms which include autonomic
instability, heart dysrhythmias (sudden death), hyperthermia (high
fever), changes in mental status (including possible coma),
hyperreflexia, and myoclonus."
"In this case," Dr Jackson
says, "the primary culprits were dextromethorphan and chlorpheniramine,
an antihistamine which also boosts serotonin levels."
probably quite likely," she explains, "that the family had not been
warned by any doctor or pharmacist that this combination of medications
could cause death – particularly, in a toddler."
"It is also
possible," she adds, "that the psychiatrist did not realize that the
family was administering dextromethorphan to the child --- it might
have been given from an over-the-counter cough remedy by unsuspecting
Dr Jackson also notes that Depakote has been shown
to increase levels of serotonin in many brain regions, "hence," she
says, "it was factor #3 in the serotonin syndrome which presumably
killed this child."
"This toddler," she explains, "may have
been receiving tiny doses of the medications prescribed, but that did
not protect her from serotonin syndrome."
investigators, based on interviews of relatives in the home who
observed Rebecca in the days before she died, describe symptoms typical
of serotonin syndrome. They said she became restless, disorientated,
incoherent, would not respond to her name and that she appeared dazed
and "out of it."
She was lethargic at school and at home, and
a neighbor described her as zombie-like, according to interviews in an
affidavit filed in Plymouth District Court.
The day before she
died, Rebecca developed a fever and was coughing uncontrollably, so her
parents went to Wal-Mart to buy cold and flu medicine. While at
Wal-Mart, Rebecca began to vomit, so Carolyn Riley purchased Pedialyte
and a plastic bowl for Rebecca to vomit in during the ride home, and
she reportedly vomited about 5 times over the course of that day.
grandmother told reporters that the doctor never told the parents not
to give her the over-the-counter cold medications now listed as
contributing to her death because of the prescription drugs she was on.
Dr Jackson suspects that Rebecca – like so many patients – was
the unwitting victim of "Evidence Based Psychiatry," which means drug,
drug, and more drug, because "somebody, somewhere, published a study
that showed a three year old responded to five or six or seven drugs in
combination," she states.
Dr Jackson is the author of,
"Rethinking Psychiatric Drugs: A Guide for Informed Consent," a book
that provides a critical appraisal of 3 classes of psychiatric drugs
that an estimated 20% of Americans consume on a regular basis,
including antidepressants, antipsychotics and stimulants.
to Harvard Instructor Dr John Abramson, author of, "Overdosed America,"
this "gruesome story" seems to have two separate and distinct
components. "First," he says, "is the question of whether or not the
child was being given medication as it was prescribed."
"And the second," he notes, "is the question of why such medicines were prescribed for such a young child."
Abraham points out that there has been a progressive medicalization of
other than desirable behaviors in children. "We have seen this in the
enormous proliferation of stimulant medication use," he notes, "far out
of proportion to use in other countries."
Now, he says, the
diagnosis of bipolar disorder in children is rising in parallel, and
clearly, it is the drug industry driving this medicalization to sell
In what can only be described as assembly-line
customer recruitment, Rebecca's psychiatrist, Dr Kifuji, also
prescribed the same powerful drug cocktail to Rebecca's older brother
and sister when they were diagnosed with the same illnesses several
The Rileys' attorneys say the parents are
unsophisticated people who did not question the doctor. Michael Riley's
lawyer, John Darrell, told the Boston Globe on February 7, 2007, that
neither parent knew enough treatment to have challenged Kifuji. "You've
got two poor parents here of minor means financially, of minor
education," he said.
A reading of all the official reports and court documents in this case definitely indicate that be true.
so often happens with families like the Riley's, who are covered by
public health care programs, and with the great assistance of Dr
Kifuji, the entire Riley family become a cash cow for the
psychiatric-pharmaceutical industry, including the mother and father.
incentive certainly worth noting is the potential monthly income Dr
Kifuji generated for herself by the legal pill-pushing to the Riley
family. A 2003 study by the American Psychiatric Association found
doctors could earn about $263 an hour for holding three 15-minute
medication management sessions per hour, compared to about $156 for a
single therapy session. That represents an hourly pay cut of 41% for
doctors doing therapy only, the APA study said.
more blame should be focused on the prescribing doctors. "While the
pharmaceutical companies certainly are getting rich providing
mind-altering drugs for psychiatry's made-up mental disorders, the
fault lies with the psychiatric community," says Kelly Patricia
O'Meara, author of "PSYCHED OUT: How Psychiatry Sells Mental Illness
and Pushes Pills That Kill".
"Until the fraud of psychiatric
diagnosing is exposed," Ms O'Meara warns, "the American people will
continue to hear about more and more of these tragic outcomes."
it always goes back to the chicken and the egg theory. Was there an
epidemic in this family where all 5 family members were so severely
mentally ill? Or did the psychiatric-pharmaceutical industry convert
them into life-long disabled customers through the administration of a
powerful drug cocktail for years on end?
According to Dr Ann
Blake Tracy, Director of International Coalition for Drug Awareness,
and author of "Prozac: Panacea or Pandora?", she expects a person
placed on one of these drug cocktails to be on disability within a 3-
to 5-year window of time.
"And for a decade and a half," she
says, "she has been trying to figure out how our economy will survive
the skyrocketing disability rates."
The chicken and the egg
theory arises a second time in this case when reviewing the allegations
lodged against the parents. Were the bizarre behaviors of the parents
cited in official reports and the media the result of ignorance, bad
parenting or a wish to harm Rebecca? Or were the behaviors in fact
brought on by the combination of drugs the parents were ingesting?
Ms O'Meara notes, "one has to wonder that if the entire family was
being 'treated' for their alleged mental illnesses, why then didn't the
Dr Tracy says, "Is it absolutely possible that
some of the alleged behaviors of the parents in this family could have
been caused by the prescribed drugs they were taking."
explains that the hypothesis behind these psychiatric drugs is
backwards, meaning they often end up causing the conditions that they
were prescribed to treat.
Leonard Frank, author of "Zyprexa: A
Prescription for Diabetes, Disease and Early Death", concurs.
"Psychiatrists and other physicians," he explains, "prescribe drugs in
attempt to suppress objectionable conduct but the drugs often make the
conduct even more objectionable, in which event the prescription is
Then he explains, one drug may be substituted for
another, or one or more drugs may be added to the mix, or the dosage
may be decreased, or more likely increased, and this process may go on
endlessly, he says.
Following Rebecca's death, the Department
of Social Services placed the other two Riley children, Kaitlynne 6,
and Gerald 11, in foster care and sought an independent opinion on
their medical care, and doctors determined that their medication needed
to be changed.
Persons injured by Serotonin Syndrome and
seeking legal advice can contact the Robert Kwok & Associates Law
Firm, at (713) 773-3380; http://www.kwoklaw.com/about.php
article is written as part of a series on emerging issues involving the
pharmaceutical industry and is sponsored by Robert Kwok &
Authors Bio: Evelyn Pringle is a columnist for OpEd News and
investigative journalist focused on exposing corruption in government
and corporate America.