Fail To Recognize
Life-Threatening Serotonin Syndrome
By Evelyn Pringle
08 May, 2007
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
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
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
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.
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,
Dextromethorphan (Cold Remedies)
Atypical antipsychotic (Zyprexa, Risperdal, Seroquel)
Valproic acid (Depakene)
St John's Wort
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
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
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
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.
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.
Carolyn Riley 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.
The affidavit 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.
The 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.
When checking 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
The 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
Those findings 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 diagnosis.
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.
However, psychiatrist Dr Grace Jackson, a leading authority on psychotropic
drugs, takes issue with the claim of the manner of death being homicide.
"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."
"It is 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 parents."
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
"This toddler," she explains, "may have been receiving
tiny doses of the medications prescribed, but that did not protect her
from serotonin syndrome."
Reports by 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
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.
Rebecca's 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
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
According 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
“And the second,” he notes, “is the question of why
such medicines were prescribed for such a young child.”
Dr 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 more products.
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 years earlier.
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.
As 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.
Another 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.
Critics say 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."
And 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
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
"Naturally," 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 drugs work?"
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."
She explains that the hypothesis behind these psychiatric drugs is backwards,
meaning they often end up causing the conditions that they were prescribed
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 changed."
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
(This article is written as part of a series on emerging issues involving
the pharmaceutical industry and is sponsored by Robert Kwok & Associated,
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