NEWS FLASH-DRUG ALERT:KIDS DYING FROM ANTIDEPRESSANTS
IMIPRAMINE & DESIPRAMINE
THE PROVINCE (Vancouver, BC, Canada)
Monday, December 18, 2000
by Ann Rees
Deaths linked to sedatives
More than 2,000 B.C. youngsters prescribed drugs associated with
fatal heart attacks
More than 2,000 B.C. children and teenagers were prescribed two
sedatives last year which are linked to fatal heart attacks.
The old-style tranquilizers
[Fred A. Baughman Jr., MD:
tricyclic antidepressantsTCAs]
are used to treat everything from bad
behaviour to bed-wetting.
The American Health Association lists the drugs as a "potential
mechanism for sudden death."
"The tricyclic antidepressants imipramine (Tofranil) and desipramine (Norpramine,
Pertofrane) have been
associated with at least seven reported deaths in young patients,"
reads the warning.
[Fred A. Baughman Jr., MD:
in the US, the reporting of adverse events, death included, to
the FDA, is wholly voluntary, accounting for no more than between one and ten percent
of the actual frequency]
"We have stopped using it altogether unless you are completely
desperate," said Dr. Wendy Roberts, director of the Child Development
Clinic at Toronto's Hospital for Sick Children.
[Fred A. Baughman Jr., MD:
What, Dr. Roberts, is 'completely
desperate'? Bear in mind, Dr. Roberts, that not a single psychiatric 'disorder' is an
actual 'disease' (disease = abnormality. All psychiatric disorders = no physical
abnormality = no disease = normal). No, Dr. Wendy, it is not like diabetes, the name
applied to having an abnormally elevated blood sugar. In diabetics, there is an
abnormality to be made more nearly normal by applying the drug insulin or one of the
oral blood sugar reducing drugs. In psychiatry, there are no demonstrable physical or
chemical abnormalities; the very first one is the toxic drug you give them to take.
(psychiatric disorder = normal = no disease + psychiatric drug = abnormal = disease) ]
Roberts said child must be closely monitored for indications the drug
is causing problems with heart rhythms.
"You are watching ECGs very carefully because of the danger of
arrhythmia," she said.
[Fred A. Baughman Jr., MD:
but, nonetheless, and despite the fact that no disease exists,
Dr. Roberts, administers the cardio-toxic drugs]
The manufacturers warn of potential cardiac problems and do not
recommend the drugs for kids.
Last year in B.C. 2,285 young patients were prescribed imipramine.
The drug is sold under the brand names Tofranil, Impril and
Novo-Pramine
the drug is
used to treat everything from bed-wetting to long-term depression,
anger and aggression.
The youngest patients on imipramine were five tots who turned two
last year. There were also eight patients who turned three and 29 who
were four years old last year.
[Fred A. Baughman Jr., MD:
in my opinion, criminal!]
The safety and effectiveness of the drug when used to treat children
under five has not been established
The sedative desipramine was prescribed to 275 young patients in B.C.
last year. The youngest six were aged four and five in 1999. The data
shows 91 children under 12 were prescribed the drug.
Dr. Pratibha Reebye, infant psychiatrist
[Fred A. Baughman Jr., MD:
The term 'infant psychiatrist' suggests
there is such a thing as infant
psychiatry, and that their are such things as diagnosable, infant psychiatric disorders, all
of which they claim to be diseases] at B.C. Children’s Hospital,
said anti-depressants such as imipramine have been used for many
years to treat depression, anxiety, school phobia and bed-wetting [fb: as if these were
diseases needing medical treatment]
.
DISCUSSION OF THE CARDIAC TOXICITY OF TCA ANTIDEPRESSANTS.
In the face of the sudden death of 4 children receiving desipramine for ADHD and other
behavior disorders, Biederman of Harvard, argued vigorously against Werry’s (Auckland)
call for an embargo of it’s use in children. The Biederman-Werry debate was published
in 1995 in the Journal of the American Academy of Child and Adolescent Psychiatry.
Biederman et al (1993) carried out clinical cardiac assessments, echocardiographic
evaluations and 24-hour Holter, ekg monitoring on children and adolescents on
desipramine to detect possible preexisting problems and, contrary to their own data,
concluded: “…no evidence of drug-associated cardiac abnormalities was found,” also that
“The Holter 24-houir ECG recordings in desipramine-treated patients were very similar
to those previously reported in the published series of healthy children.” Five of 16 of
the Holter monitor comparisons were statistically significant and three others approached
significance. There were single premature atrial contractions (PACs) in 58%, paired
PACs in 11% and runs of supraventricular tachycardia (SVT) in 10% in the desipramine
treated group. None of the 323 children in a comparison study had SVT. Scott, et al
(1980), concluded: “It seems that runs of premature beats are likely to be of pathological
significance in this age group (boys, 10-13) as are episodes of ventricular or
supraventricular tachycardia.” This lead Waslick (Waslick, B. Cardiac Effects of
Desipramine, J Am Acad Child Adolesc Psychiatry, 1995;34:125) to conclude that
although clinically well, “cardiac abnormalities” are found in the desipramine-treated
group but not in normal control or comparison groups.
Additionally, 20% of the desipramine-treated children had QTc intervals of 440 msec or
longer. Riddle et al ( ibid, 1991;30:104-108) urged: “
it may not be wise to continue the
medication in any patient whose QTc exceeds .425-.450 seconds while on medication.”
Biederman, et al, concluded, “The benign findings encountered during the desipramine
treatment make it unlikely that different conclusions would have been reached with a
blind assessment or use of a more nearly ideal within-subject design.” Waslick, not
agreeing that the findings were “benign,” concluded: “I believe that the cardiac
abnormalities in these data, though not emphasized in the article’s discussion, suggest
that is it now time for a well-blinded, prospective study…”
In his reply to Waslick, and contrary to the standard electrocardiographic assessment of
such things, Biederman remarks that the findings in their study group were asymptomatic
and therefore, not viewed (by Biederman) as clinically significant. Regarding the QTc
interval prolongation of .425 to .450 seconds, generally regarded as risky and an
indication to stop desipramine, here too, Biederman takes exception, taking 460 msec as
their point of concern, not stopping desipramine at levels lower than this. Contrary to the
views of others Biederman states “we continue to view our reported asymptomatic
laboratory findings as clinically benign.”
Biederman knows as well as every physician, regardless of specialty, that dangerous ECG
changes as in the children on desipramine, they describe, are often asymptomatic up to
the moment of conversion to a catastrophic rhythm. His one-dimensional defense of
desipramine, is not only unjustifiable, but is unconscionable. Why this one-dimensional
defense of desipramine when the standard cardiologic interpretation holds that such
changes are “likely to be of pathologic significance in this age group.” Remember,
‘pathology’ and ‘pathologic’ denotes disease–real disease. Six sudden, deaths in children
taking desipramine for ADHD, is real disease. On the other hand, ADHD, a totally
arbitrary grouping of behaviors met in biologically normal children, the other component
of the risk/benefit assessment here, has never been proven to be a disease.
Why is any conclusion reached other than that of Werry, a senior, child-adolescent
psychiatrist from New Zealand has called for a full embargo of the use of desipramine in
children. Why has Waslick, faced with the same evidence called only for only a new,
more valid assessment of desipramine, while its use in children goes on. Most
troublesome of all–why does Biederman, a psychiatrist, so passionately, so singularly,
defend the use of desipramine in children, rejecting both the cardiac implications of the
sudden deaths in these children and the electrocardiographic alterations deemed to be of
“pathological significance in this age group.” As physicians, it should go without saying
that we are first, and foremost, patient advocates. Tragically, in US marketplace
medicine, the dollar has come to rule and ties between industry and medical academia
generally and psychiatric and the pharmaceutical industry, in particular, have eclipsed
patient safety.
With ADHD, not a disease, I submit that the risk/benefit ratio regarding any drug that
bears riskssurely the case with desipramine and with addictive, Schedule II, Ritalin, as
well, could not possibly be other than negative, and, thus, justifiable.
To understand why medical, psychiatric and psychopharmacologic researchers say what
they say, one must know their every financial tie, including all of those of their medical
schools, teaching hospitals and departments. Nothing less than a financial statement of
the sort that a mortgage or the IRS requires, will do. Only then will it become apparent
who this or that professor is advocating for. Sadly, as in the case of Dr. Biederman and
desipramine, it is not for the patient. The unthinkable has happened. That Professor
Werry is still free to speak for the welfare of the patient probably has most to do with the
fact that he is from the UK where the dollar, industry and the ‘bottom line’ have not yet
come to rule health care, as has become the case here in the US.
To understand why the Biederman view is regularly articulated in the psychiatric
literature, one should know that Beiderman is highly influential in academic psychiatry
and that he is an editor of the peer-reviewed, Journal of the American Academy of Child
& Adolescent Psychiatry. Moreover, one would have to know the extent of
pharmaceutical sponsorship of this and other psychiatry journals and of all psychiaty
educational activities. It is not, after all, as simple as asking “Could this drug kill my
child?”
The 1990 “package insert” for Norpramin (desipramine, Merrell Dow Pharmaceuticals
Inc. was changed thusly: ” There has been a report of an ‘acute collapse’ and ‘sudden
death’ in an eight-year-old (18 kg.) male treated for two years for hyperactivity. There
have been additional reports of sudden death in children”
Tricyclic antidepressants, including Norpramin, Tofranil, and Elavil are not approved by
the FDA for use in individuals less than 12 years of age. The sole exception, is Tofranil,
used to treat enuresis, or bedwetting.
[Fred A. Baughman Jr., MD:
meaning that their use in children younger
than this is devoid of a scientific basis]