Presentation by Stefan P. Kruszewski, M.D.

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[sSRI-Research] Presentation by Stefan P. Kruszewski, M.D. -

FDA's Advisory Committee Meeting

 

 

 

 

Presentation by Stefan P. Kruszewski, M.D.

September 14th, 2004

 

Delivered at Alliance for Human Research Protection's Press Briefing

 

Washington Room, Holiday Inn, Bethesda, site of FDA's Advisory

Committee Meeting

 

http://www.ahrp.org/risks/SSRI0904/KruszewskiSSRI.php

I am addressing two (2) issues related to the effectiveness and safety

of the prescription of Selective Serotonin Reuptake Inhibitors (SSRIs)

to children:

 

Issue No. 1

 

What is the human cost, in terms of morbidity and mortality, when

SSRIs are prescribed without adequate clinical trials and 'off-label'

to children?

 

Specific Example: 13 y.o. Caucasian male child with a diagnosis of

dysthymia. The boy was brought to the attention of a psychiatrist

because of social isolation and inability to make friends easily.

Prior to seeking psychiatric attention, he had never been

psychiatrically hospitalized nor had he experienced suicidal or

homicidal feelings. He had no history of acting out against others. He

had been considered mild-mannered, quiet, friendly, shy and

uncomfortable in social situations with children his age. He had no

medical diagnoses.

 

The boy's psychiatrist prescribed escalating doses of paroxetine

(PAXIL). As his mood deteriorated and his behavior worsened, the

psychiatrist increased the dose of Paxil from an original dose of 10

milligrams per day to a final dose of 60 milligrams per day. He

required inpatient psychiatric hospitalization twice over a period of

one month due to increasingly self-destructive thoughts and self harm

(he broke his own arm; tried to hang himself) and demonstrated

severely aggressive acting-out against others (while walking in his

neighborhood with his mother, he violently attacked a stranger, biting

the stranger's forearm and breaking the stranger's forearm skin with

his teeth.)

 

After his act of aggression, he was re-hospitalized. His inpatient

child psychiatrist lowered his dose of Paxil to 40mgs per day and

added quetiapine (SEROQUEL, an atypical antipsychotic), to decrease

his " psychotic symptoms " and stabilize his mood.

 

I will report on the current status of this boy and comment on a few

of the important points that can be gleaned from its exposure. Those

points include:

 

a.. Production of unknown SIDE EFFECTS

b.. COMPOUNDING the problem: Treating unintended side-effects of one

SSRI (Paxil) with the off-label use of another psychiatrically active

compound (Seroquel)

c.. How significant is the problem? (Data on captive populations,

different jurisdictions)

d.. Who does the problem affect? (Patient, family, physician,

healthcare systems, healthcare finances)

 

Issue No. 2

 

The Registry of Clinical Trials is an essential step - and absolutely

necessary - to safe-guard the clinical research of all

neuropsychiatric medicines and devices. However, although it is

necessary, it is NOT sufficient.

 

What else do we need to protect the health and welfare of children,

adolescents, and adults?

 

Clinical 'SPIN' must be addressed

 

The results and conclusions of any trial, including the abstracted

information, must not be distorted in follow-up clinical research

publications or marketing efforts. The reasons for this are simple. If

the end result of a valid clinical trial shows a drug, for example, to

be ineffective, that result must not be reported as 'somewhat

effective' elsewhere. To do so invalidates the importance of the

publication of clinical trial results and minimizes the promise and

potential of the clinical registry.

 

a.. Examples: Fluoxetine (PROZAC) for obsessive-compulsive disorder.

Venlafaxine (EFFEXOR) for social anxiety. Gabapentin (NEURONTIN) in

anxiety disorders. Any SSRI for drug withdrawal-induced depressive

response.

 

b.. The information available in clinical registries, including the

statistical analyses, must be understandable.

 

c.. Discussion of limitations of a study: Acute, intermediate and

long-term adverse side-effects, limits of extrapolation to populations

not evaluated; comparative psychopharmacology and

psychopharmacological metabolic problems; reproducibility and

reliability of statistical analysis.

 

d.. Post-clinical registry reporting: Mandatory post-surveillance

reporting to comment/criticize/analyze and document the benefits and

drawbacks of any particular research endeavor and to establish its

usefulness, reliability and validity for further research.

 

Stefan P. Kruszewski, M.D. is a clinical/academic psychiatrist from

Harrisburg, Pennsylvania. He is certified by the American Board of

Psychiatry and Neurology in general and psychiatric subspecialties as

well as by the American Society of Addiction Medicine and the American

Board of Adolescent Psychiatry. He has had solo-authorship work

published in the New England Journal of Medicine, Journal of Clinical

Psychiatry, Archives of Family Medicine, Plant Physiology, as well as

in the New York Times, Barron's and other newspapers.

 

Dr. Kruszewski graduated from Princeton University and Harvard Medical

School. He completed a residency in psychiatry and post-doctoral work

in clinical research at Robert Wood Johnson Medical School and did

post-residency work at Duke University and Texas Christian University.