Pharma company Influence Medical Education Promotes OffLabel Use of Antipsychotic

The most widely prescribed treatments received a resoundinbg failing grade from
the most comprehensive schizophrenia treatment study (CATIE) conducted by a
consortium of leading U.S. psychiatrists who evaluated the efficacy of
widely prescribed atypical antipsychotics–including risperidone
(Risperdal), olanzapine (Zyprexa) quetiapine (Seroquel ), ziprasidone
(Geodon), and clozapine (Clozaril).

As Dr. Carol Tamminga–a leading research psychiatrist acknowledges in an
editorial in the American Journal of Psychiatry:
 Not only are these drugs shown to be ineffective for the condition for
which they were approved by the FDA:

"the side effect outcomes are staggering in their magnitude and extent and
demonstrate the significant medication burden for persons with
schizophrenia..  Sky-high drug discontinuation rates were seen, suggesting rampant drug
dissatisfaction and inefficacy."

Dr. Tamminga autions clinicians that these drugs’ severe adverse effects
require a major overhaul in their clinical practice: psychiatrists need to
incorporate extensive systemic MEDICAL monitoring of patients to detect any
physical signs of adverse effects:

"…..medication treatments with high side effect burden demand clinical
settings that are capable of detecting and managing serious side effects.
This knowledge means that the clinician’s office needs to be equipped to
efficiently monitor antipsychotic drug side effects. Blood pressure cuffs,
scales, body tape measures, a process for plasma chemistry monitoring and
electrocardiograms, and qualified consultants for medical questions become
important components of practice. Dynamic information of drug side effects
needs to take a prominent place in a patient’s psychiatric chart."

"Medical consequences of psychiatric drugs are real, preventable, and
require focused monitoring. Clinicians will need to have systems for the
effective monitoring of drug side effects to maintain and promote physical health among patients
as well as psychiatric health.  That these studies were NIMH-funded
increases our confidence that they are as free from marketing or other bias
or "spin" as possible."
See: Carol Tamminga, Editorial, Amer J Psychiatry, April 2006.

Yet, even as psychiatry’s leaders are wrestling with the incontrovertible
evidence, finally forced to address these drugs’ severe adverse physical
effects, Medscape continuing medical education (CME) courses accredited by
the Accreditation Council for Continuing Medical Education (ACCME),
encourage family physicians to prescribe these dangerous antipsychotics,
off-label, for children’s misconduct!!!!

Drugs whose toxic effects are finally being acknowledged as posing serious
hazards for the physical health of adult patients with schizophrenia-for
whom they were approved-are being irresponsibly promoted for children, for
whom the hazards are even greater.

Among the health hazards, Risperdal is linked to is hyperprolactinemia-a
condition in which levels of prolactin (a protein hormone) stimulates
secretion of milk and breast growth; it affects bone density–interfering
with normal growth, and increasing risk of osteoperosis.  In June 2005, the
company added an acknowledgement to the Risperdal label of a possible link
to tumors of the pituitary gland.

Risperdal is also linked to hyperglycemia, insulin resistance in children
and diabetes.  See, risk analysis, Risperidone in the Treatment of Autism,
by psychiatrist, Dr. Grace Jackson,
http://www.geocities.com/dansweb2000/rta.htm

Dr. Jackson, author of the book, Rethinking Psychiatric Drugs: A Guide for
Informed Consent. Bloomington (AuthorHouse, 2005), cites a Yale study that
reported: 78% of children /adolescents who were prescribed Risperdal had
clinically significant weight gain. See:  A. Martin, et al
"Risperidone-associated weight gain in children and adolescents: a
retrospective chart review," Journal of Child and Adolescent
Psycopharmacology 10 (2000): 259-268.

The AJP editorial stresses:  "Medical consequences of psychiatric drugs are
real, preventable, and require focused monitoring. Clinicians will need to
have systems for the effective monitoring of drug side effects to maintain
and promote physical health among patients as well as psychiatric health."  

Below, is a syllabus for a Continuing Medical Education course funded by
WebMD, encourages family physicians to prescribe Risperdal as "long-term
therapy" for children with "behavioral disorder."  That recommendation is
made on the basis of a 2003 study funded by Johnson & Johnson, manufacturer
of Risperdal.  

This is a demonstration of irresponsible–and possibly illegal–promotion of
off-label prescribing of a dangerous, toxic drug as a chemical restraint, to
control children’s behavior.  There surely ought to be a law prohibiting the
drug industry to set the agenda of physician educational training.

The CATIE study confirms that in the absence of a firewall between drug
manufacturers and physicians has resulted in hugely increasing sales of
antipsychotic drugs. The drug industry -whose only consideration is
increasing sales and profits-has diverted
physicians’ focus from the drugs’ severe adverse effects on patients.  While
enriching well-being But the price borne by patients-and ultimately by the
public-is that the adverse effects of these drugs have undermined the health
of those who ingested these drugs.

Contact: Vera Hassner Sharav
veracare@ahrp.org <mailto:veracare@ahrp.org>  
 

<http://www.medscape.com/viewarticle/528791_print#authors#authors>
This activity is supported by funding from WebMD.
Medscape Medical News
Children With Disruptive Behavioral Disorder May Benefit From Long-Term
Risperidone Therapy CME

News Author: Laurie Barclay, MD
CME Author: Penny Murata, MD

Complete author affiliations and disclosures, and other CME information
<http://www.medscape.com/viewarticle/528791_print#authors#authors> , are
available at the end of this activity.

Release Date: March 30, 2006; Valid for credit through March 30, 2007

Credits Available

Physicians – up to 0.25 AMA PRA Category 1 Credit(s)T for physicians ;
Family Physicians – up to 0.25 AAFP Prescribed for physicians

All other healthcare professionals completing continuing education credit
for this activity will be issued a certificate of participation.
Participants should claim only the number of hours actually spent in
completing the educational activity.
______________________________

March 30, 2006 – Children with disruptive behavioral disorder who respond to
risperidone will benefit from an additional 6 months of therapy, according
to the results of a randomized, double-blind study reported in the March
issue of the American Journal of Psychology.

"Treatment of disruptive behavior disorders is important because persistent
symptoms are linked to difficulty in school, social development, and adult
health," write Magali Reyes, MD, PhD, from the Tel-Aviv-Brull Community
Mental Health Center in Israel, and colleagues. "Long-term persistence and
consequences from disruptive behavior disorder often necessitate chronic
therapy, with a focus on maintenance of symptom control. However, no studies
have been conducted on the duration of treatment necessary for children with
disruptive behavior disorders."

In this study, patients with disruptive behavior disorder who had responded
to risperidone treatment for 12 weeks were randomized to 6 months of
double-blind treatment with either risperidone or placebo. The children were
5 to 17 years of age and had a range of intellect. The main efficacy
endpoint was time to symptom recurrence, defined as sustained deterioration
on either the Clinical Global Impression (CGI) severity rating (+2 points)
or the conduct problem subscale of the Nisonger Child Behavior Rating Form
(+7 points). Secondary efficacy outcomes included rates of discontinuation
due to symptom recurrence, disruptive behavior disorder symptoms, and
general function. Patients weighing less than 50 kg were given risperidone
at a dosage of 0.25 to 0.75 mg/day, and patients who weighed at least 50 kg
received 0.5 to 1.5 mg/day.

Of 527 patients who began treatment, 335 were randomized to a double-blind
maintenance condition. Compared with the placebo group, time to symptom
recurrence was significantly longer in patients who continued risperidone
treatment. Symptom recurrence in 25% of patients occurred after 119 days of
risperidone treatment and after 37 days of receiving placebo. The
risperidone group also fared better than the placebo group in terms of
secondary efficacy measures. Weight increased for the initial 12 weeks of
treatment (mean weight z score change, 0.2; SD, 2.7; N = 511) with a
subsequent plateau.

"This study is the first placebo-controlled maintenance versus withdrawal
trial of its kind in disruptive behavior disorder and provides evidence that
patients who respond to initial treatment with risperidone would benefit
from continuous treatment over the longer term," the authors write.
"Overall, risperidone was well tolerated, with infrequent symptoms of
movement disorders and no cases of tardive dyskinesia. Weight gain in excess
of that expected in a growing population occurred predominantly during the
first 12 weeks of risperidone treatment, and thereafter matched expected
weight gain associated with continued growth and development."

Study limitations include possibly too conservative criteria used to
identify symptom recurrence; and randomization only of patients who
responded to initial treatment, potentially introducing a selection bias.

"Low-dose risperidone improves a broad range of behavioral and social
symptoms in children and adolescents with disruptive behavior disorders,
including those with normal IQ," the authors conclude. "These benefits are
maintained in the long term, with substantial worsening of symptoms more
likely to occur in patients who do not continue maintenance risperidone
treatment."

Johnson & Johnson Pharmaceutical Research and Development supported this
study.
Am J Psychol. 2006;163:402-410
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:

    Compare the effects of maintenance risperidone treatment vs
withdrawal of treatment in children with disruptive behavior disorders.
    Describe the adverse effects of risperidone in the treatment of
children with disruptive behavior disorders.

Clinical Context
Up to 11.1% of children have disruptive behavior disorders, including
conduct disorder, oppositional defiant disorder, and disruptive behavior
disorder not otherwise specified. In the August 2002 issue of the Journal of
Abnormal Child Psychology, Lahey and colleagues reported resolution in less
than 15% of children with conduct disorder. Given the chronic nature of
these conditions, evaluation of long-term treatment with medication, such as
risperidone, is needed. In the November 2003 issue of the Journal of
Clinical Psychiatry, Findling and colleagues noted long-term use of
risperidone led to initial increase in prolactin levels.

The current trial is a randomized, controlled, international, multicenter
study to evaluate the efficacy and safety of long-term 6-month use of
risperidone in the treatment of children with disruptive behavior disorders
who have shown initial and sustained response to risperidone for a 12-week
trial period.

Study Highlights
    527 children aged 5 to 17 years met enrollment criteria: IQ score,
>/= 55; conduct disorder (190 [36%]), oppositional defiant disorder (318
[60%]), or disruptive behavior disorder not otherwise specified (19 [4%])
per Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
criteria; indication for risperidone treatment; conduct problem subscale
score of >/=24 on Nisonger Child Behavior Rating Form-parent version;
responsible caregiver.
    Exclusion criteria included serious medical or psychiatric
condition; additional antipsychotic, lithium, anticonvulsant, or
antidepressant use; psychostimulant use less than 30 days or variable dose.
    Mean age was 11.1 years; 44% were age >/=12 years; 87% male; 63% had
IQ higher than 84; 66% had attention-deficit/hyperactive disorder; 87% were
Caucasian.
    During open-label, 6-week, acute treatment phase, patients received
risperidone 0.25 to 1.5 mg/day. Patients were eligible for continuation
treatment phase if Nisonger Child Behavior Rating Form conduct problem
subscale score decreased by at least 50% or score </=17 and CGI change scale
score was 1 or 2 ("much" or "very much" improved).
    436 patients in single-blind, 6-week, continuation treatment phase
received stable risperidone dose and were monitored for sustained response:
Nisonger Child Behavior Rating Form conduct problem subscale score within 3
points between weeks 6 and 12; conduct problem subscale score less than 24
at weeks 8 and 10; improvement since initial screening.
    335 patients with sustained response were randomized to receive 6
months of risperidone or placebo for double-blind, maintenance treatment
phase.
    Of 172 patients in risperidone group, 100 completed treatment, 48
had symptoms recur, and 24 discontinued treatment.
    Of 163 patients in placebo group, 62 completed treatment, 76 had
symptoms recur, and 25 discontinued treatment.
    Time to symptom recurrence at end of maintenance was significantly
shorter for placebo vs risperidone group: 25% of patients had symptom
recurrence after 37 days in placebo group and 119 days in risperidone group.

    Rate of symptom recurrence was significantly lower in risperidone vs
placebo group (27.3% vs 42.3%).
    Placebo group showed significantly more deterioration vs risperidone
group for some Nisonger Child Behavior Rating Form subscales, most
troublesome symptoms visual analogue scale rating, CGI severity, and
Children’s Global Assessment Scale. There was no significant difference in
Nisonger Child Behavior Rating Form subscales of insecure/anxious,
injury/stereotypic behavior, self-isolated/ritualistic, and overly
sensitive.
    Adverse events were more frequent during acute (54.8%) vs
continuation (34.9%) and maintenance (47.7% in risperidone vs 36.2% in
placebo group).
    Most common adverse events during acute phase were somnolence
(11.6%), headache (11.2%), fatigue (10.4%), and increased appetite (10.2%).
Extrapyramidal symptoms were uncommon.
    Treatment discontinuation due to adverse events occurred in 1.7% of
patients in acute phase, 2.1% in continuation phase, 1.7% of risperidone
group, and 0.6% of placebo group in maintenance phase.
    Risperidone group had increased mean weight and body mass index
scores in first 12 weeks, but no increase during maintenance vs reference
norms; placebo group had decreased weight and body mass index scores vs
reference norms.
    Mean prolactin levels increased from 8.3 to 27.2 ng/mL during acute
and continuation phases; possible prolactin-related events in 15 patients
were unrelated to dose or prolactin level.
    There were no significant changes in vital signs, QT intervals,
cognitive test scores, and fasting glucose levels.

Pearls for Practice
    Children with disruptive behavior disorders who respond to initial
risperidone treatment continue to have decreased symptoms when continued on
long-term treatment.
    Risperidone treatment of children with disruptive behavior disorders
can lead to initial weight gain, elevated prolactin levels, and somnolence.

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Penny Murata, MD
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