Just What Kids Need - Sparlon - Another ADHD Drug

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Sun, 19 Mar 2006 12:42:07 -0500

[sSRI-Research] Pringle - Just What Kids Need - Sparlon -

Another ADHD Drug

 

 

 

 

 

http://www.opednews.com/articles/genera_evelyn_p_060319_just_what_kids_need_.htm

 

Just What Kids Need - Sparlon - Another ADHD Drug

 

by Evelyn Pringle

 

http://www.opednews.com

 

The pharmaceutical company, Cephalon Inc, is going through the motions

of legitimizing the sale of Sparlon for the treatment of ADHD even

though its active ingredient, modafinil, has been heavily promoted and

sold under the name Provigil, for off-label treatment of ADHD by

Cephalon for years.

 

Last October, the FDA sent an " approvable " letter to Cephalon for the

pediatric use of Sparlon pending a March 23, 2006, meeting of the

Psychopharmacologic Drugs Advisory Committee to review the drug's

approval.

 

Modafinil-based Provigil is currently only approved for narcolepsy,

sleep apnea and shift work sleep disorder, according to the FDA.

However, it is estimated that half of all Provigil prescriptions are

written for off-label use.

 

" Doctors now prescribe it to treat everything from attention deficit

hyperactivity disorder (ADHD) to fatigue associated with multiple

sclerosis and depression, " according to the November 1, 2004 Business

Week Online.

 

Evelyn Pringle Cephalon gets nearly

half of its $1.2 billion in annual sales from modafinil. Its original

patent ran out in December 2005. However, in a sweetheart deal, Cephalon

agreed to pay 4 generic drug makers, including Mylan Laboratories and

Teva Pharmaceutical, over $200 million to postpone marketing generic

versions of the medication until October 2011, GoozNews reported on

March 17, 2006.

 

In addition, the Cephalon will get a 6-month extension of that agreement

if it wins a pediatric approval for the drug, according to documents

filed with the Securities and Exchange Commission.

 

With Sparlon's application to FDA approval, Cephalon claimed 3 studies

involving more than 600 children aged 6 to 17, found the drug to be more

effective than a placebo.

 

Which says what? What does it mean to be more effective than a placebo?

The question is, how many trials did it take to get the drug to win out

over a placebo three times?

 

Each of the Sparlon studies lasted only 9 weeks and the most common side

effects listed were mild insomnia, headaches and loss of appetite.

Sparlon was " generally well-tolerated, " Cephalon reported.

 

What does " generally well-tolerated, " mean? Tolerated better than what?

A placebo?

 

One study of 248 patients was published in December 2005 issue of

Pediatrics, and said Sparlon's effectiveness and safety profile, along

with its low potential for abuse, may offer doctors and parents a new

option for children and adolescents with ADHD.

 

However, because the study only lasted 9 weeks, the authors said they

did not know if " the initial benefits will be sustained over longer

periods of time, " and called for more research to assess the

" longer-term efficacy and safety. "

 

Dr DuBose Ravenel, MD, who will testify on behalf of the International

Center for the Study of Psychiatry and Psychology at the advisory

committee hearing on March 23, makes the point that although " 48% of

drug treated subjects at final follow-up were " much " or " very much "

improved clinically, 52% were not. "

 

" This is a substantially lower response rate than has been reported for

traditional stimulants, " the doctor notes.

 

Dr Dubose Ravenel is a pediatrician with 25 years experience in private

practice with

a heavy emphasis upon behavioral issues, including diagnosing and

managing ADHD.

 

In addition, she notes, with regard to potential conflicts of interest,

itemized conflicts for each of the Pediatric study's authors are numerous.

 

For instance, " Dr. Biederman received research support from 10

companies, serves on speakers' bureaus for 4 companies, and is on

advisory boards of 6 companies, " Dr Dubose Ravenel reveals.

 

" Dr. Kratochvil, " she advises, " has received research support from,

served as a consultant for, and/or served on speakers' bureaus for 10

pharmaceutical companies. "

 

Other authors have numerous listed conflicts as well she notes.

 

" In light of recent widely publicized articles showing widespread

deceptive practices engaged in by pharmaceutical companies in designing,

selective reporting, and interpreting studies, " she says, " the large

number of pharmaceutical company ties with the authors of the study do

not lend confidence to the reader even beyond the aforementioned

concerns. "

 

Initial marketing of modafinil, Dr Dubose Ravenel concludes, " as a drug

for treating ADHD reveals inaccurate and exaggerated claims concerning

efficacy, safety, and the mechanism of action by which the drug works. "

 

And come to find out, it seems Sparlon is not so " well-tolerated " after

all. Last week the FDA announced that an analysis provided by Cephalon

as part of its response to the FDA's " approvable " letter found 4

suicidal events, 2 events of psychosis/mania and 9 aggression events in

the double blind clinical studies of Sparlon, in a summary report for

the Pediatric Advisory Committee.

 

In addition, two events of psychosis/mania and 14 aggression events were

seen in open-label studies of modafinil for ADHD, the FDA said. These

rates are compared to 5 aggression events and no suicidal or

psychosis/mania events in placebo patients from the double-blind trials.

 

" There were more events in all categories among modafinil treatment

patients compared to placebo, but the exposure to modafinil was

greater, " the FDA said.

 

" It will be noted, however, that the frequency of these events during

double-blind treatment was higher than during open-label treatment, " the

FDA said.

 

The FDA summary also pointed out that " two additional probable cases of

aggression during double-blind treatment, in study 207 " , were found by

the agency's Psychiatry Products Division.

 

A March 3, 2006, memorandum to various FDA's divisions on drug safety,

from FDA official Andrew Mosholder, noted that psychosis/mania events

occurred during double-blind treatment with every ADHD drug studied

except Adderall XR.

 

" With respect to psychosis and mania events, " the memorandum wrote,

" although the numbers of such events with drug treatment were small, the

complete absence of such

events with placebo treatment was notable. "

 

The memorandum also noted that suicidal events were found to be more

frequent with modafinil treatment than with placebo.

 

At a hearing last month on February 9, 2006, Dr Mosholder, told the

FDA's Drug Safety Advisory Committee that modafinil, marketed as

Provigil, is a stimulant. He said " modafinil is a different type of

stimulant, marketed for excessive sleepiness associated with various

sleep disorders. "

 

" It too may have some cardiovascular effects, " Dr Mosholder told the

panel. " There was a finding that use of antihypertensives during the

clinical trials was more frequent than on placebo, which suggests that

there are some cardiovascular effects there as well. "

 

Promoters of modafinil contend it can be useful in the treatment of

cocaine addiction. In the August 2005, American Journal of Psychiatry,

Charles O'Brien, MD, PhD, claims modafinil, the active ingredient in

Sparlon, may decrease cocaine use in some cocaine users and specifically

states:

 

" The medication has not been reported to produce euphoria, and there has

been no indication of excessive use or abuse in clinical trials " As the

scientific basis for his comments, Dr O'Brien references his own group's

work

 

According to Psychiatrist, Dr Stefan P Kruszewski, MD, " the author's

statement does not appear to be supported by his referenced work, nor is

it supported by information widely available in the 2004 edition of the

Physicians' Desk Reference. "

 

The referenced article, Dr Kruszewski says, may demonstrate that

modafinil can, in some cases, blunt cocaine euphoria. However, it does

not say anything about modafinil's intrinsic ability to produce euphoria

(or not), he says.

 

" Separately, " Dr Kruszewski advises in the March 2006, American Journal

of Psychiatry, " the 2004 PDR raises specific concerns about modafinil,

saying that it can produce " psychoactive and euphoric effects,

alterations in mood, perception, thinking and feelings typical of other

CNS stimulants. "

 

" The PDR also states that " modafinil is reinforcing, as evidenced by its

self-administration in monkeys previously trained to self-administer

cocaine, " he adds.

 

In addition, says Dr Kruszewski, the comment about the lack of

euphorigenic effects is contradicted by the FDA in a January 14, 2002,

warning letter sent to Paul Kirsch, the senior director of regulatory

affairs at Cephalon, that specifically reiterates the drug's package

insert addressing the modafinil's euphorigenic effects and its potential

for abuse.

 

That the euphorigenic side effects or abuse potential may be minimized

has current treatment implications because modafinil is increasingly

promoted for fatigue and excessive sleepiness unrelated to narcolepsy as

well as for cocaine abuse, Dr Kruszewski says in the Journal.

 

Sparlon's approval is set to be reviewed by the Psychopharmacologic

Drugs Advisory Committee on March 23, 2006.

 

Last month, Allen Jones, testifying as a representative of the Alliance

for Human Research Protection, told the advisory panel: " Most of you

have had past or current relationships with the drug industry. "

 

As it turn out, conflicts of interest exist on this month's advisory

panel as well. Wayne Goodman, the chairman of the Psychopharmacologic

Drugs Advisory Committee that will consider Sparlon's approval heads the

psychiatry department at the University of Florida, that receives

hundreds of thousands of dollars a year in research grants from 2 of

Cephalon's competitors in the field of ADHD drugs.

 

Another member of the Committee, Andrew Leon of Cornell University,

disclosed he owns less than $25,000 in stock in a Cephalon competitor,

according to GoozNews on March 18, 2006.

 

The Pediatric Advisory Committee is meeting on March 22, 2006, the day

before the Sparlon hearing, to focus on neuropsychiatric adverse event

reports and clinical trial data from approved ADHD medications, and will

also receive an update on cardiovascular adverse events possibly related

to ADHD medications, according to the FDA web site.

 

 

Evelyn Pringle

evelyn.pringle

 

(Evelyn Pringle is a columnist for Independent Media TV and an

investigative journalist focused on exposing government corruption)

 

 

 

 

 

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