Addictive Qualities of Modafinil Not Discussed by FDA Advisory

The Committee and the FDA recommended that the Celaphon provide additional
data about that risk.  However, there is concern about evidence-acknowledged
in the Physician’s Desk Reference (i.e., drug label) that modafinil is
likely to be as ‘reinforcing’ (i.e., addictive) as COCAINE.

What in Heaven’s name are we doing by encouraging the prescribing of highly
addictive drugs to our children?

What is the public health justification that prompts the FDA to support the
prescribing of powerful psychotropic drugs for children dubiously diagnosed
with ADHD?
In the case of psychostimulants-which FDA’s Pediatric Advisory Committee
examined-the drugs were found to act like Cocaine: inducing  psychosis,
hallucinations, and violence in children.
Like Cocaine, the prescribed drugs for ADHD are addictive.

The manufacturer’s label states:
"PROVIGIL produces psychoactive and euphoric effects, alterations in mood,
perception, thinking and feelings typical of other CNS
stimulants….Modafinil is reinforcing, as evidenced by its
self-administration in monkeys previously trained to self-administer
cocaine….Adverse experiences that were reported at these [high] doses
included excitation or agitation, insomnia, and slight or moderate
elevations in hemodynamic parameters. Other observed high-dose effects in
clinical studies have included anxiety, irritability, aggressiveness,
confusion, nervousness, tremor, palpitations, sleep disturbances, nausea,
diarrhea and decreased prothrombin time." See:
http://www.biopsychiatry.com/modafinil/modafinil-provigil.pdf

To overcome the documented adverse event profile disclosed in the label,
drug manufacturers hire academic-affiliated "experts" to write reports (or
merely sign off on articles) that downplay the product’s adverse effects–or
even deny they exist.

In the case of modafinil, its addictive and euphoric effect is denied in a
recent report published in the American J of Psychiatry (August 2005) by Dr.
Charles O’Brien, of the University of Pennsylvania.

Below, AHRP board member, Dr. Stefan Kruseuzki, challenges Dr. O’Brien and
the American J of Psychiatry for misrepresenting the addictive qualities of
modafinil.

 Of note, Dr. O’Brien has served as a paid consultant to Cephalon, the
drug’s manufacturer.

See financial disclosure: Charles A Dackis, Kyle M Kampman1, Kevin G Lynch1,
Helen M Pettinati1 and Charles P O’Brien
A Double-Blind, Placebo-Controlled Trial of Modafinil for Cocaine
Dependence, Neuropsychopharmacology (2005) 30, 205-211.
 
Contact: Vera Hassner Sharav
212-595-8974
veracare@ahrp.org

The American Journal of Psychiatry
 March, 2006
Euphorigenic and Abusive Properties of Modafinil
STEFAN P. KRUSZEWSKI, M.D.
Harrisburg, Pa.

To the Editor:

In the August issue of the Journal, Charles P. O’Brien, M.D., Ph.D. (1)
<http://ajp.psychiatryonline.org/cgi/content/full/163/3/549>  stated the
following about modafinil, a drug that he reported may decrease cocaine use
in some cocaine users: "The medication has not been reported to produce
euphoria, and there has been no indication of excessive use or abuse in
clinical trials" (p. 1428). As the scientific basis for his comment, the
author referenced his own group’s work (2) .

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 (PDR). The referenced article, for
example, 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). Separately, 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."

The author’s comment about the lack of euphorigenic effects of modafinil is
also contradicted by the U.S. Food and Drug Administration (FDA) in its
warning letter of Jan. 14, 2002, sent to Paul M. Kirsch, the senior director
of regulatory affairs of Cephalon, Inc., the makers of modafinil. It is
available online (3) . That letter specifically reiterates the package
insert for modafinil, addressing its abuse potential and euphorigenic
effects.

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. However, the implications loom even larger because the makers
of modafinil have submitted the "reformulated" drug to the FDA under a new
name-Attenace-for the treatment of attention deficit hyperactivity disorder
(4)

References
 1. O’Brien CP: Anticraving medications for relapse prevention:
a possible new class of psychoactive medications. Am J Psychiatry 2005;
162:1423-1431[Abstract/Free Full Text]
<http://ajp.psychiatryonline.org/cgi/ijlink?linkType=ABST&journalCode=ajp&re
sid=162/8/1423>  

 2. Dackis CA, Kampman KM, Lynch KG, Pettinati HM, O’Brien CP: A
double-blind, placebo-controlled trial of modafinil for cocaine dependence.
Neuropsychopharmacology 2005; 30:205-211[CrossRef]
<http://ajp.psychiatryonline.org/cgi/external_ref?access_num=10.1038/sj.npp.
1300600&link_type=DOI>

 3. Rogers JR: FDA Warning Letter to Paul M Kirsch, Senior
Director, Regulatory Affairs, Cephalon Inc re: NDA #20-717, Provigil
(modafinil) Tablets, MACMIS ID #10183, Jan 14, 2002.
"http://www.pharmcast.com/WarningLetters/Yr2002/Jan2002/Cephalon0102.htm

 4. Cephalon Files Application for Marketing Approval of New
Modafinil Formulation for the Treatment of Children and Adolescents With
Attention-Deficit/Hyperactivity Disorder. West Chester, Pa, Cephalon, Dec
21, 2004. "http://www.drugs.com/NDA/attenace_041221.html"

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