Clinical Psychiatry News. July 2005 v33 i7 p38(1).
Antinarcolepsy drug may improve ADHD: modafinil could prove an alternative
to stimulants for addressing symptoms
By Mary Ellen Schneider.
© 2005 International Medical News Group
ATLANTA -- Results from new research point to a possible alternative
to stimulants for the treatment of attention-deficit hyperactivity disorder
in children and adolescents.
Two phase III studies presented at the annual meeting of the American
Psychiatric Association show that a once-daily pediatric formulation of
modafinil is well tolerated and improves attention-deficit hyperactivity
disorder (ADHD) symptoms in children and adolescents.
Modafinil is currently marketed by Cephalon under the brand name Provigil
in 100-mg and 200-mg strengths. Provigil is indicated for the
treatment of excessive sleepiness associated with narcolepsy, obstructive
sleep apnea, hypopnea syndrome, and shift work sleep disorder.
The company, which funded the phase II trials, is seeking approval from
the Food and Drug Administration to market modafinil in 85-mg, 170-mg,
255-mg, 340-mg, and 425-mg strengths. If approved, the drug would be indicated
for treatment of ADHD in children and adolescents aged 6-17 years.
The company is planning to launch the drug under the brand name Attenace
by early 2006.
In one study, 189 patients with ADHD aged 6-17 years were randomized
to a 7-week double-blind, fixed-dose treatment with either modafinil or
placebo. This protocol was followed by a 2-week withdrawal period in which
half of the modafinil-treated patients were placed on placebo without
tapering, and half were continued on the drug, said Joseph Biederman,
M.D., the lead investigator in the study and professor of psychiatry at
Harvard University in Boston.
Modafinil was administered once daily, starting at 85 mg/day, and was
rapidly titrated over 7-9 days to dosages of either 340 mg/day for patients
who weighed less than 30 kg or 425 mg/day for patients who weighed 30
kg or more.
The results of the study were assessed using the school and home ADHD
Rating Scale-IV total score change from baseline to last treatment visit.
After 1 week, the 125 modafinil-treated patients had significantly greater
improvements in school scores, compared with the 64 placebo patients,
and those results were maintained through week 7.
On the school scale, patients on modafinil experienced a 17.2-point drop
in symptoms, compared with an 8.2-point drop for patients on placebo.
Modafinil also significantly improved total scores from parents, compared
with placebo.
The side effects included insomnia and appetite decrease. Overall, the
side effects were generally mild and occurred at initiation of the treatment.
There were two serious adverse events not associated with the trial, said
Dr. Biederman, who is an advisory board member for Cephalon and receives
research/grant support from the company.
The researchers also assessed ADHD symptoms and physical/emotional response
after rapid discontinuation. During the 2-week withdrawal phase there
were no reported symptom rebounds, no adverse events related to withdrawal,
and no physical or emotional responses.
Modafinil appears to work like a gentler stimulant, Dr. Biederman said
in an interview.
The findings present possible new treatment options, he said. Although
stimulants are effective, they are not universally effective. About 30%-40%
of patients are nonresponsive to stimulants, he said, and some patients
also have tolerability problems.
Stimulants also have the potential for acute deterioration and symptom
rebound if treatment is interrupted or discontinued without tapering,
Dr. Biederman said.
In the second study, researchers considered the effect of a flexible
dose of modafinil in children and adolescents.
The study included 198 patients aged 6-17 years who were started on a
dose of 85 mg/day of modafinil, which was titrated over 22 days based
on clinical effectiveness. The maximum dose was 425 mg/day with once-daily
dosing, said James Swanson, Ph.D., of the University of California at
Irvine Child Development Center, who was the lead investigator.
The results were assessed using the school and home ADHD Rating Scale-IV,
the Clinical Global Impression of Improvement (CGI-I), and Test Variables
of Attention (TOVA).
The home score showed a mean drop of 17.6 points in symptoms for the
131 patients receiving modafinil at a mean stable dose of 361 mg/day,
compared with a 7.5-point drop in symptoms for the 67 patients on placebo.
The improvement in the total school score was also significantly greater
for modafinil patients, Dr. Swanson reported.
Modafinil was shown to significantly improve inattention and hyperactivity/impulsivity,
and there was an improvement in overall clinical condition and in the
TOVA measurements of ADHD.
The researchers focused not only on decreasing symptoms of ADHD, but
on increasing positive interaction and social skills, and they saw an
increase in positive behaviors, he said.
The side effects included insomnia, headache, and appetite problems,
which are similar to the side effects for stimulants, said Dr. Swanson,
who is an advisory board member with Cephalon, receives research/grant
support from the company, and is a member of the company's speakers' bureau.
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