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A review of modafinil film-coated tablets for attention-deficit/hyperactivity disorder in children and adolescents.

Rugino T - Neuropsychiatr Dis Treat (2007)

Bottom Line: Several studies, including three double-blind, placebo-controlled studies with intent-to-treat analyses, have demonstrated the efficacy of modafinil film-coated tablets in reducing symptoms of ADHD and associated problem behaviors in children and adolescents.Modafinil is generally well tolerated, with adverse events (such as insomnia, headache, loss of appetite, weight loss, and gastrointestinal discomfort) that are generally mild to moderate, rarely leading to medication discontinuation.Due to reports of skin rash (including one case of possible erythema multiforme/Stevens Johnson Syndrome during pivotal studies), additional studies have been requested to better evaluate the risks of developing severe cutaneous adverse reactions.

View Article: PubMed Central - PubMed

Affiliation: Children's Specialized Hospital, 94 Stevens Road, Toms River, NJ 08755, USA. trugino@childrens-specialized.org

ABSTRACT
Modafinil, a wakefulness-promoting agent unrelated to classical sympathomimetic stimulants, has been studied in a total of 933 children and adolescents as a treatment for attention-deficit/hyperactivity disorder (ADHD). Several studies, including three double-blind, placebo-controlled studies with intent-to-treat analyses, have demonstrated the efficacy of modafinil film-coated tablets in reducing symptoms of ADHD and associated problem behaviors in children and adolescents. Modafinil is generally well tolerated, with adverse events (such as insomnia, headache, loss of appetite, weight loss, and gastrointestinal discomfort) that are generally mild to moderate, rarely leading to medication discontinuation. To minimize treatment-emergent side effects, titration to the target dose of 355-425 mg once a day should take place over 2-3 weeks. Due to reports of skin rash (including one case of possible erythema multiforme/Stevens Johnson Syndrome during pivotal studies), additional studies have been requested to better evaluate the risks of developing severe cutaneous adverse reactions.

No MeSH data available.


Related in: MedlinePlus

ADHD Rating Scale total scores as a function of time for a fixed-dose study of efficacy of modafinil for children and adolescents with attention-deficit/hyperactivity disorder (n = 183). *p values <0.05; endpoint represents the last obtained value carried forward Reproduced from Cephalon, Inc. 2006. Modafinil (CEP-1538) tablets Supplemental NDA 20-717/S-019 ADHD indication. Briefing document for Psychopharmacologic Drugs Advisory Committee Meeting March 26, 2006. Frazer, PA: Cephalon, Inc.
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f3c-ndt-3-293: ADHD Rating Scale total scores as a function of time for a fixed-dose study of efficacy of modafinil for children and adolescents with attention-deficit/hyperactivity disorder (n = 183). *p values <0.05; endpoint represents the last obtained value carried forward Reproduced from Cephalon, Inc. 2006. Modafinil (CEP-1538) tablets Supplemental NDA 20-717/S-019 ADHD indication. Briefing document for Psychopharmacologic Drugs Advisory Committee Meeting March 26, 2006. Frazer, PA: Cephalon, Inc.

Mentions: Two flexible-dose studies (Biederman et al 2005; Greenhill et al 2006) and one fixed-dose study (Swanson et al 2006) documented efficacy of a film-coated compressed tablet formulation of modafinil using an intent-to-treat analysis with 2:1 ratio of treatment: control and with the endpoint defined as the last obtained value carried forward. In the flexible-dose studies, the mean and modal stable doses were 361–369 mg/day and 425 mg/day (range 170–425 mg once daily every morning), whereas the final administered dose in the fixed-dose study was 340 mg for children <30 kg and 425 mg for subjects ≥30 kg. For all three studies and for pooled data (Cephalon 2006), ADHD-RS-IV scores demonstrated improvements consistently in favor of modafinil for the primary outcome measure (the School Version of the ADHD-RS-IV, see Figures 3a, b, c), the Home Version of the ADHD-RS-IV, as well as for the inattentive and hyperactive-impulsive subscale scores of each version. There were no effects of race, sex, weight, ADHD subtype, or comorbidity in the improvements seen with modafinil treatment (Cephalon 2006). More improvement was seen in patients less than 12 years of age compared with older patients. Modafinil was efficacious in treating both stimulant-naïve patients and those who had received prior stimulant therapy. ADHD-RS-IV: School Version total scores showed a reduction of ≥30% in 64%–69% of modafinil-treated subjects (as compared with 35%–39% of controls, p < 0.0001) and a reduction of ≥50% for 44%–48% of modafinil-treated subjects as compared with 19%–20% of controls, p < 0.001) for each of the studies (Biederman et al 2005; Swanson et al 2006; Cephalon 2006; Greenhill et al 2006). Using the ADHD-RS-IV: School Version total score data and Cohen’s calculations, the overall pooled effect size was 0.69; this corresponds to a medium-to-large effect (Cohen 1988). The greatest effect was seen in drug-naïve subjects, in whom the calculated effect size was 1.08 (treatment n = 221 and control n = 102).


A review of modafinil film-coated tablets for attention-deficit/hyperactivity disorder in children and adolescents.

Rugino T - Neuropsychiatr Dis Treat (2007)

ADHD Rating Scale total scores as a function of time for a fixed-dose study of efficacy of modafinil for children and adolescents with attention-deficit/hyperactivity disorder (n = 183). *p values <0.05; endpoint represents the last obtained value carried forward Reproduced from Cephalon, Inc. 2006. Modafinil (CEP-1538) tablets Supplemental NDA 20-717/S-019 ADHD indication. Briefing document for Psychopharmacologic Drugs Advisory Committee Meeting March 26, 2006. Frazer, PA: Cephalon, Inc.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654790&req=5

f3c-ndt-3-293: ADHD Rating Scale total scores as a function of time for a fixed-dose study of efficacy of modafinil for children and adolescents with attention-deficit/hyperactivity disorder (n = 183). *p values <0.05; endpoint represents the last obtained value carried forward Reproduced from Cephalon, Inc. 2006. Modafinil (CEP-1538) tablets Supplemental NDA 20-717/S-019 ADHD indication. Briefing document for Psychopharmacologic Drugs Advisory Committee Meeting March 26, 2006. Frazer, PA: Cephalon, Inc.
Mentions: Two flexible-dose studies (Biederman et al 2005; Greenhill et al 2006) and one fixed-dose study (Swanson et al 2006) documented efficacy of a film-coated compressed tablet formulation of modafinil using an intent-to-treat analysis with 2:1 ratio of treatment: control and with the endpoint defined as the last obtained value carried forward. In the flexible-dose studies, the mean and modal stable doses were 361–369 mg/day and 425 mg/day (range 170–425 mg once daily every morning), whereas the final administered dose in the fixed-dose study was 340 mg for children <30 kg and 425 mg for subjects ≥30 kg. For all three studies and for pooled data (Cephalon 2006), ADHD-RS-IV scores demonstrated improvements consistently in favor of modafinil for the primary outcome measure (the School Version of the ADHD-RS-IV, see Figures 3a, b, c), the Home Version of the ADHD-RS-IV, as well as for the inattentive and hyperactive-impulsive subscale scores of each version. There were no effects of race, sex, weight, ADHD subtype, or comorbidity in the improvements seen with modafinil treatment (Cephalon 2006). More improvement was seen in patients less than 12 years of age compared with older patients. Modafinil was efficacious in treating both stimulant-naïve patients and those who had received prior stimulant therapy. ADHD-RS-IV: School Version total scores showed a reduction of ≥30% in 64%–69% of modafinil-treated subjects (as compared with 35%–39% of controls, p < 0.0001) and a reduction of ≥50% for 44%–48% of modafinil-treated subjects as compared with 19%–20% of controls, p < 0.001) for each of the studies (Biederman et al 2005; Swanson et al 2006; Cephalon 2006; Greenhill et al 2006). Using the ADHD-RS-IV: School Version total score data and Cohen’s calculations, the overall pooled effect size was 0.69; this corresponds to a medium-to-large effect (Cohen 1988). The greatest effect was seen in drug-naïve subjects, in whom the calculated effect size was 1.08 (treatment n = 221 and control n = 102).

Bottom Line: Several studies, including three double-blind, placebo-controlled studies with intent-to-treat analyses, have demonstrated the efficacy of modafinil film-coated tablets in reducing symptoms of ADHD and associated problem behaviors in children and adolescents.Modafinil is generally well tolerated, with adverse events (such as insomnia, headache, loss of appetite, weight loss, and gastrointestinal discomfort) that are generally mild to moderate, rarely leading to medication discontinuation.Due to reports of skin rash (including one case of possible erythema multiforme/Stevens Johnson Syndrome during pivotal studies), additional studies have been requested to better evaluate the risks of developing severe cutaneous adverse reactions.

View Article: PubMed Central - PubMed

Affiliation: Children's Specialized Hospital, 94 Stevens Road, Toms River, NJ 08755, USA. trugino@childrens-specialized.org

ABSTRACT
Modafinil, a wakefulness-promoting agent unrelated to classical sympathomimetic stimulants, has been studied in a total of 933 children and adolescents as a treatment for attention-deficit/hyperactivity disorder (ADHD). Several studies, including three double-blind, placebo-controlled studies with intent-to-treat analyses, have demonstrated the efficacy of modafinil film-coated tablets in reducing symptoms of ADHD and associated problem behaviors in children and adolescents. Modafinil is generally well tolerated, with adverse events (such as insomnia, headache, loss of appetite, weight loss, and gastrointestinal discomfort) that are generally mild to moderate, rarely leading to medication discontinuation. To minimize treatment-emergent side effects, titration to the target dose of 355-425 mg once a day should take place over 2-3 weeks. Due to reports of skin rash (including one case of possible erythema multiforme/Stevens Johnson Syndrome during pivotal studies), additional studies have been requested to better evaluate the risks of developing severe cutaneous adverse reactions.

No MeSH data available.


Related in: MedlinePlus