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Long-Acting Stimulant Treatment of ADHD in Girls


To report an evaluation of the efficacy of once-daily OROS® methylphenidate (MPH) (brand name CONCERTA) in girls with attention-deficit/hyperactivity disorder (AD/HD) by reviewing data from four randomized double-blind placebo-controlled studies.


ADHD is an important cause of psychiatric disability in girls, and is currently under recognized and undertreated. More boys than girls present with AD/HD. DSM-IV estimates the male: female ratio as 9:1 (based on the proportion of girls referred to clinics), and yet community-based studies have sometimes shown the ratio to be as low as 2.5:1. This suggests that AD/HD prevalence in girls is seriously underestimated and that many school-aged girls with AD/HD are unlikely to be properly diagnosed and treated. Without adequate treatment, girls with AD/HD are likely to have academic underachievement, low self-esteem, few friends, and sleep problems. In addition, some may exhibit excessive talkativeness, introversion, and in adolescence to indulge in risky behaviours, such as promiscuity and substance abuse.

The lack of recognition of AD/HD in girls can be partly explained because symptoms that these girls exhibit are less overt than those symptoms that boys with AD/HD exhibit. Girls more often present with AD/HD inattentive- or combined- (inattention plus hyperactive/impulsive) subtypes, and less often with hyperactive/impulsive-subtype. In addition, their hyperactivity is more likely to manifest as emotional reactivity than motor hyperactivity. Coexisting disorders presenting in AD/HD girls are often different from those in boys: conduct disorder and oppositional defiant disorder, which are often the drivers for a boy’s clinical referral, are half as common in girls; while girls are more likely to internalize symptoms and become anxious, depressed, and socially withdrawn. AD/HD can lead to substance abuse disorders and sexual risks as girls enter adolescence.

Methylphenidate (MPH) is a central nervous system stimulant and is recommended as a first-line therapy for the treatment of all AD/HD subtypes. It has a 50-year history of safe and effective use in providing relief from the symptoms of AD/HD in children. In a randomized comparative study of 14 months’ treatment in 579 children with combined-subtype AD/HD, the MTA Cooperative Group (1999a,b) (representing the US National Institute of Health), found stimulant medication to be significantly more effective than standard community care or behavioral therapy alone in reducing the symptoms of AD/HD in both boys and girls. No statistically significant advantage was found over and above that provided by stimulant medication (normally MPH) when behavioral therapy was added to the treatment program.

The once-daily OROS® MPH formulation (Concerta) produces an ascending plasma profile of MPH, which provides 12 hours of sustained efficacy, equivalent to three (3) daily doses (tid) of immediate-release (IR) MPH. OROS® MPH (Concerta) has been shown in clinical studies to be significantly different than placebo, to have efficacy and safety similar to MPH three times a day and to be the preferred formulation by patients and parents alike (Pelham et al, 2001; Wolraich et al, 2001). Recent clinical trial data demonstrate that long-acting stimulant formulations are as effective in girls as in boys.

Girls are more likely to adhere to the simple dosing regimen of OROS® MPH (Concerta) compared with the three times a day dosing with short acting Methylphenidate, and to benefit from the advantage of not having to bring medication into school. Since many AD/HD girls are already suffering from difficulties with social interaction, it is beneficial that Concerta removes the social embarrassments both of taking pills in public, and of the difficulties caused by the peaks and troughs in plasma concentration (and resulting behavior) associated with shorter acting medications. Because fewer girls than boys are diagnosed with AD/HD, there are few data that demonstrate efficacy of AD/HD medication for girls. This abstract provides data drawn from several trials for one of the initial reviews of pharmacological AD/HD therapy in girls.


Data on girls were extracted from four studies: three in children (6–12 years), treated either for 7 days (each regimen; Concerta once a day, short acting MPH three times a day, placebo) in two crossover trials (n = 7 and 12 girls, respectively), or for 28 days in a parallel-group study (20 receiving Concerta, 12 receiving MPH three times a day, and 14 receiving placebo). Concerta dosing was at 18, 36 or 54 mg per day. The fourth trial was a randomized double-blind placebo-controlled trial in adolescents (13–18 years) treated for 2 weeks after earlier titration to their optimized Concerta dose of 18, 36, 54, or 72 mg per day (23 girls receiving Concerta; 12 receiving placebo).


AD/HD subtype differed between girls and boys among 6- to 12-year-old children (65 girls and 332 boys (1:5 ratio). More girls were diagnosed with inattentive-subtype AD/HD than boys (32% vs. 17%), and fewer with combined type (66% vs. 77%) or hyperactive/impulsive-subtype AD/HD (2% vs. 7%). Girls taking either of the active MPH preparations improved significantly compared with placebo in several efficacy measures. In the different studies, for Concerta and placebo respectively, the teacher IOWA Conners inattention/over activity scores were, after 7 days, 2.9 and 7.3 (n = 7, p<0.05), and 5.9 and 13.4 (n = 12), and after 28 days, 5.3 (n = 19) and 9.7 (n = 14). For Concerta and placebo, parent SNAP-IV inattention subset scores after 28 days were 1.25 (n = 20) and 2.11 (n = 10), respectively (p<0.05).

In the adolescent trial, randomization of 175 subjects produced a disproportionate number of girls in the Concerta (n = 23) vs. placebo (n = 12) groups, the sex ratios being 3:1 (64 boys, 22 girls) and 6:1 (77 boys, 12 girls), respectively. All efficacy outcomes, assessed by multiple raters, showed greater improvement in the Concerta group than the placebo group for both sexes, with the differences being statistically significant for the boys but not for the girls, in most cases due to the low number of subjects included. For the girls, mean results are given in the table below.

Measure Baseline End double-blind phase
Investigator rating on the AD/HD Rating Scale (primary efficacy measure)
Parent rating on the AD/HD Rating Scale
Adolescent rating on the Conners-Wells’ Self-Report Scale (CASS-L)
Parent rating on the Child Conflict Index (CCI)

For Concerta and placebo respectively, the investigator-assessed Global Assessment of Efficacy was “good” or “excellent” for 45% vs. 17%; and investigator-assessed condition on the Clinical Global Impressions scale was “much or very much improved” in 50% vs. 17%.


The manifestations of AD/HD are often different in girls than boys, with a higher proportion of girls diagnosed with inattentive-subtype AD/HD. Results from this analysis demonstrate that Concerta is effective in treating girls with AD/HD, a population that has not been systematically looked at before this study.


  • MTA Cooperative Group (99a). A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. Arch Gen Psychiatry; 56:1073–1086.
  • MTA Cooperative Group (99b). Moderators and mediators of treatment response for children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry; 56:1088–1096.
  • Pelham WE, et al. Once-a-day CONCERTA® methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings. Pediatrics; 107(6):105;1417–1418.
  • Wolraich M, et al. Randomized controlled trial of OROS® methylphenidate qd in children with attention-deficit/hyperactivity disorder. Pediatrics; 108(4):883–892.

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