Methylphenidate placebo-controlled trial

Gadow et al. (1995), however, found no increase in tics in a placebo-controlled trial of methylphenidate in children with ADHD and a tic disorder. Other trials of stimulants in such children have found little or no average increase in tic severity scores, but clinically significant increases of tics in a handful of subjects severe enough to prompt discontinuation of the stimulant (Castellanos et al., 1997 Law and Schachar, 1999) or to require addition of a medication to control their tic symptoms (Gadow et al., 1999). A multicenter, doubleblind, placebo-controlled, parallel group study of methylphenidate and clonidine, used alone or in combination in 136 children with ADHD and a comorbid... 

Pharmacotherapy with stimulants increases dopaminergic and noradrenergic activity, which has the potential to aggravate or precipitate tics. One study examined the comparative effects of methylphenidate and dextroamphetamine on tics in children and found the majority experienced improvement in ADHD symptoms with acceptable effects on tics. Methylphenidate was better tolerated than dextroamphetamine. Another double-blind placebo-controlled trial compared methylphenidate or clonidine monotherapy to combination methylphenidate and clonidine in patients with ADHD and Tourette s disorder. Combination therapy demonstrated the greatest benefit in reducing symptoms of ADHD and tics (p <0.0001). Clonidine appeared most helpful for impulsivity and hyperactivity, while methylphenidate was most helpful for inattention. All treatments were well tolerated. 

There are two studies of hospitalized children with mania or manic symptoms. The first, a controlled trial of lithium in 11 children (7 of whom were treated under double-blind, placebo-controlled conditions), found that 6 showed improvement over an 8-week period of hospitalization, but only 3 were well enough to be discharged on lithium. Long-standing concurrent ADHD complicated assessment of response (Carlson et al., 1992a), and the addition of methylphenidate was necessary to achieve an improvement in attention span and hyperactivity (Carlson et ah, 1992b). An open trial of lithium in 10 acutely manic/psychotic prepubertal children showed positive response in all (Varanka et ah, 1988). 

Atomoxetine, a selective norepinephrine reuptake inhibitor, is the first nonstrmulant approved by the Food and Drug Administration (FDA) for the treatment of ADHD. In contrast to the stimulants, it has no apparent abuse potential and is not a controlled substance. Placebo-controlled, short-term trials (6 to 12 weeks) have shown that atomoxetine is effective in reducing ADHD symptoms in children, teens, and adults. It is not clear whether it is as effective as the stimulants, although one preliminary open study suggested comparable efficacy with methylphenidate. ... 

To more rigorously address the pharmacotherapy of symptoms of hyperactivity and inattention in PDD, the NIMH-sponsored RUPP Autism Network is conducting a controlled investigation of methylphenidate versus placebo in children and adolescents with PDDs. Nonresponders to methylphenidate will have the opportunity to enter a prospective, open-label trial of guanfacine. 

This group of medications has been studied for the treatment of hyperactivity or ADHD since 1936 and has consistentiy shown robust efficacy in more than 150 randomized ciinicai triais (RCTs) of schooi-aged chiidren. There are more than 3,000 citations and 250 reviews of stimulant treatment (63, 64 and 65). Robust short-term stimulant-related improvement in ADHD has been reported in 161 controlled RCTs, including five preschool, 140 school-age, seven adolescent, and nine adult studies (66). There were 133 trials with methylphenidate, 22 with dextroamphetamines, and six with pemoline. In addition, two studies found treatment with mixed amphetamine salts to be superior to placebo (67, 68). 

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