Controlled Trial of High Doses of Pemoline for Adults With Attention-Deficit/Hyperactivity Disorder

Abstract

Despite the increasing awareness of attention-deficit/hyperactivity disorder (ADHD) in adults, there are a limited number of controlled pharmacologic studies of this disorder. Because the stimulant medication magnesium pemoline (Cylert, Abbott Laboratories, Abbott Park, IL) has been found effective in treating ADHD in pediatric groups, we tested its efficacy in adults with ADHD using higher daily doses than those previously studied. We conducted a 10-week, double-blind, placebo-controlled, crossover design study of pemoline at a target daily dose of 3 mg/kg per day in 35 adult patients with DSM-III-R and -IV ADHD. We used standardized structured psychiatric instruments for diagnosis. To measure improvement, we used separate assessments of ADHD, depressive, and anxiety symptoms at baseline and at each biweekly visit. ADHD outcome was determined using the ADHD symptom checklist and Clinical Global Impression scales of Severity and Improvement. Of the 35 adults with ADHD who were randomized in the trial, 27 (77%) completed the protocol. Treatment with pemoline in the final week of the 4-week active phase was best tolerated at doses substantially lower than the target dose of 3 mg/kg per day (mean dose, 2.2 mg/kg per day; mean+/-SD, 148+/-95 mg). Pemoline was significantly better at reducing ADHD symptoms compared with placebo (z = 2.4,p < 0.02). Using a predefined 30% reduction in symptoms as an indication of improvement, 50% of pemoline-treated subjects and 17% of subjects in the placebo group were considered positive responders (chi2 = 7.1, p = 0.008). These results indicate that pemoline is moderately effective in the treatment of ADHD in adults. Although robust doses were targeted, most adults preferred more moderate dosing (120-160 mg/day). Given the limited efficacy, tolerability, and concerns of hepatic dysfunction, pemoline should be considered as second-line medication for treating ADHD in adults.

An update on the pharmacotherapy of attention-deficit/hyperactivity disorder in adults

“…Plasma levels of the stimulants [44,82], as well as gender and psychiatric comorbidity [44,45,83], have not been implicated in variable medication response in ADHD adults; however, exclusion criteria and limited sample sizes constrain generalizability of these findings. Similar findings between response rates and adverse effects have been reported between ER and IR stimulants.…”

Evidence-based pharmacotherapy for attention-deficit hyperactivity disorder

“…In contrast, the few studies on pre-schoolers appear to indicate that young children respond less well to stimulant therapy suggesting that ADHD preschoolers may be more treatment refractory or may be more diagnostically heterogeneous (Byrne et al, 1998). Three recent controlled clinical trials documented the efficacy of methylphenidate, Adderall and pemoline in adults with ADHD Wilens et al, 1999c). It is remarkable that these trials documented not only a highly clinically and statistically significant separation from placebo, but also that the magnitude of effects was consistent with the paediatric trials.…”

Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) bei Erwachsenen

“…Pemolin ist in Deutschland zur Behandlung der ADHS im Kindesalter zugelassen. Studien, die den Einsatz an Jugendlichen und Erwachsenen überprüften, konnten zeigen, dass bis zu 60% der Behandelten bei einer Dosierung von bis zu 3 mg/kg Körpergewicht eine signifikante Symptomreduktion aufwiesen [2,76,93]. Aufgrund der möglichen Lebertoxizität von Pemolin sollte eine Medikation jedoch allenfalls nachrangig erwogen werden und nur unter engmaschiger Kontrolle der Leberwerte erfolgen.…”