Pharmacokinetics, tolerability, and clinical effectiveness of quetiapine fumarate: An open-label trial in adolescents with psychotic disorders

Background: This is the first investigation of the pharmacokinetics, tolera bility, and efficacy of quetiapine Fumarate in adolescents with chronic or intermittent psychotic disorders. Method: Ten patients with DSM-IV chronic or intermittent psychotic disorder s (ages 12.3 through 15.9 years) participated in an open-label, rising-dose trial and received oral doses of quetiapine twice daily (b.i.d.), starting at 25 mg b.i.d, and reaching 400 mg b,i.d. by day 20, The trial ended on d ay 23. Key assessments were pharmacokinetic analysis of plasma quetiapine c oncentrations and neurologic, safety, and efficacy evaluations. Results: No statistically significant differences were observed between 100 -mg b,i.d. and 400-mg b.i.d. quetiapine regimens for total body clearance, dose-normalized area under the plasma concentration-time curve, or dose-nor malized premorning- or postmorning-dose trough plasma values obtained under steady-state conditions after multiple-dose regimens. No unexpected side e ffects occurred with quetiapine therapy, and no statistically significant c hanges from baseline were observed for the UKU Side Effect Rating Scale ite ms that were rated. No serious adverse events or clinically important chang es in hematology or clinical chemistry variables were reported. The most co mmon adverse events were postural tachycardia and insomnia. Extrapyramidal side effects improved, as evidenced by significant (p <.05) decreases from baseline to endpoint in the mean Simpson-Angus Scale total scores and Barne s Akathisia Scale scores. Quetiapine improved positive and negative symptom s, as shown by significant (p <.05) decreases from baseline to endpoint in the mean Brief Psychiatric Rating Scale total score, the Clinical Global im pressions-Severity of Illness scale, and the Modified Scale for the Assessm ent of Negative Symptoms summary score. Conclusion: Quetiapine pharmacokinetics were dose proportional in adolescen ts and were similar to those previously reported for adults. Quetiapine was well tolerated and effective in the small number of adolescents studied.