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, tolerability, and efficacy of quetiapine Fumarate in adolescents with chronic or intermittent psychotic disorders. Method: Ten patients with DSM-IV chronic or intermittent psychotic disorders (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 day 23. Key assessments were pharmacokinetic analysis of plasma quetiapine concentrations 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-normalized premorning- or postmorning-dose trough plasma values obtained under steady-state conditions after multiple-dose regimens. No unexpected side effects occurred with quetiapine therapy, and no statistically significant changes from baseline were observed for the UKU Side Effect Rating Scale items that were rated. No serious adverse events or clinically important changes in hematology or clinical chemistry variables were reported. The most common 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 Barnes Akathisia Scale scores. Quetiapine improved positive and negative symptoms, as shown by significant (p <.05) decreases from baseline to endpoint in the mean Brief Psychiatric Rating Scale total score, the Clinical Global impressions-Severity of Illness scale, and the Modified Scale for the Assessment of Negative Symptoms summary score. Conclusion: Quetiapine pharmacokinetics were dose proportional in adolescents and were similar to those previously reported for adults. Quetiapine was well tolerated and effective in the small number of adolescents studied.