Aripiprazole induced extrapyramidal symptoms in two adolescents

Introduction: The use of aripiprazole (APZ) has increased in the pediatric population. Its pharmacological profile differs from other antipsychotics being generally considered to have a good safety and tolerability profile with a lower risk of metabolic adverse events and a low to moderate risk for extrapyramidal symptoms. Objective: Two adolescents with severe APZ induced extrapyramidal symptoms are presented. Outcomes (i.a. assessed with the global assessment of functioning scale, GAF) and other data were documented within an online patient-registry (www.tdm-kjp.de). Case 1: A 17-year-old female with schizoaffective disorder (GAF-score 5) was treated with APZ (GAF-score 40) for four weeks. After five days at the maximum dosage of 15 mg daily she developed rest tremor, stiffness, and akinesia. The APZ serum concentration was 456 ng/ml (recommended range for adults 150 – 500 ng/ml). After a single administration of 4 mg long acting biperiden (anticholinergic) symptoms immediately decreased. Under a reduced APZ dose of 12,5 mg (corresponding serum concentration of 407 ng/ml) and 2 mg biperiden daily the girl was discharged free of extrapyramidal symptoms with significantly improved clinical presentation (GAF-score 70). Case 2: A 16-year-old boy with paranoid schizophrenia (GAF-score 26) was treated with APZ after he had developed extrapyramidal symptoms under 10 mg haloperidol. Under concomitant medication with biperiden 8 mg daily APZ was increased up to a maximum of 30 mg daily (serum concentration 327 ng/ml; GAF-score 32) for 24 days. After biperiden was tapered off the patient developed a massive attack of extrapyramidal symptoms with cogwheel phenomenon, blepharospasm, dystonia, tremor, and ataxic gait. Symptoms remitted by administration of 4 mg biperiden orally and additional intravenous injection of 6 mg biperiden. Finally the adolescent was discharged after 23 weeks with 200 mg clozapine per day (GAF-score 39). Discussion: Few cases of APZ induced extrapyramidal symptoms in minors have been published. In the two patients presented APZ was approved for diagnosis and age, however due to the severity of illness administered in higher than the recommended dose of 10 mg daily (maximum 30 mg). If the claimed advantage, that APZ has a lower potential for developing extrapyramidal symptoms really exists, this advantage may disappear with higher dosages.