Long-Term Safety of Paliperidone Extended Release in Adolescents with Schizophrenia: An Open-Label, Flexible Dose Study

J Child Adolesc Psychopharmacol. 2015 Sep;25(7):548-57. doi: 10.1089/cap.2014.0130. Epub 2015 Jul 28.

Abstract

Objective: The purpose of this study was to evaluate the long-term safety and tolerability of paliperidone extended-release (ER) in adolescents with schizophrenia.

Methods: This was a 2 year open-label, multicenter study in adolescents (12-17 years of age, inclusive) with schizophrenia. Eligible patients were initially treated with 6 mg/day paliperidone ER, and the dose could be adjusted between 1.5 and 12 mg/day based on clinical need. Safety parameters were treatment-emergent adverse events (TEAEs), weight, Tanner staging, blood chemistry (including prolactin, glucose, insulin, and lipid levels), and extrapyramidal symptom (EPS) scales. The main efficacy end-point was change from baseline to endpoint in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) total score.

Results: Of 400 enrolled patients (mean age, 15.4 years; boys, 61%), 220 were completers. Median (range) exposure was 604.5 (2-765) days. TEAEs were reported in 85.3% of patients; most frequently reported TEAEs included somnolence, increased weight, headache, insomnia, nasopharyngitis, akathisia, schizophrenia exacerbation, and tremor. No deaths were reported. There were no clinically significant mean changes in growth-adjusted z score for change in weight, height, or body mass index (BMI). Tanner ratings showed normal maturation. Most frequently occurring EPS-related events were related to Parkinsonism (15.5%) and hyperkinesia (13.8%). No cases of tardive dyskinesia were reported. Hyperprolactinemia (based on laboratory values) was noted in 56% of patients and 9.3% of patients had prolactin-related TEAEs. A low percentage of patients (4.3%, n=14) had a shift from normal or impaired fasting glucose to high levels. Mean (SD) decrease (improvement) in PANSS total score from baseline to end-point was -19.1 (21.89). The majority of patients had a ≥20% improvement in PANSS total score (responders) from initial treatment with paliperidone ER. Overall, 41.7% of patients achieved remission during the study.

Conclusions: Paliperidone ER was generally tolerable, and exhibited efficacy in the maintenance treatment of schizophrenia in adolescents in this large 2 year study.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Child
  • Delayed-Action Preparations / adverse effects
  • Female
  • Humans
  • Male
  • Paliperidone Palmitate / administration & dosage
  • Paliperidone Palmitate / adverse effects
  • Paliperidone Palmitate / therapeutic use*
  • Psychiatric Status Rating Scales
  • Schizophrenia / drug therapy*

Substances

  • Antipsychotic Agents
  • Delayed-Action Preparations
  • Paliperidone Palmitate