Aripiprazole as an Adjunct to Clozapine Therapy in Adolescents with Early-onset Schizophrenia: A Retrospective Chart Review

Abstract

Introduction: Combination of antipsychotic substances is a therapeutic option increasingly applied in patients with schizophrenia, who do not respond to antipsychotic monotherapy. Recently, various reports on combination of clozapine with aripiprazole in adults have been published. As there is not yet data on adolescent patients, we aimed to study the above-mentioned augmentation strategy in this population.

Methods: We included 15 patients with schizophrenia from a child and adolescent psychiatric department (8 male; mean age 19.3 [SD±1.2, range 17.2–21.2] years). Patients had been under clozapine treatment, followed by aripiprazole augmentation. Retrospectively, patients’ medical records were reviewed, using a rating scale in analogy to the Clinical Global Impressions (CGI) scale.

Results: Mean observation time was 11.1 [SD±9.7] months. Mean CGI-Severity scores improved significantly (p=0.003, d=0.76) from 5.3 (baseline) to 4.5 (endpoint; last observation carried forward (LOCF)). CGI-Improvement scores decreased from 3.7 (after 1 month) to 3.3 (endpoint; LOCF) (p=0.212, d=0.45).

Conclusions: In adolescents with schizophrenia, aripiprazole augmentation of clozapine treatment might be an effective therapeutic strategy. Prospective studies for this age group are required to obtain more specific clinical data on clinical effectiveness.

References

• 1 Abu-Tair F, Kopitz J, Bergemann N. Clozapine augmented with aripiprazole in 5 patients with schizophrenia.  J Clin Psychopharmacol. 2006;  26 669-671
• 2 Anil Yağcioğlu AE, Kivircik Akdede BB, Turgut TI. et al . A double-blind controlled study of adjunctive treatment with risperidone in schizophrenic patients partially responsive to clozapine: efficacy and safety.  J Clin Psychiatry. 2005;  66 63-72
• 3 Assion HJ, Reinbold H, Lemanski S. et al . Amisulpride augmentation in patients with schizophrenia partially responsive or unresponsive to clozapine. A randomized, double-blind, placebo-controlled trial.  Pharmacopsychiatry. 2008;  41 24-28
• 4 Chang JS, Ahn YM, Park HJ. et al . Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial.  J Clin Psychiatry. 2008;  69 720-731
• 5 Davies MA, Sheffler DJ, Roth BL. Aripiprazole. A novel atypical antipsychotic drug with a uniquely robust pharmacology.  CNS Drug Rev. 2004;  10 317-336
• 6 Englisch S, Zink M. Combined antipsychotic treatment involving clozapine and aripiprazole.  Prog Neuropsychopharmacol Biol Psychiatry. 2008;  32 1386-1392
• 7 Freudenreich O, Henderson DC, Walsh JP. et al . Risperidone augmentation for schizophrenia partially responsive to clozapine: a double-blind, placebo-controlled trial.  Schizophr Res. 2007;  92 90-94
• 8 Genç Y, Taner E, Candansayar S. Comparison of clozapine-amisulpride and clozapine-quetiapine combinations for patients with schizophrenia who are partially responsive to clozapine: a single-blind randomized study.  Adv Ther. 2007;  24 1-13
• 9 Gibson AP, Lynn Crismon M, Mican LM. et al . Effectiveness and tolerability of aripiprazole in child and adolescent inpatients: a retrospective evaluation.  Int Clin Psychopharmacol. 2007;  22 101-105
• 10 Henderson DC, Kunkel L, Nguyen DD. et al . An exploratory open-label-trial of aripiprazole as an adjuvant to clozapine therapy in chronic schizophrenia.  Acta Psychiatr Scand. 2006;  113 142-147
• 11 Holm S. A simple sequentially rejective multiple test procedure.  Scand J Stat. 1979;  6 65-70
• 12 Honer WG, Thornton AE, Chen EY. et al . Clozapine alone versus clozapine and risperidone with refractory schizophrenia.  N Engl J Med. 2006;  354 472-482
• 13 Josiassen RC, Joseph A, Kohegyi E. et al . Clozapine augmented with risperidone in the treatment of schizophrenia: a randomized, double-blind, placebo-controlled trial.  Am J Psychiatry. 2005;  162 130-136
• 14 Karunakaran K, Tungaraza TE, Harborne GC. Is clozapine-aripiprazole combination a useful regime in the management of treatment-resistant schizophrenia?.  J Psychopharmacol. 2007;  21 453-456
• 15 Kreinin A, Novitski D, Weizman A. Amisulpride treatment of clozapine-induced hypersalivation in schizophrenia patients: a randomized, double-blind, placebo-controlled cross-over study.  Int Clin Psychopharmacol. 2006;  21 99-103
• 16 Mitsonis CI, Dimopoulos NP, Mitropoulos PA. et al . Aripiprazole augmentation in the management of residual symptoms in clozapine-treated outpatients with chronic schizophrenia: An open-label pilot study.  Prog Neuropsychopharmacol Biol Psychiatry. 2007;  31 373-377
• 17 Mouaffak F, Tranulis C, Gourevitch R. et al . Augmentation strategies of clozapine with antipsychotics in the treatment of ultraresistant schizophrenia.  Clin Neuropharmacol. 2006;  29 28-33
• 18 Paton C, Whittington C, Barnes TR. Augmentation with a second antipsychotic in patients with schizophrenia who partially respond to clozapine: a meta-analysis.  J Clin Psychopharmacol. 2007;  27 198-204
• 19 Reinstein MJ, Sonnenberg JG, Mohan SC. et al . Use of quetiapine to manage patients who experienced adverse effects with clozapine.  Clin Drug Investig. 2003;  23 63-67
• 20 Remschmidt H, Schulz E, Martin M. et al . Childhood-onset schizophrenia: history of the concept and recent studies.  Schizophr Bull. 1994;  20 727-745
• 21 Shapiro DA, Renock S, Arrington E. et al . Aripiprazole: A novel atypical antipsychotic drug with a unique and robust pharmacology.  Neuropsychopharmacol. 2003;  28 1400-1411
• 22 Shiloh R, Zemishlany Z, Aizenberg D. et al . Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo-controlled study.  Br J Psychiatry. 1997;  171 569-573
• 23 Winans E. Aripiprazole.  Am J Health Pharm. 2003;  60 2437-2445
• 24 Yoo HK, Choi SH, Park S. et al . An open-label study of the efficacy and tolerability of aripiprazole for children and adolescents with tic disorders.  J Clin Psychiatry. 2007;  68 1088-1093
• 25 Ziegenbein M, Wittmann G, Kropp S. Aripiprazole augmentation of clozapine in treatment-resistant schizophrenia: a clinical observation.  Clin Drug Investig. 2006;  26 117-124
• 26 Zink M, Dressing H. Augmentation of clozapine with atypical antipsychotic substances.  Curr Psych Rev. 2005;  1 165-172
• 27 Zink M, Kuwilsky A, Krumm B. et al . Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomised controlled clinical trial.  J Psycho-pharmacol. 2008;  , [Epub ahead of print]

Correspondence