Long-Term Assessment of Asenapine vs. Olanzapine in Patients with Schizophrenia or Schizoaffective Disorder

Abstract

Introduction: We conducted a double-blind 1-year trial of asenapine in patients with schizophrenia or schizoaffective disorder.

Methods: Patients were randomized to asenapine (5 or 10 mg BID; n=913) or olanzapine (10−20 mg QD; n=312), and monitored regularly.

Results: Trial completion rates were 38% with asenapine, 57% with olanzapine; main reasons for discontinuation were withdrawal of consent (22%, 16%) and insufficient response (25%, 14%); fewer discontinuations were due to adverse events (6%, 7%). Mean weight gain was 0.9 kg with asenapine, 4.2 kg with olanzapine. Extrapyramidal symptoms reported as adverse events were more common with asenapine. Mean reductions in PANSS total score with asenapine and olanzapine were −21.0 and −27.5 (P<0.0001); the exclusion of patients who had previous poor experience with olanzapine may have biased the results in favor of olanzapine. Scores on the subjective well-being on neuroleptics scale and functionality measures were similar between groups.

Conclusion: Asenapine was well tolerated over 1 year of treatment, causing less weight gain than olanzapine but more frequent extrapyramidal symptoms. PANSS total score improved with both agents; the improvement was greater with olanzapine than with asenapine using last observations carried forward but not in an observed-case analysis.

References

• 1 American Psychiatric Association .Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision.. Washington, DC: American Psychiatric Association; 2000
• 2 Barnes TR. A rating scale for drug-induced akathisia.  Br J Psychiatry. 1989;  154 672-676
• 3 Conley RR, Kelly DL. Second-generation antipsychotics for schizophrenia: a review of clinical pharmacology and medication-associated side effects.  Isr J Psychiatry Relat Sci. 2005;  42 51-60
• 4 de Haan L, Nimwegen L, Amelsvoort T. et al . Improvement of subjective well-being and enduring symptomatic remission, a 5-year follow-up of first episode schizophrenia.  Pharmacopsychiatry. 2008;  41 125-128
• 5 de Haan L, van Amelsvoort T, Dingemans P. et al . Risk factors for medication non-adherence in patients with first episode schizophrenia and related disorders; a prospective five year follow-up.  Pharmacopsychiatry. 2007;  40 264-268
• 6 Guy W. Abnormal Involuntary Movement Scale.. In Guy W editor ECDEU Assessment Manual for Psychopharmacology. Washington, DC: U.S. Department of Health, Education, and Welfare; 1976: 534-537
• 7 Guy W. Clinical Global Impressions.. In Guy W editor ECDEU Assessment Manual for Psychopharmacology. Washington, DC: U.S. Department of Health, Education, and Welfare; 1976: 217-222
• 8 Haddad PM, Sharma SG. Adverse effects of atypical antipsychotics: differential risk and clinical implications.  CNS Drugs. 2007;  21 911-936
• 9 Kane J, Zhao J, Cohen M. et al .Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia.. J Clin Psychopharmacol. 2010. in press;
• 10 Karow A, Czekalla J, Dittmann RW. et al . Association of subjective well-being, symptoms, and side effects with compliance after 12 months of treatment in schizophrenia.  J Clin Psychiatry. 2007;  68 75-80
• 11 Kay SR. Positive-negative symptom assessment in schizophrenia: psychometric issues and scale comparison.  Psychiatr Q. 1990;  61 163-178
• 12 Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia.  Schizophr Bull. 1987;  13 261-276
• 13 Kurtz MM. Neurocognitive impairment across the lifespan in schizophrenia: an update.  Schizophr Res. 2005;  74 15-26
• 14 Lambert M, Schimmelmann BG, Naber D. et al . Prediction of remission as a combination of symptomatic and functional remission and adequate subjective well-being in 2960 patients with schizophrenia.  J Clin Psychiatry. 2006;  67 1690-1697
• 15 Lieberman JA, Stroup TS, McEvoy JP. et al . for the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia.  N Engl J Med. 2005;  353 1209-1223
• 16 Martin JL, Perez V, Sacristan M. et al . Meta-analysis of drop-out rates in randomised clinical trials, comparing typical and atypical antipsychotics in the treatment of schizophrenia.  Eur Psychiatry. 2006;  21 11-20
• 17 Moller HJ. Occurrence and treatment of depressive comorbidity/cosyndromality in schizophrenic psychoses: conceptual and treatment issues.  World J Biol Psychiatry. 2005;  6 247-263
• 18 Motlova L, Spaniel F, Hoschl C. et al . Are there any differences in the efficacy among second generation antipsychotics in the treatment of schizophrenia and related disorders?.  Ann Clin Psychiatry. 2007;  19 133-143
• 19 Naber D, Moritz S, Lambert M. et al . Improvement of schizophrenic patients subjective well-being under atypical antipsychotic drugs.  Schizophr Res. 2001;  50 79-88
• 20 Naber D, Riedel M, Klimke A. et al . Randomized double blind comparison of olanzapine vs. clozapine on subjective well-being and clinical outcome in patients with schizophrenia.  Acta Psychiatr Scand. 2005;  111 106-115
• 21 Potkin SG, Cohen M, Panagides J. Efficacy and tolerability of asenapine in acute schizophrenia: a placebo- and risperidone-controlled trial.  J Clin Psychiatry. 2007;  68 1492-1500
• 22 Shahid M, Walker GB, Zorn SH. et al . Asenapine: a novel psychopharmacologic agent with a unique human receptor signature.  J Psychopharmacol. 2009;  23 65-73
• 23 Simon V, van Winkel R, De Hert M. Are weight gain and metabolic side effects of atypical antipsychotics dose dependent? A literature review.  J Clin Psychiatry. 2009;  70 1041-1050
• 24 Simpson GM, Angus JW. A rating scale for extrapyramidal side effects.  Acta Psychiatr Scand Suppl. 1970;  212 11-19
• 25 Tandon R, Fleischhacker WW. Comparative efficacy of antipsychotics in the treatment of schizophrenia: a critical assessment.  Schizophr Res. 2005;  79 145-155
• 26 Tenback DE, van Harten PN, Slooff CJ. et al. . the SOHO Study Group Effects of antipsychotic treatment on tardive dyskinesia: a 6-month evaluation of patients from the European Schizophrenia Outpatient Health Outcomes (SOHO) study.  J Clin Psychiatry. 2005;  66 1130-1133
• 27 van Nimwegen LJ, de Haan L, van Beveren NJ. et al . Effect of olanzapine and risperidone on subjective well-being and craving for cannabis in patients with schizophrenia or related disorders: a double-blind randomized controlled trial.  Can J Psychiatry. 2008;  53 400-405
• 28 Ware Jr JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection.  Med Care. 1992;  30 473-483

Notice:

This article was changed according to the following erratum on November 9^th 2011.

Erratum:

J. Schoemaker, D. Naber, P. Vrijland, J. Panagides, R. Emsley

Long-Term Assessment of Asenapine vs. Olanzapine in Patients with Schizophrenia or Schizoaffective Disorder Pharmacopsychiatry 2010; 43: 138–146

On p. 141, there are errors that incorrectly identify the figures which present weight gain data. The text “At week 52, using observed case data, mean ± SD change was l.6 ± 5.7 kg (3.5 ± 12.6 Ibs) for asenapine and 5.6 ± 8.4 kg (12.3 ± 18.5 lbs) for olanzapine (Fig. 3a). At endpoint, using LOCF data from all treated patients, mean ± SD changes were 0.9 ± 4.8kg (2.0 ± 10.6 Ibs) and 4.2 ± 7.6 kg (9.2 ± 16.8 Ibs), respectively (Fig. 3b).” should be “At endpoint, using LOCF data from all treated patients, mean ± SD changes were 0.9 ± 4.8 kg (2.0 ± 10.6 Ibs) and 4.2 ± 7.6 kg (9.2 ± 16.8 Ibs), respectively (Fig. 3a). At week 52, using observed case data, mean ± SD change was l.6 ± 5.7 kg (3.5 ± 12.6 Ibs) for asenapine and 5.6 ± 8.4 kg (12.3 ± 18.5 lbs) for olanzapine (Fig. 3b).”

On p. 144, the text in the legend for figure 3 noting “Weight change over time in the safety population. A. OC analysis. B. Last observations carried forward (LOCF) analysis.” should be “Weight change over time in the safety population. A. Last observations carried forward (LOCF) analysis. B. OC analysis.”

Correspondence