Comparing Schizophrenia Patients With a Predicted High/Low
                    Risk of Nonresponse Receiving Treatment with Ziprasidone and Haloperidol: A
                    Randomized-Controlled Study

Rebecca Schennach; Michael Riedel; Ilja Spellmann; Richard Musil; Michael Obermeier; Markus Jäger; Roland Bottlender; Max Schmauss; Gerd Laux; Hans-Jürgen Möller

doi:10.1055/a-0669-9461

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2019; 52(04): 180-185
DOI: 10.1055/a-0669-9461

Original Paper

Comparing Schizophrenia Patients With a Predicted High/Low Risk of Nonresponse Receiving Treatment with Ziprasidone and Haloperidol: A Randomized-Controlled Study

Rebecca Schennach

¹Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany

⁵Schoen Clinic Roseneck, Prien am Chiemsee, Germany

,

Michael Riedel

¹Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany

⁶Psychiatric Clinic Rodewisch, Rodewisch, Germany

,

Ilja Spellmann

¹Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany

⁷Psychiatric Clinic, Stuttgart, Germany

,

Richard Musil

¹Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany

,

Michael Obermeier

¹Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany

,

Markus Jäger

¹Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany

⁸Psychiatric Clinic, District Hospital Kempten, Kempten, Germany

,

Roland Bottlender

²Psychiatric Clinic, District Hospital Lüdenscheid, Lüdenscheid, Germany

,

Max Schmauss

³Psychiatric Clinic, District Hospital Augsburg, Augsburg, Germany

,

Gerd Laux

⁴Psychiatric Clinic, Inn-Salzach Hospital Wasserburg/Inn, Wasserburg, Germany

,

Hans-Jürgen Möller

¹Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany

› Author Affiliations

Abstract

Introduction The aim of this double-blind randomized study was to evaluate the response to antipsychotic treatment in schizophrenia patients with predicted high/low risk of nonresponse identified by applying a set of well-established scales and predictors of outcome and to compare efficacy between ziprasidone and haloperidol.

Methods One hundred twelve schizophrenia patients (ziprasidone: n=54; haloperidol: n=58) were rated weekly on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Global Assessment of Functioning Scale (GAF), the Social and Occupational Functioning Scale (SOFAS), the Simpson-Angus Scale (SAS), and Hillside Akathisia Scale (HAS).

Results Ninety-two patients (82%) were predicted to have a high risk of nonresponse. No significant difference regarding PANSS improvement in this subsample was found comparing ziprasidone and haloperidol (p=0.563). Also, for the total patient sample, no significant difference was found regarding the course of the PANSS total score, GAF (p=0.921), and SOFAS (p=0.658) between ziprasidone and haloperidol. Haloperidol resulted in higher scores on the SAS (p=0.001) and HAS (p=0.011).

Discussion An alarmingly high number of patients were at high risk of nonresponse to antipsychotic treatment.

Key words

high risk of nonresponse - ziprasidone - haloperidol - schizophrenia - outcome

Full Text

References

References
1 Giegling I, Porcelli S, Balzarro B. et al. Antipsychotic response in the first week predicts later efficacy. Neuropsychobiology 2012; 66: 100-105
2 Kinon BJ, Chen L, Ascher-Svanum H. et al. Early response to antipsychotic drug therapy as a clinical marker of subsequent response in the treatment of schizophrenia. Neuropsychopharmacology 2010; 35: 581-590
3 Moller HJ. The relevance of negative symptoms in schizophrenia and how to treat them with psychopharmaceuticals?. Psychiatr Danub 2016; 28: 435-440
4 Schennach-Wolff R, Meyer S, Seemuller F. et al. Influencing factors and predictors of early improvement in the acute treatment of schizophrenia and schizophrenia spectrum disorder. J Psychiatr Res 2011; 45: 1639-1647
5 Leucht S, Cipriani A, Spineli L. et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: A multiple-treatments meta-analysis. Lancet 2013; 382: 951-962
6 Jennings CA, Southam E, Cluderay JE et al. Comparison of the effects of ziprasidone and haloperidol on regional fos expression in rat forebrain. International Congress on Schizophrenia Research 2003
7 Rollema H, Lu Y, Schmidt AW. et al. 5-HT(1A) receptor activation contributes to ziprasidone-induced dopamine release in the rat prefrontal cortex. Biol Psychiatry 2000; 48: 229-237
8 Harvey PD, Pappadopulos E, Lombardo I. et al. Reduction of functional disability with atypical antipsychotic treatment: A randomized long term comparison of ziprasidone and haloperidol. Schizophr Res 2009; 115: 24-29
9 Harvey PD, Meltzer H, Simpson GM. et al. Improvement in cognitive function following a switch to ziprasidone from conventional antipsychotics, olanzapine, or risperidone in outpatients with schizophrenia. Schizophr Res 2004; 66: 101-113
10 Grunder G, Heinze M, Cordes J. et al. Effects of first-generation antipsychotics versus second-generation antipsychotics on quality of life in schizophrenia: A double-blind, randomised study. Lancet Psychiatry 2016; 3: 717-729
11 Jager M, Riedel M, Schmauss M. et al. Prediction of symptom remission in schizophrenia during inpatient treatment. World J Biol Psychiatry 2007; 10: 1-9
12 Kokes RF, Strauss JS, Klorman R. Premorbid adjustment in schizophrenia. Part II. Measuring premorbid adjustment: The instruments and their development. Schizophr Bull 1977; 3: 186-213
13 Kay SR, Opler LA, Lindenmayer JP. Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatry Res 1988; 23: 99-110
14 Phillips L. Case history data and prognosis in schizophrenia. J Nerv Ment Dis 1953; 117: 515-525
15 American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. Fourth edition. Washington, DC: American Psychiatric Association; 1994
16 Guy W. Clinical Global Impressions. ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: National Institute of Mental Health; 1976
17 Cording C. [Conceptual aspects in development and implementation of basic psychiatric documentation]. Psychiatr Prax 1998; 25: 175-178
18 Simpson GM, Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 1970; 212: 11-19
19 Fleischhacker WW, Bergmann KJ, Perovich R. et al. The Hillside Akathisia Scale: A new rating instrument for neuroleptic-induced akathisia. Psychopharmacol Bull 1989; 25: 222-226
20 Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13: 261-276
21 Wallwork RS, Fortgang R, Hashimoto R. et al. Searching for a consensus five-factor model of the Positive and Negative Syndrome Scale for schizophrenia. Schizophr Res 2012; 137: 246-250
22 Oosthuizen P, Emsley RA, Roberts MC. et al. Depressive symptoms at baseline predict fewer negative symptoms at follow-up in patients with first-episode schizophrenia. Schizophr Res 2002; 58: 247-252
23 Leucht S, Davis JM, Engel RR. et al. Definitions of response and remission in schizophrenia: Recommendations for their use and their presentation. Acta Psychiatr Scand Suppl 2009; 438: 7-14
24 Obermeier M, Mayr A, Schennach-Wolff R. et al. Should the PANSS be rescaled?. Schizophr Bull 2009; 36: 455-460
25 R Development Core Team . A language and environment for statistical computing. Vienna, Austria: Foundation for Statistical Computing; 2008
26 Leucht S, Engel RR, Bauml J. et al. Is the superior efficacy of new generation antipsychotics an artifact of LOCF?. Schizophr Bull 2007; 33: 183-191
27 Carbon M, Correll CU. Clinical predictors of therapeutic response to antipsychotics in schizophrenia. Dialogues Clin Neurosci 2014; 16: 505-524
28 Case M, Stauffer VL, Ascher-Svanum H. et al. The heterogeneity of antipsychotic response in the treatment of schizophrenia. Psychol Med 2011; 41: 1291-1300
29 Ascher-Svanum H, Nyhuis AW, Faries DE. et al. Clinical, functional, and economic ramifications of early nonresponse to antipsychotics in the naturalistic treatment of schizophrenia. Schizophr Bull 2008; 34: 1163-1171
30 Kinon BJ, Chen L, Ascher-Svanum H. et al. Predicting response to atypical antipsychotics based on early response in the treatment of schizophrenia. Schizophr Res 2008; 102: 230-240
31 Essock SM, Hargreaves WA, Dohm FA. et al. Clozapine eligibility among state hospital patients. Schizophr Bull 1996; 22: 15-25
32 Uher R, Muthen B, Souery D. et al. Trajectories of change in depression severity during treatment with antidepressants. Psychol Med 2010; 40: 1367-1377
33 Leucht S, Davis JM, Engel RR. et al. Defining ‘response’ in antipsychotic drug trials: Recommendations for the use of scale-derived cutoffs. Neuropsychopharmacology 2007; 32: 1903-1910
34 Schennach R, Meyer S, Seemuller F. et al. Response trajectories in “real-world” naturalistically treated schizophrenia patients. Schizophr Res 2012; 139: 218-224
35 Ovenden ES, McGregor NW, Emsley RA. et al. DNA methylation and antipsychotic treatment mechanisms in schizophrenia: Progress and future directions. Prog Neuropsychopharmacol Biol Psychiatry 2018; 81: 38-49
36 Nielsen RE, Levander S, Kjaersdam TG. et al. Second-generation antipsychotic effect on cognition in patients with schizophrenia – a meta-analysis of randomized clinical trials. Acta Psychiatr Scand 2015; 131: 185-196
37 Jung WY, Kim SG, Lee JS. et al. Open prospective study of ziprasidone in patients with schizophrenia with depressive symptoms: A multicenter study. Psychiatry Clin Neurosci 2015; 69: 43-48
38 Hasan A, Falkai P, Wobrock T. et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, part 1: Update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry 2012; 13: 318-378
39 Moller HJ, Riedel M, Jager M. et al. Short-term treatment with risperidone or haloperidol in first-episode schizophrenia: 8-week results of a randomized controlled trial within the German Research Network on Schizophrenia. Int J Neuropsychopharmacol 2008; 11: 985-997
40 Murray R, Correll CU, Reynolds GP. et al. Atypical antipsychotics: Recent research findings and applications to clinical practice: Proceedings of a symposium presented at the 29th Annual European College of Neuropsychopharmacology Congress, 19 September 2016, Vienna, Austria. Ther Adv Psychopharmacol 2017; 7: 1-14