Disparate effects of first and second generation antipsychotics on cognition in schizophrenia - Findings from the randomized NeSSy trial

Tanja Veselinović; Martin Scharpenberg; Martin Heinze; Joachim Cordes; Bernd Mühlbauer; Georg Juckel; Ute Habel; Eckart Rüther; Jürgen Timm; Gerhard Gründer; NeSSy Study Group

doi:10.1016/j.euroneuro.2019.03.014

Disparate effects of first and second generation antipsychotics on cognition in schizophrenia - Findings from the randomized NeSSy trial

Eur Neuropsychopharmacol. 2019 Jun;29(6):720-739. doi: 10.1016/j.euroneuro.2019.03.014. Epub 2019 Apr 10.

Authors

Collaborators

NeSSy Study Group:
Stefan Bleich¹⁰, Markus Borgmann¹¹, Vasiliki Breunig-Lyriti¹², Constanze Schulz¹², Martin Brüne⁶, Peter Falkai⁸, Sandra Feyerabend¹³, Christian Figge¹⁴, Helge Frieling¹⁰, Wolfgang Gaebel¹³, Jürgen Gallinat¹⁵, Dmitri Handschuh¹², Jörg Heller⁶, Rainer Kirchhefer¹⁶, André Kirner¹⁷, Barbara Kowalenko¹⁸, Marion Lautenschlager¹⁵, Claus Wolff-Menzler⁸, Dieter Naber¹⁹, Katharina Prumbs¹⁸, Thomas Wobrock¹⁷

Affiliations

¹ Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany. Electronic address: tveselinovic@ukaachen.de.
² Competence Center for Clinical Trials - Biometry, University of Bremen, Bremen, Germany.
³ Department of Psychiatry and Psychotherapy, Brandenburg Medical School, Immanuel Klinik, Rüdersdorf, Germany.
⁴ Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
⁵ Competence Center for Clinical Trials - Biometry, University of Bremen, Bremen, Germany; Department of Pharmacology, Klinikum Bremen Mitte, Bremen, Germany.
⁶ Department of Psychiatry, LWL University Hospital, Ruhr University Bochum, Bochum, Germany.
⁷ Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany.
⁸ Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.
⁹ Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
¹⁰ Department of Psychiatry, Social Psychiatry and Psychotherapy, Medical School of Hannover, Hannover, Germany.
¹¹ Department of Psychiatry, Psychotherapy and Psychosomatics, Brandenburg Medical School, Neuruppin, Germany.
¹² Centre of Competence for Clinical Trials - Biometry, University of Bremen, Bremen, Germany.
¹³ Department of Psychiatry and Psychotherapy, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
¹⁴ Karl-Jaspers Clinic, European Medical School Oldenburg-Groningen, Oldenburg, Germany.
¹⁵ Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹⁶ Department of Psychiatry and Psychotherapy, Dietrich Bonhoeffer Klinikum, Neubrandenburg, Germany.
¹⁷ Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany.
¹⁸ Städtisches Krankenhaus Eisenhüttenstadt, Eisenhüttenstadt, Germany.
¹⁹ Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

PMID: 30981585
DOI: 10.1016/j.euroneuro.2019.03.014

Abstract

Cognitive impairment represents a core feature of schizophrenia. Uncertainty about demonstrable benefits of available antipsychotics on cognition remains an important clinical question relevant to patients' quality of life. The aim of our multi-center, randomized, double-blind "Neuroleptic Strategy Study" (NeSSy) was to compare the effectiveness of selected antipsychotics, conventionally classified as second- (SGAs) (haloperidol, flupentixol) and first generation antipsychotics (FGAs) (aripiprazole, olanzapine, quetiapine), on quality of life in schizophrenia. The effects on cognitive deficits represented a secondary outcome. We used an innovative double randomization for assignment of treatment group, and followed the patients with a neurocognitive test-battery upon six and 24 weeks of treatment. Psychopathology and quality of life were assessed using CGI, PANSS and SF-36. Assessment of cognitive performance was conducted in 114 of the 136 randomized patients. The SGA group (N = 62) showed beneficial effects of small to moderate effect size on cognition during the initial six weeks of treatment (executive functions, verbal fluency) and at 24 weeks (executive functions, working memory). In contrast, the FGA group (N = 52) showed moderately improved executive function, but a decline in verbal fluency at six weeks, with significant declines of moderate to large effect size in executive function, verbal learning and memory, and verbal fluency at 24 weeks. Our study indicates that SGAs present an advantage over FGAs regarding cognitive function during a medium-term treatment for schizophrenia. The results further emphasize a distinction between progression to detrimental effects of FGAs with prolonged treatment in contrast to more persistent cognitive benefits with SGA treatment.

Trial registration: ClinicalTrials.gov NCT01164059.

Keywords: Antipsychotic; Cognitive impairments; Schizophrenia.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Antipsychotic Agents / therapeutic use*
Cognition / drug effects*
Double-Blind Method
Executive Function
Female
Humans
Male
Memory, Short-Term
Middle Aged
Neuropsychological Tests
Psychomotor Performance
Quality of Life
Schizophrenia / drug therapy*
Schizophrenic Psychology*
Verbal Learning
Young Adult

Substances

Antipsychotic Agents

Associated data

ClinicalTrials.gov/NCT01164059