Marc Krause1,2, Yikang Zhu1,3, Maximilian Huhn1, Johannes Schneider-Thoma1, Irene Bighelli1, Adriani Nikolakopoulou4, Stefan Leucht5. 1. Department of Psychiatry and Psychotherapy, Technical University of Munich, Klinikum rechts der Isar, Ismaningerstraße 22, 81675, Munich, Germany. 2. Ludwig-Maximilians-Universität München, Munich, Germany. 3. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong, University School of Medicine, South Wan Ping Road 600, Shanghai, 200030, China. 4. Institute of Social and Preventive Medicine (ISPM), Bern University, Bern, Switzerland. 5. Department of Psychiatry and Psychotherapy, Technical University of Munich, Klinikum rechts der Isar, Ismaningerstraße 22, 81675, Munich, Germany. stefan.leucht@tum.de.
Abstract
BACKGROUND: Negative symptoms are the core of schizophrenia, but whether antipsychotics are efficacious for their treatment is unclear. Moreover, there is debate whether patients in relevant trials should have predominant negative symptoms or whether prominent negative symptoms are also acceptable. METHODS: We systematically reviewed randomised, blinded antipsychotic drug trials in patients with schizophrenia and either predominant or prominent negative symptoms (last search Dec 12, 2017). Separate pairwise meta-analyses were conducted in these two populations. The primary outcome was negative symptoms. Depressive, symptoms, positive symptoms, and extrapyramidal side-effects were analysed as causes of secondary negative symptoms. FINDINGS: We included 21 randomized-controlled trials with 3451 participants which revealed the following significant differences in the primary outcome: in patients with predominant negative symptoms amisulpride was superior to placebo (N = 4; n = 590, SMD 0.47, CI 0.23, 0.71), olanzapine was superior to haloperidol in a small trial (n = 35) and cariprazine outperformed risperidone (N = 1, n = 456, SMD - 0.29, CI - 0.48, - 0.11). In patients with prominent negative symptoms, olanzapine and quetiapine were superior to risperidone in single trials. Overall, studies in prominent negative symptoms were potentially more confounded by improvements of secondary negative symptoms. INTERPRETATION: Amisulpride is the only antipsychotic that outperformed placebo in the treatment of predominant negative symptoms, but there was a parallel reduction of depression. Cariprazine was better than risperidone in a large trial that was well-controlled for secondary negative symptoms, but the trial was sponsored by its manufacturer. Future trials should apply scientifically developed definitions such as the deficit syndrome and the persistent negative symptoms concept.
BACKGROUND: Negative symptoms are the core of schizophrenia, but whether antipsychotics are efficacious for their treatment is unclear. Moreover, there is debate whether patients in relevant trials should have predominant negative symptoms or whether prominent negative symptoms are also acceptable. METHODS: We systematically reviewed randomised, blinded antipsychotic drug trials in patients with schizophrenia and either predominant or prominent negative symptoms (last search Dec 12, 2017). Separate pairwise meta-analyses were conducted in these two populations. The primary outcome was negative symptoms. Depressive, symptoms, positive symptoms, and extrapyramidal side-effects were analysed as causes of secondary negative symptoms. FINDINGS: We included 21 randomized-controlled trials with 3451 participants which revealed the following significant differences in the primary outcome: in patients with predominant negative symptoms amisulpride was superior to placebo (N = 4; n = 590, SMD 0.47, CI 0.23, 0.71), olanzapine was superior to haloperidol in a small trial (n = 35) and cariprazine outperformed risperidone (N = 1, n = 456, SMD - 0.29, CI - 0.48, - 0.11). In patients with prominent negative symptoms, olanzapine and quetiapine were superior to risperidone in single trials. Overall, studies in prominent negative symptoms were potentially more confounded by improvements of secondary negative symptoms. INTERPRETATION:Amisulpride is the only antipsychotic that outperformed placebo in the treatment of predominant negative symptoms, but there was a parallel reduction of depression. Cariprazine was better than risperidone in a large trial that was well-controlled for secondary negative symptoms, but the trial was sponsored by its manufacturer. Future trials should apply scientifically developed definitions such as the deficit syndrome and the persistent negative symptoms concept.
Authors: C Barnas; C H Stuppäck; C Miller; C Haring; B Sperner-Unterweger; W W Fleischhacker Journal: Int Clin Psychopharmacol Date: 1992 Impact factor: 1.659
Authors: Mario Maj; Jim van Os; Marc De Hert; Wolfgang Gaebel; Silvana Galderisi; Michael F Green; Sinan Guloksuz; Philip D Harvey; Peter B Jones; Dolores Malaspina; Patrick McGorry; Jouko Miettunen; Robin M Murray; Keith H Nuechterlein; Victor Peralta; Graham Thornicroft; Ruud van Winkel; Joseph Ventura Journal: World Psychiatry Date: 2021-02 Impact factor: 49.548