BackgroundBecause of limited efficacy of antipsychotics against negative symptoms in schizophrenia new drugs with wider spectrums of clinical efficacy are very desirable. The newer 3rd generation antipsychotic cariprazine presents the unique mode of action acting as partial agonist predominantly for dopamine D3- and in lesser extent D2-receptors. Cariprazine is found to be effective in the treatment of negative symptoms in schizophrenia comparing to second generation antipsychotic risperidone.ObjectivesTo evaluate initial effects of cariprazine in schizophrenia patients with predominantly negative symptoms.Design and PatientsOpen-label, non-controlled study included 60 adult schizophrenia patients (F20 on ICD-10, 49% males) with predominantly negative symptoms (Positive and Negative Syndrome Scale, S factor score for negative and positive symptoms, PANSS-FSNS ≥ 15 and PANSS-FSPS <19) treated with cariprazine (starting daily dose 1.5 mg followed by upward titration by 1.5 mg weekly up to 6 mg if needed) were assessed with PANSS, CAINS (The Clinical Assessment Interview for Negative Symptoms), CDSS (Calgary Depression Scale for Schizophrenia), and SAS (Simpson-Angus Scale for Extrapyramidal Symptoms) scales at baseline and on week 1, 2, and 4.ResultsMost patients (75%) improved during 28 days of cariprazine treatment. At the end of assessment (day 28) mean starting total scores for negative symptoms on PANSS-NS and CAINS scales significantly (p < 0.05) reduced by 4.3 and 4.9, respectively, with no significant changes in depression symptoms (CDSS). Cariprazine tolerability was very good, only four patients discontinued because of TEAEs (akathisia, insomnia).ConclusionsThe results of this study suggest early effect of cariprazine on negative symptoms at least in some schizophrenia patients with predominantly negative symptoms starting from 1 to 2 weeks of treatment and could be useful for determination of early clinical predictors for efficacy. Considering limitations of open-label design with no control groups these data need to be confirmed.

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There was clinical heterogeneity of the «verschroben» type defect: the differentiation of primary defect syndrome and the «second life» defect was confirmed. This typological classification is based not only on the differences in psychopathological symptoms and impaired social functioning but on the trajectory of the development of deficit syndromes related with the features of the course of endogenous disease. The typology would be useful for future studies of deficit changes in view of clinical prognosis, social context of schizophrenia spectrum disorders with negative «verschroben» type changes.

The chapter focuses on the relationship of negative and positive symptoms in schizophrenia. Negative symptoms should be evaluated in a relation to positive symptoms both cross-sectionally and long term (prospectively/retrospectively). Two types of long-term interaction between negative and positive symptoms could be distinguished: (1) relatively synchronized, and (2) relatively desynchronized. Synchronization of negative and positive symptoms is characterized by their unidirectional long-term course. Desynchronization is characterized by their bidirectional long-term relations: (1) negative schizophrenia with minimal positive symptoms at the beginning of the disease and further progression of negative symptoms; or (2) schizophrenia with negative symptoms ‘that stopped at the very beginning’, and the later course is characterized by positive symptoms. Considering every single time point of the long-term relationship between negative and positive symptoms (cross-sectionally), the chapter describes the concept of ‘mutual/common syndromes’ (consisting of both positive and negative symptoms) at different stages of schizophrenia, including residual deficit states.