ABSTRACT
BACKGROUND: Depression in patients with schizophrenia worsens the course of the disease by increasing the risk of suicide, by complicating the clinical picture of the disorder, and by reducing the quality of the social functioning; its treatment is difficult, since monotherapy, even when involving modern antipsychotics, does not always prove successful. While the prescription of additional antidepressants (ADs) can improve the likelihood of a better outcome, the effectiveness of such augmentation in many cases is yet to be proven. Therefore, it is still important that one weighs the effectiveness of various combinations between most of the known ADs and some second-generation antipsychotic (SGA) in the treatment of depression that occurs at different stages of schizophrenia. In previous studies, the use of vortioxetine as an adjunct to an antipsychotic yielded a reduction in negative symptoms, a clinically significant improvement in cognitive functions that differed from its antidepressant effect, and good tolerability, which affects how committed to treatment a patient remains. AIM: To study the changes that occur over time in the clinical manifestations of depression, negative and cognitive impairment, as well as the social adequacy of patients receiving a combination therapy with second-generation antipsychotics and vortioxetine, which were prescribed in real clinical practice at doses approved in the Russian Federation. METHODS: We performed a comparative analysis of the changes in depression symptoms and negative symptoms, cognitive impairment, as well as function of 78 patients with severe manifestations of depression at the stage of exacerbation reduction and subsequent remission of paranoid schizophrenia. Combination treatment with SGA and vortioxetine was used in 39 patients, and 39 patients who had similar clinical manifestations received just SGA. During the observation period, the mental disorder severity and depression symptom severity were assessed 3 times (before the start of treatment, after three months, and after six months) using the Clinical Global Impression (CGI) scale and Calgary Depression Scale for Schizophrenia (CDSS), respectively; patients were also assessed using the Negative Symptoms Assessment-5 (NSA-5) scale, Perceived Deficits Questionnaire-20 items (PDQ-20) scale, and Personal and Social Performance (PSP) scale. RESULTS: According to the ANOVA results, by the end of the observation period, patients, regardless of their therapeutic group, showed a statistically significant decrease in the level of depression on the CDSS scale, the severity of negative symptoms on the NSA-5 scale, cognitive symptoms on the PDQ-20 scale, as well as an improvement in personality and society, judging by the increase in the total PSP scores. There were also significant differences between the compared main (SGA + vortioxetine) and control (SGA) groups in terms of the changes in the total score on the CDSS and PSP scales. An interesting aspect of the changes in the clinical scores was a noticeable improvement in the SGA + vortioxetine group after 3 months of treatment, in the absence of a similar improvement in the control group, and the achievement of approximately the same scores in both groups after 6 months. In particular, there were significant differences between the SGA + vortioxetine and SGA groups in terms of the mean CDSS (p 0.001), NSA-5 (p=0.003), PDQ-20 (p 0.001), and PSP (p=0.004) scores after 3 months. Analysis of the time before early withdrawal from the study showed that significantly more patients in the SGA + vortioxetine group completed the study program (n=27, 69.23%) compared with the SGA group (n=13, 33.33%) (2 =14.618, df=1, p 0.001, log-rank test. The mean survival time in the SGA group was significantly (p 0.001) less and amounted to 101.436 days (95% CI: 81.518121.354), and in the SGA + vortioxetine group it amounted to 161.744 days (147.981175.506). The relative risk of full study completion in the vortioxetine + SGA group compared with that in SGA was 3.618 (1.8716.994). CONCLUSION: The addition of vortioxetine to the SGA therapy accelerates the reduction of the depression symptoms that occur at the stage of psychosis regression and early remission, contributes to the accelerated reduction in negative symptoms, positively affects the subjective assessment of cognitive impairment severity, and has a significant positive effect on the level of psychosocial functioning.
ABSTRACT
Background: Cariprazine is a new piperazine derivative atypical antipsychotic, like aripiprazole and brexpiprazole. It has been approved for treating schizophrenia in many countries and has recently been included on the List of Essential Medicines in Russia. Unlike most other atypical antipsychotics, it shows high in vivo occupancy of dopamine D2 and D3 receptors at clinically relevant doses. In animal models, cariprazine has demonstrated dopamine D3 receptor-dependent pro-cognitive and anti-anhedonic effects, suggesting its potential for treating negative symptoms. This review summarizes the efficacy of cariprazine in the treatment of negative symptoms of schizophrenia. Methods: A literature search of databases covering international and Russian journals, for articles published between 1st January 2010 and 1st June 2020. Results: Cariprazine demonstrated at least comparable efficacy in the treatment of schizophrenia symptoms to active comparators including risperidone, olanzapine or aripiprazole. The drug has a good safety profile. It appeared to be associated with a lower risk of metabolic syndromes and most extrapyramidal symptoms. The positive effect of cariprazine on the negative symptoms of schizophrenia may be associated with the elimination of secondary negative symptoms. However, of all the atypical antipsychotics to date, only cariprazine has a convincingly, methodologically robust proven advantage over risperidone in eliminating the predominant negative symptoms of schizophrenia. Yet only four studies have investigated the effect of cariprazine on the negative symptoms of schizophrenia. There is a lack of research into its direct impact on emotional-volitional disorders, anhedonia, cognitive symptoms and personality changes. However, there is evidence to suggest cariprazine is effective in treatment-resistant cases, but this requires further confirmation. Conclusion: Cariprazine is an effective and well-tolerated agent for the treatment of schizophrenia and may be effective in cases where other antipsychotics have failed. Cariprazine has been shown to have a positive effect on negative symptoms. Further studies are needed to collect more data on long-term treatment of schizophrenia and especially negative symptoms.
ABSTRACT
A method of optimisation of new extractants structure using the desirable function has been developed. Earlier the desirable function has been proposed by Harrington (Ind Qual Control 21: 494-498, 1965) for the optimisation of processes with several response functions. The developed method of optimisation of new extractants structure has been used for construction of phenolic type extractants (PTE) (a class of N-(2-hydroxy-5-nonylbenzil)-dialkylamines). It has been offered to use the charge on the nitrogen atom, the heat of dissociation of phenolic group, the logarithm of distribution factor of extractant between water and octanol (computed data) and maximum permissible concentration of extractants in aqueous phase (MPC) of the o-replaced phenols (the literary data) as the controllable parameters, defining efficiency of extractants for molecular design of PTE. During optimisation of extractants structure the quantity of alkyl substitutes at nitrogen atom, the carbon atoms number in these substitutes and the electronegative substitutes in o-position to phenolic group have been varied. As the result of the molecular design, the optimal structure of PTE found is N-(2,3-dihydroxy-5-nonylbenzil)-didecylamine, which perfectly meets the requirements to industrial extractants.
