PANSS Total Score Research Articles

Detection of Cognitive Subtypes of Schizophrenia (with Assessment of Perceptual Disorders). A Pilot Study

Background: the heterogeneity of schizophrenia impedes our efforts to provide adequate treatment. One step toward optimizing treatment is to deepen our understanding of cognitive variety in this disorder. Perhaps due to this heterogeneity, although visual impairment is a frequent symptom of schizophrenia, many studies show inconsistent data. The aim of our study was to identify homogeneous groups of patients with schizophrenia based on susceptibility to the Ponzo illusion, cognitive impairment degree (BACS T-score) and severity of mental state during therapy (Total PANSS score) and to examine the relationship between clinical parameters and the value of the illusion. Patients and methods: a prospective six-week observational study included 30 patients with the paranoid form of schizophrenia in the second week of stable antipsychotic monotherapy, 11 of whom dropped out due to exclusion criteria. At the second and eighth weeks of treatment, patients were assessed for susceptibility to the Ponzo illusion, cognitive impairment using a battery of BACS tests, and severity of mental status during a semi-structured interview using the PANSS scale. Results: the cluster analysis identified 2 clusters of patients who differed in their susceptibility to the Ponzo illusion. Patients in the first cluster (n = 9) with a significantly higher score on negative PANSS symptoms and marked cognitive impairment in the second and eighth weeks of therapy were prone to overestimate the Ponzo illusion, while patients in the second cluster (n = 10) were less susceptible to the Ponzo illusion. Conclusions: this study allowed us to identify two clusters of patients differing in the severity of cognitive and visual impairments, the relationship of susceptibility to Ponzo illusion with such clinical indicators as negative and cognitive symptoms was demonstrated, which confirms the informative value of using the visual illusion methodology as a marker of mental state.

Augmentation therapy of resistant schizophrenia with rhythmic transcranial magnetic stimulation

To identify the clinical efficacy of rhythmic transcranial magnetic stimulation (rTMS) in resistant schizophrenia. The study included 44 male patients with resistant schizophrenia, divided into 4 groups: with depressive (group 1; n=11, 25.0%), with hallucinatory (group 2; n=12, 27.3%), with negative (group 3; n=11, 25.0%) and with delusional symptoms (group 4; n=10, 22.7%). Patients received rTMS, the parameters of which were determined depending on the typological variety, for 3 weeks (15 sessions). Psychometric assessment was carried with PANSS, CGI-S, CGI-I, SANS, CDSS, AHRS when included in the study (0 day), after stimulation (21 days) and by the end of the study (42 day) that allowed evaluation of both the severity of the therapeutic effect and its duration. By the end of the course of stimulation, patients of the first three groups developed a distinct positive effect corresponding to a significant reduction in the total PANSS score: group 1 - 24.4% (p=0.002), group 2 - 8.3% (p=0.02), group 3 - 11.7% (p=0.001), which remained stable by day 42 in patients of the first (p=0.001) and second (p=0.005) groups. In patients with delusional symptoms (group 4), a subpsychotic state developed with a corresponding increase in the total PANSS score by 9.7% (p=0.007) requiring a course of relief therapy, which showed effectiveness by the end of the observation (day 42), indicating that resistance was overcome. The study demonstrated the validity of rTMS as an adjuvant method of treatment in the resistant schizophrenia. To implement the potential of rTMS, it is necessary first of all to take into account the structural features of the condition, as well as to continue improving the stimulation technique itself (increasing the duration of the course, developing supportive courses).

Intra and inter-individual variability in functional connectomes of patients with First Episode of Psychosis

Patients with Schizophrenia may show different clinical presentations, not only regarding inter-individual comparisons but also in one specific subject over time. In fMRI studies, functional connectomes have been shown to carry valuable individual level information, which can be associated with cognitive and behavioral variables. Moreover, functional connectomes have been used to identify subjects within a group, as if they were fingerprints. For the particular case of Schizophrenia, it has been shown that there is reduced connectome stability as well as higher inter-individual variability. Here, we studied inter and intra-individual heterogeneity by exploring functional connectomes’ variability and related it with clinical variables (PANSS Total scores and antipsychotic’s doses). Our sample consisted of 30 patients with First Episode of Psychosis and 32 Healthy Controls, with a test–retest approach of two resting-state fMRI scanning sessions. In our patients’ group, we found increased deviation from healthy functional connectomes and increased intragroup inter-subject variability, which was positively correlated to symptoms’ levels in six subnetworks (visual, somatomotor, dorsal attention, ventral attention, frontoparietal and DMN). Moreover, changes in symptom severity were positively related to changes in deviation from healthy functional connectomes. Regarding intra-subject variability, we were unable to replicate previous findings of reduced connectome stability (i.e., increased intra-subject variability), but we found a trend suggesting that result. Our findings highlight the relevance of variability characterization in Schizophrenia, and they can be related to evidence of Schizophrenia patients having a noisy functional connectome.

The relationship between psychopathology, occupational balance, and quality of life among people with schizophrenia.

There is an increased risk of occupational imbalance and poor quality of life (QoL) if one has schizophrenia. Although evidence suggests a relationship between psychopathology and QoL, the association of occupational balance (OB) with QoL in schizophrenia is unclear. This study aimed to investigate the associations among psychopathology, occupational balance, and QoL in schizophrenia. This was a cross-sectional study carried out in a Community Mental Health Center (CMHC). Ninety-five individuals aged 18 years or older with the diagnosis of schizophrenia participated in the study. All participants completed a sociodemographic form, Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale in Schizophrenia (CDSS), Occupational Balance Questionnaire-11 Turkish Version (OBQ11-T), and the World Health Organisation Quality of Life Assessment Instrument (WHOQOL-100-TR). Relationships among clinical and depressive symptoms, OB, and QoL variables were examined through correlation analysis, and then multiple linear regression analysis was performed to determine the variables that have influences on QOL. The study participants had low OB scores and the lowest mean in the WHOQOL-social relationships subscale. WHOQOL-overall QoL score demonstrated a moderate negative correlation with the PANSS-total score and PANSS-general psychopathology subscale score (r = -0.422, r = -0.463, P < 0.001) and a mild negative correlation with the CDSS-total score (r = -0.390, P < 0.001). OBQ11-T total score showed a moderate positive correlation with the WHOQOL-overall score (r = 0.549; P < 0.001). Findings from the multiple linear regression analysis revealed that OBQ11-T (β = -0.467, P = 0.000) and PANSS-general psychopathology (β = -0.221, P = 0.045) were significant predictors of the overall QoL, explaining 48% of the variance in the overall QoL (adjusted R2 = .43, P < 0.001). Our study findings showed that OB and general psychopathology are determinants that should be considered in improving the QoL in individuals with schizophrenia. Thereby, addressing the symptoms of general psychopathology and occupational factors to improve the QoL may be achieved with the incorporation of occupation-based programmes to routine treatment. However, further research is required.

Cytokines as Potential Biomarkers of Clinical Characteristics of Schizophrenia.

Immune activation plays a major role in the pathogenesis of schizophrenia, as confirmed by many studies, systematic reviews, and meta-analyses. The important role of neuroinflammation in the formation of the relation between impaired neurobiological processes and schizophrenia psychopathology is being actively discussed. We quantified serum concentrations of 22 cytokines in 236 patients with schizophrenia and 103 mentally and somatically healthy individuals by a multiplex assay. We found higher TGF-α (p = 0.014), IFN-γ (p = 0.036), IL-5 (p < 0.001), IL-6 (p = 0.047), IL-8 (p = 0.005), IL-10 (p <0.001), IL-15 (p = 0.007), IL-1RA (p = 0.007), and TNF-α (p < 0.001) levels in patients with schizophrenia than in healthy individuals. Subgroup analysis revealed a much greater number of statistically significant differences in cytokine levels among females than among males. Patients with a continuous course of schizophrenia showed statistically significantly higher levels of IL-12p70 (p = 0.019), IL-1α (p = 0.046), and IL-1β (p = 0.035) compared with patients with an episodic course. Most cytokines were positively correlated with positive, general, and total PANSS scores. In patients with a duration of schizophrenia of 10 years or more, the level of IL-10 was higher than that in patients with a disease duration of 5 years or less (p = 0.042). Thus, an imbalance in cytokines was revealed in patients with schizophrenia, depending on sex and clinical characteristics of the disease.

Effectiveness of KarXT (xanomeline-trospium) for cognitive impairment in schizophrenia: post hoc analyses from a randomised, double-blind, placebo-controlled phase 2 study

The muscarinic receptor agonist xanomeline improved cognition in phase 2 trials in Alzheimer’s disease and schizophrenia. We present data on the effect of KarXT (xanomeline–trospium) on cognition in schizophrenia from the 5-week, randomised, double-blind, placebo-controlled EMERGENT-1 trial (NCT03697252). Analyses included 125 patients with computerised Cogstate Brief Battery (CBB) subtest scores at baseline and endpoint. A post hoc subgroup analysis evaluated the effects of KarXT on cognitive performance in patients with or without clinically meaningful cognitive impairment at baseline, and a separate outlier analysis excluded patients with excessive intraindividual variability (IIV) across cognitive subdomains. ANCOVA models assessed treatment effects for completers and impairment subgroups, with or without removal of outliers. Sample-wide, cognitive improvement was numerically but not statistically greater with KarXT (n = 60) than placebo (n = 65), p = 0.16. However, post hoc analyses showed 65 patients did not exhibit clinically meaningful cognitive impairment at baseline, while eight patients had implausibly high IIV at one or both timepoints. Significant treatment effects were observed after removing outliers (KarXT n = 54, placebo n = 63; p = 0.04). Despite the small sample size, a robust (d = 0.50) and significant effect was observed among patients with cognitive impairment (KarXT n = 23, placebo n = 37; p = 0.03). These effects did not appear to be related to improvement in PANSS total scores (linear regression, R2 = 0.03). Collectively, these findings suggest that KarXT may have a separable and meaningful impact on cognition, particularly among patients with cognitive impairment.

Cognition, Symptomatology, and Community Living Skills in Schizophrenia

Background: Independence in community living is an important aspect of rehabilitation in schizophrenia. Previous studies investigating relationships of coginitive, symptomatic, and demographic factors in community living ability of schizophrenia showed inconsistent findings. These findings may be due to variations in functional measures used or a heterogenous sample of participants recruited. Aim: To investigate the relationships of cognitive, symptomatic and demographic factors with community living skills for people with schizophrenia living in supported living facilities. Method: This is a cross-sectional study. Thirty-seven adults with schizophrenia and 32 matched healthy controls were recruited. Both groups completed the Verbal Fluency Test, subtests of Cognistat, and the Color Trail Test. Additional assessments (i.e., Chinese version of St. Louis Inventory of Community Living Skills – SLICLS-C and Positive and Negative Syndrome Scale – PANSS) were used to evaluate participants with schizophrenia. Cognitive profile was compared between the two groups. Correlation analysis was used to explore the relationships of cognitive abilities, symptomatology, and demographic factors with community living skills in schizophrenia. Results: Results showed that participants with schizophrenia performed worse than the control group in verbal fluency, visual memory, immediate memory, delayed memory, and executive function tests. Significant moderate correlations between SLICLS-C score and participants’ years of education, positive symptoms, general psychopathology, and PANSS total score were identified. Discussions and conclusion: Results indicated cognitive impairments are persistent in schizophrenia who are in remission and have been partially integrated back into the community. Cognitive deficits that people with schizophrenia experience might be stable over most of the course of the illness. Participants’ years of education, positive symptoms, general psychopathology, and PANSS total score might be important moderating variables to include in future investigations related to predicting community living performance in schizophrenia.

Effects of bilateral, bipolar-nonbalanced, frontal transcranial Direct Current Stimulation (tDCS) on negative symptoms and neurocognition in a sample of patients living with schizophrenia: Results of a randomized double-blind sham-controlled trial

Negative symptoms (NS), conceived as Avolition-Apathy (AA) and Expressive Deficit (EXP) domains, and neurocognitive impairments represent unmet therapeutic needs for patients with schizophrenia. The present study investigated if bilateral bipolar-nonbalanced frontal transcranial Direct Current Stimulation (tDCS) could improve these psychopathological dimensions.This randomized, double-blind, sham-controlled study (active-tDCS versus sham-tDCS, both, n = 25) included 50 outpatients diagnosed with schizophrenia clinically stabilized. Patients received 20-min 2 mA active-tDCS or sham-tDCS (anode: left Dorsolateral Prefrontal Cortex; cathode: right orbitofrontal region). Primary outcomes included: PANSS-Negative subscale, Negative Factor (Neg-PANSS), AA and EXP domains; neurocognitive performance at Brief Assessment of Cognition in Schizophrenia. Secondary outcomes included: PANSS subscales and total score, Disorganized/Concrete (DiscC-PANSS) and Positive Factors, Clinical Global Impression (CGI) scores, clinical insight at Scale to Assess Unawareness of Mental Disorder (SUMD). Analysis of covariance (ANCOVA) was performed evaluating between-group changes over time.Significant improvements following active-tDCS were observed for all NS measures (all, p < 0.001; d > 0.8) and for working memory (p = 0.025, d = 0.31). Greater variations following to active treatment emerged also for PANSS-General Psychopathology subscale (p < 0.001; d = 0.54), PANSS total score (p < 0.001; d = 0.69), CGI indexes (all, p < 0.001; d > 0.6), DiscC-PANSS (p < 0.001; d = 0.80) and SUMD-general Unawareness index (p = 0.005; d = 0.15) but not for positive symptoms and others insight measures. Good safety/tolerability profiles were found.Bilateral bipolar-nonbalanced frontal-tDCS is a non-pharmacological approach in schizophrenia effectively improving NS, particularly the AA and EXP domains, probably acting by modulating dysfunctional cortical-subcortical networks. Preliminary results also suggest working memory improvements following tDCS. Further studies are needed to confirm the neurobiological basis of these results.

Mind over what matters: How training in emotional self-regulation can strengthen the immune response in lonely elders

Patients with treatment-resistant schizophrenia (TRS) suffer severe, long-term psychotic symptoms and chronic stress. Salivary kynurenic acid (KYNA) and choroid plexus were evidenced to relate to psychological stress. We hypothesized that TRS patients would have higher salivary KYNA levels than patients who respond to antipsychotics (NTRS) and healthy controls (HC), and increased salivary KYNA levels are associated with clinical phenotypes and choroid plexus volume. A total of 66 HC participants, 53 patients with TRS and 46 with NTRS were enrolled. Salivary KYNA levels were measured by liquid chromatography-tandem mass spectrometry, choroid plexus volume by magnetic resonance imaging, and cognitive functions with the MATRICS Consensus Cognitive Battery. The TRS group had significantly higher salivary KYNA levels than the NTRS group (p = 0.003), who in turn had higher salivary KYNA than HC (p = 0.02). Higher salivary KYNA levels were associated with larger choroid plexus volume (r = 0.48, p = 0.004); lower attention/vigilance (r = -0.44, p = 0.004), verbal learning (r = -0.44, p = 0.004), total MCCB score (r = -0.42, p = 0.005); and a higher total PANSS score (r = 0.48, p = 0.004) in TRS patients. An enlarged choroid plexus also related to worse attention/vigilance (r = -0.39, p = 0.03), verbal learning (r = -0.55, p = 0.001), total MCCB score (r = -0.41, p = 0.02) and clinical symptoms (r = 0.48, p = 0.004) in TRS patients only. We conclude that elevated salivary KYNA levels and associated choroid plexus enlargement are clinically relevant indicators of TRS, with salivary KYNA being particularly valuable as a peripheral marker. Our findings should benefit TRS research and benefit the improvement of personalized treatment.

Association of higher plasma leptin levels with HOMA-IR index, high sensitivity C-reactive protein and glycolipid metabolism in patients with chronic schizophrenia: A multi-center cross-sectional study.

BackgroundPrevious research has revealed that plasma leptin levels were closely related to glycolipid metabolism in schizophrenic patients. Insulin resistance (IR) and high sensitivity C-reactive protein (hs-CRP) were involved in glucolipid metabolism disorders. This study explored the correlation between plasma higher leptin levels, homeostasis model assessment of insulin resistance (HOMA-IR) index, hs-CRP and glycolipid metabolism in patients with chronic schizophrenia (CS).Methods322 subjects were enrolled, and the psychopathological symptoms of each patient were assessed by a 30-item Positive and Negative Syndrome Scale (PANSS−30). Patients' plasma leptin levels were measured by enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose (FBG) levels were determined by oxidase method. Insulin levels were tested by electrochemiluminescence, and hs-CRP levels were tested by immunoturbidimetry. IBM SPSS 22.0 was used for data analysis.ResultsCompared to the lower leptin group, patients in the higher leptin group had significantly higher body mass index (BMI), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), insulin, HOMA-IR and hs-CRP levels; and lower negative factor scores, cognitive factor scores, and PANSS total scores (P < 0.05). Plasma leptin levels in CS patients were positively correlated with BMI, TC, TG, LDL-C, insulin, HOMA-IR and hs-CRP levels, and were negatively correlated with gender (male = 1, Female = 2), positive factor scores, negative factor scores, cognitive factor scores and PANSS total scores. Multiple linear regression analysis revealed that gender, BMI, positive factor scores, PANSS total scores, FBG, LDL-C, insulin, HOMA-IR and hs-CRP levels were independent influencing factors of leptin levels in CS patients (P < 0.05).ConclusionGender, BMI, positive factor scores, PANSS total scores, FBG, LDL-C, insulin, HOMA-IR and hs-CRP levels were independent influencing factors of plasma leptin levels in CS patients. Plasma leptin, HOMA-IR and hs-CRP levels should be measured regularly in CS patients to prevent or treat the disorders of glucose and lipid metabolism comorbidity with schizophrenia patients in clinical diagnosis and treatment.

The Effect of Social Cognitive Interaction Training on Schizophrenia: A Systematic Review and Meta-Analysis of Comparison with Conventional Treatment.

Background Existing antipsychotic medications may alleviate the majority of patients' symptoms, but they have no discernible impact on improving social function and quality of life. Psychotherapy is required for the treatment of schizophrenia. However, contemporary psychotherapy technology intervention techniques are limited to a single intervention, and there is a lack of holistic and complete intervention approaches. Social cognition and interaction training is a comprehensive therapy strategy that has been employed in clinical practice; however, the therapeutic efficacy has been inconsistently reported. As a result, we included controlled clinical trials for meta-analysis in order to carefully assess the efficacy of this therapy. Methods This meta-analysis searched all RCT literatures related to social cognitive interaction training (SCIT) published before April 2022 and assessed the effect of this method in the treatment of schizophrenia. The data in the literatures were combined, and the standardized mean difference (SMD) and mean difference (MD) with 95% confidence interval (95% CI) were calculated to predict the negative symptom score, positive symptom score, PANSS score, and social function score of the patients after treatment. Results 14 RCT studies including 1167 inpatients with schizophrenia were included in this study using a retrospective observational study method, including 590 patients treated with SCIT and 577 patients treated with treatment as usual (TAU). The pooled analysis showed that patients after SCIT had lower negative symptom scores (SMD = −1.66, 95% CI (-2.32, -1.00), P < 0.0001), lower positive symptom scores (MD = −4.03, 95% CI (-7.69, -0.36), P = 0.03), lower PANSS total scores (MD = −6.33, 95% CI (-12.43, -0.23), P = 0.02), and higher social functioning scores (SMD = 0.77, 95% CI (0.34, 1.20), P < 0.001) than those after TAU. Conclusion Our findings support that SCIT is helpful to improve the relief of symptoms and the improvement of social function in patients with schizophrenia, providing a basis for the application of SCIT in hospitalized patients and community patients, and can guide the treatment and intervention of patients with schizophrenia.

Elevated salivary kynurenic acid levels related to enlarged choroid plexus and severity of clinical phenotypes in treatment-resistant schizophrenia

Patients with treatment-resistant schizophrenia (TRS) suffer severe, long-term psychotic symptoms and chronic stress. Salivary kynurenic acid (KYNA) and choroid plexus were evidenced to relate to psychological stress. We hypothesized that TRS patients would have higher salivary KYNA levels than patients who respond to antipsychotics (NTRS) and healthy controls (HC), and increased salivary KYNA levels are associated with clinical phenotypes and choroid plexus volume. A total of 66 HC participants, 53 patients with TRS and 46 with NTRS were enrolled. Salivary KYNA levels were measured by liquid chromatography-tandem mass spectrometry, choroid plexus volume by magnetic resonance imaging, and cognitive functions with the MATRICS Consensus Cognitive Battery. The TRS group had significantly higher salivary KYNA levels than the NTRS group (p = 0.003), who in turn had higher salivary KYNA than HC (p = 0.02). Higher salivary KYNA levels were associated with larger choroid plexus volume (r = 0.48, p = 0.004); lower attention/vigilance (r = -0.44, p = 0.004), verbal learning (r = -0.44, p = 0.004), total MCCB score (r = -0.42, p = 0.005); and a higher total PANSS score (r = 0.48, p = 0.004) in TRS patients. An enlarged choroid plexus also related to worse attention/vigilance (r = -0.39, p = 0.03), verbal learning (r = -0.55, p = 0.001), total MCCB score (r = -0.41, p = 0.02) and clinical symptoms (r = 0.48, p = 0.004) in TRS patients only. We conclude that elevated salivary KYNA levels and associated choroid plexus enlargement are clinically relevant indicators of TRS, with salivary KYNA being particularly valuable as a peripheral marker. Our findings should benefit TRS research and benefit the improvement of personalized treatment.

Efficacy and Safety of Low-Dose Brexpiprazole for Acute Schizophrenia: Meta-Analysis of Randomized Placebo-Controlled Trials.

PurposeThe purpose of this meta-analysis was to compare the efficacy and safety profile of low-dose brexpiprazole (<2 mg/d) compared to placebo and standard-dose brexpiprazole (2–4 mg/d).Patients and MethodsWe identified relevant studies pertaining to the specific purpose of our meta-analysis by searching PubMed, Web of Science, Embase, Cochrane library, and PsycINFO using the search terms “schizophrenia” or “schizophrenic” AND “brexpiprazole” or “REXULTI”. We systematically reviewed all randomized controlled trials (RCTs) comparing low-dose brexpiprazole with placebo. Primary efficacy outcomes were the PANSS total score change and response rate. Primary safety outcomes were total treatment discontinuation rate, and total serious adverse events (SAEs). Risk ratios (RR) and standardized mean differences (SMDs) were pooled implementing a random effect model.ResultsFour RCTs (2178 patients) were included for effect assessment of low-dose brexpiprazole treatment on the patients with acute schizophrenia. Low-dose brexpiprazole was not superior to placebo (SMD = −0.11, 95% CI = −0.23, 0.02, P = 0.10, I2 = 0%), and significantly inferior to standard-dose brexpiprazole (SMD = 0.15, 95% CI = 0.03, 0.26, P = 0.01, I2 = 0%) for PANSS total score change. Low-dose brexpiprazole did not result in significant difference for response rate when compared to placebo and standard-dose brexpiprazole (RR = 1.16, 95% CI = 0.95, 1.41, P = 0.14, I2 = 25%; RR = 0.92, 95% CI = 0.76, 1.12, P = 0.40, I2 = 38%, respectively). For ratio of total discontinuation, low-dose brexpiprazole did not exhibit significant difference when compared to placebo (RR = 0.95, 95% CI = 0.81, 1.11, P = 0.53, I2 = 0%) and standard-dose brexpiprazole group (RR = 1.11, 95% CI = 0.95, 1.29, P = 0.19, I2 = 0%). Total SAEs in low-dose brexpiprazole group did not differ significantly from placebo and standard-dose brexpiprazole group (RR = 0.96, 95% CI = 0.52, 1.80, P = 0.90, I2 = 0%; RR = 1.29, 95% CI = 0.65, 2.57, P = 0.47, I2 = 26%, respectively).ConclusionThe results indicated that low-dose brexpiprazole may be not superior for improving the efficacy and safety for acute schizophrenia compared to placebo and standard-dose brexpiprazole, and may cause additional risk of increasing body weight. Therefore, using low-dose brexpiprazole in acute schizophrenia patients may be not recommended.

Benzodiazepine use during cariprazine treatment in acute schizophrenia

IntroductionAlthough antipsychotics are first-line treatments for schizophrenia, benzodiazepines (BZDs) are often used as concomitant medications in acutely exacerbated patients due to their anxiolytic and sedative effects. Cariprazine (CAR), a D3-preferring dopamine D2/D3 partial agonist antipsychotic, has been examined in many clinical studies for the treatment of acute schizophrenia, with and without benzodiazepines.ObjectivesTo delineate the effects of benzodiazepine-use during cariprazine treatment in acute schizophrenia.MethodsPooled data of cariprazine-treated (1.5-6mg/day) and placebo-treated patients from four short-term, randomised, double-blind trials (NCT00404573, NCT01104766, NCT01104779, NCT00694707) were analysed. Baseline characteristics (age, duration of illness) and efficacy outcome parameters (Total and Hostility Factor Score of the Positive and Negative Syndrome Scale [PANSS]) were compared in patients receiving benzodiazepines (for more ≥3 consecutive days) and not receiving benzodiazepines (&lt;3 consecutive days).ResultsAltogether, 36.7% and 40.7% of the CAR-treated and PBO-treated patients required BZDs. BZD-taking was associated with a higher age in both the CAR-treated (p=0.0002) and PBO-treated (p&lt;0.0001) patients, and with longer illness-duration in both treatment groups (p&lt;0.0001). PANSS Total Score at baseline was similar for BZD users and non-users (CAR: LS Mean=96.36 and 96.27; PBO: LS Mean=95.55 and 96.66). Change from baseline in the PANSS Total Score was greater for patients who did not use BZD vs those who did (CAR: LS Mean= -23.8 vs LS Mean 17.2, p&lt;0.0001; PBO: LS Mean= -14.0 vs LS Mean 12.9, p=0.5776).ConclusionsThese findings may suggest that requiring benzodiazepines is a potential indicator of longer illness duration and poorer response in acute schizophrenia.DisclosureI am an employee of Gedeon Richter Plc.

Aripiprazole lai two-injection start in a 16 year-old with Schizophrenia

IntroductionAripiprazole LAI is approved for the treatment of schizophrenia in adults. Recently, Europe and Canada approved the use of the two-injection start (TIS) regimen: two separate injections of 400 mg long-acting aripiprazole along with a single 20 mg dose of oral aripiprazole. Aripiprazole showed efficacy in the treatment of adolescents with acute schizophrenia in several controlled trials, leading to its approval for 13-17 year-old adolescents with schizophrenia by the EMA. However, the LAI formulation still remains off-label in adolescents.ObjectivesTo demonstrate the efficacy and safety of the TIS regimen of aripiprazole LAI formulation in a 16 year-old adolescent with schizophrenia.MethodsWe evaluated the symptoms of schizophrenia and general severity by means of the PANSS and CGI scales. The scales were administered at hospital admission, after 3 weeks, 5 weeks, and at 4-weeks follow-up.ResultsAt the admission the patient PANSS total score was 136, the CGI score of 7. Aripiprazole was started and up-titrated to 30 mg/day. After 3 weeks, the positive symptoms were significantly reduced; due to the persistence of negative symptoms, clozapine 100 mg/day was added. At week 5 the PANSS total score decreased to 81. Due to poor insight we proposed aripiprazole LAI with the two-injection start. One month later, global functioning and illness insight improved; PANSS score was 43, CGI score 2. There was no evidence of akathisia or other side effects.ConclusionsAripiprazole LAI showed good efficacy and tolerability in an adolescent with schizophrenia. The two-injection start regimen was a safe and viable option.DisclosureNo significant relationships.

The efficacy of cariprazine in chronic schizophrenia – post hoc analyses of phase II/III clinical trials

IntroductionChronic schizophrenia patients are experiencing persistent and severe illness for more than 15-20 years and are usually suffering from long-term negative symptoms. Cariprazine, a novel D3-D2 partial agonist has been proven to be effective in the treatment of acute schizophrenia, however its ability to treat chronic patients has not been assessed yet.ObjectivesThe primary aim of the present post-hoc analysis is to assess the efficacy of cariprazine in treating patients with chronic schizophrenia (late-stage and residual schizophrenia patients).MethodsData from 3 phase II/III 6-week, randomized, double-blind, placebo-controlled trials with similar design in patients with acute exacerbation of schizophrenia were pooled and patients with more than 15 years of schizophrenia were analysed (late-stage patients). Furthermore, schizophrenia patients experiencing predominantly negative symptoms from a 26-week, randomized, double-blind, active-controlled, fixed-flexible-dose trial with an ICD-10 code of F20.5 were analysed post-hoc (residual patients).ResultsAltogether, 414 late stage (286 cariprazine and 128 placebo) and 35 residual (23 cariprazine and 12 risperidone) patients were identified. The pooled analysis evaluating mean change from baseline to week 6 in the PANSS total score indicated statistically significant difference in favour of cariprazine in the late stage (LSMD -6.7, p&lt;0.01) subpopulation compared to placebo. The mean change from baseline in patients with residual schizophrenia in the cariprazine arm was -9.6 on the PANSS-FSNS scale, while -7.9 in the risperidone arm.ConclusionsBased on the results, it seems that cariprazine might be a good treatment option for patients with chronic schizophrenia. Nonetheless, further studies are needed to confirm this.DisclosureI am an employee of Gedeon Richter Plc.

Negative symptoms and social and occupational functioning differentiate systematic paraphrenia from schizophrenia: results from a cross-sectional study

IntroductionKraepelin’s systematic paraphrenia (SP) has been historically used to identify a group of patients in the psychosis-spectrum with good global functioning and reduced impairment in volition and emotions.ObjectivesCross-sectional study comparing a group of patients with SP with another with schizophrenia (SZ).MethodsWe consecutively recruited SP cases from a single centre. SZ cases were selected to match those in the SP group in terms of age and sex. We diagnosed SP using the Munro Criteria and SZ using ICD-10. We collected standard sociodemographic and clinical data. All patients were under follow-up in a community mental health team at the time of the study. We used PANSS total score (PANSS-TS) to assess disease severity and its subscales to evaluate positive (PANSS-P) and negative (PANSS-N) symptoms, and general psychopathology (PANSS-GP). We applied SOFAS to assess social and occupational functioning.ResultsWe recruited 32 patients, 16 with a diagnosis of SP and 16 with a diagnosis of SZ. The two groups did not differ in terms of sociodemographic data. SP cases showed lower values for PANSS-TS (SP: mean=51.63±12.49; SZ=77.76±14.12; p&lt;0.001), PANSS-NS (SP: mean=15.50±5.97; SZ: mean=26.06±5.39; p&lt;0.001), and PANSS-GP (SP: mean=24.31±5.51; SZ: mean=37.13±5.62; p&lt;0.001). Groups did not differ in terms of positive symptoms. SOFAS scores were significantly higher in SP (SP: median=68, interquartile range (IQR)=19; SZ: median=41, IQR=24; p&lt;0.01). PNSS-NS negatively correlated with SOFAS only in the SP group (r=-0.716; p=0.002).ConclusionsSP differs from SZ in negative symptoms and social and occupational functioning. These findings suggest clinical features can differentiate SP from SZ.DisclosureNo significant relationships.

Clozapine-Treatment-Resistant Schizophrenia Successfully Managed with Brexpiprazole Combination Therapy: Two Case Reports

IntroductionClozapine has proven to have a unique efficacy on treatment-resistant schizophrenia (TRS). Nevertheless, studies show that 47%-63% of clozapine-treated patients may fail to respond after around 12-years of treatment (CRS). Several augmentation strategies have been proven to be effective in CRS.ObjectivesHereby, we present two clinical cases of CRS successfully managed with brexpiprazole augmentation.MethodsA 48-year-old man without comorbid substance use, treated with clozapine-brexpiprazole augmentation, and a 20-year-old man with comorbid substance use, treated with clozapine-brexpiprazole combination and subsequently with twice-injection aripiprazole (TIA). They were administered with the following assessments at t0, t1-3 (first month), t4-8 (monthly until 6-month follow-up): CGI, BPRS, PANSS, CDSS, Craving VAS, BARS, BIS-11, HRS-A, MADRS, YMRS, AIMS.ResultsAt 1-month follow-up, both patients showed a considerable improvement (respectively 75% and 55.9% reduction of PANSS total score). At 6-month follow-up, reached only with the first patient, we noticed a further improvement (an overall 37.5% reduction of PANSS total score from the baseline).ConclusionsThe present work is the first report describing combination treatment strategies with clozapine and brexpiprazole which appear to give promising results.DisclosureNo significant relationships.

Superoxide dismutase activity of serum IgG in acute illness and remission period of schizophrenia

IntroductionAccording to recent research violations of the oxidative-antioxidant balance may play an important role in the pathogenesis of schizophrenia, by changing generate, conduct and reproduce a nerve impulse. Antibodies with oxidoreductase activity may be involved in protection against oxidative stress in schizophrenia.ObjectivesThe study was to compare the superoxide dismutase (SOD) activity of IgG in patients with acute schizophrenia and during remission.MethodsThe study included 20 patients with acute schizophrenia (mean PANSS total score 94,3±14), 18 people with schizophrenia during remission (mean PANSS total score 54,7±9), and 10 healthy individuals. All participants signed informed consent for the research. Isolation of IgG from blood serum was performed using affinity chromatography on Protein-G-Sepharose columns. The homogeneity of the substances is confirmed by the SDS PAGE method. SOD activity of IgG was carried out spectrophotometrically. Statistical processing was conducted with Statistica v.10.ResultsIgG of schizophrenia patients and healthy individuals have a SOD activity and studied activity is proved to be antibodies intrinsic property. The activity of antibodies in acute schizophrenia was 1.7 times higher than in healthy individuals (p&lt;0.05). In patients with schizophrenia during remission SOD activity of IgG was 2.4 times higher than in healthy individuals (p&lt;0.05).ConclusionsWe can assume that in the conditions of oppression antioxidant activity in schizophrenia patients, antibodies partially take over the function of protecting the body from patients with generalized oxidative stress. This work is supported by the Russian Scientific Foundation, grant # 18-15-00053P.DisclosureNo significant relationships.

Investigating repetitive transcranial magnetic stimulation on cannabis use and cognition in people with schizophrenia

Cannabis use disorder (CUD) occurs at high rates in schizophrenia, which negatively impacts its clinical prognosis. These patients have greater difficulty quitting cannabis which may reflect putative deficits in the dorsolateral prefrontal cortex (DLPFC), a potential target for treatment development. We examined the effects of active versus sham high-frequency (20-Hz) repetitive transcranial magnetic stimulation (rTMS) on cannabis use in outpatients with schizophrenia and CUD. Secondary outcomes included cannabis craving/withdrawal, psychiatric symptoms, cognition and tobacco use. Twenty-four outpatients with schizophrenia and CUD were enrolled in a preliminary double-blind, sham-controlled randomized trial. Nineteen participants were randomized to receive active (n = 9) or sham (n = 10) rTMS (20-Hz) applied bilaterally to the DLPFC 5x/week for 4 weeks. Cannabis use was monitored twice weekly. A cognitive battery was administered pre- and post-treatment. rTMS was safe and well-tolerated with high treatment retention (~90%). Contrast estimates suggested greater reduction in self-reported cannabis use (measured in grams/day) in the active versus sham group (Estimate = 0.33, p = 0.21; Cohen’s d = 0.72), suggesting a clinically relevant effect of rTMS. A trend toward greater reduction in craving (Estimate = 3.92, p = 0.06), and significant reductions in PANSS positive (Estimate = 2.42, p = 0.02) and total (Estimate = 5.03, p = 0.02) symptom scores were found in the active versus sham group. Active rTMS also improved attention (Estimate = 6.58, p < 0.05), and suppressed increased tobacco use that was associated with cannabis reductions (Treatment x Time: p = 0.01). Our preliminary findings suggest that rTMS to the DLPFC is safe and potentially efficacious for treating CUD in schizophrenia.