Clinical Global Impression-Severity Research Articles

Single trajectory treatment response for predominant negative symptoms: Post-hoc analysis of a clinical trial with cariprazine and risperidone.

Examining the heterogeneity of negative symptoms of schizophrenia contributes to the identification of available treatment targets. Generally, prior evidence classified three to four symptom treatment response trajectory groups over the course of positive symptoms, yet, no evidence exists regarding the heterogeneity of medium-term response to predominant negative symptoms. The current post-hoc analysis aims to identify the heterogeneity in negative symptom treatment response trajectories among patients with predominant negative symptoms who received either cariprazine or risperidone for 26weeks. Treatment response was analyzed based on the: the Positive and Negative Syndrome Scale Factor Score for Negative Symptoms (PANSS-FSNS), and the Clinical Global Impression Severity (CGIS) and Improvement (CGII) scales. To identify subgroups of patients with a similar course of treatment response, group-based trajectory modelling was utilized. Results demonstrated that in comparison with competing models, a single trajectory best described the treatment response of patients with predominant negative symptoms. The results indicate that patients with predominant negative symptoms with over ten years of schizophrenia respond rapidly to adequate treatment and follow a course of steady improvement.

Remote crisis intervention and suicide risk management in COVID-19 frontline healthcare workers.

Despite the propagation of virtual mental health services for vulnerable groups during COVID-19 pandemic, the implementation and evaluation of remote evidence-based practices (EBP) to manage them in low- and middle-income countries remains scarce. In the current study, we describe and evaluate the implementation process and clinical impact of brief, remote, manualized EBP for crisis intervention and suicide risk management among healthcare workers attending patients with COVID-19 (COVID-19-HCWs) in Mexico. The implementation process comprised community engagement of volunteer mental health specialists, creation of new clinical teams with different disciplines and skills, intervention systematization through manuals and education through 4-h remote training as main strategies. Mexican COVID-19-HCWs who had used a free 24-h helpline rated their pre- and post-intervention emotional distress. Therapists recorded patients' pre-intervention diagnosis, severity, and suicide risk, the techniques used in each case, and their post-treatment perception of COVID-19-HCWs' improvement at the end of the intervention. All techniques included in the intervention manual were employed at least in one case (n = 51). At the beginning of the intervention, 65.9% of the COVID-19-HCWs were considered moderately ill or worse according to Clinical Global Impression-Severity (CGI-S) scores, whereas at the end, 79.4% of them were perceived as much or very much improved according to CGI-Improvement scores (CGI-I), and their emotional distress had been significantly reduced (p < 0.001). This prospective study provides evidence that implementation of remote EBP is feasible and useful to reduce emotional distress and suicide risk among COVID-19-HCWs from a middle-income country. However, this study was limited by lack of a control group, improvement ratings provided by therapists and non-anonymous satisfaction ratings.

Retinal changes in generalized anxiety disorder patients.

Optical coherence tomography (OCT) is a method that allows high-resolution cross-sectional imaging of biological tissues. It was suggested that changes in the cranial structure or functions would be reflected in the retina. OCT has been an important method in the diagnosis and follow-up of diseases via morphometric or quantitative retinal measurements. Free radicals, inflammatory processes, and neurotransmission disorders play a role in the etiology of generalized anxiety disorder (GAD). The study aimed to demonstrate the retinal changes in GAD patients due to neurodegeneration based on the comparison of the OCT data of the GAD patients and controls, and the differences between OCT findings of GAD patients and those of controls. The study group included 21 GAD patients. The control group included 21 individuals without any known psychiatric or organic disease, including eye diseases. There was a statistically significant difference between the macular volumes (MV) of the GAD and control groups, the macular volume was lower in the GAD group. There were positive correlations between BDI scores and MV, GCLT, RNFLT-i, RNFLT-n, between BAE scores and (RNFLT-n), and between the CGI severity scale scores and MV, RNFLT-n, and RNFLT-t. OCT analysis of the GAD patients demonstrated that MV values were lower when compared to the control group. Patients with GAD should be screened for these retinal changes. OCT, a simple, non-invasive, and relatively inexpensive method could be employed as a supplementary method in the follow-up of GAD patients.

Neurodevelopmental problems, general health and academic achievements in a school-based cohort of 11-year-old Swedish children.

Assessing rates of neurodevelopmental problems (NDPs) in 11-year-old children and possible association with other health complaints and school performance. In-school study of 11-year-old children as an add-on assessment to the 4th grade regular health check-up, comprising a structured physical neurodevelopmental examination, neuropsychological assessment, behavioural ratings, maternal interview, review of medical records and academic achievements. Out of 348 children recruited from eight schools, 223 (64%) participated. Any physical condition was found in 102/222 (46%), most commonly atopy (18%). One in five had a BMI z-score >2 standard deviations over the reference mean. One or more NDP was found in 86/221 (40%) children. The number of failed national tests correlated positively with NDP severity rated with the clinical global impression severity instrument (Spearman's r = 0.41, p < 0.001). The majority of participants with failed national tests, also had co-occurring health complaints (≥2 of: stomach or extremity ache, headache, difficulties sleeping, internalising symptoms or obesity) and NDPs. Health complaints, physical conditions and NDPs are very common in 11-year-old children and warrant adequately staffed, thoroughly equipped school healthcare services.

IL2RA rs2104286 and IL2 rs2069762 polymorphisms may be associated with bipolar disorder and its clinical findings

Study results supported that immuno-inflammatory pathways in the brain and environment contribute to the etiopathogenesis of bipolar disorder (BD), a chronic affective disease. Our study aimed to assess the relationship between BD risk and interleukin 2 (IL2) and interleukin 2 receptor subunit alpha (IL2RA) variants in a Turkish population. Genomic DNA from 86 diagnosed BD patients and 100 healthy blood donors was extracted. IL2RA rs2104286, IL2 rs2069762, and IL2 rs2069763 variants were genotyped using the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. It was compared to the relationship between the genotype distributions of these variants and clinical characteristics. Results were evaluated statistically. A statistically significant difference in the genotype distribution of the IL2RA rs2104286 variant was found between patients and controls. There was no GG genotype in the patient group. The IL2RA rs2104286 AA genotype was more common in the patient group than the controls, and the AG genotype was higher in the controls compared to the patients (p = 0.001, p = 0.001, respectively). The IL2 rs2069762 and IL2 rs2069763 genotype distributions did not differ between the patient and control groups (p > 0.05). We found that the clinical global impression severity (CGI-S) score was higher in those with IL2 rs2069762 TG and GG genotypes. In this study, we showed for the first time that the genotype distribution of IL2RA rs2104286 and IL2 rs2069762 is associated with BD susceptibility and CGI-S score in a Turkish population.

Multi-trial, aggregated, individual participant data mega-analysis of short-term antidepressant versus mood stabilizer monotherapy of bipolar type II major depressive episode.

Few studies have systematically examined the safety and effectiveness of antidepressant versus mood stabilizer monotherapy of bipolar II depression. To date, there are no aggregated or mega-analyses of prospective trials of individual participant-level data (IPD) to inform future treatment guidelines on the relative safety and effectiveness of antidepressant or lithium monotherapy. Data from a series of four independent, similarly designed trials of antidepressant or lithium monotherapy (where longitudinal IPD were available) (n = 393) were aggregated into an IPD dataset (i.e., mega-analysis). Hierarchical log-linear growth models were used to analyze primary outcome of change over time in Hamilton Rating Scale for Depression (HRSD) scores; while secondary outcomes examined Clinical Global Impressions severity (CGI/S) and change (CGI/C) scores, and change over time in Young Mania Rating (YMR) scores. Relative to lithium monotherapy, antidepressant monotherapy demonstrated significantly greater symptom reduction on HRSD scores across time (b = -2.33, t = -6.68, p < 0.0001), significantly greater symptom reduction on the CGI/S across time (b = -0.414, t = -6.32, p < 0.001), and a significant improvement in CGI/C across time (b = -0.47, t = -7.43, p < 0.0001). No differences were observed in change over time for YMR scores between antidepressant and lithium monotherapy (b = 0.06, t = 0.49, p = 0.62). Findings from this IPD mega-analysis of bipolar II depression trials suggest a divergence from current evidence-based guidelines recommending combined mood stabilizer plus antidepressant therapy. The current mega-analysis suggests that antidepressant monotherapy may provide superior short-term effectiveness without clinically meaningful increase in treatment-emergent hypomanic symptoms compared to lithium monotherapy.

START – physical exercise and person-centred cognitive skills training as treatment for adult ADHD: protocol for a randomized controlled trial

BackgroundCore symptoms in attention deficit hyperactivity disorder (ADHD) are inattention, impulsivity and hyperactivity. Many individuals with this disorder also have a sedentary lifestyle, co-morbid mental illness such as depressive and anxiety disorders, and reduced quality of life. People with ADHD often have impaired executive function, which among other things may include difficulty in time management and structuring of everyday life. Pharmacological treatment is often the first-line option, but non-pharmacological treatment is also available and is used in clinical settings. In children and adolescents with ADHD, physical exercise is used as a non-pharmacological treatment. However, the evidence for the effectiveness of exercise in adults is sparse.ObjectiveTo implement the START intervention (START = Stöd i Aktivitet, Rörelse och Träning [Support in activity, movement and exercise]) consisting of a 12-week, structured mixed exercise programme with or without a cognitive intervention, in adults with ADHD, and study whether it has an effect on core symptoms of ADHD as well as physical, cognitive, mental and everyday functioning compared with usual treatment. A secondary aim is to investigate the participants’ experiences of the intervention and its possible benefits, and to evaluate the cost-effectiveness of START compared with usual treatment.MethodsThis is a randomized controlled trial planned to be conducted in 120 adults with ADHD, aged 18–65. The intervention will be given as an add-on to standard care. Participants will be randomized to three groups. Group 1 will be given a physiotherapist-led mixed exercise programme for 12 weeks. Group 2 will receive the same intervention as group 1 with the addition of occupational therapist-led cognitive skills training. Group 3 will be the control group who will receive standard care only. The primary outcome will be reduction of ADHD symptoms measured using the World Health Organization (WHO) Adult ADHD Self-Report Scale (ASRS-v1.1), Clinical Global Impression-Severity scale (CGI-S) and CGI-Improvement scale (CGI-I). The effect will be measured within 1 week after the end of the intervention and 6 and 12 months later.DiscussionData collection began in March 2021. The final 12-month follow-up is anticipated to be completed by autumn 2024.Trial registrationClinicalTrials.gov (Identifier: NCT05049239). Registered on 20 September 2021 (last verified: May 2021).

Predictors of Treatment Response in Patients with Treatment-Resistant Depression: Outcomes of a Randomized Trial

Objective: This report aims to compare the effectiveness between electroconvulsive therapy (ECT) and transcranial direct stimulation (tDCS) among patients with treatment-resistant depression (TRD) and the associated factors. Methods: This was a secondary data analysis of a randomized, controlled, open-label trial conducted from 1 July 2018, to 31 December 2018. The dataset of 90 patients included in the study was retrieved from Mendeley Data. Patients with TRD were randomized 1:1 into either receiving ECT or tDCS. A good treatment response was determined as an improvement from the Hamilton Depression (HAM-D) baseline score at a rate of more than or equal to 50% at the end of a 2-week intervention. A mixed-effect logistic regression was performed to explain the hierarchical data structure of predictors to successful treatment outcome. Results: The largest magnitude of change was consistently observed in the ECT treatment arm across both HAM-D score and the clinical global impression severity scale (CGI-S) scale (p &lt; 0.001). Lower baseline HAM-D scores (OR: 0.72, 95% CI: 0.58, 0.92), lower baseline CGI-S scale (OR: 0.30, 95% CI: 0.17, 0.55), and ECT as the choice of treatment modality (OR: 14.0, 95% CI: 5.08, 38.58) independently predicted successful therapy among TRD patients, while modelling with multiple logistic regression determined that low socio-economic status (aOR: 20.01, 95% CI: 1.89, 211.47), ECT (aOR: 31.7, 95% CI: 6.32, 159.0) and a lower baseline CGI-S scale (aOR: 0.18, 95% CI: 0.06, 0.57) were significantly predictive of a positive treatment outcome among patients with TRD. Conclusions: ECT was more effective in alleviating depressive symptoms in TRD as compared to tDCS.

Mild Behavioral Impairment in Psychogeriatric Patients: Clinical Features and Psychopathology Severity.

The Mild Behavioral Impairment (MBI) concept was developed to determine whether late-onset persistent neuropsychiatric symptoms (NPSs) may be early manifestations of cognitive decline. Our study aims to investigate the prevalence and differentiating features of MBI with respect to major neurocognitive disorders (MNDs) and primary psychiatric disorders (PPDs). A total of 144 elderly patients who were referred to our psychogeriatric outpatient service were recruited. The severity of mental illness was evaluated by means of the Clinical Global Impression Severity scale, the severity of psychopathology was evaluated by means of the Brief Psychiatric Rating Scale (BPRS), and overall functioning was evaluated by means of the Global Assessment of Functioning scale. The sample included 73 (50.6%) patients with PPDs, 40 (27.8%) patients with MBI, and 31 (21.5%) patients with MNDs. Patients with MNDs reported the greatest severity of mental illness, the highest BPRS Total, Psychosis, Activation, and Negative Symptom scores, and the lowest functioning. Patients with MBI and PPDs had comparable levels of severity of mental illness and overall functioning, but MBI patients reported higher BPRS Total and Negative Symptom scores than PPD patients. Patients with MBI frequently reported specific clinical features, including a higher severity of apathy and motor retardation. These features merit further investigation since they may help the differential diagnosis between MBI and PPDs.

Effects of transcranial pulse stimulation on autism spectrum disorder: a double-blind, randomized, sham-controlled trial.

Transcranial pulse stimulation has been proven effective to improve cognition, memory and depressive symptoms of Alzheimer's disease, but supporting evidence on other neurological diseases or neuropsychiatric disorders remains limited. This study aimed to investigate the effects of transcranial pulse stimulation on the right temporoparietal junction, which is a key node for social cognition for autism spectrum disorder, and to examine the association between transcranial pulse stimulation and executive and social functions. This double-blinded, randomized, sham-controlled trial included 32 participants (27 males), aged 12-17 years with autism spectrum disorder. All eligible participants were randomized into either the verum or sham transcranial pulse stimulation group, on a 1:1 ratio, based on the Childhood Autism Rating Scale screening score. Sixteen participants received six verum transcranial pulse stimulation sessions (energy level: 0.2-0.25 mJ/mm2; pulse frequency: 2.5-4.0 Hz, 800 pulse/session) in 2 weeks on alternate days. The remaining 16 participants received sham transcranial pulse stimulation. The primary outcome measure included Childhood Autism Rating Scale score changes, evaluated by parents, from baseline to 3-month follow-ups. Secondary outcomes included a self-reported questionnaire responded to by parents and cognitive tests responded to by participants. A licensed mental health professional evaluated clinical global impression severity, improvement, efficacy and total score. Results revealed significant interactions in Childhood Autism Rating Scale and other secondary outcomes. Significant group and time effects were found in most secondary outcomes. Additionally, significant differences were found between the transcranial pulse stimulation and sham transcranial pulse stimulation groups in Childhood Autism Rating Scale and clinical global impression improvement and total score immediately after 2 weeks of transcranial pulse stimulation intervention (all P < 0.05), and effects were sustainable at 1- and 3-month follow-up, compared with baseline. The effect size of Childhood Autism Rating Scale (d = 0.83-0.95) and clinical global impression improvement (d = 4.12-4.37) were large to medium immediately after intervention and sustained at 1-month post-stimulation; however, the effects were reduced to small at 3-month post-stimulation (d = 2.31). These findings indicated that transcranial pulse stimulation over right temporoparietal junction was effective to reduce the core symptoms of autism spectrum disorder, as evidenced by a 24% reduction in the total Childhood Autism Rating Scale score in the verum transcranial pulse stimulation group. Additionally, the clinical global impression total score was reduced by 53.7% in the verum transcranial pulse stimulation group at a 3-month follow-up, compared with the baseline. Participants in the verum transcranial pulse stimulation group had shown substantial improvement at 1- and 3-month follow-ups, compared with baseline, although some of the neuropsychological test results were deemed statistically insignificant. Future replication of this study should include a larger sample derived from multi-nations to determine transcranial pulse stimulation as an alternative top-on treatment option in neuropsychiatry.

Esketamine vs Midazolam in Boosting the Efficacy of Oral Antidepressants for Major Depressive Disorder

Loss of a previously effective response while still using adequate antidepressant treatment occurs in a relatively high proportion of patients with major depressive disorder (MDD); therefore, there is a need to develop novel effective treatment strategies. To assess the efficacy and safety of a single subanesthetic dose of esketamine in boosting the efficacy of oral antidepressants for treating fluctuating antidepressant response in MDD. This single-center, double-blind, midazolam-controlled pilot randomized clinical trial was conducted at Beijing Anding Hospital, Capital Medical University in China. The study enrolled participants aged 18 years and older with fluctuating antidepressant response, defined as patients with MDD experiencing fluctuating symptoms after symptom relief and stabilization. Patient recruitment was conducted from August 2021 to January 2022, and participants were followed-up for 6 weeks. Data were analyzed as intention-to-treat from July to September 2022. All participants in the esketamine-treated group received intravenous esketamine at 0.2 mg/kg in 40 minutes. Participants in the midazolam control group received intravenous midazolam at 0.045 mg/kg in 40 minutes. The primary outcome was the response rate at 2 weeks, defined as a 50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary outcomes included response rate at 6 weeks, remission rates at 2 and 6 weeks, and change in MADRS and Clinical Global Impression-Severity score from baseline to 6 weeks; remission was defined by a MADRS score of 10 or lower. A total of 30 patients (median [IQR] age, 28.0 [24.0-40.0] years; 17 [56.7%] female) were randomized, including 15 patients randomized to midazolam and 15 patients randomized to esketamine; 29 patients completed the study. Response rates at 2 weeks were significantly higher in the esketamine-treated group than in the midazolam control group (10 patients [66.7%] vs 1 patient [6.7%]; P < .001). Participants treated with esketamine experienced significantly greater reduction in MADRS score from baseline to 2 weeks compared with those treated with midazolam (mean [SD] reduction, 15.7 [1.5] vs 3.1 [1.3]; P < .001). No serious adverse events were observed in this trial, and no psychotogenic effects and clinically significant manic symptoms were reported. This pilot randomized clinical trial found that a single subanesthetic dose of esketamine could boost the efficacy of oral antidepressants in treating fluctuating antidepressant response, with a good safety profile. Chinese Clinical Trial Registry Identifier: ChiCTR2100050335.

Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality

BackgroundEsketamine (ESK) nasal spray, taken with oral antidepressant therapy, is approved for the treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. In pooled analyses of two pivotal phase 3 studies, ASPIRE I and II, remission rates were consistently higher among patients with MDD with active suicidality who were treated with ESK + standard of care (SOC) versus placebo (PBO) + SOC at all time points in the double-blind and most time points in the follow-up phases. The current analysis of the ASPIRE data sets assessed the effect of ESK + SOC versus PBO + SOC on additional remission-related endpoints: time to achieving remission and consistent remission, proportion of patients in remission and consistent remission, and days in remission.MethodsPost hoc analysis of pooled data from ASPIRE I and II (N = 451). Remission and consistent remission were defined as Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤ 12 at any given visit or two consecutive visits, respectively. Combined endpoints utilizing Clinical Global Impression-Severity of Suicidality-revised version [CGI-SS-r] ≤ 1 (i.e., not suicidal/questionably suicidal) along with the remission and consistent remission definitions (i.e., MADRS total score ≤ 12) were also examined.ResultsThe median times to remission and consistent remission of MDD were significantly shorter in ESK + SOC versus PBO + SOC (15 versus 23 [p = 0.005] and 23 versus 50 days [p = 0.007], respectively) and a greater proportion of patients in ESK + SOC achieved remission and consistent remission by Day 25 (65.2% versus 55.5% and 54.2% versus 39.8%, respectively). Similar results were obtained using the combined endpoint for both remission definitions. The median percent of days in remission during the double-blind treatment phase was significantly greater in ESK + SOC (27.1% or 5 days) versus PBO + SOC (8.3% or 2 days; p = 0.006), and the significant difference was maintained during follow-up.ConclusionTreatment with ESK + SOC versus PBO + SOC resulted in significantly shorter time to remission, greater proportion of patients in remission, and greater percent of days in remission using increasingly rigorous definitions of remission. These findings underscore the clinical benefits of ESK for adults with MDD with suicidality.Trial registrationClinicalTrials.gov registry NCT03039192 (registered February 1, 2017) and NCT03097133 (registered March 31, 2017).

Immunotherapy responsiveness and risk of relapse in Down syndrome regression disorder

Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean-off therapy after 9–12 months of treatment. Baseline, on-therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush–Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: −6.68; 95% CI: −8.23, −5.14), CGI-S (MD: −1.27; 95% CI: −1.73, −0.81), and NPITS scores (MD: −6.50; 95% CI: −7.53, −5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ2 = 11.82, P = 0.001), abnormal MRI (χ2 = 7.78, P = 0.005), and abnormal LP (χ2 = 5.45, P = 0.02), and a personal history of autoimmunity (OR: 6.11, P < 0.001) compared to patients without relapse. IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD.

Prevalence and correlates of suicide attempts in young patients with first-episode and drug-naïve major depressive disorder: A large cross-sectional study

BackgroundFew studies in China have reported factors influencing suicide attempt in young first-episode drug-free (FEDN) MDD patients. This study aimed to investigate the incidence and potential relevant factors of suicide attempt among young Chinese patients with FEDN MDD to prevent suicidal behavior in this population. MethodsWe recruited 1076 FEDN MDD outpatients aged 18–45 years. Patients' mental states were measured by the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Positive and Negative Syndrome Scale (PANSS) positive subscale, and Clinical Global Impression Severity Scale (CGIS). Fasting blood glucose, lipid levels, and thyroid function parameters were also measured. ResultsThe prevalence of suicide attempt for FEDN MDD patients was 18.31 %. Compared to patients without suicide attempt, patients with suicide attempt had an older age of onset, higher HAMA, HAMD, PANSS-positive subscale and CGI-S scores, higher blood pressure, fasting blood glucose, thyroid peroxidases antibody (A-TPO), anti-thyroglobulin (A-TG), thyroid stimulating hormone (TSH), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC), but lower high-density lipoprotein cholesterol (HDLC) (all p < 0.05). Logistic regression analysis showed that duration of illness, hypertension, PANSS-positive subscale, HAMA and CGI-S scores, and A-TPO, LDL-C, TC, and HDL-C were associated with suicide attempt in patients with MDD. LimitationsThe main limitations are cross-sectional design and inability to control selection bias. ConclusionsThis study suggests that young patients with FEDN MDD have a high rate of suicide attempts. Several clinical and metabolic indicators related to lipids and thyroid function may be involved in suicide attempts in FEDN MDD patients.

Thiol-disulphide Homeostasis in Patients with Schizophrenia: The Potential Biomarkers of Oxidative Stress in Acute Exacerbation of Schizophrenia.

: Recent evidence suggests that oxidative stress contributes to the pathophysiology of schizophrenia. This study aimed to compare thiol-disulphide homeostasis in acute and stable phases of schizophrenia for the first time. : Among the patients with schizophrenia, 61 in the acute-phase and 61 in the stable phase of their illness were enrolled in the study. Native thiol (NT), total thiol (TT), disulphide (SS), disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol for thiol-disulphide homeostasis were compared between the groups. The Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive/Negative Symptoms (SAPS/SANS), Clinical Global Impression-Severity Scale (CGI-S), Barnes Akathisia Rating Scale, and Simpson-Angus Scale were used to assess symptoms. : After controlling for age, sex, body mass index, and smoking status there were significant differences in NT, TT, SS/NT, SS/TT, and NT/TT, but not SS. Thiol/disulphide homeostasis has shifted in favour of the oxidative side in patients with acute-phase compared to that in stable schizophrenia. BPRS, SAPS, and CGI-S scores were significantly correlated with all six thiol-disulphide parameters, but not SANS, when controlling for age and sex. Significant receiver operating characteristic (ROC) curves were obtained for all thiol-disulphide homeostasis parameters. Discriminant analysis was found to be statistically significant in discriminating between groups. : These results show that oxidative status increases thiol-disulphide homeostasis in patients with acute-phase schizophrenia compared to those with stable schizophrenia. These findings suggest that thiol-disulphide parameters can be used as biomarkers for the acute exacerbation of schizophrenia.

Differences in the prevalence and clinical correlates of comorbid suicide attempts in patients with early- and late-onset major depressive disorder.

There are many studies on differences in the onset age of major depressive disorder (MDD) patients. However, study on differences in clinical correlates of suicide attempts between early- and late-onset MDD patients is limited. The aim of this study was to investigate the differences in the prevalence and clinical correlates of suicide attempts in patients with early- and late-onset MDD in China. A total of 1718 adult outpatients with MDD were recruited. Demographic and clinical data were collected. The 17-item Hamilton Rating Scale for Depression (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), Positive and Negative Syndrome Scale (PANSS) positive subscale, and Clinical Global Impression-Severity (CGI-S) Scales were used to assess their depressive, anxiety, psychotic symptoms, and the severity of the clinical symptoms, respectively. The prevalence of suicide attempts was higher in late-onset MDD patients (291/1369, 21.3%) than in early-onset MDD patients (55/349, 15.8%) (p = 0.023). However after Bonferroni correction no significant difference was found in the prevalence of suicide attempts in late-onset and late-onset MDD patients (p > 0.05). In both early- and late-onset groups, univariate analysis showed that the following characteristics were significantly associated with suicide attempts: HAMA, HAMD and PANSS positive subscale scores, thyroid stimulating hormone (TSH) levels, blood glucose levels, systolic blood pressure (SBP), and diastolic blood pressure (DBP). In both the early- and late-onset groups, the prevalence rates of severe anxiety disorder and psychotic symptoms were significantly higher in the suicide attempt group than in the non-suicide attempt group. In regression analysis, disease duration, TSH levels and HAMA score were independently associated with suicide attempts in the early-onset group, while TSH levels, HAMA and HAMD score were independently associated with suicide attempts in the late-onset group. This study suggests that suicide attempts are not frequent in early-onset outpatients with MDD compared with late-onset, and some clinical correlates are associated with suicide attempt in early- and late-onset MDD.

Subjective assessment of brexpiprazole in patients with schizophrenia: a prospective observational study.

To investigate the subjective assessments of an antipsychotic treatment with brexpiprazole. This was a 14-week prospective observational study. Nineteen patients participated in the study between February 2019 and January 2020. Patients had a mean age of 40.6±14.2 years and a Clinical Global Impressions-Severity of Illness scale (CGI-S) score of 4.6±1.2 at the initiation of brexpiprazole treatment. The Subjective Well-being under Neuroleptic drug treatment Short form, Japanese version (SWNS-J) total score significantly improved from 68.1±22.3 in week 2 to 79.5±21.0 in week 14 (p=0.0084). The SWNS-J subscales of self-control and social integration status also significantly improved from 14.0±4.7 and 13.9±6.0 in week 2 to 17.0±4.7 and 16.0±5.1 in week 14, respectively (p=0.0053 and 0.012, respectively). No significant improvements were observed in any other SWNS-J subscales or the Drug Attitude Inventory-10 (DAI-10) in the 14-week observation period. Moreover, the SWNS-J total score did not correlate with the DAI-10 (r=0.31, p=0.19), or CGI-S (r=-0.18, p=0.47) scores. The present results suggest that brexpiprazole might improve subjective well-being, although this may not necessarily reflect psychopathological improvements. To enhance medication adherence, it is important to perform subjective assessments on patients over time.

Effectiveness and Safety of Switching from Oral Antipsychotics to Once-Monthly Paliperidone Palmitate (PP1M) in the Management of Schizophrenia: A Systematic Review and Meta-Analysis.

Considering the improvement in adherence and convenience, once-monthly paliperidone palmitate (PP1M) has been increasingly used in the treatment of schizophrenia. However, the outcomes for patients who switch from oral antipsychotics (OAPs) to PP1M have not been reliably assessed. The objective of this systematic review and meta-analysis was to investigate the efficacy and safety of PP1M in the management of patients with schizophrenia with a prior history of OAP use. We conducted a systematic search in PubMed, EMBASE, and the Cochrane Library on 19 July 2022 to identify eligible studies. All studies that examined the effectiveness and safety of switching from OAPs to PP1M in patients with schizophrenia were included. The primary outcomes were relapse rate, hospitalisation rate, and the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score. The secondary outcomes included the changed number of inpatient visits, changed length of stay hospitalisation, change from baseline in the Clinical Global Impressions-Severity (CGI-S) score and the personal and social performance (PSP) total score, response rate, proportion of treatment discontinuation, and adverse events. We included randomised-controlled trials (RCTs), single-arm studies, and observational studies. Case reports, case series, and reviews were excluded. The quality assessment of included studies was performed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB2), the 9-point Newcastle-Ottawa Scale (NOS) instrument for non-randomised studies and cohort studies, and the 12-item National Institutes of Health (NIH) quality assessment tool for before-after (Pre-Post) study without control group. Follow-up times were reported as short- (≤ 13 weeks), medium- (14-26 weeks), and long term (≥ 27 weeks). Data were pooled using meta-analysis. Fifteen studies with a total of 4740 patients were included. The long-term relapse rates and hospitalisation rates were 12% (95% CI 0.07-0.18) and 18% (95% CI 0.15-0.20), respectively. The short-, medium-, and long-term change in PANSS total score was - 21.69 (95% CI - 30.02 to -13.36), - 14.98 (95% CI - 21.45 to - 8.51) and - 17.88 (95% CI - 31.94 to -3.82), respectively. Approximately 50% of patients reported at least a 30% reduction in the PANSS score at the short-term follow-up. Improvements in CGI-S and PSP score were observed during various periods. There was a reduction in the length of stay hospitalisation and the number of inpatient visits at the medium- and long-term follow-ups. Low discontinuation and adverse event rates were reported. Based on our findings, this study may support the efficacy and safety of switching from OAPs to PP1M for the treatment of patients with schizophrenia. Future large-scale studies are warranted to confirm our findings.

Early neutrophil trajectory following clozapine may predict clozapine response – Results from an observational study using electronic health records

BackgroundClozapine has unique effectiveness in treatment-resistant schizophrenia and is known to cause immunological side-effects. A transient spike in neutrophils commonly occurs in the first weeks of clozapine therapy. There is contradictory evidence in the literature as to whether neutrophil changes with clozapine are linked to treatment response. AimsThe current study aims to further examine the neutrophil changes in response to clozapine and explore any association between neutrophil trajectory and treatment response. MethodsA retrospective cohort study of patients undergoing their first treatment with clozapine and continuing for at least 2 years identified 425 patients (69% male/31% female). Neutrophil counts at baseline, 3 weeks and 1 month were obtained predominantly by linkage with data from the clozapine monitoring service. Clinical Global Impression- Severity (CGI-S) was rated from case notes at the time of clozapine initiation and at 2 years. Latent class growth analysis (LCGA) was performed to define distinct trajectories of neutrophil changes during the first month of treatment. Logistic regression was then conducted to investigate for association between the trajectory of neutrophil count changes in month 1 and clinical response at 2 years as well as between baseline neutrophil count and response. ResultsOf the original cohort, 397 (93%) patients had useable neutrophil data during the first 6 weeks of clozapine treatment. LCGA revealed significant differences in neutrophil trajectories with a three-class model being the most parsimonious. The classes had similar trajectory profiles but differed primarily on overall neutrophil count: with low, high-normal and high neutrophil classes, comprising 52%, 40% and 8% of the sample respectively. Membership of the high-normal group was associated with significantly increased odds of a positive response to clozapine, as compared to the low neutrophil group [Odds ratio (OR) = 2.10, p-value = 0.002; 95% confidence interval (95% CI) = 1.31–3.36]. Baseline neutrophil count was a predictor of response to clozapine at 2 years, with counts of ≥5 × 109/l significantly associated with positive response (OR = 1.60, p-value = 0.03; 95% CI = 1.03–2.49). ConclusionsOur data are consistent with the hypothesis that patients with low-level inflammation, reflected in a high-normal neutrophil count, are more likely to respond to clozapine, raising the possibility that clozapine exerts its superior efficacy via immune mechanisms.

Long-term Efficacy and Safety of Paliperidone 6-month Formulation: An Open-label 2-year Extension of a 1-year Double-blind Study in Adult Participants With Schizophrenia.

Paliperidone palmitate 6-month (PP6M) demonstrated noninferiority to paliperidone palmitate 3-month (PP3M) in preventing relapse in patients with schizophrenia in a phase-3 double-blind (DB) study (NCT03345342). Here, we report long-term efficacy and safety results from a 2-year single-arm, open-label extension (OLE; NCT04072575) of this DB study. Participants who completed the DB study without relapse were enrolled and followed-up every 3 months up to 2 years. Participants received 4 PP6M gluteal-injections (700/1000mg eq.) at baseline, 6-month, 12-month, and 18-month visits. Efficacy endpoints included assessment of relapse, Positive and Negative Syndrome Scale (PANSS) total score, Personal and Social Performance (PSP) score, and Clinical Global Impression-Severity (CGI-S) scale change from baseline. Safety was assessed by treatment-emergent adverse events (TEAEs), physical examinations, and laboratory tests. Of 178 participants enrolled, 154 (86.5%) completed the OLE; mean age: 40.4 years, men: 70.8%. Mean duration of PP6M exposure during OLE was 682.1 days. Overall, 7/178 (3.9%) participants relapsed between 20-703 days after enrolment. Mean (SD) change from baseline to endpoint: PANSS total score, 0.7 (8.22); CGI-S, 0.0 (0.51); PSP Scale, 0.5 (7.47). Overall, 111/178 participants (62.4%) reported ≥1 TEAE; most common (>5%) TEAEs were headaches (13.5%) and increased blood prolactin/hyperprolactinemia (18.0%); 8/178 (4.5%) participants experienced serious TEAEs, and 6/178 (3.4%) participants withdrew due to TEAEs; no deaths were reported. The relapse rate observed with PP6M during the 2-year OLE was low (3.9%). Clinical and functional improvements demonstrated in the DB study were maintained during OLE and no new safety concerns were identified.