Clinical Global Impression-Severity Research Articles

Abnormal Electroencephalogram Findings and Its Correlation With Clinical Features From Pediatric Patients in Psychiatric Clinic.

Objective: We aimed to evaluate the occurrence of electroencephalogram (EEG) abnormalities in pediatric patients attending an outpatient psychiatry clinic at a tertiary center. We examined the rates of abnormalities and specific findings based on demographics, specific diagnoses, and clinical severity. Methods: This study included pediatric patients who underwent EEG at the outpatient psychiatry clinic. Patient demographics, psychiatric diagnosis, intellectual disability, intelligent quotient (IQ) score, family history of psychiatric disorders, and Clinical Global Impression-Severity (CGI-S) score were obtained through retrospective electronic health record analysis. The rate of EEG abnormalities was calculated, and specific abnormal findings were reviewed. Relationships between the rate of EEG abnormalities and diagnosis, severity, IQ, and age at EEG examination were analyzed. Results: Of 319 patients who underwent EEG, 21.3% (68 patients) of patients exhibited abnormalities, including background abnormalities (14.7%, 47 patients), interictal epileptiform discharges (IEDs) (10.3%, 33 patients), and a slow posterior dominant rhythm (3.8%, 10 patients). The frontal region was the most commonly affected area. Neurodevelopmental disorders (NDDs) had the most frequent abnormalities (29.8%), followed by anxiety (16.7%), sleep (14.3%), mood (11.7%), psychotic (5%), and conduct disorders (0%). Disease severity did not correlate with the rate of EEG abnormalities. Adjusted for age, sex, severity, and family history, patients with EEG abnormalities exhibited lower IQ scores. Conclusion: EEG abnormalities were common in pediatric patients with psychiatric disorders, with background abnormalities detected as frequently as IEDs. Disease severity was not associated with EEG abnormality, while IQ scores showed a negative correlation.

Safety and Efficacy of Paliperidone Palmitate in Pediatric Patients with Autism and Intellectual Disability.

This retrospective chart review examines the safety, tolerability and effectiveness of long acting injectable paliperidone palmitate (P-LAI) targeting irritability in twenty-six youth and transition-aged individuals with autism spectrum disorder (ASD) and/or intellectual disability (ID) over a 3-year window. Clinical response was evaluated via prospectively assigned Clinical Global Impressions Severity (CGI-S) and Improvement (CGI-I) scales as well as number of hospital presentations. P-LAI was well tolerated with only 3 patients stopping P-LAI due to side effects. The average duration of P-LAI treatment was 21.1months. Difficulty with medication compliance was the most common reason for initiating P-LAI. There was a statistically significant improvement in CGI-I, CGI-S and hospital visits and no change in BMI noted. Given the potential difficulty of medication administration in this population, this evidence of safety, tolerability as well as preliminary data supporting effectiveness is an important addition to the literature regarding psychopharmacologic management of irritability in youth with ASD and ID.

Safety and Efficacy of Levomilnacipran Extended Release in Pediatric Patients Aged 7-17 Years with Major Depressive Disorder: Results of Two Phase 3, Randomized, Double-Blind Studies.

Objective: Major depressive disorder (MDD) presents a significant psychosocial burden, and there is an unmet need for additional treatment options in pediatric patients. Here, we report the results of two phase 3 multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group studies evaluating the efficacy and safety of levomilnacipran extended release in children and adolescents with MDD. Methods: In the first study, LVM-MD-11, patients aged 12-17 years received daily doses of levomilnacipran 40 mg (n = 134), levomilnacipran 80 mg (n = 138), fluoxetine 20 mg (n = 134), or placebo (n = 141). In the second study, LVM-MD-14, patients aged 7-17 years received levomilnacipran 40 to 80 mg (n = 166), fluoxetine 20 mg (n = 166), or placebo (n = 160) daily. Primary and secondary efficacy endpoints were changes in Children's Depression Rating Scale-Revised (CDRS-R) total score and Clinical Global Impressions-Severity (CGI-S) score, respectively. Results: In LVM-MD-11, there were no significant differences in change in CDRS-R total score between patients treated daily with placebo (least squares mean [LSM] change in CDRS-R total score -22.9) versus levomilnacipran 40 mg (-23.3; p = 0.8035) or 80 mg (-22.6; p = 0.8681). Similarly, in LVM-MD-14, there were no significant differences in LSM change in CDRS-R total score with placebo (-21.3) versus levomilnacipran 40 to 80 mg daily (-23.0; p = 0.2215). There were also no significant differences between the fluoxetine and placebo groups in either study for changes in CDRS-R total score. Changes in CGI-S score were not significant between placebo and levomilnacipran 40 to 80 mg daily or between placebo and fluoxetine. Levomilnacipran was generally well tolerated. Conclusions: The high placebo response in this study prevented the detection of an effect of levomilnacipran in children and adolescents. Clinical Trial Registration numbers: NCT02431806 and NCT03569475.

The influence of gender-specific factors influencing severe anxiety in psychotic major depression: role of thyroid hormones and depression severity.

Psychotic major depression (PMD) is characterized by major depressive disorder (MDD) accompanied by delusions or hallucinations. While the prevalence of PMD and its association with anxiety have been studied, gender-specific differences and the role of thyroid hormones in PMD-related anxiety remain less explored. A total of 1718 first-episode and drug-naïve MDD patients was assessed for the presence of PMD and severe anxiety. Clinical assessments, including Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impressions-Severity (CGI-S) scale, were conducted to assess depression, anxiety, psychotic symptoms, and clinical severity, respectively. Blood samples were collected to measure thyroid function parameters. The prevalence of severe anxiety was higher in PMD patients compared to non-psychotic MDD patients (71.3% vs. 5.3%). No significant gender differences were observed in the prevalence of severe anxiety among PMD patients. However, elevated thyroid-stimulating hormone (TSH) levels and increased depression severity (HAMD scores) were identified as independent risk factors for severe anxiety in female PMD patients. In contrast, no significant risk factors were found in male PMD patients. The area under the receiver operating characteristic (AUCROC) analysis revealed that the HAMD score and TSH level showed acceptable discriminatory capacity for distinguishing between female PMD patients with and without severe anxiety. This study highlights the heightened prevalence of severe anxiety in PMD patients, with TSH levels and depression severity emerging as gender-specific risk factors for anxiety in females. These findings suggest the importance of thyroid hormone assessment and tailored interventions for managing anxiety in female PMD patients.

Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia

A significant need exists for new antipsychotic medications with different mechanisms of action, greater efficacy, and better tolerability than existing agents. Xanomeline is a dual M1/M4 preferring muscarinic receptor agonist with no direct D2 dopamine receptor blocking activity. KarXT combines xanomeline with the peripheral muscarinic receptor antagonist trospium chloride with the goal of reducing adverse events due to xanomeline-related peripheral muscarinic receptor activation. In prior trials, xanomeline-trospium chloride was effective in reducing symptoms of psychosis and generally well tolerated in people with schizophrenia. To evaluate the efficacy and safety of xanomeline-trospium vs placebo in adults with schizophrenia. EMERGENT-3 (NCT04738123) was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 5-week trial of xanomeline-trospium in people with schizophrenia experiencing acute psychosis, conducted between April 1, 2021, and December 7, 2022, at 30 inpatient sites in the US and Ukraine. Data were analyzed from February to June 2023. Participants were randomized 1:1 to receive xanomeline-trospium chloride (maximum dose xanomeline 125 mg/trospium 30 mg) or placebo for 5 weeks. The prespecified primary end point was change from baseline to week 5 in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcome measures were change from baseline to week 5 in PANSS positive subscale score, PANSS negative subscale score, PANSS Marder negative factor score, Clinical Global Impression-Severity score, and proportion of participants with at least a 30% reduction in PANSS total score. Safety and tolerability were also evaluated. A total of 256 participants (mean [SD] age, 43.1 [11.8] years; 191 men [74.6%]; 156 of 256 participants [60.9%] were Black or African American, 98 [38.3%] were White, and 1 [0.4%] was Asian) were randomized (125 in xanomeline-trospium group and 131 in placebo group). At week 5, xanomeline-trospium significantly reduced PANSS total score compared with placebo (xanomeline-trospium , -20.6; placebo, -12.2; least squares mean difference, -8.4; 95% CI, -12.4 to -4.3; P < .001; Cohen d effect size, 0.60). Discontinuation rates due to treatment-emergent adverse events (TEAEs) were similar between the xanomeline-trospium (8 participants [6.4%]) and placebo (7 participants [5.5%]) groups. The most common TEAEs in the xanomeline-trospium vs placebo group were nausea (24 participants [19.2%] vs 2 participants [1.6%]), dyspepsia (20 participants [16.0%] vs 2 participants [1.6%]), vomiting (20 participants [16.0%] vs 1 participant [0.8%]), and constipation (16 participants [12.8%] vs 5 participants [3.9%]). Measures of extrapyramidal symptoms, weight gain, and somnolence were similar between treatment groups. Xanomeline-trospium was efficacious and well tolerated in people with schizophrenia experiencing acute psychosis. These findings, together with the previously reported and consistent results from the EMERGENT-1 and EMERGENT-2 trials, support the potential of xanomeline-trospium to be the first in a putative new class of antipsychotic medications without D2 dopamine receptor blocking activity. ClinicalTrials.gov Identifier: NCT04738123.

Efficacy and safety of lurasidone for schizophrenia: A systematic review and meta‑analysis of eight short‑term, randomized, double‑blind, placebo‑controlled clinical trials.

Lurasidone is an atypical anti-psychotic approved by the US Food and Drug Administration. It is mainly used to treat schizophrenia in adults through its antagonistic action on dopamine and 5-hydroxytryptamine receptors. The present study systematically assessed the efficacy and safety of lurasidone in the treatment of schizophrenia. Clinical, double-blind, parallel, randomized controlled trials (RCTs) of lurasidone in the treatment of schizophrenia were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and related clinical trial registration websites up to May 2023. A total of two investigators independently screened the included references and evaluated their quality. RevMan 5.3 software was used for meta-analysis of each measure outcome. The present systematic review was registered in PROSPERO (ID=CRD42018108178). A total of eight RCTs were included in the present study, including a total of 2,456 patients with schizophrenia. All eight references were randomized, double-blind and parallel control trials. All eight references were evaluated as high quality. The meta-analysis results demonstrated that there were no significant change in total Positive and Negative Syndrome Scale (PANSS) score, Clinical Global Impression of Severity (CGI-S) score and Montgomery-Asberg Depression Rating Scale (MADRS) between the 40 mg lurasidone group and the placebo group (P>0.05). However, as the dosage increased, the 80, 120 and 160 mg lurasidone groups had significant changes in total PANSS score, CGI-S score and MADRS Compared with placebo (P<0.05), although changes in MADRS in the 120 mg lurasidone group were not statistically significant (P>0.05). In terms of safety, the changes in the incidence of agitation in the 40 mg lurasidone group (P<0.05), vomiting in the 80 mg group (P<0.05) and akathisia in the 160 mg group (P<0.05) were statistically significant and there were also statistically significant changes in the incidence of akathisia, nausea, somnolence and extrapyramidal disorder among the 40, 80 and 120 mg lurasidone groups (P<0.05); No statistically significant changes in the in the incidence of other adverse reactions (P>0.05). In conclusion, existing evidence suggests that the initial dose of lurasidone for schizophrenia can be adjusted to 80 mg. As the condition aggravates, the dose can be incrementally increased to 160 mg. A dose of 160 mg lurasidone is recommended as the most efficacious and safe dose for acute schizophrenia and the risk of occurrence of akathisia, nausea, somnolence and extrapyramidal disorder is still high when lurasidone is administered at a dose of 80-120 mg. The dose should be promptly adjusted or the drug should be withdrawn if the aforementioned adverse reactions worsen. Multi-center, high-quality and long-term clinical RCTs influenced by the included references are still necessary to support the aforementioned conclusions.

Pharmacogenetic intervention improves treatment outcomes in Chinese adult men with schizophrenia

To investigate the clinical application value of pharmacogenetic testing in individualized drug therapy for adult male patients with schizophrenia. A total of 186 adult patients with schizophrenia were enrolled and randomised into the pharmacogenetic (PGx) intervention group and the standard care group. In the PGx intervention group, PGx testing was performed, and the medication regimen was adjusted according to the results of the pharmacogenomic analysis. In contrast, in the standard care group, patients were treated according to the physician's medication experience. Differences in the primary indicator of schizophrenia, the Positive and Negative Symptom Scale (PANSS), and the secondary efficacy measures, the Clinical Global Impressions–Severity of Illness scale (CGI-SI) and Clinical Global Impressions–Global Improvement (CGI-GI) scale, were compared between the intervention and standard care groups. At baseline, the PGx intervention group consisted of 109 individuals, while the standard care group had 77 participants. After 12 weeks of treatment, 49 individuals withdrew from the PGx group (a dropout rate of 45.0%), and 34 withdrew from the standard care group (a dropout rate of 44.2%), with no significant difference in dropout rates between the two groups. The PANSS score reduction rate in the PGx intervention group significantly exceeded that of the standard care group during weeks 3, 6, and 12 of follow-up (P < 0.05). At the 12th week, the PGx intervention group achieved a treatment response rate of 81.7%, significantly surpassing the 48.8% of the standard care group (odds ratio of 4.67, 95% confidence interval of 1.96–11.41; P = 0.001). Furthermore, the PGx intervention was significantly more effective than standard care regardless of whether the patient had a first episode or a relapse (P < 0.05). Furthermore, the Global Assessment of Functioning (GAF) scores and the Personal and Social Performance Scale (PSP) score changes in the PGx intervention group were both significantly different from those in the standard care group (P < 0.05). It is noteworthy that the PGx intervention similarly improves the prognostic outcomes for patients with and without a family history of mental disorders.In conclusion, the application of a PGx intervention treatment model based on PGx testing can significantly improve medication efficacy and shorten the time to achieve the effects of medication in schizophrenia.

Treatment of Refractory Bipolar Depression With Stereotactic Radiosurgery Targeting the Subgenual Cingulate Cortex.

Background The subgenual cingulate cortex (SGC) has been identified as a key structure within multiple neural circuits whose dysfunction is implicated in the neurobiology of depression. Deep brain stimulation in the SGC is thought to reduce and normalize local metabolism, causing normalization of circuit behavior and an improvement in depressive symptoms. We hypothesized that nonablative stereotactic radiosurgery (SRS) to the SGC would reduce local metabolism and reduce the severity of depression in patients with treatment-resistant bipolar depression. Methods Under the FDA's Humanitarian Device Exemption program, patients were screened for inclusion and exclusion criteria. Three volunteers meeting the criteria provided informed consent. Bilateral SGC targets were irradiated to a maximum dose of 75 Gy in one fraction. Subjects were followed for one year following the procedure with mood assessments (Hamilton Depression Rating Scale (HDRS), Clinical Global Impression-Improvement, Clinical Global Impression-Severity, and Young Mania Rating Scale), neurocognitive testing (Delis-Kaplan Executive Function System, Wechsler Adult Intelligence Scale III digit span, and California Verbal Learning Test II), and imaging. Further imaging was completed approximately two years after the procedure. Clinical improvement was defined as a ≥50% reduction in HDRS. Results Two of the three subjects showed clinical improvement in depressive symptoms during the follow-up period, while one subject showed no change in symptom severity. One of three subjects was hospitalized for the emergence of an episode of psychotic mania after discontinuing antipsychotic medications against medical advice but promptly recovered with the reinstitution of an antipsychotic. Sequential assessments did not reveal impairment in any cognitive domain assessed. For one of the three subjects, MRI imaging showed evidence of edema at 12 months post-SRS, which resolved at 22 months post-procedure. In a second of three patients, there was evidence of local edema at the target site at long-term follow-up. All imaging changes were asymptomatic. Conclusion Radiosurgical targeting of the SGC may be a noninvasive strategy for the reduction of severe depression in treatment-resistant bipolar disorder. Two out of three patients showed clinical improvement. While these results are promising, further study, including improvements in target selection and dosing considerations, is needed.

Effectiveness of internet-delivered cognitive behavioural therapy for anxiety and obsessive-compulsive disorders within routine clinical care in rural Sweden

Few studies have evaluated the implementation of ICBT in regular child and adolescent mental health services (CAMHS). This study aimed to explore the acceptability, feasibility, and effectiveness of ICBT for children and adolescents with anxiety disorders and obsessive-compulsive disorder (OCD) within a rural CAMHS. The study also explored outcome predictors and long-term outcomes.Eighty-three participants were consecutively recruited from a non-specialized CAMHS in Region Jämtland Härjedalen in northern Sweden. Therapist-guided ICBT was offered during 12 weeks to children aged 8–17 with an anxiety disorder or OCD. Acceptability and feasibility measures included treatment adherence, treatment satisfaction, and adverse events. The primary outcome measure was the Clinical Global Impression–Severity. Secondary measures of effectiveness included clinician-, self-, and parent-ratings of symptom severity and functional impairment. Assessments were completed at baseline, post-treatment, and three-month follow-up (primary endpoint). A two-year follow up was conducted using medical records. Potential predictors included both patient characteristics and treatment variables.Results indicated that ICBT was both acceptable and feasible according to study measures. Statistically significant improvements were found from baseline to the three-month follow-up on clinician rated severity (B [SE] = −0.92 [0.09]; p < .001), as well as on all secondary measures. Forty-three percent of participants no longer fulfilled criteria for their principal disorder at the three-month follow-up. No serious adverse events were reported. Clinical improvement was highest among children with higher functioning at baseline (B [SE] = −0.05 [0.02]; p < .05). Forty-six percent of participants had been in contact with CAMHS during the two-year follow-up period, mainly for reasons other than their initial diagnosis. Findings suggest that ICBT could be an acceptable and feasible treatment option for young people with anxiety disorders and OCD in rural non-specialized CAMHS settings. Further studies are needed to confirm treatment effectiveness in this setting. Trial registration: NCT02926365.

Oxcarbazepine for the treatment of bipolar and depressive disorders in the outpatient setting: A retrospective chart review

Oxcarbazepine is often utilized off-label for bipolar and depressive disorders in outpatient settings despite limited evidence. We performed a retrospective chart review on 38 adult outpatients diagnosed with bipolar and depressive disorders (ICD-10 codes F30-39), treated with oxcarbazepine by psychiatrists and psychiatric nurse practitioners between 2015 and 2021. Primary outcomes were Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) scores, assigned retrospectively from clinical documentation. Patients were predominantly female (70%), aged 20–76 (mean 36), with a mean of 1.8 DSM diagnoses (range 1–4) and 1.7 (range 0–5) concurrent psychotropic medications. A starting mean oxcarbazepine dose of 489 mg/day, titrated to a mean final dose of 663 mg/day, was associated with a CGI-I of 2.5 [2.25, 2.75] and a pre-to-post treatment decrease in CGI-S from 3.4 to 2.4. Overall response and remission rates were 52% and 29%, respectively. Limitations of this study include potential sample bias, documentation bias and rater bias among other limitations inherent to retrospective study designs.

Clozapine Treatment for Aggressive Behaviors in Youths with Neurodevelopmental Disorders.

Objectives: The aim of this study was to assess effectiveness and tolerability of Clozapine in the treatment of aggression in youth with Neurodevelopmental Disorders. Methods: Patients were consecutively admitted at our third-level university hospital with nationwide catchment from June 2018 to October 2022, and followed up to July 2023. Eligibility criteria were as follows: (1) Autism Spectrum Disorder (ASD) and/or Intellectual Disability/Borderline Cognitive Functioning, (2) behavioral dyscontrol with physical aggression; (3) age range between 8 and 18 years; (4) clinical indication for Clozapine treatment after at least two failed trials with other Second-Generation Antipsychotics (SGAs); (5) availability of an at least 6-month-long follow-up. To evaluate the response to Clozapine, we used the Clinical Global Impressions (CGI) rating scales (Clinical Global Impressions-Severity [CGI-S] and Clinical Global Impressions-Improvement [CGI-I]), the Children's Global Assessment Scale (CGAS), and the Aberrant Behavior Checklist (ABC). Results: Twenty-six children and adolescents (21 boys, age 13.47 ± 2.05 years, follow-up duration 9.77 ± 3.50 months) were included in the analysis. Clinical severity (CGI-S) and functional impairment (Clinical Global Assessment Scale) significantly improved, as well as the ABC Total Score and the scores in several subscales. Sixteen patients (61.54%) were responders (CGI-I ≤2), and 13 (50.00%) displayed remission of aberrant behaviors (ΔABC-Total >35), while response/remission condition was not affected by add-on medications and psychotherapy. Most frequent side effects were increased appetite (50.00%), sialorrhea (38.46%), and increased repetitive behaviors (26.92%). Two patients presented epileptic seizures, while no patients presented leucopoenia. Conclusions: Our results suggest that Clozapine may be helpful in ameliorating treatment-resistant aggression in youth with neurodevelopmental conditions. Possible pharmacological strategies for the management of most frequent side effects are also suggested.

An evaluation of treatment response and remission definitions in adult obsessive-compulsive disorder: A systematic review and individual-patient data meta-analysis

IntroductionExpert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. MethodsWe conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. ResultsIndividual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. ConclusionWhile the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.

Association between cytokines and suicidality in patients with psychosis: A multicentre longitudinal analysis

Suicide is a common cause of death in all phases of schizophrenia spectrum disorder, particularly in the youngest patients. Clinical measures have demonstrated limited value in suicide prediction, spurring the search for potential biomarkers. The causes of suicidal behaviour are complex, but the immune system seems to be involved as it reflects or even causes mental suffering. We aimed to identify cytokines with associations to suicidality in a sample of patients with symptoms of active psychosis. Patients with schizophrenia spectrum disorder (N = 144) participating in a semi-randomized antipsychotic drug trial (the BeSt InTro study) were assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) at eight visits across 12 months. The Clinical Global Impression for Severity of Suicidality scale (CGI-SS) was used for assessing suicidality. Serum concentrations of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, and IL-10 were measured using immunoassays. A logistic regression model was used to investigate the association between cytokine levels and suicidality. To enhance clinical significance, the CGI-SS scores were dichotomized into two groups before analyses: low (=1) and high (≥2) risk for suicidality. Both uni- and multi-variate analyses revealed an inverse correlation between IL-2 and IL-10 serum levels and suicidality, where lower cytokine concentrations of IL-2 and IL-10 were associated with higher suicidality scores. The results were consistent when adjusted for depression and substance use. These results indicate that inflammatory processes are linked to the risk of suicidality in patients with schizophrenia spectrum disorders.

Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial

The ketogenic diet (KD, also known as metabolic therapy) has been successful in the treatment of obesity, type 2 diabetes, and epilepsy. More recently, this treatment has shown promise in the treatment of psychiatric illness. We conducted a 4–month pilot study to investigate the effects of a KD on individuals with schizophrenia or bipolar disorder with existing metabolic abnormalities. Twenty–three participants were enrolled in a single–arm trial. Results showcased improvements in metabolic health, with no participants meeting metabolic syndrome criteria by study conclusion. Adherent individuals experienced significant reduction in weight (12 %), BMI (12 %), waist circumference (13 %), and visceral adipose tissue (36 %). Observed biomarker enhancements in this population include a 27 % decrease in HOMA–IR, and a 25 % drop in triglyceride levels. In psychiatric measurements, participants with schizophrenia showed a 32 % reduction in Brief Psychiatric Rating Scale scores. Overall Clinical Global Impression (CGI) severity improved by an average of 31 %, and the proportion of participants that started with elevated symptomatology improved at least 1–point on CGI (79 %). Psychiatric outcomes across the cohort encompassed increased life satisfaction (17 %) and enhanced sleep quality (19 %). This pilot trial underscores the potential advantages of adjunctive ketogenic dietary treatment in individuals grappling with serious mental illness.

Reliability and validity of the Estonian version of the Clinical Institute of Withdrawal Assessment for Alcohol scale

Aims Our aim was to adapt the Clinical Institute of Withdrawal Assessment for Alcohol scale (CIWA-Ar) into Estonian and test its reliability and validity. Methods A total of 72 patients with alcohol withdrawal syndrome participated in the study. In order to assess the interrater reliability, at first assessment the CIWA-Ar was simultaneously completed by two nurses. In order to assess the sensitivity of the CIWA-Ar to the changes in the severity of the withdrawal syndrome, as well as its correlations to several indices characterizing the subjects’ current condition, the CIWA-Ar, the Clinical Global Impression Severity subscale (CGI-S), the visual analogue scales for the assessment of the general feeling of malaise, anxiety and depression were filled in and the vital signs were measured at inclusion, in 4 h and after the withdrawal syndrome had been resolved. Results The intraclass correlation coefficient (ICC) for the Estonian version of the CIWA-Ar total score, used as an indicator of interrater reliability, was excellent. The CIWA-Ar had significant correlations with the psychiatrists’ CGI-S ratings of the severity of the patient’s condition at all assessment points. Significant correlations were also found between CIWA-Ar and patients’ self-ratings, the highest correlations found with self-rated anxiety and general feeling of malaise. CIWA-Ar total score did not correlate with simultaneously measured heart rate, systolic and diastolic blood pressure at the first assessment. At the second assessment, heart rate had a significant correlation with the CIWA-Ar total score. Conclusion Our study provides confirmation that the CIWA-Ar tool is well applicable in the Estonian language and culture setting.

Time is ticking for TikTok tics: A retrospective follow-up study in the post-COVID-19 isolation era.

During the COVID-19 pandemic, an influx of adolescents presented worldwide with acute onset of functional tic-like behaviors (FTLBs). Our goal was to evaluate psychosocial factors around onset, to elucidate outcomes after pandemic isolation protocols were lifted, and to examine therapy and medication management. A retrospective review was performed of 56 patients ages 10-18 years with new-onset FTLBs seen at Boston Children's Hospital beginning in March 2020. Demographic factors, medical history, and treatment were evaluated. Patient outcomes were determined retrospectively based on the Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales from follow-up visits. CGI-I scores assessed the progression of FTLBs; CGI-S assessed overall function. Ninety-six percent of patients were female-assigned at birth with high rates of comorbid anxiety (93%) and depression (71%). Forty-five percent were gender-diverse. Based on scales that assessed FTLBs (CGI-I) and overall functioning (CGI-S), up to 79% of patients improved independent of comorbid diagnosis or treatment. Evidence-based tic-specific treatments were not more effective than other treatments. A subset of patients had improvement in their FTLBs but not in their general functioning and continued to have other psychosomatic presentations. While many patients' FTLBs improved, it is critical to remain alert to patients' overall function and to assess for other functional neurological disorders and mental health concerns. The tendency of FTLBs to improve in this population, independent of treatment, highlights the unique pathophysiology of FTLBs. Future research on contributing psychosocial factors and specific treatment protocols will allow optimal support for these patients.

Developing a machine learning-based short form of the positive and negative syndrome scale

Background and hypothesisThe Positive and Negative Syndrome Scale (PANSS) consists of 30 items and takes up to 50 minutes to administer and score. Therefore, this study aimed to develop and validate a machine learning-based short form of the PANSS (PANSS-MLSF) that reproduces the PANSS scores. Moreover, the PANSS-MLSF estimated the removed-item scores. Study designThe PANSS-MLSF was developed using an artificial neural network, and the removed-item scores were estimated using the eXtreme Gradient Boosting classifier algorithm. The reliability of the PANSS-MLSF was examined using Cronbach's alpha. The concurrent validity was examined by the association (Pearson’s r) between the PANSS-MLSF and the PANSS. The convergent validity was examined by the association (Pearson’s r) between the PANSS-MLSF and the Clinical Global Impression-Severity, Mini-Mental State Examination, and Lawton Instrumental Activities of Daily Living Scale. The agreement of the estimated removed-item scores with their original scores was examined using Cohen’s kappa. Study resultsOur analysis included data from 573 patients with moderate severity. The two versions of the PANSS-MLSF comprised 15 items and 9 items were proposed. The PANSS-MLSF scores were similar to the PANSS scores (mean squared error=2.6–24.4 points). The reliability, concurrent validity, and convergent validity of the PANSS-MLSF were good. Moderate to good agreement between the estimated removed-item scores and the original item scores was found in 60% of the removed items. ConclusionThe PANSS-MLSF offers a viable way to reduce PANSS administration time, maintain score comparability, uphold reliability and validity, and even estimate scores for the removed items.

ZO-1 Serum Levels as a Potential Biomarker for Psychotic Disorder.

There are limited studies in the literature on the relationship between intestinal and blood-brain barrier permeability and the etiology of schizophrenia. We hypothesized that the difference in serum ZO-1 levels in patients with schizophrenia may affect the severity of the disease. The aim of this study was to investigate the role of changes in serum ZO-1 concentrations in the etiopathogenesis of patients with schizophrenia. A total of 46 patients, 34 with schizophrenia, 12 with a first psychotic attack, and 37 healthy controls, were included in the study. Symptom severity was determined by applying the Positive and Negative Syndrome Scale and the Clinical Global Impression-Severity Scale. Serum ZO-1 levels were measured from venous blood samples. Serum ZO-1 levels were higher in patients with psychotic disorder compared to healthy controls. There was no statistically significant difference between the groups in the first psychotic attack group and the schizophrenia patients. There was a statistically significant positive correlation between serum ZO-1 levels and Positive and Negative Syndrome Scale positive symptom score. These findings regarding ZO-1 levels suggest that dysregulation of the blood-brain barrier in psychotic disorder may play a role in the etiology of the disorder.

Characteristics of patients with schizophrenia switching from oral antipsychotics to once-monthly paliperidone palmitate (PP1M): a systematic review

BackgroundThe utilization of once-monthly paliperidone palmitate (PP1M) in schizophrenia treatment has increased due to its enhanced adherence and convenience. However, there is limited evidence on patient characteristics that may influence treatment outcomes when switching from oral antipsychotics (OAPs) to PP1M therapy. This systematic review aims to identify such patient characteristics and explore potential beneficial factors to aid healthcare professionals in clinical practice.MethodsA systematic literature search was conducted in the PubMed, Embase, and Cochrane Library databases up to July 19, 2022. Studies related to patients with schizophrenia who had been previously treated with OAPs and switched to PP1M were identified and included. Outcomes included the Positive and Negative Syndrome Scale (PANSS) total score, the clinical Global Impressions – Severity (CGI-S) score, the Personal and Social Performance (PSP) total score, and hospitalisation rate. Data were independently extracted and analysed. The results were presented through a narrative synthesis.ResultsEleven studies with a total of 4150 patients were included, identifying nine potential characteristics. The most commonly reported characteristics was patient’s prior treatment with OAPs, followed by the stage of disease, duration of illness (DI), ethnicity, reason for switching to PP1M, history of hospitalisation, time of start injection of PP1M, the PANSS and PSP total score at baseline. Patients in the acute stage, with a shorter DI, a less than 1-week time interval to PP1M injection, and a lower PANSS total score at baseline may have a trend on providing better improvements on PANSS total score. Acute stage and shorter DI also showed potential trends in reducing CGI-S score. Early initiation of PP1M, switching for reasons other than lack of efficacy, and a higher PSP score at baseline exhibited potential trends towards better PSP total score improvements.ConclusionOur findings may suggest that patients in acute stage, with a shorter duration of illness, with early initiation of PP1M injection, and lower PANSS or PSP scores may trend towards better clinical results when transitioning to PP1M from OAPs. Further research is necessary to validate these potential associations and identify any unexplored characteristics. Such investigations are crucial for providing comprehensive clinical recommendations and informing treatment strategies in this context.

Comparison of brexpiprazole, aripiprazole, and placebo for Japanese major depressive disorder: A systematic review and network meta-analysis.

This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy, acceptability, tolerability, and safety profiles of brexpiprazole (BRE) and aripiprazole (ARI) for Japanese with major depressive disorder (MDD) who were inadequately responsive to antidepressants. Outcome measures were scores on the Montgomery Åsberg Depression Rating Scale (primary), the Clinical Global Impression severity scale, and social functioning scale; the non-response rate; the non-remission rate; all-cause discontinuation; discontinuation due to adverse events (DAE); at least one adverse event (1AE); serious adverse event, akathisia; tremor; weight gain. A literature search identified three double-blind, randomized, placebo-controlled trials. These comprised one BRE study (with a 1 mg/day [BRE1] and a 2 mg/day [BRE2]) and two ARI studies (with a 3 mg/day arm and a flexible-dose arm[within the dosage range approved in Japan]) (n = 1736). Both BRE and ARI demonstrated better efficacy than the placebo. BRE but not ARI had a higher DAE than the placebo. ARI but not BRE had a higher 1AE than the placebo. BRE and ARI had a higher risk of akathisia and weight gain than the placebo. There were no significant differences between BRE and ARI for any of the outcomes. Although BRE1 had good efficacy, it carried risk of weight gain. Although BRE2 also had efficacy, it carried risks of DAE, akathisia, and weight gain. However, the risk of akathisia in BRE2 was reduced by an initial dose of 0.5 mg/day rather than 1.0 mg/day. Overall BRE showed similar utility to ARI and a good risk-benefit balance.