BackgroundUnlike typical categorical definitions of treatment-resistant depression (TRD) based on antidepressant (AD) trial failures, the Maudsley Staging Method (MSM) is a dimensional measure of resistance also rating episode duration, baseline depression severity and failure of augmentation strategies and ECT. However, MSM has not previously been used longitudinally across the full depressive episode, from episode onset to remission. We applied episode-wide MSM (EW-MSM) in patients with Major Depressive Disorder naturalistically followed to remission in a tertiary-care setting and categorized as 1st and 2nd AD trial remitters, TRD remitters and TRD non-remitters (categorical outcomes). The study aimed to investigate clinicodemographic and treatment-related correlates of EW-MSM and categorical outcomes, comparatively assess their predictive value for depression improvement, and explore the discriminative utility of EW-MSM across categorical outcomes.MethodsWe recruited 267 patients. EW-MSM was scored at remission (MADRS ≤ 9 in two consecutive visits), if achieved. Associations of clinicodemographic and treatment-related characteristics with EW-MSM and categorical outcomes were explored in multivariate models. Their comparative predictive value for depression improvement was tested in hierarchical linear regressions. ROC curves assessed EW-MSM discriminative utility across categorical outcomes.ResultsAnalysis focused on 233 remitters (105 1st AD trial remitters, 62 2nd AD trial remitters and 66 TRD remitters). Both EW-MSM and categorical outcomes were associated with baseline severity, obsessive-compulsive disorder comorbidity, episode duration, number of ADs or AD combination. EW-MSM was additionally associated with psychotic features and use of augmentation strategies. EW-MSM was more strongly associated with baseline severity than categorical outcomes (R2 = 0.24 vs. 0.14) and consequently predicted depression improvement to remission more efficiently in hierarchical regressions (ΔR2 = 0.13 vs. 0.05). EW-MSM discriminated well TRD remitters from 1st AD trial remitters (AUC = 0.91, 95% CI = 0.86-0.95) or from early remitters combined (AUC = 0.865, 95% CI = 0.81-0.92) but not among adjacent categories.LimitationsSingle, tertiary-care setting, unavailability of ECT/esketamine and exclusion of patients on psychotherapy (not rated by MSM) limit study generalizability.ConclusionsEW-MSM reflects clinical and treatment intensity aspects of resistance in depression more strongly and comprehensively than categorical outcomes. Therefore, it offers precision for staging and could be used to more efficiently investigate clinical, biological and psychological correlates of resistance.

BACKGROUND:This was a 4-year mirror-image study of adult patients diagnosed with bipolar disorder (BD) assessing the effects on treatment continuation and hospitalisation between aripiprazole 1-month (A1M), risperidone-LAI (R-LAI) and the monthly and 3-monthly formulations of paliperidone palmitate (PP1M, PP3M). We aimed to evaluate and compare the use of A1M, R-LAI, and the monthly and 3-monthly formulations of paliperidone palmitate (PP1M, PP3M) by using the change of number and length of hospitalisations 2 years before compared to 2 years after initiation of LAIs for continuers and discontinuers. Secondary outcomes were: (1) discontinuation rates at 2 years and reasons per LAI, (2) time to discontinuation per LAI, and (3) time to first hospitalisation per LAI. RESULTS:A total of 122 BD were included; 74 continued LAI treatment at two years. Reasons for discontinuation were poor compliance (50%), ineffectiveness (43.2%), and tolerability issues (13.6%). Both time to individual LAI discontinuation and time to first hospital admission were significantly lower in the R-LAI group. There was a significant overall reduction in the number and length of hospitalisations two years before and after LAI initiation, although multivariate logistic regression analysis showed that A1M, PP1M and R-LAI were associated with an increased risk (OR = 1.89, 95% CI = 1.54-3.68, p = 0.015; OR = 1.63, 95% CI = 1.29-2.77, p = 0.022; OR = 3.08, 95% CI = 1.48-6.05, p = 0.008, respectively) of bed usage compared to PP3M. Last, study completers showed a considerable drop of 79% in number of hospital admissions and 83% in bed days (p = 0.001) as opposed to non-completers. CONCLUSIONS:Study findings suggest that long-acting antipsychotics such as A1M, PP1M, and particularly PP3M are associated with high retention and lower hospitalisation rates after 2 years of treatment in patients with BD.

Abstract Background The aripiprazole once-monthly 400 mg two-injection start (AOM 400-TIS) enables treatment initiation at a single clinic visit, without the need for 14 days of concurrent oral aripiprazole supplementation. Previously, results from a survey outlined the views and experiences of healthcare professionals (HCPs) with the AOM 400-TIS in a real-world setting in Europe. The current work extends these findings to include a broader pool of participants from more European countries. Methods This was a non-interventional, cross-sectional survey of HCPs from Germany, Italy, the United Kingdom, Denmark, and Sweden. Participants were licensed nurses/physicians with experience prescribing and/or administering the AOM 400-TIS to patients diagnosed with schizophrenia. Two waves of survey data were pooled and analysed using descriptive methods. Results Data from 229 HCPs were evaluated. Poor treatment adherence (88.6%), relapse (51.1%), and patient preference (47.6%) were common reasons for using the AOM 400-TIS, while patients not wanting two injections at the same time (52.4%) and concerns about safety (34.1%) and tolerability (33.6%) were common barriers. Among HCPs, 86.0% agreed/strongly agreed they were satisfied with outcomes of patients treated with the AOM 400-TIS, with most agreeing/strongly agreeing that patients appeared satisfied in general (73.4%) and with sustained quality of life and functioning (66.4%). Conclusions This survey provides a pan-European account of HCPs’ views and experiences with the AOM 400-TIS in adults diagnosed with schizophrenia. Initiatives to overcome barriers to AOM 400-TIS use include providing clearer evidence and education on its efficacy and safety and consideration of how the regimen is presented in patient−provider discussions.

OBJECTIVE:To evaluate the effectiveness, time to discharge, functioning, and tolerability of Risperidone-ISM® in hospitalised patients with schizophrenia relapse. METHODS:Non-interventional, multicentre, prospective study of adults admitted for acute exacerbation of schizophrenia and treated with Risperidone-ISM®. Effectiveness was assessed using the Clinical Global Impression-Severity scale (CGI-S) and 6-item Positive and Negative Syndrome Scale (PANSS-6) at days 8 (FU1), 28 (FU2), and 56 (FV). Functioning was evaluated with the Personal and Social Performance scale (PSP), patient satisfaction with the Medication Satisfaction Questionnaire (MSQ). Admission/discharge data and adverse events were recorded. RESULTS:In 275 patients, significant reductions from baseline in CGI-S and PANSS-6 scores occurred as early as day 8, with continued improvement through day 56 (CGI-S: -1.4 and PANSS-6: -7.6; p < 0.0001), regardless of use of concomitant antipsychotics. Median discharge occurred 8 days after first Risperidone-ISM® injection. PSP improved by 17.6 points at day 28. No new/unexpected safety information was reported; 4% discontinued due to related adverse events. At final visit, 78% reported satisfaction with treatment, and therapeutic alliance improved in 89.4% of participants. CONCLUSIONS:Risperidone-ISM® demonstrated rapid and sustained effectiveness, functional improvement, and favourable tolerability, enabling early stabilisation and discharge. Adding another antipsychotic provided no additional benefits. Results support Risperidone-ISM® for treating acute schizophrenia relapse in real-world settings.

Schizophrenia trials have been too small, short and exclusionary, leaving the most disabled patients under-represented and key outcomes neglected. Future research should match the illness burden through sustained funding, representative recruitment, multidomain assessment, and adaptive, platform and SMART designs that test treatments efficiently and produce evidence relevant to patients' lives.

Background Major depressive disorder (MDD) is a leading cause of global disability. Despite availability of effective therapies, many patients with MDD develop treatment-resistant depression (TRD). Aims To evaluate and compare treatment outcomes, comorbidities and healthcare resource usage and costs in patients with major depressive disorder (MDD) and treatment-resistant depression (TRD). Methods This was a population-based, retrospective analysis of linked primary and secondary care NHS data in the northwest London Discover-NOW dataset. This is the access platform for the longitudinal Whole Systems Integrated Care (WSIC) database, which is hosted by Imperial College Health Partners and contains linked coded primary, acute, mental health, community health, and social care records fed by over 400 provider organisations and covering more than 2.5 million patients. Eligible patients were adults who were registered with a General Practitioner in the area, had diagnostic codes for depression and had been prescribed at least one antidepressant between 2015 and 2020. Results A total of 110,406 patients were eligible for inclusion (101,333 [92%] with MDD and 9,073 [8%] with TRD). Mean duration of depression was 52.8 (SD 41.7) months and 70.8 (SD 37.8), respectively. Remission was recorded in 42,348 (42%) patients with MDD and 1,188 (13%) with TRD (p<0.0001) while relapse was seen in 20,970 (21%) and 4,923 (54%), respectively (p<0.0001) during the study period. Patients with TRD had significantly higher risks of suicidal behaviour and comorbidities such as anxiety, asthma, and alcohol/substance misuse (all p<0.0001). Mean times from diagnosis to first contact with mental health services were 38.9 [SD 33.6] months for MDD and 41.5 [SD 32.0] months for TRD (p<0.0001). Individuals with TRD had considerably higher primary care and emergency attendance rates, more inpatient hospitalizations, longer hospital stays, and greater total healthcare costs than MDD patients. Demand increased with the duration of depression and the number of lines of treatment. Primary care usage was greatest overall (TRD mean 162 [SD 96] vs. MDD 108 [SD 90] visits per patient, p<0.0001; cost per patient £17,348 [SD £33,040] vs. £12,011 [£25,588], p<0.0001). In secondary care, accident and emergency visits accounted for the highest use (TRD mean 5.5 [10.6] vs. MDD 3.54 [SD 6.0] visits per patient, p<0.0001) while non-elective hospitalisations incurred the highest costs (mean £ 2,518 [£8,064] vs. £1,909 [SD £6,807], p<0.0001). Conclusions The study highlights the substantial individual patient and economic burden associated with MDD and particularly TRD in both primary and secondary care settings. Findings suggest that evidence- based treatment optimisation, timely access to newer therapies and the development of stratified care pathways and specialist services could improve patients’ outcomes.

Treatment-resistant schizophrenia affects over half of individuals with schizophrenia. Clozapine is the only approved treatment in the United States but often provides limited relief. Augmenting clozapine with cariprazine (CAR) (a D3-preferring dopamine D2-D3 partial agonist) may improve outcomes. This systematic review evaluated the efficacy and safety of this combination in patients with sub-optimal response. A search of PubMed, Embase, and Cochrane Library yielded 52 cases from 21 eligible studies to be included in the analysis. Patient and treatment characteristics and clinical outcomes were synthesized. Cariprazine replaced another antipsychotic or was added to clozapine monotherapy in 44.2% and 34.6% of cases, respectively. Before treatment, 90% of patients had positive and 81% had negative symptoms. Combination therapy improved these symptoms in 66% and 83% of cases, respectively. In 19 patients with Positive and Negative Symptom Scale scores available before and after treatment, total scores decreased by 43.4%, with positive and negative subscale reductions of 23.0% and 59.1%. The combination was generally well tolerated; some patients experienced weight loss and reduced clozapine-related side effects. New adverse events occurred in 19% (most commonly akathisia at 6%). Cariprazine was discontinued in 17% of cases due to side effects or lack of efficacy. Overall, the combination appears safe and promising, especially for persistent negative symptoms, likely due to complementary neuroreceptor effects. Larger controlled trials are needed to confirm these findings.

BACKGROUND/AIMS:Insomnia increases the risk of, and relapses in, depressive disorders. The treatment of insomnia in people with depression is associated with improvements in sleep, depressive symptoms, and overall patient outcomes. However, clinical services remain largely focused on depressive symptoms and access to gold standard evidence-based insomnia treatments remains limited. Accurate prevalence rate estimates of insomnia in depression are important for optimising effective clinical services. We aimed, therefore, to estimate in a systematic review of all relevant studies, the prevalence rate of insomnia in depressed adults. METHODS:We searched databases including Ovid and PubMed from inception to October 2024 for studies of currently depressed adults which reported the prevalence of insomnia symptoms. Two independent reviewers assessed articles and extracted data. RESULTS:5021 unique references were identified, of which 82 full texts were reviewed after title and abstract screening. Fourteen studies, with a combined 10,337 participants, met the inclusion criteria. Eight studies were from the US, and one each from Belgium, China, the Netherlands, Republic of Korea, and Turkey, while one included participants from both Malaysia and Australia. The mean prevalence rate of insomnia symptoms in depressed adults was 78 % (95 % CI 70 % to 85 %), N = 10,337. CONCLUSIONS:The high prevalence rate, consistent with previously reported estimates, suggests that insomnia is both common and under-treated in depressed adults. Given this, and that insomnia symptoms in adults with depression are infrequently treated directly despite evidenced-based, effective, acceptable treatments existing, clinical services should routinely offer targeted interventions to identify and manage co-incident insomnia symptoms.

Schizophrenia is a complex psychiatric disorder frequently complicated by comorbidities that contribute to functional impairment, poor treatment adherence, and elevated mortality. Among the most prevalent and burdensome are affective symptoms, sexual dysfunction, metabolic disturbances, and substance use disorders, which remain underrecognized and insufficiently addressed in routine care. This expert consensus aimed to develop comorbidity-informed pharmacological strategies for schizophrenia, grounded in real-world challenges and individualized treatment needs. A multidisciplinary panel of 10 European psychiatrists convened for an in-person meeting. Four expert-led presentations, each addressing a key comorbidity, were followed by open discussion. A modified two-round Delphi process was subsequently used to validate the consensus statements, which were thematically synthesized into actionable recommendations. Consensus-based recommendations were developed across four comorbidity domains, integrating current evidence with real-world clinical expertise. The panel emphasized the importance of individualized, patient-centered pharmacological strategies that balance efficacy, tolerability, and long-term functional outcomes. Partial dopamine agonists and other metabolically or hormonally favorable agents were identified as clinically useful across several comorbid profiles. Recommendations also addressed the optimization of antipsychotic selection, management of treatment-emergent side effects, and coordinated care for patients with dual diagnosis (also referred to as co-occurring disorders). Measurement-based monitoring and integrated service models were consistently highlighted as essential for improving outcomes. Effective management of schizophrenia requires a shift toward comorbidity-informed, recovery-oriented pharmacological care. These expert recommendations provide practical strategies to support individualized treatment planning in real-world clinical settings.

Purpose:This qualitative study explored patient, caregiver, and prescriber preferences for long-acting injectable (LAI) dosing frequency, and factors influencing preferences for a hypothetical LAI administered once every 2 months for the treatment of schizophrenia. Patient and Methods:This single-person interview study recruited people living with schizophrenia, caregivers, and prescribers across France, Germany, Italy, Spain, and the UK. Semi-structured interviews were conducted in which participants were asked about their treatment experiences, views on an ideal treatment, and preferences on LAI dosing frequency. A qualitative analysis of interview transcripts was performed to identify key themes. Results:Fifteen people living with clinically stable schizophrenia, 11 caregivers, and 13 prescribers were interviewed. When talking about current treatment (a once-monthly LAI), people living with schizophrenia and caregivers expressed mixed views, with some describing treatment as "easy", whilst others described a fear that treatment will stop working or are frustrated with the frequency of appointments. When asked about treatment goals, a common theme was wishing for the person living with schizophrenia to be clinically stable, leading to a reduction in symptoms and emotional outbursts. When asked about an LAI administered once every 2 months, people living with schizophrenia and caregivers expressed positive views, and perceived that such a treatment would be less burdensome than current treatment. Prescribers were open to recommending an LAI given once every 2 months to clinically stable patients, or those expressing a preference for a decreased dosing frequency or for LAIs in general. Conclusion:In this qualitative study, participants expressed overall positive views on a potential transition to an LAI given once every 2 months, due to the advantages of greater freedom and less treatment burden. Selection of a specific LAI should acknowledge individual patient and caregiver preferences regarding formulation and frequency, to ensure that targeted disease management goals are met.

Aripiprazole once-monthly 400 mg (AOM 400) is a long-acting injectable (LAI) for the maintenance treatment of adults with schizophrenia. The AOM 400 two-injection start initiation regimen (AOM 400-TIS) is an alternative to treatment initiation with one injection of AOM 400 plus 14 days of oral aripiprazole supplementation. This survey investigated the real-world experiences of European healthcare professionals (HCPs) with AOM 400-TIS. Physicians and nurses in Germany, Italy, and the United Kingdom who had prescribed and/or administered AOM 400-TIS ≥ 3 times to patients with schizophrenia were invited to participate in an online survey. The primary objective was to investigate HCPs’ experiences and satisfaction with AOM 400-TIS. Descriptive analysis was performed on data collected between 1 February and 21 March 2024. Data from 94 HCPs were analysed. Most were psychiatrists (62.8

Background:Patient satisfaction and perceived treatment effectiveness play a critical role in healthcare outcomes and overall well-being. Understanding patient experiences can help identify barriers to adherence and guide improvements in therapy. Previous studies, such as those conducted with PP3M and PP1M, have highlighted the importance of patient satisfaction in optimizing the management of chronic conditions, demonstrating that satisfaction is linked to better adherence and overall treatment success. Nonetheless, there was no data available with patients treated with paliperidone 6-month (PP6M). Therefore, we aimed to evaluate the perspectives, including the perceived effectiveness and satisfaction of patients, their relatives and mental health professionals on the twice-yearly treatment with PP6M in usual clinical practice. Methods:The cohort of patients derived from the P2Y study. This is a multicenter, prospective study across different sites in Europe. Patients, relatives and psychiatrists were asked for satisfaction, by using the Medication Satisfaction Questionnaire (MSQ), and perceived effectiveness. We included all patients who were initiated or switched to PP6M and completed one year of treatment. Results:A total of 233 patients were included in this study, of which 9 (4%) discontinued PP6M at 12 months. Most patients were male (69%, 160 participants), 66% (156 patients) carried a diagnosis of schizophrenia and 16% (38 patients) of comorbid substance use disorder. Furthermore, 22% (51 patients), 70% (164 patients) and 8% (19 patients) were treated with PP1M, PP3M and other oral/LAIs antipsychotics, respectively. The majority of patients (81.5%, n = 190/233), relatives/carers (81.1%, n = 189/233) and clinicians (90.9%, n = 212/233) were extremely satisfied, very satisfied or satisfied 1 year after switching from PP1M, PP3M and other antipsychotic to PP6M with similar findings between patients diagnosed with schizophrenia and other diagnoses. Last, 42% of patients, 45% of their relatives and 40% of clinicians perceived PP6M as more effective compared to the previous treatment. In contrast, only 3% of patients, relatives and clinicians perceived PP6M as less effective. Conclusion:Patients, their carers and relatives as well as mental health professionals reported a high satisfaction rate with PP6M, and equally good or even better perceived effectiveness compared to PP1M, PP3M or other oral or LAIs antipsychotics in the majority of cases. Improved patient experience with PP6M could improve treatment continuity and reduce hospitalization rates.

BackgroundLAIs with longer dosing intervals appear to be associated with improved clinical outcomes and added real-world benefits in the management of schizophrenia. Paliperidone palmitate six-monthly (PP6M) LAI provides the longest dosing interval, twice-yearly dosing, among all currently available LAIs. In clinical trials PP6M was found to be non-inferior in preventing relapses in patients with schizophrenia compared to the three monthly formulation (PP3M) though real world data remain limited. Therefore, the aim of this study was to evaluate the acceptability, effectiveness, and safety of PP6M in patients with schizophrenia in real world practice.MethodsData were derived from a naturalistic cohort of patients enrolled in the international, multicenter, prospective Paliperidone-2-per Year (P2Y) study. In this 2-year mirror-image study we compare the number of hospital admissions 1 year pre- and post-PP6M initiation as well as the CGI scores at baseline and the point of each PP6M administration. Discontinuation rates and reasons were also collected.ResultsA total of 201 patients (107 outpatients and 94 chronic long-stay inpatients) were included. The majority of patients had switched to PP6M from either PP3M (76%) or PP1M (19%) while the 3% switched from aripiprazole 1-monthly and the 2% from risperidone-LAI and zuclopenthixol-LAI. The mean CGI-Severity score significantly reduced from baseline to the second and third PP6M administrations in the global cohort (2.31 ± 0.14 vs. 3.23, p=0.001) as well as in both subgroups. Moreover, the number of hospital admissions decreased from 0.2 ± 0.04 1-year period before to 0.07 ± 0.02 1 year after PP6M initiation (p=0.001). Only 6%, (12 patients, 10 out- and 2 inpatients) discontinued treatment at 1 year of follow-up; Kaplan-Meier curves demonstrated significant differences in PP6M treatment discontinuation between out- and inpatients (p=0.012). The main reason for discontinuation was lack of adherence (5 patients) while only 1 patient stopped treatment due to tolerability issues (extrapyramidal side effects).ConclusionsThis is the first mirror-image study in patients with schizophrenia treated with PP6M in real-world settings showing very high treatment persistence, reduced hospital admissions compared to previous LAIs and no major safety concerns. Our findings suggest that six-monthly treatment with a long-acting antipsychotic may confer additional benefits in the management of schizophrenia. Nonetheless, we were unable to determine the precise changes in symptoms. Therefore, future studies are needed to truly establish the role of PP6M.

Relapses are frequent in schizophrenia and other psychotic disorders. While long-acting injectable antipsychotics (LAIs) are effective in preventing hospital admissions and improving adherence and patient outcomes, they are still under-utilised. Furthermore, evidence from newer formulations and longitudinal studies, despite their commonly long-term use, remains limited. To address this scarcity of data, this study aims to evaluate the long-term effectiveness and acceptability of once-monthly Aripiprazole long-acting injectable (ALAI), the only third-generation antipsychotic available in long-acting formulation. In this pragmatic, independent, ten-year mirror-image study conducted within a large urban mental health service in London, UK, we assessed hospital admission rates and treatment retention over 5 years following ALAI initiation in a naturalistic adult cohort. Frequency and length of hospitalisations in the 5 years pre- and post-initiation were recorded using electronic records, as were discontinuation rates and reasons. Separate analyses were performed comparing outcomes between treatment completers and discontinuers, as well as between those with schizophrenia vs other diagnoses. In total, 135 patients were included in the study (63% with Schizophrenia, 37% with other diagnoses). The discontinuation rate was 47% at 5 years (23.7%, 13.6%, 7.9%, 7.3% and 5.3% in years 1 to 5 respectively). Among the 53% who completed 5 years of ALAI treatment, we observed an 88.5% reduction in mean number (1.57 to 0.18, p < 0.001) and a 90% reduction in mean length of hospitalizations compared to 5 years pre-ALAI initiation (103 to 10 days, p < 0.0001). Median admissions and length fell from 1 to 0 and 68 to 0 days (p < 0.001), respectively. In contrast, discontinuers (47%) exhibited inferior outcomes and showed only a 29.9% reduction in admissions over 5 years. Patients were more likely to discontinue due to poor compliance and ineffectiveness and rarely due to tolerability issues. Apart from switching to ALAI from another LAI, there were no major clinical or demographic predictors of treatment continuation. Outcomes were consistent independent of diagnosis. Potential confounders however must not be overlooked, such as the exclusion of a large number of patients due to strict eligibility criteria as well as changes to healthcare policy over the study period. This is the first study to report 5-year hospitalisation and treatment persistence outcomes with ALAI. Its sustained use was associated with substantial reductions in hospital use, with 85% of completers requiring no further admissions, compared to 30% of discontinuers. These real-world findings support the long-term value of ALAI and may help address common barriers to LAI adoption in clinical decision-making.

IntroductionNon-verbal behaviours (NVBs) reveal information about mood and emotions, potentially providing an objective means to measure and monitor early treatment responses. Previous research has examined NVB changes during treatment in patients with depression and psychosis but a systematic evaluation of the evidence is lacking. Furthermore, this review could inform the fast moving field of digital and precision psychiatry due to the use of AI-based technology that could transform the potential of NVBs as reliable biomarkers for treatment response. MethodsMedline, Embase, PsycINFO and CINAHL were searched in June 2024. Included papers studied adults diagnosed with depression or schizophrenia and measured NVBs at least twice during separate clinical interviews. Outcomes of interest were changes in clinical symptoms and NVBs following treatment initiation. Treatment strategies included hospitalisation, pharmacological, psychological, neuromodulatory, other non-standardised interventions, or a combination of approaches. Two reviewers independently extracted data and assessed risk of bias. The protocol for the review was registered on PROSPERO.Results20 papers were identified; 15 on depression, two on schizophrenia and three evaluating both conditions separately. Methodological variations across studies made comparisons challenging. NVBs consistently associated with improvement in depression symptoms included: increased smiling, facial expressivity, and amplified head and body movements. Results across studies were more consistent when considering general categories of behaviour, versus discrete facial behaviours. No commonalities were observed in NVB changes over time for patients with schizophrenia. DiscussionThe existing evidence is presently insufficient to establish distinct behavioural profiles for clinical improvement depression or schizophrenia. Despite implicit challenges, there is considerable future scope in the evaluation of NVBs as predictors of clinical outcomes or change.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42022368599.

BACKGROUND: Post-COVID-19 syndrome has affected millions of people, with rehabilitation being at the center of non-pharmacologic care. However, numerous published studies show conflicting results due to, among other factors, considerable variation in subject characteristics. Currently, the effects of age, sex, time of implementation, and prior disease severity on the outcomes of a supervised rehabilitation program after COVID-19 remain unknown. METHODS: This was a non-randomized case-control study. Subjects with post-COVID-19 sequelae were enrolled. Among study participants, those who could attend an 8-week, supervised rehabilitation program composed the intervention group, whereas those who couldn't the control group. Measurements were collected at baseline and 8 weeks thereafter. RESULTS: Study groups (N = 119) had similar baseline measurements. Participation in rehabilitation (n = 47) was associated with clinically important improvements in the 6-min walk test (6MWT) distance, adjusted (for potential confounders) odds ratio (AOR) 4.56 (95% CI 1.95-10.66); 1-min sit-to-stand test, AOR 4.64 (1.88-11.48); Short Physical Performance Battery, AOR 7.93 (2.82-22.26); health-related quality of life (HRQOL) 5-level EuroQol-5D (Visual Analog Scale), AOR 3.12 (1.37-7.08); Montreal Cognitive Assessment, AOR 6.25 (2.16-18.04); International Physical Activity Questionnaire, AOR 3.63 (1.53-8.59); Fatigue Severity Scale, AOR 4.07 (1.51-10.98); Chalder Fatigue Scale (bimodal score), AOR 3.33 (1.45-7.67); Modified Medical Research Council dyspnea scale (mMRC), AOR 4.43 (1.83-10.74); Post-COVID-19 Functional Scale (PCFS), AOR 3.46 (1.51-7.95); and COPD Assessment Test, AOR 7.40 (2.92-18.75). Time from disease onset was marginally associated only with 6MWT distance, AOR 0.99 (0.99-1.00). Prior hospitalization was associated with clinically important improvements in the mMRC dyspnea scale, AOR 3.50 (1.06-11.51); and PCFS, AOR 3.42 (1.16-10.06). Age, sex, and ICU admission were not associated with the results of any of the aforementioned tests/grading scales. CONCLUSIONS: In this non-randomized, case-control study, post-COVID-19 rehabilitation was associated with improvements in physical function, activity, HRQOL, respiratory symptoms, fatigue, and cognitive impairment. These associations were observed independently of timing of rehabilitation, age, sex, prior hospitalization, and ICU admission.

Background:Emotionally unstable personality disorder (EUPD) is debilitating psychiatric disorder, particularly common in female and forensic populations. However, appropriate pharmacological treatment to effectively manage symptoms of EUPD remains an unmet clinical need. Dopamine receptor partial agonists (DRPAs), such as aripiprazole, have a favourable tolerability profile and have demonstrated some benefits in targeting symptoms of emotional dysregulation, although, evidence regarding the effects of novel D2/D3 DRPA cariprazine in EUPD patients has been limited. Objectives:To evaluate the efficacy and tolerability of cariprazine for EUPD in a case series of female forensic inpatients where the diagnosis is more prevalent. Methods:Demographic and clinical information of the patients were collected from patient electronic records during their admission in a specialized NHS forensic service. Treatment response was measured using the Positive and Negative Syndrome Scale (PANSS) at baseline, 3 and 6 months and Global Clinical Impression Scale (CGI-scores) at baseline and 6 months. Tolerability and BMI, ECG QTc interval and prolactin levels were recorded prior to initiation and at 6 months. Results:Eight female patients with EUPD (mean age 29.8 years, SD 5.3) were treated with cariprazine (range 3-6mg). Total CGI-scores modestly improved from 5.6 baseline to 5.0 at 6 months. There was a reduction in mean total PANSS scores from baseline to 6 months (92.5, SD 8.1 to 72.4, SD 15.8), general psychopathology (56.1 SD 6.7 to 42.5, SD9.7), positive (21.9 SD 4.6 to 17.1, SD4.8) and negative PANSS scores (14.5 SD 6.3 to 12.8, SD4.6), corresponding to a 21%, 23%, 20% and 3% mean score reduction, respectively. Cariprazine demonstrated a favourable metabolic and hormonal side effect profile with no treatment discontinuation at 6 months follow up. Conclusion:This is the first case series to evaluate the effectiveness of cariprazine in EUPD. Its efficacy in improving PANSS and CGI-S scores was overall modest and highly variable, reflective of an inherently heterogenous and comorbid patient sample but the benefits on treatment perseverance and tolerability were considerable. Cariprazine may be of particular benefit in EUPD where psychotic symptoms are co-morbid, as an augmentation strategy to clozapine, or where previous antipsychotics have caused metabolic or hormonal side effects.

Background The aim of this systematic review and meta-analysis is to evaluate and compare the prevalence rates of spontaneous movement disorders (SMDs), including dyskinesia, parkinsonism, akathisia and dystonia, in antipsychotic-na & iuml;ve individuals with chronic psychosis and first-episode psychosis (FEP) and gain a more nuanced understanding of factors influencing their presence. Methods Several literature databases were systematically searched and screened based on predetermined eligibility criteria. Included articles underwent risk of bias assessment. The prevalence rates of SMDs were calculated using a random-effects model. Results Out of 711 articles screened, 27 were included in this meta-analysis. The pooled prevalence of spontaneous dyskinesia was 7% (3% FEP and 17% chronic schizophrenia) across 24 studies (95% CI 3 to 11; I2=94%, p<0.01) and 15% for spontaneous parkinsonism (14% FEP and 19% chronic schizophrenia) in 21 studies (95% CI 12 to 20; I2=81%, p<0.01). A meta-regression analysis found a significant positive correlation between age (p<0.05) and duration of untreated psychosis (DUP) (p<0.05) with dyskinesia but not parkinsonism prevalence. Akathisia and dystonia appear to be both less studied and less frequent in occurrence with a pooled prevalence of 4% (95% CI: 3 to 6; I2=0%, p=0.65) for akathisia in eight studies and a mean prevalence of 6% (range 0%-16%) for dystonia in five studies. Conclusion The presence of varying degrees of neurodysfunction in antipsychotic-na & iuml;ve patients with schizophrenia underscores the need for individualised treatment approaches that consider each patient's unique predisposition and neuromotor profile. Further research is warranted into the role of specific SMDs and risk factors including sex, race and diagnostic variations. PROSPERO registration number CRD42024501951.