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: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.

Background Cariprazine, a novel antipsychotic drug that is a partial agonist with preferential binding to the D3 receptor, has demonstrated efficacy in clinical trials across all symptom domains, including negative symptoms, which can occur early in the course of psychotic illness. However, evidence, to date regarding its effects in early psychosis patients with primary negative symptoms has been limited. Objectives To evaluate the efficacy of cariprazine for negative symptoms in early psychosis patients. Methods Demographic and clinical information of the study population were collected from the electronic records and PANSS scale administered at baseline, 3 and 6 months. Tolerability and discontinuation reasons, where applicable, were also recorded. Results Ten patients with early psychosis (four men and six women, mean age – 25.5 years) with prominent or predominant negative symptoms were treated with cariprazine (range 1.5 – 3 mg). Three patients discontinued cariprazine within the first 3 months due to patient choice, lack of response and non-compliance, respectively. In the remaining patients, there was a significant reduction in the mean negative PANSS score from baseline to 6 months (from 26.3 to 10.6), mean total PANSS score (from 81.4 to 43.3) and in the mean positive PANSS score (from 14.4 to 9.9) which correspond to a 53.1, 41.5, and 28.5% mean score reduction. Conclusion This pilot study suggests that cariprazine is a safe and effective treatment in early psychosis, particularly for the alleviation of negative symptoms which remains an area of unmet treatment need.

Background: Cariprazine, a novel antipsychotic drug, is a partial agonist of dopamine D2/D3 receptors with preferential binding to the D3 receptor. There has been an increasing interest in cariprazine augmentation to clozapine; however, the evidence thus far has been only limited to case reports and case series. Objectives: To evaluate the efficacy and safety of the augmentation of clozapine with cariprazine in patients with sub-optimal treatment response. Methods: Demographic and clinical information of the study population were collected from the electronic records and PANSS scale administered at baseline and 3 months. Tolerability and discontinuation reasons where applicable were also recorded. Results: Ten patients (four men and six women) with a mean age of 36.5 years (range = 26–45) were included. Reasons for cariprazine initiation included inadequate treatment response, persistent negative symptoms and/or tolerability issues with clozapine or previous augmentation options. Two patients discontinued cariprazine within the first 6 weeks due to restlessness and poor response, respectively. There was a significant reduction in the median total PANSS score from baseline to 3 months (from 59 to 22.5, p < 0.05), median positive PANSS score (from 11.5 to 5.5, p < 0.05) and in the median negative PANSS score (from 15.5 to 3, p < 0.05) which correspond to a 48%, 33.8% and 65.8% mean score reduction, respectively. Conclusion: This is the first pilot study evaluating the effectiveness of clozapine augmentation. The preliminary evidence suggests that this may be a safe and effective practice in patients failing to adequately respond to or tolerate clozapine and/or previous augmentation strategies.

1West London NHS Trust, London, UK; 2Division of Psychiatry, Imperial College London, London, UK; 3Central and North West London NHS Foundation Trust, London, UK Objective: We aim to systematically review evidence for a relationship between antipsychotic-induced akathisia and suicidal behaviour, in order to guide further clinical decision making in this area. Methods: Several electronic databases (Embase, Medline, Cochrane and PsychINFO) were systemically searched for articles published up to February 2021, using search terms related to akathisia, antipsychotics and suicidal behaviour. Two reviewers independently evaluated all the relevant studies using predetermined criteria and assessed the risk of bias for each included study. The systematic review was conducted in line with PRISMA methodology and reporting. Results: Following de-duplication, screening and application of exclusion criteria, four eligible studies were identified. All of the available studies were in English and included adult patients. Nevertheless, there was significant variability regarding methodology and overall quality was deemed low due to small sample sizes. There was insufficient data to perform statistical analyses of the results. Of the four studies, two found a weak correlation between antipsychotic-related akathisia and suicidal behaviour, a finding that was not supported by the remaining two studies. Conclusion: The search yielded very few studies for inclusion. On the basis of the existing evidence, akathisia cannot be reliably linked to the presence of suicidal behaviour in patients treated with antipsychotic medication. However, proactive screening for emerging suicidal behaviour in this vulnerable patient group is advisable. Our findings highlight the pressing need for further research in this area.

OBJECTIVE:We aim to systematically review evidence for a relationship between antipsychotic-induced akathisia and suicidal behaviour, in order to guide further clinical decision making in this area.METHODS:Several electronic databases (Embase, Medline, Cochrane and PsychINFO) were systemically searched for articles published up to February 2021, using search terms related to akathisia, antipsychotics and suicidal behaviour. Two reviewers independently evaluated all the relevant studies using predetermined criteria and assessed the risk of bias for each included study. The systematic review was conducted in line with PRISMA methodology and reporting.RESULTS:Following de-duplication, screening and application of exclusion criteria, four eligible studies were identified. All of the available studies were in English and included adult patients. Nevertheless, there was significant variability regarding methodology and overall quality was deemed low due to small sample sizes. There was insufficient data to perform statistical analyses of the results. Of the four studies, two found a weak correlation between antipsychotic-related akathisia and suicidal behaviour, a finding that was not supported by the remaining two studies.CONCLUSION:The search yielded very few studies for inclusion. On the basis of the existing evidence, akathisia cannot be reliably linked to the presence of suicidal behaviour in patients treated with antipsychotic medication. However, proactive screening for emerging suicidal behaviour in this vulnerable patient group is advisable. Our findings highlight the pressing need for further research in this area.

Serious mental illnesses (SMI) such as schizophrenia and bipolar disorder first develop between ages 14 and 25. Once diagnosed, young peoples’ health can deteriorate, and it is therefore vital to detect this early to prevent severe outcomes including hospitalisations and deaths by suicide. The main study aim is to describe and discuss observational studies that examine signs of deterioration in young patients with SMI. A systematic review guided by the published protocol was conducted. Cumulative Index to Nursing and allied Health Literature (CINAHL), MEDLINE, Embase, PsycINFO, Health Management Information Consortium (HMIC) and Web of Science were searched against pre-defined criteria until 1 March 2021. Observational studies were extracted according to design, country, participant, indicator, outcome and main finding categories. Quality was assessed independently using the Newcastle Ottawa Scale (NOS). Of the 15,788 publications identified, 5 studies were included and subjected to narrative synthesis. Two indicators of mental health deterioration were identified: cognitive functioning (decline, worsening and poor school/academic performance) and expressed emotion status. Indicators revealed mixed views on predicting deterioration. Worsening cognitive functioning and expressed emotion status significantly predicted medication non-adherence and relapse respectively. However, a decline in cognitive functioning (poor academic performance) was not found to significantly correlate to deaths by suicide. Study quality was mostly poor and associations between indicators and varied outcomes were weak. The heterogeneous nature of the data made comparisons difficult and did not allow for further statistical analysis. To our knowledge, this is the first review of observational studies to identify indicators of deterioration in young patients with SMI. Worsening cognitive functioning and expressed emotion status could indicate non-adherence and relapse in young patients with SMI but larger sample sizes in good quality studies are needed. The dearth of observational studies means further research is required to ascertain other indicators of deterioration before serious outcomes occur. This work was supported by the National Institute for Health Research (NIHR) Imperial Patient Safety Translational Research Centre via an NIHR programme grant. The authors are also grateful for support from the NIHR under the Applied Health Research programme for North West London and the NIHR Imperial Biomedical Research Centre. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This systematic review has been registered on PROSPERO (registration number: CRD42017075755 ).