Baseline Antipsychotic Dose and Transition to Psychosis in Individuals at Clinical High Risk: A Systematic Review and Meta-Analysis.

Importance: Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics is associated with an increased risk of transitioning to psychosis in individuals at clinical high-risk for psychosis (CHR-P) and that such effect is not a result of pretest risk enrichment. However, to maximize its translational utility for prognostic stratification in clinical practice, testing for the potential presence of a dose-response association is crucial. Objective: To test whether the negative prognostic effect of baseline antipsychotic exposure in individuals at CHR-P follows a dose-effect pattern, as indicated by mean chlorpromazine equivalent doses (CPZ-ED). Data Sources: MEDLINE and Cochrane Library, performed up to August 31, 2023, searching for English-language studies on individuals at CHR-P reporting data on exposure to antipsychotics at baseline and detailed information on dosage by transition status. Study Selection: Studies that provided information on antipsychotic exposure at baseline and included detailed dosage data categorized by transition status. Data Extraction and Synthesis: Eligible studies were identified following PRISMA guidelines and evaluated independently by 2 reviewers with the Newcastle-Ottawa Scale for assessing the quality of nonrandomized studies in meta-analyses. Main Outcomes and Measures: The primary outcome was transition to psychosis in individuals at CHR-P who were receiving antipsychotic treatment at baseline, measured by baseline mean CPZ-ED in individuals at CHR-P who transitioned to psychosis compared to those who did not. Results: Eight studies were included in the systematic review and meta-analysis. Among 290 individuals at CHR-P (mean [SD] age, 19.4 [2.6] years) who were exposed to antipsychotics at baseline and remained in contact up to the completion of the study, 66 converted to psychosis and 224 did not. The mean CPZ-ED ranged 60 to 395 mg/d in those who converted and 13 to 224 mg/d in those who did not. Those who converted to psychosis had higher CPZ-ED than those who did not in both the common-effects model (Hedges g, 0.41; 95% CI, 0.12-0.70; z, 2.78; P = .005) and in the random-effects model (Hedges g, 0.41; 95% CI, 0.15-0.67; z, 3.69; P = .008; τ2, 0.0). There was no relevant heterogeneity (Cochran Q, 3.99; df, 7; P = .78; I2, 0.0%; 95% CI, 0.0-68.0). The radial plot indicated a good fit of the model. Conclusions and Relevance: In individuals at CHR-P who were exposed to antipsychotics at baseline, those receiving higher antipsychotic doses demonstrated an increased likelihood of transitioning to psychosis. This meta-analytic evidence of putative dose-effect association confirms that baseline antipsychotic exposure and the corresponding dosage carry salient prognostic information that could improve current CHR-P criteria-based risk stratification at inception.

Debate: The prevention of psychosis in child and adolescent mental health services.

Psychopathological conditions in adolescence and young adulthood often result from an altered neurodevelopment already phenotypically expressed in childhood. Child and adolescent mental health services are ideally placed to intercept in the developmental trajectories of younger adolescents and contribute to the early detection of a risk for psychosis, as proposed by Salazar de Pablo and Arango (2023, Child and Adolescent Mental Health), opening a debate to which we contribute. The early detection of a specific risk for psychosis and of a broader risk for severe mental illness requires an understanding of the clinical staging of psychosis, neurodevelopmental antecedents of severe mental illness and of heterotypic trajectories between childhood phenotypes and adult disorders.

Development and Validation of the Questionnaire for Adaptive Hyperactivity and Goal Achievement (AHGA).

Objective: This paper illustrates the preliminary psychometric properties of the Questionnaire for Adaptive Hyperactivity and Goal Achievement (AHGA), aimed at measuring adaptive characteristics of hyperactivity and goal pursuit in older adults. Methods: The 12-item scale was administered to a sample of 120 subjects (older adults) between February 2022 and June 2022. The reliability of AHGA was measured using Cronbach's alpha, and factor structure was established using parallel analysis (PA) and principal component analysis (PCA). Convergent validity was tested against the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). Results: All included subjects have an average age of 74.1±5.1 years. AHGA reliability was good (Cronbach's alpha: 0.713 [95%CI: 0.630 to 0.783]). Factor analysis suggested two main components: goal achievement and hyperactivity, which explained 41% of the variance in the data. The results support the convergent validity of the scale: AHGA measures adaptive characteristics of hyperactivity and goal pursuit, in contrast to BRIAN, which measures pathological characteristics. Conclusion: The reported findings represent an innovative approach to hyperthymic features by embracing a broader spectrum concept that conceptualizes the potential transition between pathological and adaptive aspects as a continuum.

The impact of MDQ positivity on quality of life impairment: Does it support the hypothesis of "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS)?

Background: DSM-5 separates bipolar (BD) from depressive disorders, but some experts consider BD as part of a spectrum of mood disorders. The interpretation of numerous false positives of BD screened by the Mood Disorders Questionnaire (MDQ) is part of this debate. Recent study results suggest that the worsening of health-related quality of life (H-Qol) associated with MDQ positivity does not depend solely on mood disorders. This study aims to clarify whether the impairment may be due to other concomitant disorders, unrelated to mood disorders, leading to a worsening of H-Qol. Additionally, the study aims to explore if MDQ positivity itself observe clinical significance. Design and methods: The study involved pairs of cases (MDQ+) and controls (MDQ-) matched for sex, age, and absence of DSM-IV psychiatric comorbidity. The impact of MDQ positivity on the quality of life in a sample of MDQ+ comorbid with MDD was measured and compared to impact of MDD in other chronic disorders. Results: The H-Qol was significantly worse in MDQ+ than in controls (both groups without any psychiatric co-morbidity). The worsening was similar to severe chronic disorders The burden of worsening quality of life due to MDD was mild in another sample of MDQ positives with comorbid MDD. Conclusion: The study hypothesizes that MDQ positivity may be related to hyperactivation and dysregulation of rhythms typical of stress disorders. In fact, MDQ+ was found strongly related to sleep disturbances. Future studies could verify if a "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS), causes worsening the H-Qol in MDQ+.

An update on the pharmacotherapeutic strategies for the treatment of dysthymic disorder: a systematic review.

INTRODUCTION: Longer treatment times, more comorbidity, more severe impairments in social, psychological, and emotional functioning, increased healthcare use, and more hospitalizations are all factors that are related to dysthymia. Given the significant prevalence of dysthymia (including persistent depressive disorder) worldwide, its comorbidity with several mental disorders, and the detrimental effects of these comorbidities, it is important to conduct a systematic review to compare the effects of pharmacological acute and maintenance treatments for dysthymia with placebo and standard care in the last 10 years, based on the publication of DSM5. AREAS COVERED: This systematic review was performed according to PRISMA guidelines. Databases, including PubMed and Cochrane Central Register of Controlled Trials, were searched to assess the effects of pharmacological acute and maintenance treatments for dysthymia in comparison with placebo and treatment as usual. EXPERT OPINION: Our review shows that SSRIs and SNRIs present efficacy for dysthymia treatment, and L-Acetylcarnitine should be investigated further for this condition in elderly patients. The comparison of antidepressant medication versus placebo showed coherent results based on three studies favoring pharmacotherapy as an effective treatment for participants with dysthymia. However, the scarcity of research on continuation and maintenance therapy in people with dysthymia highlights the need for more primary research.

The Nepean Belief Scale (NBS) as a tool to investigate the intensity of beliefs in anorexia nervosa: psychometric properties of the Italian version.

BACKGROUND: People with anorexia nervosa (AN) show a peculiar impairment of insight regarding their condition, often manifesting a denial of extreme emaciation and sometimes hiding or underreporting socially undesirable abnormal eating patterns. Sometimes the intensity of the beliefs held by patients with AN reach a delusional intensity. OBJECTIVES: In this study, the Italian version of the Nepean Belief Scale was applied to a sample of patients diagnosed with AN to investigate the intensity of their beliefs and convictions and its clinical correlates. METHODS: The Nepean Belief Scale (NBS) was translated and adapted to Italian and applied to a sample of patients diagnosed with AN based on the Structured Clinical Interview for DSM-5 (SCID-5). RESULTS: The Italian version of the 5-item NBS showed excellent reliability. Convergent validity was proved by negative association with levels of insight measured with the Schedule for the Assessment of Insight in Eating Disorders. Beliefs of delusional intensity were reported by 10% of participants. Those with a greater intensity of beliefs, either overvalued or delusional ideas, were more likely to report poorer general cognitive performances on the Montreal Cognitive Assessment. No association was observed between NBS score and age, body mass index, symptoms of eating disorders, body dissatisfaction, or levels of depression. Fear of weight gain and control seeking were the most often reported themes at the NBS. CONCLUSIONS: The Italian version of the NBS is a reasonably reliable, valid, and usable tool for the multidimensional assessment of insight in AN. Level of evidence Level III, Evidence obtained from well-designed cohort or case-control analytic studies.

Baseline benzodiazepine exposure is associated with greater risk of transition in clinical high-risk for psychosis (CHR-P): a meta-analysis.

BACKGROUND: Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics and to antidepressants in individuals at clinical high-risk for psychosis (CHR-P) have opposite prognostic effects as regards imminent transition to psychosis, with antipsychotics associated with higher risk and antidepressants associated with a lower risk in comparison to not-exposed individuals. Despite their common use, baseline exposure to benzodiazepines (BDZ) in CHR-P has surprisingly received poor attention as a potential risk modulator for transition to psychosis. The current systematic review and meta-analysis were performed to fix such a knowledge gap. METHODS: Systematic scrutiny of Medline and Cochrane library, performed up to 31 December 2022, searching for English-language studies on CHR-P reporting numeric data about the sample, the transition outcome at a predefined follow-up time and raw data on BDZ baseline exposure in relation to such outcome. RESULTS: Of 1893 identified records, five studies were included in the systematic review and meta-analysis. The proportion of participants with exposure to BDZ at baseline ranged from 5.5% (one study) to 46.2%, with an average of 16.8%. At the end of the period of observation, i.e., the follow-up as reported in the study, 28.4% [95% confidence interval (CI) 19.7-39.1%] participants developed psychosis among the BDZ-exposed against 9.3% (7.3 to 11.9%) among the controls. CHR-P participants who were already under BDZ treatment at baseline had more than double chance of transition to psychosis than CHR-P participants who were BDZ-naïve. The risk ratio (RR) was 2.42 (95% CI 1.38-4.23) in the common effects model (z = 3.09; p = 0.002), and 2.40 (1.53 to 3.77) in the random-effects model (z = 5.40; p = 0.006; tau-squared = 0.0). There was no relevant heterogeneity: Cochran's Q = 1.49; df = 4; p = 0.828; I2 = 0.0% (95% CI 0.0-79%). Quality was good in four studies. CONCLUSIONS: Ongoing BDZ exposure at inception in CHR-P is associated with a higher risk of transition to psychosis at follow up. This meta-analytic association, which echoes a similar effect of baseline antipsychotic exposure, plausibly indicates that the clinicians' prescription of pharmacological intervention captures some form of prognostically-relevant information (e.g. an anxiety permeated mental state requiring BDZ prescription) that are not adequately encompassed by current CHR-P categorical criteria.

Prevalence and outcomes of rapid cycling bipolar disorder: Mixed method systematic meta-review.

Rapid-cycling in bipolar disorder (RC-BD) is associated with greater illness morbidity and inferior treatment response but many aspects remain unclear, prompting this systematic review of its definitions, prevalence, and clinical characteristics. We searched multiple literature databases through April 2022 for systematic reviews or meta-analyses on RC-BD and extracted associated definitions, prevalence, risk-factors, and clinical outcomes. We assessed study quality (NIH Quality Assessment Tool) and levels of evidence (Oxford criteria). Of 146 identified reviews, 22 fulfilling selection criteria were included, yielding 30 studies involving 13,698 BD patients, of whom 3777 (27.6% [CI: 26.8-28.3]) were considered RC-BD, as defined in 14 reports by ≥4 recurrences/year within the past 12 months or in any year, without considering responsiveness to treatment. Random-effects meta-analytically pooled one-year prevalence was 22.3% [CI: 14.4-32.9] in 12 reports and lifetime prevalence was 35.5% [27.6-44.3] in 18 heterogenous reports. Meta-regression indicated greater lifetime prevalence of RC-BD among women than men (p=0.003). Association of RC-BD with suicide attempts, and unsatisfactory response to mood-stabilizers was supported by strong evidence (Level 1); associations with childhood maltreatment, mixed-features, female sex, and type-II BD had moderate evidence (Level 2). Other factors: genetic predisposition, metabolic disturbances or hypothyroidism, antidepressant exposure, predominant depressive polarity (Level 3), along with greater illness duration and immune-inflammatory dysfunction (Level 4) require further study. RC-BD was consistently recognized as having high prevalence (22.3%-35.5% of BD cases) and inferior treatment response. Identified associated factors can inform clinical practice. Long-term illness-course, metabolic factors, and optimal treatment require further investigation.

Psychosocial determinants of healthcare use costs in kidney transplant recipients.

Introduction: Psychosocial factors frequently occur in kidney transplant recipients (KTRs), leading to behavioral alterations and reduced therapeutic adherence. However, the burden of psychosocial disorders on costs for KTRs is unknown. The aim of the study is to identify predictors of healthcare costs due to hospital admissions and emergency department access in KTRs. Methods: This is a longitudinal observational study conducted on KTRs aged >18 years, excluding patients with an insufficient level of autonomy and cognitive disorder. KTRs underwent psychosocial assessment via two interviews, namely the Mini-International Neuropsychiatric Interview 6.0 (MINI 6.0) and the Diagnostic Criteria for Psychosomatic Research Interview (DCPR) and via the Edmonton Symptom Assessment System Revised (ESAS-R) scale, a self-administrated questionnaire. Sociodemographic data and healthcare costs for hospital admissions and emergency department access were collected in the 2016-2021 period. Psychosocial determinants were as follows: (1) ESAS-R psychological and physical score; (2) symptomatic clusters determined by DCPR (illness behavior cluster, somatization cluster, and personological cluster); and (3) ICD diagnosis of adjustment disorder, anxiety disorder, and mood disorder. A multivariate regression model was used to test the association between psychosocial determinants and total healthcare costs. Results: A total of 134 KTRs were enrolled, of whom 90 (67%) were men with a mean age of 56 years. A preliminary analysis of healthcare costs highlighted that higher healthcare costs are correlated with worse outcomes and death (p < 0.001). Somatization clusters (p = 0.020) and mood disorder (p < 0.001) were positively associated with costs due to total healthcare costs. Conclusions: This study showed somatization and mood disorders could predict costs for hospital admissions and emergency department access and be possible risk factors for poor outcomes, including death, in KTRs.

The temporal dynamics of transition to psychosis in individuals at clinical high-risk (CHR-P) shows negative prognostic effects of baseline antipsychotic exposure: a meta-analysis.

Meta-analytic evidence indicates that baseline exposure to antipsychotics (AP) in individuals at clinical high-risk for psychosis (CHR-P) is associated with an even higher risk of transition to psychosis. However, the temporal dynamics of such prognostic effect have not been clarified yet. This study was therefore designed to address this knowledge gap. We performed a systematic review and meta-analysis of all longitudinal studies published up to 31 December 2021 on CHR-P individuals identified according to a validated diagnostic procedure and reporting numeric data of transition to psychosis according to baseline antipsychotic exposure. 28 studies covering a total of 2405 CHR-P were included. 554 (23.0%) were exposed to AP at baseline, whereas 1851 (77.0%) were not. At follow-up (12 to 72 months), 182 individuals among AP-exposed (32.9%; 95% CI: 29.4% to 37.8%) and 382 among AP-naive CHR-P (20.6%; 18.8% to 22.8%) developed psychosis. Transition rates increased over time, with the best-fit for an ascending curve peaking at 24 months and reaching then a plateau, with a further increase at 48 months. Baseline AP-exposed CHR-P had higher transition risk at 12 months and then again at 36 and 48 months, with an overall higher risk of transition (fixed-effect model: risk ratio = 1.56 [95% CI: 1.32-1.85]; z = 5.32; p < 0.0001; Random-effect model: risk ratio = 1.56 [95% CI: 1.07-2.26]; z = 2.54; p = 0.0196). In conclusion, the temporal dynamics of transition to psychosis differ in AP-exposed vs. AP-naive CHR-P. Baseline AP exposure in CHR-P is associated with a persistently higher risk of transition at follow up, supporting the rationale for more stringent clinical monitoring in AP-exposed CHR-P. The insufficiency of more granular information in available primary literature (e.g., temporal and quantitative details of AP exposure as well as psychopathological dimensions in CHR-P) did not allow the testing of causal hypotheses on this negative prognostic association.

A Recovery-Oriented Program for People with Bipolar Disorder through Virtual Reality-Based Cognitive Remediation: Results of a Feasibility Randomized Clinical Trial.

BACKGROUND: Cognitive impairment is a frequent consequence of bipolar disorder (BD) that is difficult to prevent and treat. In addition, the quality of the preliminary evidence on the treatment of BD through Cognitive Remediation (CR) with traditional methods is poor. This study aims to evaluate the feasibility of a CR intervention with fully immersive Virtual Reality (VR) as an additional treatment for BD and offers preliminary data on its efficacy. METHODS: Feasibility randomized controlled cross-over clinical study, with experimental condition lasting three months, crossed between two groups. Experimental condition: CR fully immersive VR recovery-oriented program plus conventional care; Control condition: conventional care. The control group began the experimental condition after a three months period of conventional care (waiting list). After the randomization of 50 people with BD diagnosis, the final sample consists of 39 participants in the experimental condition and 25 in the control condition because of dropouts. RESULTS: Acceptability and tolerability of the intervention were good. Compared to the waitlist group, the experimental group reported a significant improvement regarding cognitive functions (memory: p = 0.003; attention: p = 0.002, verbal fluency: p = 0.010, executive function: p = 0.003), depressive symptoms (p = 0.030), emotional awareness (p = 0.007) and biological rhythms (p = 0.029). CONCLUSIONS: The results are preliminary and cannot be considered exhaustive due to the small sample size. However, the evidence of efficacy, together with the good acceptability of the intervention, is of interest. These results suggest the need to conduct studies with larger samples that can confirm this data. TRIAL REGISTRATION: ClinicalTrialsgov NCT05070065, registered in September 2021.

The Impact of COVID-19 Lockdown on Adults with Major Depressive Disorder from Catalonia: A Decentralized Longitudinal Study.

The present study analyzes the effects of each containment phase of the first COVID-19 wave on depression levels in a cohort of 121 adults with a history of major depressive disorder (MDD) from Catalonia recruited from 1 November 2019, to 16 October 2020. This analysis is part of the Remote Assessment of Disease and Relapse-MDD (RADAR-MDD) study. Depression was evaluated with the Patient Health Questionnaire-8 (PHQ-8), and anxiety was evaluated with the Generalized Anxiety Disorder-7 (GAD-7). Depression's levels were explored across the phases (pre-lockdown, lockdown, and four post-lockdown phases) according to the restrictions of Spanish/Catalan governments. Then, a mixed model was fitted to estimate how depression varied over the phases. A significant rise in depression severity was found during the lockdown and phase 0 (early post-lockdown), compared with the pre-lockdown. Those with low pre-lockdown depression experienced an increase in depression severity during the "new normality", while those with high pre-lockdown depression decreased compared with the pre-lockdown. These findings suggest that COVID-19 restrictions affected the depression level depending on their pre-lockdown depression severity. Individuals with low levels of depression are more reactive to external stimuli than those with more severe depression, so the lockdown may have worse detrimental effects on them.

Psychosocial and behavioural interventions for the negative symptoms of schizophrenia: a systematic review of efficacy meta-analyses.

BACKGROUND: Currently there is no first-line treatment recommended for the negative symptoms of schizophrenia. Psychosocial and behavioural interventions are widely used to reduce the burden of negative symptoms. Meta-analytic studies have summarised the evidence for specific approaches but not compared evidence quality and benefit. AIM: To review and evaluate the evidence from meta-analytic studies of psychosocial and behavioural interventions for the negative symptoms of schizophrenia. METHOD: A systematic literature search was undertaken to identify all meta-analyses evaluating psychosocial and behavioural interventions reporting on negative symptom outcomes in people with schizophrenia. Data on intervention, study characteristics, acceptability and outcome were extracted. Risk of bias was evaluated. Results were summarised descriptively, and evidence ranked on methodological quality. RESULTS: In total, 31 systematic reviews met the inclusion criteria evaluating the efficacy of negative symptom interventions on 33 141 participants. Exercise interventions showed effect sizes (reduction in negative symptoms) ranging from -0.59 to -0.24 and psychological interventions ranging from -0.65 to -0.04. Attrition ranged between 12% to 32%. Across the studies considered heterogeneity varied substantially (range 0-100). Most of the reviews were of very low to low methodological quality. Methodological quality ranking suggested that the effect size for cognitive remediation and exercise therapy may be more robust compared with other approaches. CONCLUSIONS: Most of the interventions considered had a small-to-moderate effect size, good acceptability levels but very few had negative symptoms as the primary intervention target. To improve the confidence of these effect sizes being replicated in clinical settings future studies should minimise risk of bias.

Implementation of early intervention clinical services within the National Health System in Italy: Third wave survey with focus on structures, resources, and fidelity to the evidence-based model.

BACKGROUND: Early intervention in psychosis (EIP) is a well-established approach aimed at detecting and treating early signs and symptoms of psychosis to prevent its long-term consequences. The present study aimed at detailing the current status of EIP services in Italy, covering all the Departments of Mental Health (DMHs) operating in 2018. METHODS: All directors of public DMHs operating in Italy in 2018 (n = 127) were invited to fill in a Census form about EIP structure and activities. The first episode psychosis services fidelity scale (FEPS-FS) was used to investigate fidelity to the EIP model of the centre. RESULTS: An active EIP service was reported by 41 DMHs (32% of the total DMHs; 56% of those who took part in the survey). Most EIP services had an autonomous team. The large majority of the Italian EIP centres provided psychosocial interventions to their patients, principally psychotherapy, family support, and psychoeducation. Among those with an active EIP, 29 DMHs filled in the FEPS-FS. Internal consistency was good when based on the replies of the respondents, but reliability was weak when measured on the basis of an independent evaluation (Cohen's kappa = 0.571). The fidelity to the guidelines for early intervention was uneven, with some criteria met by most centres, especially those peculiar to the Italian community psychiatry. CONCLUSION: A further spreading of the early intervention model across the Italian DMHs was found. A lack of resources might limit the use of specific psychosocial treatments, such as cognitive-behavioural therapy or manualized family support.

Subclinical psychotic symptoms in Indian adults: Application of the Community Assessment of Psychic Experiences (CAPE).

BACKGROUND: The study investigated the psychometric properties of the Community, Assessment of Psychic Experiences (CAPE-42), a self-report instrument in Indians. METHOD: CAPE-42 was translated in Hindi and tested on 312 Indian adults recruited online and through paper-pencil assessment. Confirmatory factor analysis (CFA) was employed to establish the factor structure of the positive, negative and depressive dimensions of CAPE-42: the bifactor model was tested to evaluate whether items converge into a major single factor defining psychotic-proneness in individuals. Latent class analysis (LCA) was conducted to identify subgroups with a different endorsement of subclinical psychotic symptoms. , RESULTS: CAPE-Hindi showed good reliability (Cronbach's alpha>0.80). CFA confirmed, a good fit for the bifactor model, factor loading was acceptable for all items in the general factor (Omega-h =0.83) and explained the primary variance of the subscales. Residual variance was explained by the positive, negative and depressive factors (Omega H =0.33, 0.04 and 0.12, respectively). LCA identified three classes traceable, to the three dimensions; a low endorsement group (n = 155; 50 %); a less consistent, group with endorsement on positive and depressive items (n = 117; 38 %), and a high, endorsement group (n = 40;13 %). CONCLUSION: Hindi CAPE-42 showed good reliability and factorial validity.

Fully Immersive Virtual Reality-Based Cognitive Remediation for Adults with Psychosocial Disabilities: A Systematic Scoping Review of Methods Intervention Gaps and Meta-Analysis of Published Effectiveness Studies.

BACKGROUND: Cognitive Remediation (CR) programs are effective for the treatment of mental diseases; in recent years, Virtual Reality (VR) rehabilitation tools are increasingly used. This study aimed to systematically review and meta-analyze the published randomized controlled trials that used fully immersive VR tools for CR programs in psychiatric rehabilitation. We also wanted to map currently published CR/VR interventions, their methods components, and their evidence base, including the framework of the development intervention of CR in fully immersive VR. METHODS: Level 1 of evidence. This study followed the PRISMA extension for Scoping Reviews and Systematic Review. Three electronic databases (Pubmed, Cochrane Library, Embase) were systematically searched, and studies were included if they met the eligibility criteria: only randomized clinical trials, only studies with fully immersive VR, and only CR for the adult population with mental disorders. RESULTS: We found 4905 (database) plus 7 (manual/citation searching articles) eligible studies. According to inclusion criteria, 11 studies were finally reviewed. Of these, nine included patients with mild cognitive impairment, one with schizophrenia, and one with mild dementia. Most studies used an ecological scenario, with improvement across all cognitive domains. Although eight studies showed significant efficacy of CR/VR, the interventions' development was poorly described, and few details were given on the interventions' components. CONCLUSIONS: Although CR/VR seems to be effective in clinical and feasibility outcomes, the interventions and their components are not clearly described. This limits the understanding of the effectiveness and undermines their real-world implementation and the establishment of a gold standard for fully immersive VR/CR.