Objective: Evidence on the clinical and metabolic characterization of mixed features (MFs) in bipolar disorder (BD) is limited. We performed a cross-sectional study analyzing clinical and metabolic correlates of MFs in people with bipolar depression or mania/hypomania. Methods: We included people with BD consecutively admitted for inpatient treatment from May 2020 to July 2023 as part of the Northern Milan Area Cohort (NOMIAC) project. The SCID-5 was used to confirm the diagnosis and assess DSM-5 specifiers. Young Mania Rating Scale and Montgomery-Asberg Depression Rating Scale were used to measure symptom severity. Information on socio-demographic, clinical, and metabolic conditions - including obesity, diabetes, hypertension, dyslipidemia, and hypothyroidism - were collected. Multiple logistic regression models were used to compare clinical and metabolic correlates between subjects with and without DSM-5 MFs. Results: We included 163 inpatients with BD (111 admitted for a manic/hypomanic episode and 52 for a major depressive episode), 39 of whom with MFs. The overall logistic regression model showed that MFs were associated with anxious distress (z = 2.44; p = 0.015) and obesity (z = 2.39; p = 0.017), also being less frequent among moderately/markedly ill people as compared with those borderline/mildly ill (z = 2.71; p = 0.007). Additional analyses corroborated the association between MFs and these characteristics in people with a depressive episode, though not in those with mania/hypomania. Conclusion: Notwithstanding some limitations, our study provides additional insight into the characterization of individuals with MFs, highlighting that anxious distress and symptom severity, along with obesity, may represent core features helpful for the assessment and management of MFs in BD.

Background Identification of the predominant polarity, i.e. hypomanic/manic (mPP) or depressive predominant polarity (dPP), might help clinicians to improve personalised management of bipolar disorder. Aims We performed a systematic review and meta-analysis to estimate prevalence and correlates of mPP and dPP in bipolar disorder. Method The protocol was registered in the Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/8S2HU). We searched main electronic databases up to December 2023 and performed random-effects meta-analyses of weighted prevalence of mPP and dPP. Odds ratios and weighted mean differences (WMDs) were used for relevant correlates. Results We included 28 studies, providing information on rates and/or correlates of mPP and dPP. We estimated similar rates of mPP (weighted prevalence = 30.0%, 95% CI: 23.1 to 37.4%) and dPP (weighted prevalence = 28.5%, 95% CI: 23.7 to 33.7%) in bipolar disorder. Younger age (WMD = −3.19, 95% CI: −5.30 to −1.08 years), male gender (odds ratio = 1.39, 95% CI: 1.10 to 1.76), bipolar-I disorder (odds ratio = 4.82, 95% CI: 2.27 to 10.24), psychotic features (odds ratio = 1.56, 95% CI: 1.01 to 2.41), earlier onset (WMD = −1.57, 95% CI: −2.88 to −0.26 years) and manic onset (odds ratio = 13.54, 95% CI: 5.83 to 31.46) were associated with mPP (P < 0.05). Depressive onset (odds ratio = 12.09, 95% CI: 6.38 to 22.90), number of mood episodes (WMD = 0.99, 95% CI: 0.28 to 1.70 episodes), history of suicide attempts (odds ratio = 2.09, 95% CI: 1.49 to 2.93) and being in a relationship (odds ratio = 1.98, 95% CI: 1.22 to 3.22) were associated with dPP (P < 0.05). No differences were estimated for other variables. Conclusions Despite some limitations, our findings support the hypothesis that predominant polarity might be a useful specifier of bipolar disorder. Evidence quality was mixed, considering effects magnitude, consistency, precision and publication bias. Different predominant polarities may identify subgroups of patients with specific clinical characteristics.

This first special issue of the International Journal of Psychiatric Trainees (previously named European Journal of Psychiatric Trainees) features four articles based on posters presented at the 31 st Forum of the European Federation of Psychiatric Trainees in Zurich. Focusing on mental health challenges faced by psychiatric trainees across Europe – including key themes such as burnout, depression, and the impact of patient suicide – this special issue highlights the need for systematic support programs, improved awareness and utilisation of mental health resources, and structural changes in medical education. By considering these matters, the Journal supports discussion and action towards improving the mental health of psychiatric trainees worldwide.

The antidepressant effects of ketamine and esketamine are well-documented. Nonetheless, most of the underlying molecular mechanisms have to be uncovered yet. In the last decade, metabolomics has emerged as a useful means to investigate the metabolic phenotype associated with depression as well as changes induced by antidepressant treatments. This mini-review aims at summarizing the main findings from preclinical and clinical studies that used metabolomics to investigate the metabolic effects of subanesthetic, antidepressant doses of ketamine and esketamine and their relationship with clinical response. Both animal and human studies report alterations in several metabolic pathways - including the tricarboxylic acid cycle, glycolysis, the pentose phosphate pathway, lipid metabolism, amino acid metabolism, the kynurenine pathway, and the urea cycle - following the administration of ketamine or its enantiomers. Although more research is needed to clarify commonalities and differences in molecular mechanisms of action between the racemic compound and its enantiomers, these findings comprehensively support an influence of ketamine and esketamine on mitochondrial and cellular energy production, membrane homeostasis, neurotransmission, and signaling. Metabolomics may thus represent a promising strategy to clarify molecular mechanisms underlying treatment-resistant depression and related markers of clinical response to ketamine and esketamine. This body of preclinical and clinical evidence, if further substantiated, has the potential to guide clinicians towards personalized approaches, contributing to new paradigms in the clinical management of depression.

Introduction: Schizophrenia spectrum disorders (SSDs) are associated with immune-inflammatory activation. Recently, complete blood count (CBC)-based inflammation indexes such as the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), and the platelet-to-lymphocyte ratio (PLR) have emerged as reproducible and cost-effective inflammation markers in mental disorders. In this study, we aimed at investigating the relationship of NLR, MLR, and PLR with symptom severity in people with SSDs, testing interactions with relevant clinical variables. Methods: We included inpatients with SSDs aged 18-65 consecutively hospitalized from May 2020 to March 2024. Socio-demographic and clinical data were recorded. CBC-based ratios were estimated from routinely collected blood samples. Structural equation modelling (SEM) was performed to test relationships involving symptom severity constructs and CBC-based ratios, accounting for substance use disorder, antipsychotic treatment, and obesity. Results: Two hundred sixty-six participants met inclusion criteria. The SEM analysis uncovered a significant relationship of MLR with positive (coeff.: 0.19, p=0.048) and negative (coeff.: 0.27, p=0.004) symptoms, also showing a significant link of substance use disorder and antipsychotic treatment with symptom severity as well as of antipsychotic treatment with obesity. Conclusions: Notwithstanding the cross-sectional design and the somewhat limited sample representativeness, this study showed a significant relationship between the MLR - but not the NLR or the PLR - and the severity of both positive and negative symptoms, testing at the same time the interactions with other clinical variables. Considering the insufficiency and inconsistency of data in this field, further research is needed to validate our findings and elucidate the underlying mechanisms driving the observed relationships between the MLR and SSD symptoms.

Objective: Treatment-resistant depression (TRD) affects around 20-30% of people with major depressive disorder. In 2019, esketamine nasal spray was approved for TRD by both the US Food and Drug Administration and the European Medicines Agency. While its clinical efficacy and safety are proven, the mechanisms underlying its antidepressant effect remain unclear. The use of metabolomics may allow understanding the metabolic effects of esketamine and predicting biological features associated with clinical response in TRD. Nonetheless, there is a lack of studies exploring the predictive value of metabolomics. The Resistant Depression Response to Esketamine Assessing Metabolomics (ReDREAM) project aims at identifying metabolic biosignatures that may represent novel correlates of response to esketamine treatment. Study Design: This is the protocol of an observational, prospective study. Methods: We plan to select 60 people with TRD from 3 clinical sites in Italy. The participants will be administered with esketamine nasal spray, following standard clinical practice, twice a week for 4 weeks ("induction phase"), then once a week for 4 additional weeks ("maintenance phase"). We will test the correlations between baseline metabolic profile and depressive symptom improvement at study endpoints (weeks 4 and 8) and we will explore the likelihood of different metabolic phenotypes between responders and non-responders. Expected results: An involvement of energy metabolism, amino acid metabolism, urea cycle, and nitric oxide synthesis in response to treatment with esketamine nasal spray is hypothesized. Conclusion: Unbiased data from untargeted metabolomics associated with clinical changes after esketamine treatment may contribute to define new paradigms for precision psychiatry-oriented, personalized care of TRD.

Preliminary evidence shows that the kynurenine pathway (KP) may be altered in attention-deficit/hyperactivity disorder (ADHD). We thus conducted a systematic review and meta-analysis exploring the peripheral blood concentrations of tryptophan catabolites (TRYCATs) in people with ADHD. We searched the main electronic databases up to 7th December 2023. Standardised mean differences (SMDs) with 95% confidence intervals (95%CIs) were used to compare TRYCAT concentrations between participants with ADHD and healthy controls (HCs). We included eight studies. Random-effects meta-analyses found higher kynurenine (SMD = 0.56; 95%CI: 0.04 to 1.08; p = 0.033; I-2 = 90.3%) and lower kynurenic acid (SMD = -0.33; 95%CI: -0.49 to -0.17; p < 0.001; I-2 = 0%) concentrations in people with ADHD compared to HCs. Additional analyses on drug-free children with ADHD showed higher tryptophan (SMD = 0.31; 95%CI: 0.11 to 0.50; p = 0.002; I-2 = 0%) and kynurenine (SMD = 0.74; 95%CI: 0.30 to 1.17; p < 0.001; I-2 = 76.5%), as well as lower kynurenic acid (SMD = -0.37; 95%CI: -0.59 to -0.15; p < 0.001; I-2 = 0%) blood levels, as compared to HCs. Despite some limitations, our work provides preliminary evidence on KP alterations in ADHD that may suggest decreased neuroprotection. Further research is needed to clarify the role of the KP in ADHD.

Participating in scientific conferences and professional networking support productivity in research. However, there are barriers for early career scientists to benefit from these activities. In 2023, the International College of Neuropsychopharmacology (CINP) Committee for Early Careers organised the first edition of the CINP Research Fellowship for Early Careers to support international collaboration of junior neuroscientists and facilitate in-person exchange between early career and senior investigators. The programme included online and in-person sessions, the latter during the 34th CINP World Congress in Montreal. Selected fellows had the opportunity to learn and make round-table discussions with renowned scientists, including Professors Paola Dazzan, Alan Frazer, Gabriella Gobbi, Anthony Grace, Oliver Howes, Kazutaka Ikeda, Kazuyuki Nakagome, Maria Oquendo, Dan Rujescu, Eric Vermetten, and Joseph Zohar, enabling early career researchers to understand each mentor’s main scientific trajectory and research methodology. The underpinning aim to support the global networking of early career researchers was achieved through the programme, as evidenced by the ensuing collaborative projects.

The brain-derived neurotrophic factor (BDNF) has received considerable attention as a potential biomarker of major depressive disorder (MDD) and antidepressant response. We conducted an overview of meta-analyses investigating the relationship of BDNF with MDD, related clinical features, and antidepressant treatment. Based on a systematic screening on main electronic databases, 11 systematic reviews with meta-analyses were included. Available evidence suggests that people with MDD have peripheral and central BDNF levels lower than non-depressed individuals. A negative correlation between blood BDNF and symptom severity emerged, while no association with suicidality was detected. Moreover, an increase in blood BDNF levels after antidepressant treatment, proportional to symptom improvement, was reported. BDNF levels seem to be increased in both treatment responders and remitters, remaining stable in non-responders. Conversely, no variations of BDNF concentrations after non-pharmacological interventions (electroconvulsive therapy, repetitive transcranial magnetic stimulation, and physical activity) were found. The findings of this overview appear consistent with the neurotrophic hypothesis of depression, suggesting that BDNF may play a role in both MDD pathophysiology and pharmacological treatment response.

Objective: Attention deficit hyperactivity disorder is a frequent comorbid condition in adults with bipolar disorder. We performed a meta-analysis aimed at assessing sociodemographic and clinical correlates of attention deficit hyperactivity disorder in bipolar disorder. Method: We searched main electronic databases up to June 2021. Random-effects meta-analyses, with relevant meta-regression and quality-based sensitivity analyses, were carried out to estimate the association between attention deficit hyperactivity disorder and putative correlates, grading the quality of evidence. Results: We included 43 studies, based on 38 independent samples. Attention deficit hyperactivity disorder participants were more likely to be males (odds ratio = 1.46; p < 0.001) and unemployed (odds ratio = 1.45; p = 0.045), and less likely to be married (odds ratio = 0.62; p = 0.014). They had an earlier onset of bipolar disorder (standardized mean difference = -0.36; p < 0.001); more mood episodes (standardized mean difference = 0.35; p = 0.007), particularly depressive (standardized mean difference = 0.30; p = 0.011) and mixed (standardized mean difference = 0.30; p = 0.031) ones; higher odds of using antidepressants (odds ratio = 1.80; p = 0.024) and attempted suicides (odds ratio = 1.83; p < 0.001) and lower odds of psychotic features (odds ratio = 0.63; p = 0.010). Moreover, they were more likely to have generalized anxiety disorder (odds ratio = 1.50; p = 0.019), panic disorder (odds ratio = 1.89; p < 0.001), social phobia (odds ratio = 1.61; p = 0.017), eating disorders (odds ratio = 1.91; p = 0.007), antisocial personality disorder (odds ratio = 3.59; p = 0.004) and substance (odds ratio = 2.29; p < 0.001) or alcohol (odds ratio = 2.28; p < 0.001) use disorders. Quality of the evidence was generally low or very low for the majority of correlates, except for bipolar disorder onset and alcohol/substance use disorders (high), and suicide attempts (moderate). Conclusion: Comorbid bipolar disorder/attention deficit hyperactivity disorder may have some distinctive clinical features including an earlier onset of bipolar disorder and higher comorbid alcohol/substance use disorder rates. Further research is needed to identify additional clinical characteristics of this comorbidity.

University students are particularly vulnerable to mental health issues, with anxiety and depression identified as the most common conditions. During the COVID-19 pandemic, social distancing, self-isolation, and difficulties linked to online teaching and learning have increased their burden of anxiety and depressive symptoms. Thus, the urgent need to intervene in favour of these vulnerable subjects, together with the difficulties in delivering in-person interventions because of lockdowns and restrictions, has led to prioritize digital mental health strategies. This study aimed at systematically reviewing the existing literature on digital mental health interventions targeting anxiety and depressive symptoms in university students during the COVID-19 emergency. Systematic searches of Medline, Embase, and PsycInfo databases identified eight randomized controlled trials. Regarding anxiety symptoms, digitally delivered cognitive behavioural therapy, dialectical behaviour therapy, and mind-body practice techniques emerged as valid strategies, while digital positive psychology and mindfulness-based interventions showed mixed results. On the other hand, digitally delivered dialectical behaviour therapy and positive psychology interventions have shown some efficacy in reducing depressive symptoms. Overall, the available literature, albeit of low quality, seems to support the role of digital interventions in promoting the mental health of university students during the COVID-19 pandemic. (c) 2022 SEP y SEPB. Published by Elsevier Espana, S.L.U. All rights reserved.

Introduction: The role of anterior pituitary hormones - i.e., adrenocorticotropic hormone (ACTH), luteinizing and follicle stimulating hormones (LH and FSH), growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) - in early schizophrenia and psychoses unclear. We thus performed a systematic review and meta-analysis on the blood concentrations of ACTH, LH and FSH, GH, PRL, and TSH in drug-naive people with first-episode psychosis (FEP) as compared with healthy controls.Methods: We searched Embase, MEDLINE, and PsycInfo for articles indexed until September 2022. Data quality was appraised. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Between-study heterogeneity was estimated using the I-2 statistic. Sensitivity and meta-regression analyses were performed.Results: Twenty-six studies were included. Drug-naive people with FEP, compared to healthy subjects, had higher blood concentrations of ACTH (k = 7; N = 548; SMD = 0.62; 95%CI: 0.29 to 0.94; p < 0.001; I-2 = 60.9%) and PRL (k = 17; N = 1757; SMD = 0.85; 95%CI: 0.56 to 1.14; p < 0.001; I-2 = 85.5%) as well as lower levels of TSH (k = 6; N = 677; SMD = -0.34; 95%CI: -0.54 to -0.14; p = 0.001; I-2 = 29.1%). Meta-regressions did not show any moderating effect of age (p = 0.78), sex (p = 0.21), or symptom severity (p = 0.87) on PRL concentrations in drug-naive FEP. Available data were not sufficient to perform meta-analyses on FSH, LH, and GH. Conclusions: Drug-naive people with FEP have altered ACTH, PRL, and TSH blood concentrations, supporting the hypothesis that an abnormal anterior pituitary hormone secretion may be involved in the onset of schizophrenia and psychoses. Further research is needed to elucidate the role of pituitary hormones in FEP.

The European Journal of Psychiatric Trainee is the official journal of the European Federation of Psychiatric Trainees. It is a fully open-access peer-reviewed scientific journal which will prioritize work by psychiatric trainees while also publishing a wide range of papers on mental health by other authors from diverse professional backgrounds. This editorial marks the first issue of the European Journal of Psychiatric Trainees and outlines its vision, mission and the articles this issue includes. It is the hope of the editorial board that this issue and the future ones reach a wide network of readers with original, informative and engaging papers.

University students are particularly vulnerable to mental health issues, with anxiety and depression identified as the most common conditions. During the COVID-19 pandemic, social distancing, self-isolation, and difficulties linked to online teaching and learning have increased their burden of anxiety and depressive symptoms. Thus, the urgent need to intervene in favour of these vulnerable subjects, together with the difficulties in delivering in-person interventions because of lockdowns and restrictions, has led to prioritize digital mental health strategies. This study aimed at systematically reviewing the existing literature on digital mental health interventions targeting anxiety and depressive symptoms in university students during the COVID-19 emergency. Systematic searches of Medline, Embase, and PsycInfo databases identified eight randomized controlled trials. Regarding anxiety symptoms, digitally delivered cognitive behavioural therapy, dialectical behaviour therapy, and mind-body practice techniques emerged as valid strategies, while digital positive psychology and mindfulness-based interventions showed mixed results. On the other hand, digitally delivered dialectical behaviour therapy and positive psychology interventions have shown some efficacy in reducing depressive symptoms. Overall, the available literature, albeit of low quality, seems to support the role of digital interventions in promoting the mental health of university students during the COVID-19 pandemic.Los estudiantes universitarios son particularmente vulnerables a los problemas de salud mental, siendo la ansiedad y la depresión las condiciones más comunes. Durante la pandemia de COVID-19, el distanciamiento social, el autoaislamiento y las dificultades relacionadas con la enseñanza y el aprendizaje en línea han aumentado su carga de ansiedad y síntomas depresivos. Así, la urgente necesidad de intervenir a favor de estos sujetos vulnerables, junto con las dificultades para realizar intervenciones presenciales a causa de los confinamientos y restricciones, ha llevado a priorizar estrategias de salud mental digital. Este estudio tuvo como objetivo revisar sistemáticamente la literatura existente sobre intervenciones digitales de salud mental dirigidas a la ansiedad y los síntomas depresivos en estudiantes universitarios durante la emergencia de COVID-19. Las búsquedas sistemáticas en las bases de datos Medline, Embase y PsycInfo identificaron ocho ensayos controlados aleatorios. Con respecto a los síntomas de ansiedad, la terapia cognitiva conductual, la terapia conductual dialéctica y las técnicas de práctica mente-cuerpo entregadas digitalmente surgieron como estrategias válidas, mientras que la psicología positiva digital y las intervenciones basadas en el mindfulness mostraron resultados mixtos. Por otro lado, la terapia conductual dialéctica y las intervenciones de psicología positiva proporcionadas digitalmente han demostrado cierta eficacia en la reducción de los síntomas depresivos. En general, la literatura disponible, aunque de baja calidad, parece respaldar el papel de las intervenciones digitales en la promoción de la salud mental de los estudiantes universitarios durante la pandemia de COVID-19.

Introduction: Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH4), may be involved in depression pathophysiology owing to their links to immune-inflammatory response, oxidative and nitrosative stress, and monoaminergic transmission. Nonetheless, studies assessing pteridines in depression are inconsistent. We conducted a systematic review and meta-analysis of observational studies comparing blood pteridine con-centrations between subjects with depression and healthy controls (HCs).Methods: We searched Embase, MEDLINE, and PsycInfo for articles indexed through November 2021. Study quality was appraised, evaluating age and gender comparability between groups, sample representativeness, and methods to assess depression. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity across studies was estimated using the I2 statistic.Results: Twenty-four studies, involving 3075 subjects, were included. Individuals with depression showed blood neopterin concentrations higher than HCs (k = 19; SMD = 0.36; p < 0.001) with moderate heterogeneity across studies (I2 = 58.2%). No moderating role of age, gender, or type of blood sample was found. Sensitivity analyses showed no impact of inconsistency and quality of studies on findings. Neopterin concentrations were higher among individuals with major depressive disorder compared to HCs (SMD = 0.44; p < 0.001). This held true also when considering only drug-free subjects (SMD = 0.68; p = 0.003). No differences in biopterin concentrations were found between subjects with depression and HCs (k = 5; SMD = -0.35; p = 0.086), though this result was limited by inconsistency of findings (I2 = 77.9%) and quality of studies. Finally, no sufficient data were available for a meta-analysis on BH4. Conclusions: As a whole, our work partly supports the hypothesis of an imbalance of pteridine metabolism in depression.

The experience of patient suicide (PS) represents a challenging event that most psychiatrists may deal with during their careers. We conducted a qualitative study to evaluate the emotional impact and reactions to PS, in a small sample of psychiatric trainees and early career psychiatrists (n=15) in one university hospital in Italy. Psychiatric trainees and early career psychiatrists working at the Clinical Psychiatry Unit of Polytechnic University of Marche (Ancona, Italy) were surveyed to assess emotional impact of PS, influence on future work, perceived support, and how the PS experience should be managed. An online survey was conducted, and a qualitative approach (thematic analysis) was used to analyse the data. Fifteen professionals completed the survey. Sadness (47%) and shock (33%) were the most reported emotions, along with feelings of guilt, impotence and inadequacy, disappointment, frustration, and anger. PS seemed to have a strong influence on clinical activity, increasing attention towards the patient and commitment, although the impression of being of limited help to the patient was commonly reported. Albeit valuing the opportunity to share their emotional experience with peers, the respondents highlighted the lack of professional support and the relevant need to implement discussion and interventions to deal with PS. Overall, our findings support the importance of addressing the strong emotional effect of PS on psychiatric trainees and early career psychiatrists as well as the necessity for more structured support strategies in the aftermath of PS. Larger investigations on this topic are warranted.

BackgroundThe balance between neurotoxic and neuroprotective effects of kynurenine pathway (KP) components has been recently proposed as a key element in the pathophysiology of bipolar disorder (BD) and related mood episodes. This comprehensive overview explored the link of KP with symptom severity and other clinical features of BD.MethodsWe searched Medline, Embase, and PsycInfo electronic databases for studies assessing the association of peripheral and/or central concentrations of KP metabolites with putative clinical features, including symptom severity and other clinical domains in BD.ResultsWe included the findings of 13 observational studies investigating the possible variations of KP metabolites according to symptom severity, psychotic features, suicidal behaviors, and sleep disturbances in BD. Studies testing the relationship between KP metabolites and depression severity generated mixed and inconsistent findings. No statistically significant correlations with manic symptoms were found. Moreover, heterogeneous variations of the KP across different clinical domains were shown. Few available studies found (a) higher levels of cerebrospinal fluid kynurenic acid and lower of plasma quinolinic acid in BD with psychotic features, (b) lower central and peripheral picolinic acid levels in BD with suicide attempts, and (c) no significant correlations between KP metabolites and BD-related sleep disturbances.ConclusionsAn imbalance of KP metabolism toward the neurotoxic branches is likely to occur in people with BD, though evidence on variations according to specific clinical features of BD is less clear. Additional research is needed to clarify the role of KP in the etiopathogenesis of BD and related clinical features.

Schizophrenia is a severe mental illness causing a high degree of disability. First-and second-generation antipsychotics (FGAs and SGAs) represent key resources for its acute and long-term management. Since a poor adherence to oral treatments may negatively impact the course of the disorder, long-acting injectable antipsychotics (LAIs) are often used to reduce clinical relapses. Notwithstanding their potential beneficial features, LAIs use in clinical practice remains somewhat hampered by the limited amount of relevant systematic information. This review thus aims at providing a clinical, practical guidance for the use of LAIs in the treatment of schizophrenia. We synthetized main information on indications, dosage, and administration of LAIs approved by the US Food and Drug Administration (FDA) and/or in EU countries, as well as evidence from the most recent systematic reviews and meta-analyses. Currently available information, though heterogeneous, shows that LAIs can prevent relapses and rehospitalizations, improving clinical outcomes and favouring sustained remission among people with schizophrenia. The use of SGA LAIs is supported by more robust evidence than FGA LAIs. Along with their positive impact on the prevention of treatment discontinuation, some LAIs might also enhance individual global functioning and quality of life, without additional adverse events or health-care costs, as compared with oral antipsychotics. Although which LAIs can be considered a first-choice option, as well as their superiority over oral antipsychotics, remain unclear issues, this review offers a comprehensive overview of information available on the use of LAIs for people with schizophrenia, providing clinicians with practical guidance in terms of efficacy and acceptability of single agents. Literature gaps and future research needs are also described.