New trends of drug abuse in custodial settings: A systematic review on the misuse of over-the-counter drugs, prescription-only-medications, and new psychoactive substances.

The article presents a systematic literature review on the use and the psychiatric implications of over-the-counter drugs (OTC), prescription-only-medications (POM), and new psychoactive substances (NPS) within custodial settings. The searches wer carried out on 2 November 2022 on PubMed, Scopus, and Web of Science in line with PRISMA guidelines. A total of 538 records were identified, of which 37 met the inclusion criteria. Findings showed the most prevalent NPS and OTC and POM classes reported in prisons were synthetic cannabinoids receptor agonists (SCRAs) and opioids, respectively. NPS markets were shown to be in constant evolution following the pace of legislations aimed to reduce their spread. The use of such substances heavily impacts the conditions and rehabilitation of persons in custody, with consequent physical and mental health risks. It is important to raise awareness of the use and misuse of such substances in prisons (i) from an early warning perspective for law enforcement and policy makers (ii) to prompt doctors to cautiously prescribe substances that may be misused with caution (iii) to improve and increase access to treatment provided (iv) to add such substances to routine toxicological screening procedures (v) to improve harm reduction programmes.

Investigating the Effectiveness of Brexpiprazole in Subjects with Schizophrenia Spectrum Illness and Co-Occurring Substance Use Disorder: A Prospective, Multicentric, Real-World Study.

BACKGROUND: Dual disorders (DDs) involve the coexistence of a substance use disorder (SUD) with another mental illness, often from the psychotic and affective categories. They are quite common in clinical practice and present significant challenges for both diagnosis and treatment. This study explores the effectiveness of brexpiprazole, a third-generation antipsychotic, in an Italian sample of individuals diagnosed with schizophrenia spectrum disorder and a comorbid SUD. METHODS: Twenty-four patients, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and enrolled in several Italian hospitals, underwent a psychometric assessment at baseline (T0) and one month (T1) after starting brexpiprazole treatment administered at a mean dosage of 2 mg/day. RESULTS: Brexpiprazole demonstrated significant reductions in psychopathological burden (Positive and Negative Syndrome Scale/PANSS total score: p < 0.001). Positive (p = 0.003) and negative (p = 0.028) symptoms, substance cravings (VAS craving: p = 0.039), and aggression (MOAS scale: p = 0.003) were notably reduced. Quality of life improved according to the 36-item Short Form Health Survey (SF-36) subscales (p < 0.005). CONCLUSIONS: This study provides initial evidence supporting brexpiprazole's efficacy and safety in this complex patient population, with positive effects not only on psychopathology and quality of life, but also on cravings. Further studies involving larger cohorts of subjects and extended follow-up periods are needed.

Examining Lurasidone Efficacy in Patients with Schizophrenia Spectrum Illness and Concurrent Alcohol and Substance Use Disorder: A Prospective, Multicentric, Real-World Investigation.

Background: Dual disorders (DD) entail the coexistence of a substance use disorder (SUD) and another mental health condition, often within psychotic and affective disorders. This study aims to evaluate lurasidone, an innovative atypical antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder and concurrent comorbidities of alcohol use disorder/substance use disorder (AUD/SUD). Methods: A cohort of 23 subjects diagnosed with schizophrenia spectrum disorder and comorbid AUD/SUD underwent psychometric assessments at baseline (T0) and one-month (T1) post-lurasidone initiation. Results: Lurasidone exhibited significant reductions in psychopathological burden, evidenced by decreased total PANSS scores (Z = 2.574, p = 0.011). Positive symptoms, substance craving (VAS Craving; Z = 3.202, p = 0.001), and aggressivity (MOAS scale; Z = 2.000, p = 0.050) were notably reduced. Clinical Global Impression (CGI) scores significantly improved (Z = 2.934, p = 0.003). Quality of life enhancements were observed in SF-36 subscales (energy, emotional well-being, and social functioning) (p < 0.05) and Q-LES-Q-SF scale (Z = -2.341, p = 0.021). A safety analysis indicated lurasidone's good tolerability, with only 8.7% reporting discontinuation due to side effects. Conclusions: This study offers initial evidence supporting lurasidone's efficacy and safety in dual diagnoses, highlighting positive effects on psychopathology, substance craving, and quality of life. These findings emphasize the need for tailored, comprehensive treatment strategies in managing the complexities of this patient population.

Dopaminergic dysfunction in the left putamen of patients with major depressive disorder.

INTRODUCTION: Dopaminergic transmission impairment has been identified as one of the main neurobiological correlates of both depression and clinical symptoms commonly associated with its spectrum such as anhedonia and psychomotor retardation. OBJECTIVES: We examined the relationship between dopaminergic deficit in the striatum, as measured by 123I-FP-CIT SPECT imaging, and specific psychopathological dimensions in patients with major depressive disorder. METHODS: To our knowledge this is the first study with a sample of >120 subjects. After check for inclusion and exclusion criteria, 121 (67 females, 54 males) patients were chosen retrospectively from an extensive 1106 patients database of 123I-FP-CIT SPECT scans obtained at the Nuclear Medicine Unit of Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome. These individuals had undergone striatal dopamine transporter (DAT) assessments based on the recommendation of their referring clinicians, who were either neurologists or psychiatrists. At the time of SPECT imaging, each participant underwent psychiatric and psychometric evaluations. We used the following psychometric scales: Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Snaith Hamilton Pleasure Scale, and Depression Retardation Rating Scale. RESULTS: We found a negative correlation between levels of depression (p = 0.007), anxiety (p = 0.035), anhedonia (p = 0.028) and psychomotor retardation (p = 0.014) and DAT availability in the left putamen. We further stratified the sample and found that DAT availability in the left putamen was lower in seriously depressed patients (p = 0.027) and in patients with significant psychomotor retardation (p = 0.048). CONCLUSION: To our knowledge this is the first study to have such a high number of sample. Our study reveals a pivotal role of dopaminergic dysfunction in patients with major depressive disorder. Elevated levels of depression, anxiety, anhedonia, and psychomotor retardation appear to be associated with reduced DAT availability specifically in the left putamen.

Enhanced peripheral levels of BDNF and proBDNF: elucidating neurotrophin dynamics in cocaine use disorder.

Brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF, are known to significantly contribute to brain homeostasis, neuroplasticity, and neuronal remodeling. Although these neurotrophins are thought to have opposing roles, both play a critical part in shaping long-lasting behavioral changes following substance use. In this context, our study sought to explore the implications of these neurotrophins in the pathophysiology of cocaine use disorder (CUD). We conducted a case-control study, which included 28 individuals seeking treatment for CUD and 38 matched healthy participants. We measured peripheral neurotrophin concentrations via an enzyme-linked immunosorbent assay. Additionally, all participants were screened for cocaine-associated pathways (e.g., cocaine intake, craving intensity), along with associated psychopathological data. Our findings highlighted an increased concentration of BDNF and proBDNF in CUD individuals when compared to healthy controls (BDNF: 18092.80 ± 6844.62 vs. 11334.42 ± 5061.85 pg/ml, p < 0.001; proBDNF: 87.03 ± 33.23 vs. 55.70 ± 23.26 ng/ml, p < 0.001). We further corroborated the relationship between neurotrophin levels and CUD using a linear regression model. Nevertheless, there was no significant difference in the proBDNF to BDNF ratio between the two groups. Interestingly, our study also demonstrated the influence of factors like usage of psychotropic medications, history of psychiatric hospitalizations, and psychiatric diagnoses on neurotrophin dynamics. In conclusion, our study underscores the significance of neurotrophin fluctuations in CUD. The observed increase in BDNF and proBDNF levels could play a pivotal role in driving craving and relapse risk. Thus, a nuanced understanding of these neurobiological underpinnings in CUD might contribute to the development of more targeted and effective therapeutic strategies.

Staying connected: An umbrella review of meta-analyses on the push-and-pull of social connection in depression.

BACKGROUND: Depression affects approximately 4 % of the global population and has huge social and economic implications. Social factors, including support, engagement, and stigma, play a crucial role in the development and severity of depression. METHODS: We provide a synthesis of the consistency and magnitude of the association between measures of social connection and depression. We searched PubMed, PsycINFO, Cochrane Library, and EMBASE and 47 meta-analyses were included in the umbrella review. The strength of the associations was extracted and compared among different populations. The quality/certainty of evidence was assessed using AMSTAR-2 and GRADE tool. RESULTS: Results indicate that social support serves as a protective factor against depression, particularly in peripartum populations, while its impact is weaker in clinical populations. No association was found between social support and depression in post-disaster populations. Stigma and discrimination favour the development and maintenance of depressive symptoms in clinical populations, but have a weaker effect in ethnic minorities. LIMITATIONS: The quality and certainty of evidence should be taken into account when interpreting our findings. Further research with more rigorous methodology and higher-quality evidence is needed to better understand the complex relationship between depression and social connection across various populations and contexts. CONCLUSIONS: Our findings confirm the role of social determinants in the emergence and severity of depression, particularly in the case of vulnerable populations. Efforts to counteract disconnection at the societal and individual levels and to reduce stigma should be central to an effective depression prevention agenda.

The rapid antidepressant effectiveness of repeated dose of intravenous ketamine and intranasal esketamine: A post-hoc analysis of pooled real-world data.

INTRODUCTION: Intravenous ketamine (KET-IV) and intranasal esketamine (ESK-NS) are effective in the acute treatment of Treatment-Resistant Depression (TRD). Studies comparing KET-IV and ESK-NS concerning their action, safety, and tolerability are currently lacking. MATERIALS AND METHODS: We combined patients' data from two unipolar TRD cohorts that received KET-IV (n = 171) at the Canadian Rapid Treatment Center of Excellence in Toronto, Canada, or ESK-NS (n = 140) at several TRD clinics in Italy. The Quick Inventory for Depression Symptomatology-Self-Report-16/QIDS-SR16 in the KET-IV group and Montgomery-Åsberg Depression Rating Scale/MADRS in the ESK-NS group measured depressive symptoms at baseline (T0) and after the acute treatment phase (T1) (i.e., four infusions of KET-IV and eight administrations of ESK-NS). As different scales were used, the primary outcome was to compare the improvement in depression severity in the two cohorts by measuring effect sizes, response and remission rates. Finally, we compare side effects and discontinuation rates. RESULTS: At T1, KET-IV and ESK-NS significantly reduced depressive symptoms (respectively: QIDS-SR16 mean reduction = 5.65, p < 0.001; MADRS mean reduction = 11.41, p = 0.025). KET-IV showed larger effect sizes compared to ESK-NS (1.666 vs. 1.244). KET-IV had higher response rates (36 % vs. 25 %; p = 0.042) but not superior remission rates (13 % vs. 12 %; p = 0.845) than ESK-NS at T1. Despite more reported side effects, KET-IV did not cause more discontinuations for adverse events (4.6 % vs. 2.12 %; p = 0.228) than ESK-NS. CONCLUSION: KET-IV showed a higher short-term antidepressant effect, whereas ESK-NS exhibited lower side effects. Both were generally well tolerated. Future head-to-head studies should consider the long-term efficacy of these treatments.

Connected minds in disconnected bodies: Exploring the role of interoceptive sensibility and alexithymia in problematic use of the internet.

INTRODUCTION: The ever-increasing prominence of the internet and digital technology in our society requires a deeper examination of how these developments alter perception of our bodies and emotions. One such consequence is the emergence of Problematic Use of the Internet (PUI) - an array of compulsive or addictive behaviors mediated by the web that detrimentally affect an individual's functioning. This suggests that some people may be shifting their consciousness from the physical realm to the digital world. The objective of this study was to investigate how shortcomings in interoception (the sensibility to bodily signals) and alexithymia (an inability to identify and express emotions) might contribute to PUI. METHODS: The Internet Addiction Test (IAT), the Toronto Alexithymia Scale (TAS-20), and the Multidimensional Assessment of Interoceptive Awareness (MAIA) were used to assess a sample of 1076 adolescents and young adults aged between 16 and 26 years via an online survey. Data analysis was based on t-test, correlations and multivariate regression. RESULTS: 26.8% (n = 288) of participants met the criteria for moderate PUI. Individuals with PUI displayed higher levels of alexithymia (p < 0.001) and diminished abilities in certain aspects of interoceptive sensibility, including placing trust in their own bodily signals (p = 0.006), not responding excessively to uncomfortable sensations with worry (p < 0.001), and not denying them (p = 0.006). Multivariate modelling revealed associations between PUI and the following factors: having a boyfriend/girlfriend (aOR = 5.70), substance use (aOR = 1.78), difficulty in identifying feelings (aOR = 1.09), externally oriented thinking (aOR = 1.05), low disposition in perceiving body sensations (aOR = 0.25), tendency to become distracted (aOR = 0.82) or excessively worried (aOR = 0.11) in the face of pain. Furthermore, the analysis indicated how these aspects of body perception may be interrelated, either enhancing or reducing the risk of PUI when examined individually, collectively, or in combination. CONCLUSIONS: This study underlines the potential connection between difficulties in the mind-body interaction and the development of PUI. It suggests a bidirectional relationship between excessive digital device use and distorted bodily interoceptive processes in PUI, reinforcing the notion that individuals struggling with emotion identification and expression may be more prone to excessive internet usage. To further comprehend the relevance of these constructs in PUI, it is necessary to conduct more targeted investigations and longitudinal studies.

The association between traumatic experiences and substance and behavioral addictions in late adolescence: A role for PTSD and cPTSD as potential mediators.

BACKGROUND & AIM: Traumatic experiences (TEs) are a risk factor for behavioral and substance addictions (SBAs). However, the role of post-traumatic stress disorder (PTSD) and complex PTSD (cPTSD) deserves further elucidation. The present study assesses the association between different types of TEs on cannabis, alcohol, gambling, and problematic internet use in late adolescents. Furthermore, this study aims at evaluating the role of PTSD and cPTSD as potential mediators. METHODS: An observational cross-sectional study was conducted on one thousand ten late adolescents (510 males, 498 females; age: mean = 18.7, SD = 0.65). Data regarding intentional (iTEs) and unintentional TEs (uTEs), cannabis, alcohol, gambling and problematic use of the internet (PIU), PTSD, and cPTSD were collected. Association between TEs, SBAs, and PTSD/cPTSD symptoms were explored by means of logistic regressions. Mediation was assessed using a path analysis. RESULTS: uTEs were associated with cannabis use (OR = 1.34 [1.13,1.59]) and alcohol use (OR = 1.21 [1.10,1.35]), iTEs were associated with cannabis use (OR = 1.15 [1.06,1.25]), alcohol use (OR = 1.08 [1.02,1.13]), and PIU (OR = 1.17 [1.10,1.24]). PTSD was associated with alcohol use (OR = 1.59 [1.03,2.46]) and PIU (OR = 1.92 [1.18,3.13]). cPTSD was associated with cannabis use (OR = 3.54 [1.56,8.04]) and PIU (OR = 5.13 [2.71,9.70]). cPTSD mediated 58.75% of the total effect of iTEs on cannabis. Regarding PIU, PTSD mediated 68.18% of the effect of uTEs; the effect of iTEs on PIU was mediated by 65.5% via cPTSD and 34.45% via PTSD. CONCLUSION: cPTSD and SBAs show a complex pattern of association. A thorough assessment of stress-related conditions, including cPTSD, is of pivotal importance in treating SBAs.

Efficacy of Psychosocial and Psychological Interventions in Addition to Drug Therapy to Improve Global Functioning of Inpatients with Schizophrenia Spectrum and Mood Disorders: A Real-World Observational Study.

Introduction and Aim: Psychotic and mood disorders are associated with significant functional impairment, premature mortality, physical morbidity, and great social and economic burden. The aim of this study is to evaluate the effectiveness of psychosocial, psychological, and rehabilitative interventions implemented in an Italian psychiatric inpatient facility, with a focus on patients with schizophrenia spectrum versus those with mood disorders. Methods: A retrospective observational study was conducted in the psychiatric hospital Villa Maria Pia in Rome, Italy, during 2022. Patients with an established diagnosis of schizophrenia spectrum and mood disorder (ICD-9-CM) were assessed on admission (T0) and at the end of treatment (T1), using the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment of Functioning (GAF). Interventions involved a multidisciplinary team and included individual and group activities. The t-test for independent samples was used to compare continuous variables between groups and Spearman correlation coefficient to calculate correlations between variables. Results: The study sample consisted of 141 patients, the majority of them being adults (51.3 years ± 12.4) men (F/M= 68/73). Among them, 85 patients (60.3%) actively engaged in psychosocial and rehabilitative interventions and, compared to non-participating individuals, they showed lower functioning and symptoms at discharge (delta GAF was significantly higher among patients who had taken part in the psychosocial activities, t = -2.095; p = 0.038). Considering the index computed (n of interventions/days of hospitalization), the number of psychosocial activities was positively correlated with the improvement in patients' functioning in the sample taking part in activities (r = 0.272, p = 0.012), especially with psychotherapy and support groups (r = 0.202, p = 0.017 and r = 0.188, p = 0.025, respectively). Splitting the total sample into schizophrenia-spectrum disorder (N = 37) and mood disorder (N = 48) groups, the positive correlations between GAF improvement and participation in psychosocial activities were confirmed only in the schizophrenia-spectrum group. These correlations were not significant for symptomatology (BPRS) either in the total or the individual group. Conclusion: Evidence from our study suggests that inpatient rehabilitation can be effective and useful for people with severe mental disorders. Further investigations are needed to better understand its effectiveness on improving quality of life and social functioning in the long term.

Predicting outcome with Intranasal Esketamine treatment: A machine-learning, three-month study in Treatment-Resistant Depression (ESK-LEARNING).

Treatment-resistant depression (TRD) represents a severe clinical condition with high social and economic costs. Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD by EMA and FDA, but data about predictors of response are still lacking. Thus, a tool that can predict the individual patients' probability of response to ESK-NS is needed. This study investigates sociodemographic and clinical features predicting responses to ESK-NS in TRD patients using machine learning techniques. In a retrospective, multicentric, real-world study involving 149 TRD subjects, psychometric data (Montgomery-Asberg-Depression-Rating-Scale/MADRS, Brief-Psychiatric-Rating-Scale/BPRS, Hamilton-Anxiety-Rating-Scale/HAM-A, Hamilton-Depression-Rating-Scale/HAMD-17) were collected at baseline and at one month/T1 and three months/T2 post-treatment initiation. We trained three different random forest classifiers, able to predict responses to ESK-NS with accuracies of 68.53% at T1 and 66.26% at T2 and remission at T2 with 68.60% of accuracy. Features like severe anhedonia, anxious distress, mixed symptoms as well as bipolarity were found to positively predict response and remission. At the same time, benzodiazepine usage and depression severity were linked to delayed responses. Despite some limitations (i.e., retrospective study, lack of biomarkers, lack of a correct interrater-reliability across the different centers), these findings suggest the potential of machine learning in personalized intervention for TRD.

Investigating the Effectiveness and Tolerability of Intranasal Esketamine Among Older Adults With Treatment-Resistant Depression (TRD): A Post-hoc Analysis from the REAL-ESK Study Group.

INTRODUCTION: Treatment-resistant depression (TRD) is a serious and debilitating psychiatric disorder that frequently affects older patients. Esketamine nasal spray (ESK-NS) has recently been approved as a treatment for TRD, with multiple studies establishing its efficacy and tolerability. However, the real-world effectiveness, tolerability, and safety of this treatment in older adults is still unclear. OBJECTIVES: To evaluate the efficacy and tolerability of ESK-NS in older subjects with TRD. METHODS: This is a post-hoc analysis of the REAL-ESK study, a multicenter, retrospective, observational study. Participants here selected were 65 years or older at baseline. The Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A) were used to assess depressive and anxiety symptoms, respectively. Data were collected at three-time points: baseline, 1 month after the start of treatment (T1), and 3 months after treatment (T2). RESULTS: The sample included older adults with TRD (n = 30). MADRS and HAM-A values decreased significantly at T1 (T0 versus T1: pholm <0.001, Cohen's d = 0.840) and T2 follow-ups (T0 versus T2: pholm <0.001, Cohen's d = 1.419). At T2, 53.3% of subjects were responders (MADRS score reduced ≥50%), while 33.33% were in remission (MADRS<10). ESK-NS-related adverse effects were in order of frequency dizziness (50%), followed by dissociation (33.3%), sedation (30%), and hypertension (13.33%). Six out of 30 participants (20%) discontinued treatment. CONCLUSIONS: Our findings provide preliminary evidence of ESK-NS effectiveness in older adults with TRD, a highly debilitating depressive presentation. Furthermore, we observe high levels of treatment-emergent adverse events, which, in the majority of instances, did not require treatment suspension.

High-Risk Gaming Is Associated with Frequent Substance Use: An Exploratory Survey among Young Adults.

INTRODUCTION: Internet gaming disorder (IGD) is an emerging condition within the field of behavioural addictions. IGD has been demonstrated to be highly comorbid with many other mental health disorders. Among these, substance use has been associated with IGD, and there are underlying similarities between behavioural addictions and substance use disorders. The main aims of the present study were (i) to investigate the association between high-risk gaming and substance use among young adults drawn from the general Italian population; and (ii) to explore the psychopathological correlates of high-risk gaming. METHODS: Lifetime substance use, type of substances consumed, and frequency of use were investigated through an online survey in a sample of 913 adults aged 18-40 years. High-risk gaming was assessed using the ten-item Internet Gaming Disorder Test (IGDT-10). Psychopathology was assessed using the Revised 90-item Symptom Checklist (SCL-90-R). RESULTS: High-risk gaming prevalence rate was 4.4%. High-risk gamers scored higher on all dimensions of psychopathology, confirming the association between high-risk gaming and psychiatric distress. Regarding substance use, high-risk gamers were more commonly polysubstance users and more commonly made use of psychodysleptic substances. High-risk gamers were more commonly frequent substance users, and 32.5% of high-risk gamers used or had used psychoactive substances often or everyday throughout their lives. DISCUSSION AND CONCLUSION: The findings are in line with the concept of a common neurobiological vulnerability for both gaming and substance use. There is the need for more research to examine the phenomenology of gaming and its interplay with substance use to help develop effective interventions and prevention strategies.

Beyond the efficacy of transcranial magnetic stimulation in peripartum depression: A systematic review exploring perinatal safety for newborns.

OBJECTIVE: Peripartum depression is defined as the onset of depressive symptoms during pregnancy or within 12 months postpartum and affects 11.9% of women. Currently, its treatment often involves psychotherapy and antidepressants, though only one medication has been specifically approved to treat it. In this context, novel, safe non-pharmacological treatment options have gained growing interest. The present review aims to assess current literature on possible side effects on the developing fetus/newborn of Transcranial Magnetic Stimulation (TMS) use in women with peripartum depression. METHOD: A systematic search was performed using the PubMed, Scopus and Web of Science databases. PRISMA and PROSPERO guidelines were applied. The risk of bias assessment was performed using the Cochrane risk of bias tool version 2.0. RESULTS: Twenty-three studies were included in our systematic review, two were randomized controlled trials. Eleven studies reported mothers experienced mild side effects; none of the included studies reported major side effects for newborns. CONCLUSION: The present systematic review demonstrated that TMS use in women with peripartum depression is safe, feasible and well-tolerated by the developing fetus/newborn, with a good safety and tolerability profile even during breastfeeding.

Esketamine in treatment-resistant depression patients comorbid with substance-use disorder: A viewpoint on its safety and effectiveness in a subsample of patients from the REAL-ESK study.

Esketamine, the S-enantiomer of ketamine, has recently emerged as a therapy for treatment-resistant depression (TRD), showing both rapid antidepressant action and good efficacy and high safety. It is also indicated for the acute short-term treatment of psychiatric emergency due to major depressive disorder (MDD) and for depressive symptoms in adults with MDD with acute suicidal thoughts/behavior. We here provide preliminary insights on esketamine nasal spray (ESK-NS) effectiveness and safety among patients with a substance use disorder (SUD) within the sample of patients with TRD collected for the observational, retrospective, multicentre REAL-ESK study. Twenty-six subjects were retrospectively selected according to the presence of a SUD in comorbidity. Subjects enrolled completed the three different follow-up phases (T0/baseline, T1/after one month, and T2/after three months) and there were no dropouts. A decrease in Montgomery-Asberg depression rating scale (MADRS) scores was recorded, thus highlighting the antidepressant efficacy of ESK-NS (MADRS decreased from T0 to T1, t = 6.533, df=23, p<0.001, and from T1 to T2, t = 2.029, df=20, p = 0.056). Considering tolerability and safety issues, one or more side effects were reported by 19/26 subjects (73%) after treatment administration. All reported side effects were time-dependent and did not cause significant sequelae; among them, dissociative symptoms (38%) and sedation (26%) were the most frequently reported. Finally, no cases of abuse or misuse of ESK-NS were reported. Despite study limitations related to the inherent nature of the study, a limited number of patients, and a short follow-up period, ESK-NS showed to be effective and safe in patients diagnosed with TRD comorbid with a SUD.

Investigating the Role of Maintenance TMS Protocols for Major Depression: Systematic Review and Future Perspectives for Personalized Interventions.

Repetitive Transcranial Magnetic Stimulation (rTMS) has been approved by the FDA as an effective intervention for Treatment-Resistant Depression (TRD). However, there is little evidence about maintenance protocol necessity. The aim of this systematic review is to identify, characterize, and evaluate the current maintenance TMS protocols for MDD and TRD patients who have received acute treatment. A literature search was conducted following the PRISMA guidelines of 2015 on PubMed, Scopus, and Web of Science databases for publications up to March 2022. Fourteen articles were included. High protocol heterogeneity was observed. Most studies highlighted significant efficacy of maintenance protocols in decreasing relapse risk, suggesting that administering two or fewer stimulations per month is ineffective in sustaining an antidepressant effect or in reducing the risk of relapse in responder patients. The risk of relapse was most pronounced after five months from the acute treatment. Maintenance TMS appears to be a resourceful strategy to maintain acute antidepressant treatment effects, significantly reducing relapse risk. The ease of administering and the ability to monitor treatment adherence should be considered when evaluating the future use of maintenance TMS protocols. Further studies are needed to clarify the clinical relevance of overlapping acute TMS effects with maintenance protocols and to evaluate their long-term effectiveness.