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.

Introduction: Treatment-Resistant Depression (TRD) affects approximately 30–50% of patients with Major Depressive Disorder (MDD) who fail to respond to at least two adequate antidepressant trials. This condition presents substantial clinical and functional challenges, and no universally accepted treatment algorithm currently exists. Emerging therapeutic strategies, particularly glutamatergic modulators and psychedelics, have shown promising results in managing TRD. Methods: We conducted a narrative review using PubMed and Scopus with the query “(treatment resistant depression OR TRD) AND (glutamatergic OR glutamate OR psychedelic OR psilocybin OR antipsychotic augmentation) NOT (review OR animal OR mouse).” After applying inclusion/exclusion criteria, 60 articles were selected. Results: The most frequently studied treatments (43 studies) are glutamatergic agents, particularly intravenous ketamine and intranasal esketamine, which have consistently demonstrated rapid and clinically meaningful reductions in depressive symptoms. Augmentation with atypical antipsychotics also showed effectiveness for partial responders. Psychedelic-assisted therapies yielded sustained antidepressant benefits and modulated biomarkers such as BDNF and inflammatory markers. Discussion and Conclusion: The findings support a potential paradigm shift away from traditional monoaminergic-based treatments toward more personalized, mechanism-driven strategies for managing TRD. Ketamine and esketamine offer rapid-onset relief suitable for acute high-risk cases, while augmentation strategies remain valuable for partial responders. Psychedelic interventions, although still experimental, hold promise as adjunctive options. Furthermore, biomarkers and early response predictors may help guide individualized treatment decisions.

Novel psychoactive substances (NPS) are increasingly used by young individuals for their psychoactive effects and have been frequently associated with the emergence of psychotic symptoms and schizophrenia spectrum disorders. However, it remains unclear whether NPS use directly increases the risk of psychosis onset or whether individuals with a predisposition to psychosis are more likely to engage in NPS use. This systematic review aims to explore the relationship between NPS consumption and the risk of developing psychotic symptoms. Out of 4477 identified studies, 95 met the inclusion criteria. FINDINGS: indicate that synthetic cannabinoids are the most frequently implicated substances, showing a strong association with acute psychosis and, in some cases, with persistent or relapsing psychotic disorders. The presence of Schneiderian First Rank Symptoms in some cases highlights a phenomenological overlap with schizophrenia, suggesting a possible risk of transition. Synthetic cathinones, phenethylamines, and other NPS classes were also linked to a broad range of psychotic manifestations, including disturbances in thought content and perceptual abnormalities. Although many episodes appeared transient, a notable proportion evolved into persistent psychotic states, supporting the hypothesis that NPS may either unmask latent vulnerabilities or directly contribute to the development of chronic psychotic disorders. These results underline the critical importance of systematically assessing NPS use in individuals presenting with first-episode psychosis and call for increased clinical and public health awareness regarding the psychiatric risks associated with these substances.

Substance Use Disorders (SUDs) are frequently associated with impairments in emotional regulation and behavioural control. Among the most prevalent substances of abuse, alcohol and cocaine are known to exert distinct effects on neuropsychological functioning. This study aimed to compare individuals with Alcohol Use Disorder (AUD) and Cocaine Use Disorder (CUD) in terms of impulsivity and alexithymia, and to examine the clinical implications of poly-substance use involving both alcohol and cocaine. Participants completed standardized psychometric assessments, including the Barratt Impulsiveness Scale (BIS-11), the Brief Psychiatric Rating Scale (BPRS), and the Toronto Alexithymia Scale (TAS-20). Group comparisons were conducted using non-parametric tests, and logistic regression models were applied to control for demographic covariates. The findings showed that impulsivity levels were comparable across groups, whereas alexithymia scores were significantly higher in individuals with AUD and in those with poly-substance use, relative to CUD-only participants. These findings underscore the relevance of targeting emotional regulation difficulties, particularly alexithymia, in the assessment and treatment of SUDs. Integrating emotion-focused interventions may enhance treatment outcomes, especially for individuals with co-occurring substance use patterns. Future research is needed to clarify the underlying neuropsychological mechanisms contributing to these differences and to inform more personalized approaches to addiction care.

Ketamine, initially developed as an anesthetic and now increasingly prescribed for treatment-resistant depression, is also widely misused in recreational contexts. Chronic ketamine use, often leading to dependence, has been associated with severe physical complications, including ulcerative cystitis and gastrointestinal dysfunction, as well as cognitive, affective, and psychotic disturbances. Despite the growing clinical and public health relevance of ketamine misuse, the evidence on effective treatment approaches remains fragmented. A systematic review was conducted in accordance with PRISMA guidelines. We searched three literature databases (PubMed, Scopus, and Web of Science) from inception to April 2025. Original studies in English reporting clinical interventions for ketamine misuse were included. Data were extracted on sociodemographic and clinical characteristics, patterns of use, comorbidities, management strategies, and outcomes.. From 3183 records screened, 73 studies met the inclusion criteria, including 5 controlled clinical studies, 15 observational studies, 15 case series, and 38 case reports. Findings highlighted that management of ketamine misuse is heterogeneous and often based on evidence taken from either case reports or small series. Approaches included symptomatic medical care, psychotherapeutic interventions (e.g., motivational interviewing, cognitive-behavioral therapy, occupational therapy), and pharmacological treatments such as benzodiazepines, SSRIs, naltrexone, lamotrigine, and gabapentinoids, with varying degrees of effectiveness. Multidisciplinary strategies addressing both psychiatric and somatic complications, including "K-bladder" and "K-cramps", emerged as an essential component of the treatment/management package. Overall, the high rates of relapse into ketamine misuse and the limited length of follow-up may have reduced the strength of available evidence. Current management of ketamine misuse relies mainly on supportive care, psychotherapy, and off-label pharmacological options, but robust evidence on efficacy is lacking. There is an urgent need for controlled studies and standardized treatment protocols. Integrated, multidisciplinary, models appear most promising in addressing the complex medical and psychiatric consequences of ketamine misuse.

Background: illegal drugs significantly contribute to global health issues, with health complications often occurring not only in regular users with Substance Use Disorders (SUDs) but also in first-time and occasional users. Methods: this study examines five clinical cases from a public hospital in Ibiza, Spain, where patients presented with acute psychiatric symptoms due to recreational drug use. Results: Contrary to previous studies on SUDs, our patients typically had higher education levels and stable employment. Most of them used multiple substances, with cannabis, cocaine, and alcohol being the most frequently used. There was also a common occurrence of consuming drugs with uncertain contents. Upon admission, typical symptoms included aggression, hallucinations, mood swings, and disorientation in time and space. Conclusions: Our findings underscore the significant mental health risks posed by illicit drugs, even for individuals with no prior psychiatric history. Factors like the drug’s potency, frequency and amount of use, past mental health issues, personality traits, and previous traumatic experiences might influence the onset of these symptoms.