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Yayın Treatment and long-term outcome of mental disorders: The grim picture from a quasi-epidemiological investigation in 54,826 subjects from 40 countries(Elsevier Ireland Ltd, 2025-06) Fountoulakis, Konstantinos N.; Karakatsoulis, Gregory; Abraham, Seri; Adorjan, Kristina; Uddin Ahmed, Helal; Alarcòn, Renato Daniel; Arai, Kiyomi; Auwal, Sani Salihu; Berk, Michael; Levaj, Sarah; Yılmaz Kafalı, HelinIntroduction: This study registered rates of specific treatment options for mental disorders as well as their long-term outcome. Material and methods: The history of mental disorders was used as a proxy for diagnosis. The data came from the COMET-G study (40 countries; 54,826 subjects, 64.73 % females, 35.45±13.51 years old). The analysis included descriptive statistics, Risk Ratios, t-tests, and ANCOVA's. Results: 24.14 % reported a history of any mental disorder (depression >12 %, non-affective psychosis and Bipolar disorder 1 % each, >20 % self-injury, >10 % had attempted suicide, 7.17 % illegal substance abuse). Most patients were not under any kind of treatment (59.44 %) and most were not receiving treatment as recommended (e.g. 90 % of Bipolar and 2/3 of psychotic patients). No treatment at all and psychotherapy as monotherapy were consistently related to poorer outcomes. In anxiety or depression, only antidepressant monotherapy and benzodiazepines, in Bipolar disorder only antipsychotic monotherapy in males and antidepressant monotherapy in females and in non-affective psychosis antipsychotics and psychotherapy in females only, were related to good outcomes. No treatment modality was related to a good outcome in those with a history of self-harm, suicidal attempts, or illegal substance use. Only depression and treatment with antidepressants were related to metabolic syndrome. Discussion: In the community, the overwhelming majority of mental patients do not receive appropriate treatment or, even worse, no treatment at all. The outcome is unfavourable for the majority and only a few selective treatment options seem to make a difference.Yayın Efficacy, all-cause discontinuation, and safety of serotonergic psychedelics and MDMA to treat mental disorders: a living systematic review with meta-analysis(Elsevier B.V., 2025-12) Højlund, Mikkel; Yılmaz Kafalı, Helin; Kırmızı, Begüm; Fusar-Poli, Paolo; Correll, Christoph U.; Cortese, Samuele; Sabé, Michel; Fiedorowicz, Jess; Saraf, Gayatri; Zein, Josephine; Berk, Michael; Husain, Muhammad I.; Rosenblat, Joshua D.; Rubaiyat, Ruby; Corace, Kim; Wong, Stanley; Hatcher, Simon; Kaluzienski, Mark; Yatham, Lakshmi N.; Cipriani, Andrea; Gosling, Corentin J.; Carhart-Harris, Robin; Tanuseputro, Peter; Myran, Daniel T.; Fabiano, Nicholas; Moher, David; Mayo, Leah M.; Nicholls, Stuart G.; White, Tracy; Prisco, Michele De; Radua, Joaquim; Vieta, Eduard; Ladha, Karim S.; Katz, Jay; Veroniki, Areti A.; Solmi, MarcoSerotonergic psychedelics and 3,4-methylendioxtmethamphetamine (MDMA) are promising treatments for mental disorders with a continuously evolving evidence base. We searched Pubmed/Scopus/clinical trial registries up to 08july2025 for double-blind randomized controlled trials (RCTs) testing MDMA or serotonergic psychedelics in patients with mental disorders. Primary outcomes were change in disease-specific symptoms and all-cause discontinuation. Standardized mean differences (SMD) and relative risk (RR) were estimated using random-effects meta-analysis. Risk of bias (RoB) was assessed with Cochrane’s RoB-tool version 2 and certainty of evidence with GRADE. The review is maintained as living systematic review ( https://ebipsyche-database.org/ ). We included 30 RCTs (1480 participants; female=45.8 %; with psychological support=83.3 %; high RoB=83.3 %). In post-traumatic stress disorder (PTSD), MDMA reduced PTSD symptoms compared to any control ( k = 11; SMD=-0.85 [-1.09; -0.60]; I2=0 %; GRADE=low). In major depressive disorder (MDD), psilocybin/ayahuasca/LSD reduced depressive symptoms ( k = 8; SMD=-0.62 [-0.97; -0.28]; I2=55 %; GRADE=very low). In anxiety disorders, both MDMA and serotonergic psychedelics reduced anxiety symptoms (SMDMDMA=-1.18 [-2.04; -0.32]; I2=0 %; k = 2; GRADE=low and SMDserotonergic=-0.88 [-1.70; -0.06]; I2=54 %; k = 5; GRADE=very low). In alcohol use disorder, neither psilocybin nor LSD reduced abstinence rates ( k = 6; RR=1.42 [0.89; 2.26]; I2=7 %; GRADE=very low). In attention-deficit hyperactivity disorder (ADHD), LSD did not reduce ADHD symptoms ( k = 1; SMD=0.22 [-0.32; 0.76]; GRADE=very low). Moderate certainty in evidence was only found for MDMA on PTSD symptoms when compared to placebo. MDMA/serotonergic psychedelics were not associated with higher risk of all-cause discontinuation (RRMDMA=0.74 [0.32; 1.72]; RRserotonergic=0.81 [0.56; 1.15]). Overall, MDMA/serotonergic psychedelics are promising for the treatment of PTSD, MDD, and anxiety disorders with moderate to large effect sizes. Pragmatic trials, long-term, head-to-head trials exploring the role of psychological support, aiming to identify predictors of response, and accounting for expectancy and functional unblinding are needed. Studies addressing these limitations will likely be required for regulatory approval of psychedelic drugs.
