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Introduction: Antipsychotic psychopharmacotherapy is associated with the risk of drug-induced liver injury (DILI). However, understanding specific risk factors remains challenging due to limited data. This study investigates the relationship between receptor binding affinities and occupancies of antipsychotics and their associated hepatotoxic risks. Methods: A disproportionality analysis with calculation of the Reporting Odds Ratio (ROR) and the Information Component (IC) was conducted using data from the FDA Adverse Event Reporting System (FAERS) to identify signals related to the Standardised MedDRA Query "drug-related hepatic disorders", which served as a proxy for drug-induced hepatotoxicity. This was followed by a pharmacoepidemiologic-pharmacodynamic approach to investigate the relationship between the ROR and substance-related receptor binding affinities and occupancy, which was estimated based on in vitro receptor-binding profiles. Results: Significant signals were identified for several antipsychotics, including chlorpromazine, loxapine, olanzapine, and quetiapine, with chlorpromazine and loxapine showing the highest RORs for DILI. Gender-specific analysis revealed a higher frequency of signals in female patients. Statistically significant negative correlations were identified between the ROR for drug-related hepatic disorders and the affinity for serotonin receptor 5-HT1A (r (17) = -0.68, p = 0.0012), while a positive correlation was observed for cholinergic receptors (r (17) = 0.46, p = 0.048). No significant correlations were found related to other receptors or drug properties. Conclusion: Our findings suggest that the serotonin and probably the cholinergic system may play a role in the development of DILI related to antipsychotic medications. The identification of antipsychotics with a higher association with DILI, such as chlorpromazine, underscores the need for careful monitoring in clinical practice. However, our findings need further longitudinal studies to confirm causality. A better understanding of the associations may inform clinical decision-making, particularly in patients with an increased susceptibility to liver damage. [ABSTRACT FROM AUTHOR]

Major depressive disorder is a mental disorder affecting millions of people worldwide. A considerable proportion of patients demonstrate a lack of response to conventional treatment. With the recent introduction of esketamine, a new treatment option has been approved for treatment-resistant depression. Although the medication is efficacious in a substantial portion of cases, rare, but possibly serious, adverse effects may occur. This case series shows two cases of rhabdomyolysis, a destruction of muscle tissuewith elevated creatine kinase levels, after administration of esketamine. The first case presented is about a 33 year old male patient who suffered from a severe episode of a depressive disorder. He got nasal esketamine as an emergency treatment. While there was an initial improvement regarding the depressive symptoms, the patient developed muscle pain and fatigue after the administration of the fourth dose, with creatine kinase (CK) levels above 22,000 U/L, indicating rhabdomyolysis. Following the discontinuation of esketamine and the implementation of supportive care, the CK levels returned to normal and the depressive symptoms abated. The second case is about a 22-year-old male patient who also suffered from a severe depressive episode and got eketamine as an emergency treatment. Following the tenth dose, the patient exhibited muscle weakness and elevated CK levels (8,032 U/L), which persisted even after dose reduction. Esketamine administration was stopped, and the following monitoring demonstrated a slow return to normal levels of CK and liver enzymes. In both cases, there was no known medical history and both patients developed rhabdomyolysis after administration of esketamine. The temporal connection suggests a possible causal relationship. We found no literature on esketamine-induced rhabdomyolysis following the administration of nasal esketamine. However, these two cases emphasize the need of monitoring for laboratory changes like elevated CK-levels in patients receiving esketamine, especially considering its growing use in treatment-resistant depression. [ABSTRACT FROM AUTHOR]

Sexual dysfunction is a common side effect of antidepressants, significantly impacting patients' quality of life and treatment adherence. This study investigates the relationship between sexual dysfunction and antidepressants by analyzing data from VigiBase™, the World Health Organization's global database of individual case safety reports. In this study, we examined, for the first time, reports related to sexual response—desire, arousal, and orgasm—by grouping appropriate side effect terms and calculated the reporting odds ratios (RORs) for various antidepressants. The findings of this study highlight a high disproportional reporting of sexual dysfunction, particularly with selective serotonin reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors. In contrast, agents such as agomelatine, bupropion, and mirtazapine showed a lower association. Furthermore, we investigated the correlation between reporting odds ratios and the binding affinities of antidepressants to specific neurotransmitter receptors and transporters, unveiling significant relationships that provide insights into the pharmacodynamic pathways underlying these adverse effects. For instance, a positive correlation was observed between the serotonin transporter and side effects in the category desire: r (19) = 0.67, p = 0.001 These insights underscore the necessity for clinicians to consider sexual side effects when prescribing antidepressants and to monitor and address these issues to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Non-suicidal self-injury (NSSI), which refers to the deliberate act of causing harm to one's own body without the intent to commit suicide, occurs in 20% of youth. Interestingly, approximately 90% of individuals who engage in self-harm report intrusive mental imagery thereof shortly prior to the act of NSSI. Previous research has demonstrated that imagery rescripting (IR) is an effective technique to treat intrusive mental images and associated clinical symptoms, such as emotion dysregulation, in various psychiatric disorders. However, there is no research on IR for adolescents who self-harm. Therefore, the present study aims to investigate the efficacy and feasibility of a two-session short-intervention using IR to reduce NSSI and associated clinical symptoms in adolescents. The intervention was supported by an app-based digital health intervention (DHI). Methods: A single case series A-B design with three post-assessments (1 week, 1 month, and 3 months post-intervention) was implemented. Seven adolescents received two treatment sessions of IR, supported by a DHI between sessions. NSSI (SITBI), emotion regulation (ERQ), emotional distress (BDI-II, STAI-T), self-efficacy (WIRKALL_r), and treatment satisfaction (BIKEP) were evaluated. Results: There was an increase in adaptive emotion regulation strategies up to 3 months post-intervention. Furthermore, patients improved regarding their self-efficacy, depressiveness, anxiety, and NSSI symptomatology. The developed DHI was described as a helpful and supportive tool. Conclusion: The intervention has shown initial evidence to be feasible and beneficial for adolescents conducting NSSI. The DHI has demonstrated to be a valuable tool in the treatment of self-harming youth. [ABSTRACT FROM AUTHOR]

Introduction In the past 2 decades, functional and structural neuroimaging techniques have been developing rapidly, yielding a large body of research addressing neural correlates of major depressive disorder (MDD). Neuroimaging [...], Background: Abnormal regional cerebral blood flow (rCBF) and grey matter volume have been frequently reported in patients with major depressive disorder (MDD). However, it is unclear to what extent structural and functional change co-occurs in patients with MDD and whether markers of neural activity, such as rCBF, can be predicted by structural change. Methods: Using MRI, we investigated resting-state rCBF and brain structure in patients with MDD and healthy controls between July 2008 and January 2013. We acquired perfusion images obtained with continuous arterial spin labelling, used voxel-based morphometry to assess grey matter volume and integrated biological parametric mapping analyses to investigate the impact of brain atrophy on rCBF. Results: We included 43 patients and 29 controls in our study. Frontotemporal grey matter volume was reduced in patients compared with controls. In patients, rCBF was reduced in the anterior cingulate and bilateral parahippocampal areas and increased in frontoparietal and striatal regions. These abnormalities were confirmed by analyses with brain volume as a covariate. In patients with MDD there were significant negative correlations between the extent of depressive symptoms and bilateral parahippocampal rCBF. We found a positive correlation between depressive symptoms and rCBF for right middle frontal cortical blood flow. Limitations: Medication use in patients has to be considered as a limitation of our study. Conclusion: Our data suggest that while changes of cerebral blood flow and brain volume co-occur in patients with MDD, structural change is not sufficient to explain altered neural activity in patients at rest. Abnormal brain structure and function in patients with MDD appear to reflect distinct levels of neuropathology.