The sixth edition of the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) was published in 2025. This review compared KMAP-DD 2025 with four major international clinical practice guidelines: Canadian Network for Mood and Anxiety Treatments Clinical Guidelines for the Management of Major Depressive Disorders, National Institute for Health and Care Excellence Depression Guideline, Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines for Mood Disorders, and British Association for Psychopharmacology Guideline. While KMAP-DD is based on expert consensus, and others on evidence-based methods, overall treatment strategies for depressive episodes were fairly consistent. Especially, KMAP-DD 2025 offers more structured recommendations in areas lacking strong evidence, such as premenstrual dysphoric disorder, perinatal depression, and depression with medical comorbidities. KMAP-DD 2025 also reflected Korean clinical practice patterns emphasizing rapid symptom relief and early use of combination strategies. Despite limitations as a consensus-based guideline, KMAP-DD 2025 complements evidence-based approaches and provides practical, situation-specific guidance for real-world clinical decision-making in Korea.

Delirium is a common acute neuropsychiatric syndrome, and its early detection may improve clinical outcomes. This narrative review synthesized findings from 11 original studies and two systematic reviews that employed wearable sensors (actigraphy) to predict or detect delirium. In surgical, intensive care unit, and geriatric populations, delirium has consistently been associated with disrupted rest–activity rhythms, including lower daytime activity, increased nighttime activity, and fragmented sleep–wake cycles. Characteristic motor patterns also differed based on the motor subtype (hyperactive vs. hypoactive). Several studies have demonstrated that continuous wrist accelerometry can objectively detect the onset of delirium and classify motor subtypes. Notably, one machine learning model showed improved prediction accuracy, increasing from approximately 62% to 74% when motion features were included. Overall, continuous motion monitoring appears feasible and may serve as a promising non-invasive tool for early delirium detection and risk stratification. However, the findings remain heterogeneous, and motion-based algorithms alone show only moderate sensitivity. Further validation in larger and more diverse cohorts, as well as integration with clinical risk factors, is required before clinical implementation.

Dementia is a neuropsychiatric disorder that primarily affects the elderly, leading to a widespread decline in cognitive function and significant impairment of occupational, social, and personal functioning. In addition to cognitive deficits, dementia is frequently comorbid with behavioral and psychological symptoms of dementia (BPSD), such as agitation.When present, these secondary symptoms can exacerbate the clinical course of the disease, reduced treatment responsiveness, increased rates of admission to long-term care facilities, extended hospitalization, higher risk of personal injury and a substantial socioeconomic burden. Given these consequences, early management of BPSD—particularly agitation—is critical to mitigating these risks. Although antipsychotics are commonly prescribed to manage agitation, risperidone remains the only agent approved by regulatory authorities for this indication. Recently, however, brexpiprazole, a medication with a pharmacological profile distinct from that of risperidone, received U.S. FDA approval (on May 11, 2023) for the treatment of agitation associated with Alzheimer’s disease. Agitation is among the most prevalent BPSD manifestations, with symptoms ranging from verbal to physical aggression. Given its recent approval and unique pharmacodynamic properties, brexpiprazole may have strong potential as a therapeutic option for this population. This paper aims to review the pharmacological mechanisms, clinical evidence, and future perspectives of brexpiprazole as a novel therapeutic option for managing agitation in patients with Alzheimer’s disease.

To report two cases of psychiatric symptoms associated with zonisamide, an antiepileptic drug, and raise clinical awareness of this potential adverse effect. Two male patients with epilepsy treated with zonisamide were retrospectively analyzed. Case 1 (25 years old) developed acute emotional and behavioral abnormalities (e.g., insomnia, aggression, incoherent speech) after switching from sodium valproate to zonisamide (200 mg/day). Case 2 (48 years old) had long-term zonisamide use (≥5 years) with persistent treatment-resistant psychotic symptoms (e.g., delusions, command hallucinations). Clinical courses, medication adjustments, and symptom responses were documented. In Case 1, psychiatric symptoms resolved after discontinuing zonisamide and switching to sodium valproate, with improved mood stability and reduced impulsivity. In Case 2, despite escalating antipsychotic medications (risperidone, clozapine), psychotic symptoms persisted, likely due to ongoing zonisamide use. Both cases highlighted zonisamide’s potential to exacerbate or induce psychiatric manifestations, possibly via mechanisms involving sodium/calcium channel inhibition and neurotransmitter dysregulation (e.g., dopamine, serotonin). Zonisamide can cause or worsen psychiatric symptoms, particularly in vulnerable individuals. Clinicians should monitor for mental health changes during zonisamide treatment and consider drug discontinuation or substitution with alternative antiepileptics (e.g., sodium valproate) if psychiatric adverse effects emerge. Awareness of this association is crucial to avoid misdiagnosis and optimize epilepsy management.

The decision to use multiple long-acting injectable antipsychotics (LAIAs) is difficult since there is no evidence base for their use in treatment guidelines. In this case series, we aimed to present our experiences with the use of triple LAIAs in four patients diagnosed with schizophrenia. The study included four treatment-resistant schizophrenia cases who were followed in the inpatient ward of a university hospital, who could not use clozapine due to non-compliance with treatment, who did not benefit from multiple electroconvulsive therapy procedures, who did not respond to dual antipsychotic treatments and who were using triple LAIAs. The clinical histories of the cases were analysed retrospectively by experienced psychiatrists. All patients responded to the treatment with a decrease in their psychotic symptoms and the number of hospitalizations without any significant side effects. Also, improvement in daily functioning and adherence to treatment was observed in all cases. Based on these results, the use of multiple LAIAs can be safely applied, especially in appropriate treatment-resistant schizophrenia patients and with close follow-up by a clinician.

Objective: Biological processes are the sum of metabolic reactions that result in intermediate and end metabolite products. These processes are the reflection of genetic regulation and are profoundly impacted by environmental influence and changes, including those associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to assess the untargeted plasma metabolomic profile of children and adolescents with ADHD and to compare them with healthy controls and to study associations of dysregulated metabolic parameters with the clinical and socio-demographic parameters of ADHD. Methods: This study involved 42 registered cases of ADHD among children aged 6 to 16 years, diagnosed based on DSM-5 criteria. Each case was matched by age and gender with 24 healthy controls. The severity of ADHD was evaluated using the ADHD Rating Scale, while behavioral issues were assessed through the Child Behavior Checklist. The gas chromatography-mass spectrometry technique was employed to examine changes in plasma metabolite content. Results: We identified a total of 45 metabolites in the ADHD subtypes, which exhibited altered levels compared to the control group. The content of these metabolites and associated metabolic pathways showed significant differences between ADHD subjects and controls. Furthermore, we analyzed biomarkers derived from the compounds with the greatest fold changes in accumulation levels. Conclusion The identification and analysis of these metabolites and metabolic pathways represent a promising new approach for tracking disease progression in ADHD. The findings of this study indicate that metabolite-based biomarkers may hold considerable potential for effective disease management.

Objective: This study examined whether baseline levels of 14 serum biomarkers predicted antidepressant remission differently by sex at 12 weeks and 12 months. Methods: In a prospective cohort, 1,086 outpatients with depressive disorders received stepwise antidepressant treatment following a naturalistic protocol. Baseline serum samples were analyzed for biomarkers from six systems: immune (high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-4, interleukin-10), metabolic (leptin, ghrelin, total cholesterol), neurotrophic (brain-derived neurotrophic factor), neurotransmitter (serotonin), endocrine (cortisol), and nutritional (folate, homocysteine). Remission, defined as a Hamilton Depression Rating Scale scores ≤ 7, was assessed at 12 weeks and 12 months. Logistic regression models with biomarker-by-sex interaction and stratified analyses were used, adjusting for clinical covariates. Results: Higher baseline serotonin predicted 12-week remission in males but not in females. At 12 months, lower leptin and higher folate predicted remission only in males, while lower cortisol predicted remission only in females. These showed significant biomarker-sex interactions. No sex-specific interactions were found for immune markers. Conclusion Baseline serum biomarkers across biological systems showed sex-specific associations with treatment outcomes. Neurotransmitter, metabolic, endocrine, and nutritional markers may offer predictive value for sex-tailored, biomarker-informed treatment strategies in depression.

Objective: Youths with disruptive behavior disorders (DBDs) and a history of trauma exposure often exhibit deficits in neural mechanisms related to reward anticipation and assessment. This preliminary investigation examines the potential of a serotonergic agent (fluoxetine) to modulate neural activity in reward-related pathways for this population. Methods: Three participant groups were: (i) youth with DBDs and trauma exposure who received fluoxetine treatment for 8 weeks (n = 12); (ii) a matched group of youth with DBDs and trauma exposure who received routine regular followup in an outpatient clinic (n = 9); and (iii) typically developing youth (n = 19). All participants completed a passive avoidance fMRI task twice, 8 weeks apart (pre-treatment and post treatment for youth with DBDs). Results: Youth with DBDs and trauma exposure who received fluoxetine treatment compared to the other two groups showed: (i) significant improvement in externalizing, oppositional defiant disorder, irritability, anxiety-depression, and trauma-related symptoms; (ii) significantly increased recruitment of regions implicated in reward expectation (e.g., ventral tegmental area, nucleus accumbens), monitoring prediction error (e.g., dorsolateral prefrontal cortex, posterior parietal cortex), and inhibitory control (e.g., anterior insula, pre-supplementary motor area, anterior prefrontal cortex. Conclusion We provide preliminary data suggesting that a serotonergic medication can correct reward processing and provide symptom improvement in youth with DBDs and a history of trauma exposure. Given the small sample size, more rigorous studies with larger sample size are needed to confirm these results. The findings of this study could aid future clinical research and treatment for this challenging population.

Objective: Rewarding properties of androgens have been suggested. This research aimed to assess the effect of androgen system during the extinction period on morphine induced conditioned place preference (CPP). Androgen and μ-opioid receptor (μ-OR) gene expression were also evaluated in prefrontal cortex (PFC) and nucleus accumbens (NAc) in the male rats. Methods: CPP was induced by morphine injection (3, 5 and 7 mg/kg, s.c.) for three consecutive days. Testosterone (androgen receptor [AR] agonist, 2.5 mg/kg; i.m.) or flutamide (AR antagonist 10 mg/kg, i.m.) were administered in subsequent extinction period. In two castration groups, one group was considered as control and the other one received testosterone during extinction phase. The mRNA expression levels of μ-OR and ARs in PFC and NAc were evaluated using quantitative real-time PCR following CPP reinstatement. Results: Testosterone prolonged while flutamide shortened extinction period. Castration facilitated morphine-extinction and testosterone could not reverse this effect. The expression of μ-OR and ARs were increased in PFC and NAc of castrated animals compared to control group which were reversed by testosterone. This effect was not reversed by testosterone for μ-OR in PFC. Conclusion Our data indicated that decreased level of testosterone facilitates extinction period in morphine CPP model in male rats. This result could be due to the changes in the expression of opioid and androgenic receptors in PFC and NAc. This study confirms the crucial role of androgen system in modulating drug reward.