Major depressive disorder (MDD) is a tremendous global disease burden and the leading cause of disability worldwide. Unfortunately, individuals diagnosed with MDD typically experience a delayed response to traditional antidepressants and many do not adequately respond to pharmacotherapy, even after multiple trials. The critical need for novel antidepressant treatments has led to a recent resurgence in the clinical application of psychedelics, and intravenous ketamine, which has been investigated as a rapid-acting treatment for treatment resistant depression (TRD) as well acute suicidal ideation and behavior. However, variations in the type and quality of experimental design as well as a range of treatment outcomes in clinical trials of ketamine make interpretation of this large body of literature challenging.

This umbrella review aims to advance our understanding of the effectiveness of intravenous ketamine as a pharmacotherapy for TRD by providing a systematic, quantitative, large-scale synthesis of the empirical literature.

We performed a comprehensive PubMed search for peer-reviewed meta-analyses of primary studies of intravenous ketamine used in the treatment of TRD. Meta-analysis and primary studies were then screened by two independent coding teams according to pre-established inclusion criteria as well as PRISMA and METRICS guidelines. We then employed metaumbrella, a statistical package developed in R, to perform effect size calculations and conversions as well as statistical tests.

In a large-scale analysis of 1,182 participants across 51 primary studies, repeated-dose administration of intravenous ketamine demonstrated statistically significant effects (p<0.05) compared to placebo-controlled as well as other experimental conditions in patients with TRD, as measured by standardized clinician-administered and self-report depression symptom severity scales.

This study provides large-scale, quantitative support for the effectiveness of intravenous, repeated-dose ketamine as a therapy for TRD and a report of the relative effectiveness of several treatment parameters across a large and rapidly growing literature. Future investigations should use similar analytic tools to examine evidence-stratified conditions and the comparative effectiveness of other routes of administration and treatment schedules as well as the moderating influence of other clinical and demographic variables on the effectiveness of ketamine on TRD and suicidal ideation and behavior.

None Declared

Panic disorder (PD) and agoraphobia (AG) are highly comorbid anxiety disorders with an increasing prevalence that have a significant clinical and public health impact but are not adequately recognized and treated. Although the current functional neuroimaging literature has documented a range of neural abnormalities in these disorders, primary studies are often not sufficiently powered and their findings have been inconsistent.

This meta-analysis aims to advance our understanding of the neural underpinnings of PD and AG by identifying the most robust patterns of differential neural activation that differentiate individuals diagnosed with one of or both these disorders from age-matched healthy controls.

We conducted a comprehensive literature search in the PubMed database for all peer-reviewed, whole-brain, task-based functional magnetic resonance imaging (fMRI) activation studies that compared adults diagnosed with PD and/or AG with age-matched healthy controls. Each of these articles was screened by two independent coding teams using formal inclusion criteria and according to current PRISMA guidelines. We then performed a voxelwise, whole-brain, meta-analytic comparison of PD/AG participants with age-matched healthy controls using multilevel kernel density analysis (MKDA) with ensemble thresholding (p<0.05-0.0001) to minimize cluster size detection bias and 10,000 Monte Carlo simulations to correct for multiple comparisons.

With data from 34 primary studies and a substantial sample size (N=2138), PD/AG participants, relative to age-matched healthy controls, exhibited a reliable pattern of statistically significant, (p<.05-0.0001; FWE-corrected) abnormal neural activation in multiple brain regions of the cerebral cortex and basal ganglia across a variety of experimental tasks.

In this meta-analysis we found robust patterns of differential neural activation in participants diagnosed with PD/AG relative to age-matched healthy controls. These findings advance our understanding of the neural underpinnings of PD and AG and inform the development of brain-based clinical interventions such as non-invasive brain stimulation (NIBS) and treatment prediction and matching algorithms. Future studies should also investigate the neural similarities and differences between PD and AG to increase our understanding of possible differences in their etiology, diagnosis, and treatment.

None Declared

There has been rapidly growing interest in understanding the pharmaceutical and clinical properties of psychedelic and dissociative drugs, with a particular focus on ketamine. This compound, long known for its anesthetic and dissociative properties, has garnered attention due to its potential to rapidly alleviate symptoms of depression, especially in individuals with treatment-resistant depression (TRD) or acute suicidal ideation or behavior. However, while ketamine’s psychopharmacological effects are increasingly well-documented, the specific patterns of its neural impact remain a subject of exploration and basic questions remain about its effects on functional activation in both clinical and healthy populations.

This meta-analysis seeks to contribute to the evolving landscape of neuroscience research on dissociative drugs such as ketamine by comprehensively examining the effects of acute ketamine administration on neural activation, as measured by functional magnetic resonance imaging (fMRI), in healthy participants.

We conducted a meta-analysis of existing fMRI activation studies of ketamine using multilevel kernel density analysis (MKDA). Following a comprehensive PubMed search, we quantitatively synthesized all published primary fMRI whole-brain activation studies of the effects of ketamine in healthy subjects with no overlapping samples (N=18). This approach also incorporated ensemble thresholding (α=0.05-0.0001) to minimize cluster-size detection bias and Monte Carlo simulations to correct for multiple comparisons.

Our meta-analysis revealed statistically significant (p<0.05-0.0001; FWE-corrected) alterations in neural activation in multiple cortical and subcortical regions following the administration of ketamine to healthy participants (N=306).

These results offer valuable insights into the functional neuroanatomical effects caused by acute ketamine administration. These findings may also inform development of therapeutic applications of ketamine for various psychiatric and neurological conditions. Future studies should investigate the neural effects of ketamine administration, including both short-term and long-term effects, in clinical populations and their relation to clinical and functional improvements.

None Declared

Bipolar I disorder (BD-I) is a chronic and recurrent mood disorder characterized by alternating episodes of depression and mania; it is also associated with substantial morbidity and mortality and with clinically significant functional impairments. While previous studies have used functional magnetic resonance imaging (fMRI) to examine neural abnormalities associated with BD-I, they have yielded mixed findings, perhaps due to differences in sampling and experimental design, including highly variable mood states at the time of scan.

The purpose of this study is to advance our understanding of the neural basis of BD-I and mania, as measured by fMRI activation studies, and to inform the development of more effective brain-based diagnostic systems and clinical treatments.

We conducted a large-scale meta-analysis of whole-brain fMRI activation studies that compared participants with BD-I, assessed during a manic episode, to age-matched healthy controls. Following PRISMA guidelines, we conducted a comprehensive PubMed literature search using two independent coding teams to evaluate primary studies according to pre-established inclusion criteria. We then used multilevel kernel density analysis (MKDA), a well-established, voxel-wise, whole-brain, meta-analytic approach, to quantitatively synthesize all qualifying primary fMRI activation studies of mania. We used ensemble thresholding (p<0.05-0.0001) to minimize cluster size detection bias, and 10,000 Monte Carlo simulations to correct for multiple comparisons.

We found that participants with BD-I (N=2,042), during an active episode of mania and relative to age-matched healthy controls (N=1,764), exhibit a pattern of significantly (p<0.05-0.0001; FWE-corrected) different activation in multiple brain regions of the cerebral cortex and basal ganglia across a variety of experimental tasks.

This study supports the formulation of a robust neural basis for BD-I during manic episodes and advances our understanding of the pattern of abnormal activation in this disorder. These results may inform the development of novel brain-based clinical tools for bipolar disorder such as diagnostic biomarkers, non-invasive brain stimulation, and treatment-matching protocols. Future studies should compare the neural signatures of BD-I to other related disorders to facilitate the development of protocols for differential diagnosis and improve treatment outcomes in patients with BD-I.

None Declared

Accordingly, the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) working committee, composed of domestic experts, developed Korea’s first KMAP-BP in 2002 and later in 2006, 2010, and 2010. A revised version of KMAP-BP was announced every four years four times in 2014 and 2018.6-10). The treatment strategy considering the safety and tolerability of KMAP-BP 2022 was developed by collecting opinions from domestic bipolar disorder experts.

Safety and tolerability of drugs are very important factors in the treatment of bipolar disorder. An expert opinion survey was conducted on treatment strategies in various special clinical situations, such as significant weight gain, characteristic drug side effects, low drug adherence, pregnant and reproductive women, and genetic counseling.

A written survey about treatment strategies related to safety and tolerability was prepared and focused on significant weight gain, characteristic drug side effects, low drug adherence, pregnant and reproductive women, and genetic counseling. Ninety-three experts of the review committee completed the survey.

In the case of weight gain occurring during drug treatment, it was preferred to replace it with a drug that caused less weight gain, such as lamotrigine, aripiprazole, or ziprasidone. If there was a significant weight gain due to the treatment drug, it was preferred to intervene as soon as possible. In the case of hyperprolactinemia, it was selected to change the medication and discontinue it for benign rash caused by lamotrigine. In improving drug adherence, the preference for long-acting injections increased. Antipsychotics can be used with great caution in pregnant or reproductive women.

Treatment strategies in various clinical situations related to safety and tolerability in drug treatment for bipolar disorder were described. It is hoped that it will be useful in practical clinical situations.

None Declared

Majority of international guidelines for bipolar disorders are based on evidences from clinical trials. In contrast, the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed to adopt an expert-consensus paradigm which was more practical and specific to the atmosphere in Korea.

In this study, preferred medication strategies for acute mania over six consecutively published KMAP-BP (2002, 2006, 2010, 2014, 2018, and 2022) were investigated.

A written survey using a nine-point scale was asked to Korean experts about the appropriateness of various treatment strategies and treatment agents. A written survey asked about the appropriateness of various treatment strategies and treatment agents commonly used by clinicians as the first-line.

The most preferred option for the initial treatment of mania was a combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP) in every edition. Preference for combined treatment for euphoric mania increased, peaked in KMAP-BP 2010, and declined slightly. Either MS or AAP monotherapy was also considered a first-line strategy for mania, but not for all types of episodes, including mixed/psychotic mania. Among MSs, lithium and valproate are almost equally preferred except in the mixed subtype where valproate is the most recommended MS. The preference of valproate showed reverse U-shaped curve. This preference change of valproate may indicate the concern about teratotoxicity in women. Quetiapine, aripiprazole, and olanzapine were the preferred AAP for acute mania since 2014. This change might depend on the recent evidences and safety profile. In cases of unsatisfactory response to initial medications, switching or adding another first-line agent was recommended. The most notable changes over time included the increasing preference for AAPs.

The Korean experts have been increasingly convinced of the effectiveness of a combination therapy for acute mania. There have been evident preference changes: increased for AAP and decreased for carbamazepine.

None Declared

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent psychiatric condition that frequently originates in early development and is associated with a variety of functional impairments. Despite a large functional neuroimaging literature on ADHD, our understanding of the neural basis of this disorder remains limited, and existing primary studies on the topic include somewhat divergent results.

The present meta-analysis aims to advance our understanding of the neural basis of ADHD by identifying the most statistically robust patterns of abnormal neural activation throughout the whole-brain in individuals diagnosed with ADHD compared to age-matched healthy controls.

We conducted a meta-analysis of task-based functional magnetic resonance imaging (fMRI) activation studies of ADHD. This included, according to PRISMA guidelines, a comprehensive PubMed search and predetermined inclusion criteria as well as two independent coding teams who evaluated studies and included all task-based, whole-brain, fMRI activation studies that compared participants diagnosed with ADHD to age-matched healthy controls. We then performed multilevel kernel density analysis (MKDA) a well-established, whole-brain, voxelwise approach that quantitatively combines existing primary fMRI studies, with ensemble thresholding (p<0.05-0.0001) and multiple comparisons correction.

Participants diagnosed with ADHD (N=1,550), relative to age-matched healthy controls (N=1,340), exhibited statistically significant (p<0.05-0.0001; FWE-corrected) patterns of abnormal activation in multiple brains of the cerebral cortex and basal ganglia across a variety of cognitive control tasks.

This study advances our understanding of the neural basis of ADHD and may aid in the development of new brain-based clinical interventions as well as diagnostic tools and treatment matching protocols for patients with ADHD. Future studies should also investigate the similarities and differences in neural signatures between ADHD and other highly comorbid psychiatric disorders.

None Declared

Olanzapine (OLA) is a common first-prescribed antipsychotic and has shown favorable efficacy in acutely exacerbated patients with schizophrenia. The mixed receptor activity of OLA and its greater affinity for serotonin 5-HT2A rather than dopamine D2 receptors are similar to those of clozapine. Pharmacokinetically, OLA is metabolized mainly by hepatic cytochrome enzyme P450 1A2 (CYP1A2). Because risks of antipsychotic polypharmacy include increased drug-drug interactions, pharmacokinetic considerations are important for selection of antipsychotics to be combined. Due to its pharmacological characteristics, amisulpride (AMI), another atypical antipsychotic with proven efficacy, is a promising adjuvant agent of special interest. AMI is unlikely to interact with other drugs due to the low plasma protein binding and metabolism and does not affect the activity of the CYP system. Furthermore, AMI is highly selective for dopamine D2/D3 receptors; has minimal or no affinity for D1, D4, or D5 receptors. Despite the potential benefits of the combination of OLA and AMI, only a few open-label studies have been conducted, and no randomized clinical trial has been performed to date to examine the efficacy and tolerability of the combination. Hence, the goals of this study were to test the hypothesis that AMI augmentation would improve psychotic symptoms and be well tolerated in schizophrenic patients who showed poor response to OLA monotherapy.

The purpose of this study was to compare the efficacy and tolerability of continued olanzapine (OLA) versus amisulpride (AMI) augmentation in schizophrenic patients with poor response to OLA monotherapy.

The present 4-week, randomized, rater-blinded study included 25 patients with schizophrenia who were partially or completely unresponsive to treatment with OLA monotherapy. Eligible subjects were randomly assigned at a 1:1 ratio to continuation of OLA monotherapy (OLA group) or OLA with AMI augmentation (AMI group). Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at 1, 2, and 4 weeks.

The changes in PANSS total score and PANSS-positive subscale score were significantly different (p < 0.05) between the OLA and AMI groups. The differences between the two groups in PANSS-negative subscale, PANSS-general subscale, Brief Psychiatric Rating Scale, and Clinical Global Impression-Severity (CGI-S) scale scores were not statistically significant.

AMI augmentation could be an effective strategy for patients with schizophrenia who show inadequate early response to OLA monotherapy.

W.-M. Bahk Grant / Research support from: Handok Pharmaceuticals, Seoul, Korea, Y. S. Woo: None Declared, S.-Y. Park: None Declared, B.-H. Yoon: None Declared, S.-M. Wang: None Declared, M.-D. Kim: None Declared

This study examined the effectiveness of an integrated care pathway (ICP), including a medication algorithm, to treat agitation associated with dementia.

Analyses of data (both prospective and retrospective) collected during routine clinical care.

Geriatric Psychiatry Inpatient Unit.

Patients with agitation associated with dementia (n = 28) who were treated as part of the implementation of the ICP and those who received treatment-as-usual (TAU) (n = 28) on the same inpatient unit before the implementation of the ICP. Two control groups of patients without dementia treated on the same unit contemporaneously to the TAU (n = 17) and ICP groups (n = 36) were included to account for any secular trends.

ICP.

Cohen Mansfield Agitation Inventory (CMAI), Neuropsychiatric Inventory Questionnaire (NPIQ), and assessment of motor symptoms were completed during the ICP implementation. Chart review was used to obtain length of inpatient stay and rates of psychotropic polypharmacy.

Patients in the ICP group experienced a reduction in their scores on the CMAI and NPIQ and no changes in motor symptoms. Compared to the TAU group, the ICP group had a higher chance of an earlier discharge from hospital, a lower rate of psychotropic polypharmacy, and a lower chance of having a fall during hospital stay. In contrast, these outcomes did not differ between the two control groups.

These preliminary results suggest that an ICP can be used effectively to treat agitation associated with dementia in inpatients. A larger randomized study is needed to confirm these results.

To examine associations between sociodemographic and mental health characteristics with household risk for food insecurity during the COVID-19 outbreak.

Cross-sectional online survey analysed using univariable tests and a multivariable logistic regression model.

The United States during the week of 30 March 2020.

A convenience sample of 1965 American adults using Amazon’s Mechanical Turk platform. Participants reporting household food insecurity prior to the pandemic were excluded from analyses.

One thousand two hundred and fifty participants reported household food security before the COVID-19 outbreak. Among this subset, 41 % were identified as at risk for food insecurity after COVID-19, 55 % were women and 73 % were white. On a multivariable analysis, race, income, relationship status, living situation, anxiety and depression were significantly associated with an incident risk for food insecurity. Black, Asian and Hispanic/Latino respondents, respondents with an annual income <$100 000 and those living with children or others were significantly more likely to be newly at risk for food insecurity. Individuals at risk for food insecurity were 2·60 (95 % CI 1·91, 3·55) times more likely to screen positively for anxiety and 1·71 (95 % CI 1·21, 2·42) times more likely to screen positively for depression.

An increased risk for food insecurity during the COVID-19 pandemic is common, and certain populations are particularly vulnerable. There are strong associations between being at risk for food insecurity and anxiety/depression. Interventions to increase access to healthful foods, especially among minority and low-income individuals, and ease the socioemotional effects of the outbreak are crucial to relieving the economic stress of this pandemic.