Current Understanding on Psilocybin for Major Depressive Disorder: A Review Focusing on Clinical Trials.

Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a "breakthrough therapy" for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin's potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials [DB-RCTs]) trials exploring psilocybin's impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over six months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects.

The Potential Role of Aripiprazole Augmentation for Major Depressive Disorder with Anxious Distress in Naturalistic Treatment Setting.

Objective: : This study tried to observe clinical benefit of aripiprazole augmentation (ARPA) treatment for major depressive disorder with anxious distress (MDDA) in routine practice. Methods: : Retrospective chart review (n = 41) was conducted for clinical benefit of ARPA in patients with MDDA in routine practice. The primary endpoint was the mean change of Hamilton Anxiety Rating scale (HAMA) total scores from baseline to the endpoint. Additional secondary endpoints were also retrieved. Results: : The changes of primary endpoint HAMA (t = 5.731, -4.6, p = 0.001), and secondary endpoints including Hamilton Depression Rating scale (HAMD, t = 4.284, -3.4, p ＜ 0.001), Clinical Global Impression-Clinical Benefit (CGI-CB, -0.9, t = 1.821, p = 0.026), and Clinical Global Impression Score-Severity (CGI-S, t = 3.556, -0.4, p ＜ 0.001) scores were also significantly improved during the study. No significant adverse events were observed. Conclusion: : This study has shown additional benefit of ARPA treatment for MDDA patients in routine practice. However, adequately-powered and well-controlled studies are necessary for generalization of the present findings.

Defining "High Recurrence" of Depressive Episodes for Predicting Diagnostic Conversion from Major Depressive Disorder to Bipolar Disorder: A 5-year Retrospective Study.

Objective: This study determined the threshold for recurrent depressive episodes that predicted conversion from major depressive disorder (MDD) to bipolar disorder (BD). Methods: We retrospectively reviewed the medical records of 296 patients diagnosed with MDD for a minimum of 5 years in two university hospitals. We examined their the Diagnostic and Statistical Manual of Mental Disorders, 5th edition diagnoses and detailed clinical information at the initial admission and yearly assessments after discharge to establish the threshold for recurrent depressive episodes indicating a risk of diagnostic conversion from MDD to BD. Optimal cut-offs were derived using receiver operating characteristic (ROC) curves. Results: ROC curve analysis revealed that more than four recurrent depressive episodes was indicative of potential diagnostic conversion from MDD to BD (area under the curve, 0.604; sensitivity, 0.353; specificity, 0.855; positive predictive value, 0.421; negative predictive value, 0.816). Conclusion: These findings suggest that the best predictor of conversion from MDD to BD is more than four recurrent depressive episodes. Our findings have the potential to enhance diagnostic accuracy and treatment efficiency. To validate our results, longitudinal prospective studies are necessary.

Preventive effect of aripiprazole once-monthly on relapse into mood episodes in bipolar disorder: A multicenter, one-year, retrospective, mirror image study.

BACKGROUND: We conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with bipolar disorder (BD). We compared pre-treatment conditions with outcomes after 12 months of AOM treatment. METHODS: Seventy-five bipolar patients were recruited from 12 hospitals in Korea. We included 75 patients with BD who had received at least three AOM treatments from September 2019 to September 2022 and had accessible electronic medical record (EMRs) for the year before and after the baseline visit. RESULTS: The overall number of mood episodes significantly decreased from a mean of 1.5 ± 1.2 episodes pre-AOM to 0.5 ± 1.2 episodes post-AOM. Manic episodes significantly decreased from 0.8 ± 0.8 episodes pre-AOM to 0.2 ± 0.5 episodes post-AOM, and depressive episodes significantly decreased from 0.5 ± 0.8 episodes pre-AOM to 0.2 ± 0.6 episodes post-AOM (p = 0.017). Moreover, the number of psychiatric medications and pills and the proportion of patients treated with complex polypharmacy were significantly decreased post-AOM. LIMITATIONS: The small sample size was insufficient to fully represent the entire population of individuals with BD, and potential selection bias was introduced due to only including subjects who received AOM three or more times. CONCLUSION: The results of this study suggest that AOM can reduce mood episode relapse and may be clinically beneficial in the treatment of BD patients, potentially reducing issues associated with polypharmacy in some individuals.

Patient's Perspective on Psychiatric Drugs: A Multicenter Survey-Based Study.

OBJECTIVE: We aimed to identify the expectations and preferences for medication and medical decision-making in patients with major psychiatric disorders. METHODS: A survey was conducted among patients with major psychiatric disorders who visited psychiatric outpatient clinics at 15 hospitals between 2016 and 2018 in Korea. The survey consisted of 12 questions about demographic variables and opinions on their expectations for medication, important medical decision-makers, and preferred drug type. The most preferred value in each category in the total population was identified, and differences in the preference ratio of each item among the disease groups were compared. RESULTS: A total of 707 participants were surveyed. In the total population, patients reported high efficacy (44.01%±21.44%) as the main wish for medication, themselves (37.39%±22.57%) and a doctor (35.27%±22.88%) as the main decision makers, and tablet/capsule (36.16%±30.69%) as the preferred type of drug. In the depressive disorders group, the preference ratio of high efficacy was significantly lower, and the preference ratio of a small amount was significantly higher than that of the psychotic disorder and bipolar disorder groups. The preference ratio of a doctor as an important decision maker in the bipolar disorder group was higher compared to the other groups. CONCLUSION: This study revealed the preference for medications and showed differences among patients with psychiatric disorders. Providing personalized medicine that considers a patient's preference for the drug may contribute to the improvement of drug compliance and outcomes.

Prevalence and Comorbidities of Adult Attention-deficit/hyperactivity Disorder in a Community Sample from Korea.

Objective: : Attention-deficit/hyperactivity disorder (ADHD) is prevalent in adults, and psychiatric comorbidities are common in adults with ADHD. We aimed to examine the prevalence of adult ADHD with several common psychiatric conditions in a community sample in Korea and the association between adult ADHD and risk of psychiatric comorbidities. Methods: : This study used a cross-sectional survey design. We provided supplementary and optional self-report questionnaires, including the Korean version of the World Health Organization Adult ADHD Self-Report Scale (ASRS) short screening scale, Patient Health Questionnaire-9 for screening for depression, Alcohol Use Disorders Identification Test alcohol consumption questions, and the Korean version of the Mood Disorders Questionnaire, to Korean adults who visited one of six centers of a large private healthcare company for the National General Health Examination. Results: : A total of 17,799 subjects included in this study, and 430 (2.4%) were positive on the ASRS screen. ADHD was significantly associated with the 19-30-year-old age group (odds ratio [OR] = 3.938), lower income (OR = 1.298), depression (OR = 11.563), and bipolar disorder (OR = 3.162). Conclusion: : Adult ADHD was highly associated with depression and bipolar disorder, suggesting that clinicians should carefully evaluate and treat such psychiatric disorders in adults with ADHD symptoms.

The Impact of COVID-19 on Psychiatric Health in the Korean Population.

Coronavirus disease 2019 (COVID-19) has multiple negative impacts on the psychiatric health of both those previously infected and not infected with severe acute respiratory syndrome coronavirus 2. Moreover, the negative impacts of COVID-19 are closely associated with geographical region, culture, medical system, and ethnic background. We summarized the evidence of the impact of COVID-19 on the psychiatric health of the Korean population. This narrative review included thirteen research articles, which investigated the impact of COVID-19 on the psychiatric health of Koreans. COVID-19 survivors were reported to have a 2.4 times greater risk of developing psychiatric disorders compared to members of a control group, and anxiety and stress-related disorders were the most common newly diagnosed psychiatric illnesses. Studies also reported that COVID-19 survivors had a 3.33-fold higher prevalence of insomnia, a 2.72-fold higher prevalence of mild cognitive impairment, and a 3.09-fold higher prevalence of dementia compared to the control group. In addition, more than four studies have highlighted that the medical staff members, including nurses and medical students, exhibit a greater negative psychiatric impact of COVID-19. However, none of the articles investigated the biological pathophysiology or mechanism linking COVID-19 and the risk of diverse psychiatric disorders. Moreover, none of the studies were actual prospective studies. Thus, longitudinal studies are needed to more clearly elucidate the effect of COVID-19 on the psychiatric health of the Korean population. Lastly, studies focusing on preventing and treating COVID-19-associated psychiatric problems are needed to provide a benefit in real clinical settings.

Additional Clinical Benefit of Agomelatine Treatment for Major Depressive Disorder in Naturalistic Treatment Setting.

Objective: This study tried to observe additional benefit of agomelatine (AGO) treatment for major depressive disorder (MDD) in routine practice. Methods: Retrospective chart review (n = 63) was conducted for additional benefit of combination with or switching to AGO in MDD patients without full remission. The primary endpoint was the mean change of Clinical Global Impression-Clinical Benefit (CGI-CB) total scores from baseline to the endpoint. Additional secondary endpoints were also collected. Results: The changes of CGI-CB (Z = -3.073, p = 0.002) and Montgomery-Åsberg Depression Rating Scale (Z = -3.483, p < 0.001) total scores were significantly decreased from baseline to the endpoint, respectively. At the endpoint, the remission rate was 22.6% (n = 18) and 28.6% of patient had improvement in CGI-CB total scores at the endpoint. No significant adverse events were observed. Conclusion: This study has shown additional benefit of AGO treatment as combination or switching agent for MDD patients without full remission in routine practice. However, adequately-powered and well-controlled studies are necessary for generalization of the present findings.

The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD): Changes in Preferred Treatment Strategies and Medications over 20 Years and Five Editions.

BACKGROUND: The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) is an expert consensus guideline for depressive disorder created in 2002, and since then, four revisions (2006, 2012, 2017, 2021) have been published. In this study, changes in the content of the KMAP-DD survey and recommendations for each period were examined. METHODS: The development process of the KMAP-DD was composed of two stages. First, opinions from experts with abundant clinical experience were gathered through surveys. Next, a final guideline was prepared through discussion within the working committee regarding the suitability of the results with reference to recent clinical studies or other guidelines. RESULTS: In mild depressive symptoms, antidepressant (AD) monotherapy was preferred, but when severe depression or when psychotic features were present, a combination of AD and atypical antipsychotics (AD + AAP) was preferred. AD monotherapy was preferred in most clinical subtypes. AD monotherapy was preferred for mild depressive symptoms, and AD + AAP was preferred for severe depression and depression with psychotic features in children, adolescents, and the elderly. CONCLUSIONS: This study identified the changes in the KMAP-DD treatment strategies and drug preferences in each period over the past 20 years. This work is expected to aid clinicians in establishing effective treatment strategies.

Korean Medication Algorithm Project for Bipolar Disorder 2022: Comparisons with Other Treatment Guidelines.

The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2022 (KMAP-BP 2022) with other recently published guidelines for treating bipolar disorder. We reviewed a total of six recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2022 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy in a same degree for mania. However, the KMAP-BP 2022 recommended MS + AAP combination therapy for psychotic mania, mixed mania and psychotic depression as treatment of choice. Aripiprazole, quetiapine and olanzapine were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Some guideline suggested olanzapine is a second-line options during maintenance treatment, related to concern about long-term tolerability. Most guidelines advocated newer AAPs (asenapine, cariprazine, long-acting injectable risperidone, and aripiprazole once monthly) as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. KMAP-BP 2022 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2022, predominantly in the treatment of psychotic mania, mixed mania and psychotic depression.

Psychometric Properties of the Korean Version of Functioning Assessment Short Test in Bipolar Disorder.

Objective: The Functioning Assessment Short Test (FAST) is a relatively specific test for bipolar disorders designed to assess the main functioning problems experienced by patients. This brief instrument includes 24 items assessing impairment or disability in 6 domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time. It has already been translated into standardized versions in several languages. The aim of this study is to measure the validity and reliability of the Korean version of FAST (K-FAST). Methods: A total of 209 bipolar disorder patients were recruited from 14 centers in Korea. K-FAST, Young Mania Rating Scale (YMRS), Bipolar Depression Rating Scale (BDRS), Global Assessment of Functioning (GAF) and the World Health Organization Quality of Life Assessment Instrument Brief Form (WHOQOL-BREF) were administered, and psychometric analysis of the K-FAST was conducted. Results: The internal consistency (Cronbach's alpha) of the K-FAST was 0.95. Test-retest reliability analysis showed a strong correlation between the two measures assessed at a 1-week interval (ICC = 0.97; p < 0.001). The K-FAST exhibited significant correlations with GAF (r = -0.771), WHOQOL-BREF (r = -0.326), YMRS (r = 0.509) and BDRS (r = 0.598). A strong negative correlation with GAF pointed to a reasonable degree of concurrent validity. Although the exploratory factor analysis showed four factors, the confirmatory factor analysis of questionnaires had a good fit for a six factors model (CFI = 0.925; TLI = 0.912; RMSEA = 0.078). Conclusion: The K-FAST has good psychometric properties, good internal consistency, and can be applicable and acceptable to the Korean context.

Sex Differences in COVID-19 Infection Fear in a Community Sample of Korean Adults Using Quantile Regression.

This study aims to explore the impact of distributional changes in coronavirus disease 2019 (COVID-19) infection fear with sex differences. A quota sampling strategy was followed and 483 Korean adults were surveyed in a community sample. Self-report questionnaires were used to assess COVID-19 infection fear, depressive symptoms, and general characteristics. Quantile regression was used to explore the regression relationship of COVID-19 infection fear and an individual's sex. There was a significant difference in COVID-19 infection fear (P = 0.001) and depression (P = 0.008) between the sexes - male and female. The differences between sexes at the 20th and 30th percentiles were significant (ß = 2.04, P = 0.006; ß = 1.5, P = 0.004, respectively). The results demonstrate that sex significantly predicts COVID-19 infection fear and women had significantly greater fear than men in the mild-level of COVID-19 infection fear.

The prevalence of psychiatric comorbidities in adult ADHD compared with non-ADHD populations: A systematic literature review.

Comorbid psychiatric disorders in adults with ADHD are important because these comorbidities might complicate the diagnosis of ADHD and also worsen the prognosis. However, the prevalence of comorbid psychiatric disorders in adult ADHD varies according to the diagnostic tools used and the characteristics of target populations. The purpose of this review was to describe the prevalence of comorbid psychiatric disorders in adults with ADHD compared with adults without ADHD. Thirty-two studies published before August 2022 were identified and classified according to diagnosis of other psychiatric disorder in those with ADHD. The most frequent comorbid psychiatric disorder in the ADHD group was substance use disorder (SUD), followed by mood disorders, anxiety disorders, and personality disorders. The prevalence of these four disorders was higher in the ADHD group, whether or not subjects were diagnosed with other psychiatric disorders. In addition, the diversity of ADHD diagnostic tools was observed. This also might have affected the variability in prevalence of comorbidities. Standardization of ADHD diagnostic tools is necessary in the future.

COVID-19-Related Functional Impairment in a Community Sample of Korean Adults: Associations With Depression, COVID-19 Infection Fear, and Resilience.

OBJECTIVE: We aimed to determine the effects of depression, COVID-19 infection fear, and resilience on COVID-19-related functional impairment. METHODS: We obtained data from 476 community-dwelling adults aged 20-69 years living in Jeju, South Korea, and evaluated the relationships between COVID-19-related functional impairment (work/school, social, and home life) and sociodemographic and healthrelated characteristics, COVID-19-related life changes (financial difficulties since the pandemic, employment change, interpersonal conflict), and clinical characteristics, including depression, COVID-19 infection fear, and resilience. RESULTS: Functional impairment in the home life domain was associated with marital status and monthly income. Greater work/school, social, and home life functional impairment was significantly associated with all COVID-19-related life changes. Regression analysis indicated that resilience modulated the positive associations of COVID-19-related functional impairment with symptoms of depression and COVID-19 infection fear when relevant factors were controlled for. CONCLUSION: Our results suggest the importance of clinical characteristics, including depression, COVID-19 infection fear, and resilience for understanding functional impairment related to COVID-19. These results have important implications for interventions aimed at reducing depression and COVID-19 infection fear, and enhancing resilience.

Korean Medication Algorithm Project for Bipolar Disorder 2022, Fifth Revision: An Executive Summary.

Objective: We revised the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP), first published in 2002 and revised in 2006, 2010, 2014, and 2018, to reflect recent progress in the treatment of bipolar disorder. Methods: The questionnaires consisted of 56 items for adult patients and 7 items for child/adolescent patients, and were used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of bipolar disorder. The review committee included 87 Korean psychiatrists and 40 child and adolescent psychiatry experts. Results: For treatment of manic episodes, a combination of a mood stabilizer (MS) and atypical antipsychotics (AAP), or monotherapy with MS or AAP were recommended as first-line treatments. Combinations of MS and AAP, or AAP and lamotrigine (LMT) were recommended as first-line treatments for depressive episodes regardless of the severity. Monotherapy with MS, AAP, or LMT were also first-line treatments for mild to moderate depressive episodes. For mixed features, a combination of MS and AAP, or monotherapy with AAP or MS were recommended as first-line treatments, and a combination of AAP and LMT, or MS and LMT were the first-line treatments for depressive mixed state. Conclusion: The recommendations of the KMAP-BP 2022 have changed from the previous version, to reflect the evolution of the social culture and healthcare system in Korea and recent evidence regarding pharmacotherapy of bipolar disorder. The KMAP-BP 2022 provides clinicians with a wealth of information regarding appropriate strategies to treat patients with bipolar disorder.

Amisulpride Augmentation in Schizophrenia Patients with Poor Response to Olanzapine: A 4-week, Randomized, Rater-Blind, Controlled, Pilot Study.

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

Neuromolecular Etiology of Bipolar Disorder: Possible Therapeutic Targets of Mood Stabilizers.

Bipolar disorder is a mental illness that causes extreme mood swings and has a chronic course. However, the mechanism by which mood episodes with completely opposite characteristics appear repeatedly, or a mixture of symptoms appears, in patients with bipolar disorder remains unknown. Therefore, mood stabilizers are indicated only for single mood episodes, such as manic episodes and depressive episodes, and no true mood-stabilizing drugs effective for treating both manic and depressive episodes currently exist. Therefore, in this review, therapeutic targets that facilitate the development of mood stabilizers were examined by reviewing the current understanding of the neuromolecular etiology of bipolar disorder.

The Korean Medication Algorithm Project for Depressive Disorder 2021: Comparisons with Other Treatment Guidelines.

The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) first was published in 2002, and has been revised four times, in 2006, 2012, 2017, and 2021. In this review, we compared recommendations from the recently revised KMAP-DD 2021 to four global clinical practice guidelines (CPGs) for depression published after 2010. The recommendations from the KMAP-DD 2021 were similar to those from other CPGs, although there were some differences. The KMAP-DD 2021 reflected social culture and the healthcare system in Korea and recent evidence about pharmacotherapy for depression, as did other recently published evidence-based guidelines. Despite some intrinsic limitations as an expert consensus-based guideline, the KMAP-DD 2021 can be helpful for Korean psychiatrists making decisions in clinical settings by complementing previously published evidence-based guidelines, especially for some clinical situations lacking evidence from rigorously designed clinical trials.

Prevalence and Comorbidities of Attention Deficit Hyperactivity Disorder Among Adults and Children/Adolescents in Korea.

OBJECTIVE: This study investigated the prevalence and comorbidities of attention deficit hyperactivity disorder (ADHD) among adults and children/adolescents in Korea. METHODS: This study used data from the Korea Health Insurance Review and Assessment Service collected from 2008 to 2018. Study participants comprised patients with at least one diagnosis of ADHD (International Statistical Classification of Diseases and Related Health Provisions, 10th revision code F90.0). Prevalence rates and psychiatric comorbidities were also analyzed. RESULTS: We identified 878,996 patients diagnosed with ADHD between 2008 and 2018. The overall prevalence rate of diagnosed ADHD increased steeply from 127.1/100,000 in 2008 to 192.9/100,000 in 2018; it increased 1.47 times in children/adolescents (≤ 18 years) and 10.1 times in adults (＞ 18 years) during this period. Among adult and children/ adolescent ADHD patients, 61.84% (95% confidence interval [95% CI] 61.74-61.93) and 78.72% (95% CI 78.53- 78.91) had at least one psychiatric comorbidity, respectively. CONCLUSION: Our results showed that the prevalence rate of diagnosed ADHD has increased in Korea; however, it is lower than the global average. Further studies are required to identify and treat vulnerable populations appropriately.