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  1. Watabe M, Kato TA, Teo AR, Horikawa H, Tateno M, Hayakawa K, et al.
    PLoS One, 2015;10(3):e0120183.
    PMID: 25836972 DOI: 10.1371/journal.pone.0120183
    Maladaptive social interaction and its related psychopathology have been highlighted in psychiatry especially among younger generations. In Japan, novel expressive forms of psychiatric phenomena such as "modern-type depression" and "hikikomori" (a syndrome of severe social withdrawal lasting for at least six months) have been reported especially among young people. Economic games such as the trust game have been utilized to evaluate real-world interpersonal relationships as a novel candidate for psychiatric evaluations. To investigate the relationship between trusting behaviors and various psychometric scales, we conducted a trust game experiment with eighty-one Japanese university students as a pilot study. Participants made a risky financial decision about whether to trust each of 40 photographed partners. Participants then answered a set of questionnaires with seven scales including the Lubben Social Network Scale (LSNS)-6 and the Patient Health Questionnaire (PHQ)-9. Consistent with previous research, male participants trusted partners more than female participants. Regression analysis revealed that LSNS-family (perceived support from family) for male participants, and item 8 of PHQ-9 (subjective agitation and/or retardation) for female participants were associated with participants' trusting behaviors. Consistent with claims by social scientists, our data suggest that, for males, support from family was negatively associated with cooperative behavior toward non-family members. Females with higher subjective agitation (and/or retardation) gave less money toward males and high attractive females, but not toward low attractive females in interpersonal relationships. We believe that our data indicate the possible impact of economic games in psychiatric research and clinical practice, and validation in clinical samples including modern-type depression and hikikomori should be investigated.
  2. Tateno M, Teo AR, Shirasaka T, Tayama M, Watabe M, Kato TA
    Psychiatry Clin Neurosci, 2016 Dec;70(12):567-572.
    PMID: 27573254 DOI: 10.1111/pcn.12454
    AIM: Internet addiction (IA), also referred to as Internet use disorder, is a serious problem all over the world, especially in Asian countries. Severe IA in students may be linked to academic failure, attention-deficit hyperactivity disorder (ADHD), and forms of social withdrawal, such as hikikomori. In this study, we performed a survey to investigate the relation between IA and ADHD symptoms among college students.

    METHODS: Severity of IA and ADHD traits was assessed by self-report scales. Subjects were 403 college students (response rate 78%) who completed a questionnaire including Young's Internet Addiction Test (IAT) and the Adult ADHD Self-Report Scale-V1.1.

    RESULTS: Out of 403 subjects, 165 were male. The mean age was 18.4 ± 1.2 years, and mean total IAT score was 45.2 ± 12.6. One hundred forty-eight respondents (36.7%) were average Internet users (IAT < 40), 240 (59.6%) had possible addiction (IAT 40-69), and 15 (3.7%) had severe addiction (IAT ≥ 70). Mean length of Internet use was 4.1 ± 2.8 h/day on weekdays and 5.9 ± 3.7 h/day on the weekend. Females used the Internet mainly for social networking services while males preferred online games. Students with a positive ADHD screen scored significantly higher on the IAT than those negative for ADHD screen (50.2 ± 12.9 vs 43.3 ± 12.0).

    CONCLUSION: Our results suggest that Internet misuse may be related to ADHD traits among Japanese youth. Further investigation of the links between IA and ADHD is warranted.

  3. Kato TA, Teo AR, Tateno M, Watabe M, Kubo H, Kanba S
    Psychiatry Clin Neurosci, 2017 Jan;71(1):75-76.
    PMID: 27862668 DOI: 10.1111/pcn.12481
  4. Kato TA, Hashimoto R, Hayakawa K, Kubo H, Watabe M, Teo AR, et al.
    Psychiatry Clin Neurosci, 2016 Jan;70(1):7-23.
    PMID: 26350304 DOI: 10.1111/pcn.12360
    Japan's prototype of depression was traditionally a melancholic depression based on the premorbid personality known as shūchaku-kishitsu proposed by Mitsuzo Shimoda in the 1930s. However, since around 2000, a novel form of depression has emerged among Japanese youth. Called 'modern type depression (MTD)' by the mass media, the term has quickly gained popularity among the general public, though it has not been regarded as an official medical term. Likewise, lack of consensus guidelines for its diagnosis and treatment, and a dearth of scientific literature on MTD has led to confusion when dealing with it in clinical practice in Japan. In this review article, we summarize and discuss the present situation and issues regarding MTD by focusing on historical, diagnostic, psychosocial, and cultural perspectives. We also draw on international perspectives that begin to suggest that MTD is a phenomenon that may exist not only in Japan but also in many other countries with different sociocultural and historical backgrounds. It is therefore of interest to establish whether MTD is a culture-specific phenomenon in Japan or a syndrome that can be classified using international diagnostic criteria as contained in the ICD or the DSM. We propose a novel diagnostic approach for depression that addresses MTD in order to combat the current confusion about depression under the present diagnostic systems.
  5. Kubo H, Setoyama D, Watabe M, Ohgidani M, Hayakawa K, Kuwano N, et al.
    Sci Rep, 2021 01 26;11(1):2199.
    PMID: 33500434 DOI: 10.1038/s41598-020-75115-4
    Interpersonal difficulties are often observed in major depressive disorder (MDD), while the underlying psychological and biological mechanisms have not yet been elucidated. In the present case-control study, a PC-based trust game was conducted for 38 drug-free MDD patients and 38 healthy controls (HC). In the trust game, participants invested money in a partner (trusting behaviors), and also rated each partner's attractiveness (preference for others). In addition, blood biomarkers including metabolites were measured. Both MDD and HC males exhibited more trusting behaviors compared to females. MDD males' preference for ordinary-attractive partners (lay-person photographs) was lower than HC males, whereas their preference for high-attractive females (fashion-model photographs) was similar levels to HC males. This tendency in MDD males could reflect a "focused (narrowed) preference for females". As for blood biomarker analysis, the levels of 37 metabolites including acetylcholine, AMP, GMP, nicotinic acid and tryptophan were significantly different between two groups. Interestingly, among male participants, acetylcholine and nicotinic acid were negatively correlated with the level of focused preference for photographed females. In sum, we have revealed some behavioral, psychological and biological traits of trusting behaviors and preference for others especially in MDD males. Larger studies should be conducted to validate our preliminary findings.
  6. Kato TA, Katsuki R, Kubo H, Shimokawa N, Sato-Kasai M, Hayakawa K, et al.
    Psychiatry Clin Neurosci, 2019 Aug;73(8):448-457.
    PMID: 30900331 DOI: 10.1111/pcn.12842
    AIM: Understanding premorbid personality is important, especially when considering treatment selection. Historically, the premorbid personality of patients with major depression in Japan was described as Shuchaku-kishitsu [similar to Typus melancholicus], as proposed by Shimoda in the 1930s. Since around 2000, there have been increased reports in Japan of young adults with depression who have had premorbid personality differing from the traditional type. In 2005, Tarumi termed this novel condition 'dysthymic-type depression,' and more recently the condition has been called Shin-gata/Gendai-gata Utsu-byo [modern-type depression (MTD)]. We recently developed a semi-structured diagnostic interview to evaluate MTD. Development of a tool that enables understanding of premorbid personality in a short time, especially at the early stage of treatment, is desirable. The object of this study was to develop a self-report scale to evaluate the traits of MTD, and to assess the scale's psychometric properties, diagnostic accuracy, and biological validity.

    METHODS: A sample of 340 participants from clinical and community settings completed measures. Psychometric properties were assessed with factor analysis. Diagnostic accuracy of the MTD traits was compared against a semi-structured interview.

    RESULTS: The questionnaire contained 22 items across three subscales, thus we termed it the 22-item Tarumi's Modern-Type Depression Trait Scale: Avoidance of Social Roles, Complaint, and Low Self-Esteem (TACS-22). Internal consistency, test-retest reliability, and convergent validity were all satisfactory. Among patients with major depression, the area under the curve was 0.757 (sensitivity of 63.1% and specificity of 82.9%) and the score was positively correlated with plasma tryptophan.

    CONCLUSION: The TACS-22 possessed adequate psychometric properties and diagnostic accuracy in an initial sample of Japanese adults. Additional research on its ability to support clinical assessment of MTD is warranted.

  7. Hayakawa K, Kato TA, Watabe M, Teo AR, Horikawa H, Kuwano N, et al.
    Sci Rep, 2018 02 13;8(1):2884.
    PMID: 29440704 DOI: 10.1038/s41598-018-21260-w
    Hikikomori, a severe form of social withdrawal syndrome, is a growing social issue in Japan and internationally. The pathophysiology of hikikomori has not yet been elucidated and an effective treatment remains to be established. Recently, we revealed that avoidant personality disorder is the most common comorbidity of hikikomori. Thus, we have postulated that avoidant personality is the personality underpinning hikikomori. First, we herein show relationships between avoidant personality traits, blood biomarkers, hikikomori-related psychological features, and behavioural characteristics assessed by a trust game in non-hikikomori volunteers. Avoidant personality traits were negatively associated with high-density lipoprotein cholesterol (HDL-C) and uric acid (UA) in men, and positively associated with fibrin degeneration products (FDP) and high sensitivity C-reactive protein (hsCRP) in women. Next, we recruited actual individuals with hikikomori, and compared avoidant personality traits, blood biomarkers, and psychological features between individuals with hikikomori and age-matched healthy controls. Individuals with hikikomori had higher avoidant personality scores in both sexes, and showed lower serum UA levels in men and lower HDL-C levels in women compared with healthy controls. This is the first report showing possible blood biomarkers for hikikomori, and opens the door to clarify the underlying biological pathophysiology of hikikomori.
  8. Park SC, Oh HS, Tripathi A, Abraham Kallivayalil R, Avasthi A, Grover S, et al.
    Nord J Psychiatry, 2019 Jun 26.
    PMID: 31240984 DOI: 10.1080/08039488.2019.1632381
    Background: Although cannabis use has been linked with schizophrenia in a dose-response pattern, to our knowledge, the relationship between cannabis and schizophrenia has rarely been reported in Asian population. Aim: We compared the clinical characteristics and psychotropic prescription patterns between cannabis users and non-users among Asian patients with schizophrenia. Moreover, we aimed to identify the independent correlates of cannabis use in these subjects. Methods: We performed the analysis of the data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), a collaborative consortium survey used to collate the prescription patterns for antipsychotic and other psychotropic medications in patients with schizophrenia in Asia. We included 132 schizophrenia patients in the group of lifetime cannabis use and 1756 in the group that had never used cannabis. A binary logistic model was fitted to detect the clinical correlates of lifetime cannabis use. Results: Adjusting for the effects of age, sex, geographical region, income group, duration of untreated psychosis, and Charlson comordity index level, a binary logistic regression model revealed that lifetime cannabis use was independently associated with aggressive behavior [adjusted odds ratio (aOR) = 1.582, 95% confidence interval (CI) = 1.006-2.490, p = .047] and with long-acting injectable antipsychotic treatment (aOR = 1.796, 95% CI = 1.444-2.820, p = .001). Conclusion: Our findings indicate a close link between lifetime cannabis use and aggressive behavior. The use of long-acting, injectable antipsychotics preferentially treats the aggressive behavior cannabis users among patients with schizophrenia in Asia, especially, the South or Southeast Asia.
  9. Park SC, Kim GM, Kato TA, Chong MY, Lin SK, Yang SY, et al.
    Nord J Psychiatry, 2021 Jan;75(1):9-17.
    PMID: 32580668 DOI: 10.1080/08039488.2020.1777462
    BACKGROUND: Network analysis provides a new viewpoint that explicates intertwined and interrelated symptoms into dynamic causal architectures of symptom clusters. This is a process called 'symptomics' and is concurrently applied to various areas of symptomatology.

    AIMS: Using the data from Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), we aimed to estimate a network model of extrapyramidal syndrome in patients with schizophrenia.

    METHODS: Using data from REAP-AP, extrapyramidal symptoms of 1046 Asian patients with schizophrenia were evaluated using the nine items of the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The estimated network of the ordered-categorical DIEPSS items consisted of nodes (symptoms) and edges (interconnections). A community detection algorithm was also used to identify distinctive symptom clusters, and correlation stability coefficients were used to evaluate the centrality stability.

    RESULTS: An interpretable level of node strength centrality was ensured with a correlation coefficient. An estimated network of extrapyramidal syndrome showed that 26 (72.2%) of all possible 35 edges were estimated to be greater than zero. Dyskinesia was most centrally situated within the estimated network. In addition, earlier antipsychotic-induced extrapyramidal symptoms were divided into three distinctive clusters - extrapyramidal syndrome without parkinsonism, postural instability and gait difficulty-dominant parkinsonism, and tremor-dominant parkinsonism.

    CONCLUSIONS: Our findings showed that dyskinesia is the most central domain in an estimated network structure of extrapyramidal syndrome in Asian patients with schizophrenia. These findings are consistent with the speculation that acute dystonia, akathisia, and parkinsonism could be the risk factors of tardive dyskinesia.

  10. Park SC, Jang EY, Xiang YT, Kanba S, Kato TA, Chong MY, et al.
    Psychiatry Clin Neurosci, 2020 Jun;74(6):344-353.
    PMID: 32048773 DOI: 10.1111/pcn.12989
    AIM: We aimed to estimate the network structures of depressive symptoms using network analysis and evaluated the geographic regional differences in theses network structures among Asian patients with depressive disorders.

    METHODS: Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD), the network of the ICD-10 diagnostic criteria for depressive episode was estimated from 1174 Asian patients with depressive disorders. The node strength centrality of all ICD-10 diagnostic criteria for a depressive episode was estimated using a community-detection algorithm. In addition, networks of depressive symptoms were estimated separately among East Asian patients and South or Southeast Asian patients. Moreover, networks were estimated separately among Asian patients from high-income countries and those from middle-income countries.

    RESULTS: Persistent sadness, fatigue, and loss of interest were the most centrally situated within the network of depressive symptoms in Asian patients with depressive disorders overall. A community-detection algorithm estimated that when excluding psychomotor disturbance as an outlier, the other nine symptoms formed the largest clinically meaningful cluster. Geographic and economic variations in networks of depressive symptoms were evaluated.

    CONCLUSION: Our findings demonstrated that the typical symptoms of the ICD-10 diagnostic criteria for depressive episode are the most centrally situated within the network of depressive symptoms. Furthermore, our findings suggested that cultural influences related to geographic and economic distributions of participants could influence the estimated depressive symptom network in Asian patients with depressive disorders.

  11. Lin SK, Yang SY, Park SC, Jang OJ, Zhu X, Xiang YT, et al.
    Clin Psychopharmacol Neurosci, 2022 Feb 28;20(1):61-69.
    PMID: 35078949 DOI: 10.9758/cpn.2022.20.1.61
    Objective: Pharmacotherapy including mood stabilizers and antipsychotics are frequently used in bipolar disorder (BD); however, the lack of consensus regarding the definition of polypharmacy hinders conducting comparative studies across different settings and countries. Research on Asian Prescription Pattern (REAP) is the largest and the longest lasting international collaborative research in psychiatry in Asia. The objective of REAP BD was to investigate the prescription patterns of psychotropic medications across Asian countries. The rates of polypharmacy and psychotropic drug load were also analyzed.

    Methods: The data collection was web-based. Prescription patterns were categorized as (1) mood stabilizer monotherapy: one mood stabilizer; (2) antipsychotic monotherapy: one antipsychotic; (3) simple polypharmacy: one mood stabilizer and one antipsychotic; and (4) complex polypharmacy: ≥ 2 mood stabilizers or/and antipsychotics. The psychotropic drug load in each patient was calculated using the defined daily dose method.

    Results: Among 2003 patients with BD (52.1% female, 42.4 years) from 12 countries, 1,619 (80.8%) patients received mood stabilizers, 1,644 (82.14%) received antipsychotics, and 424 (21.2%) received antidepressants, with 14.7% mood stabilizer monotherapy, 13.4% antipsychotic monotherapy, 48.9% simple polypharmacy, 20.3% complex polypharmacy, and 2.6% other therapy. The average psychotropic drug load was 2.05 ± 1.40. Results varied widely between countries.

    Conclusion: Over 70% of psychotropic regimens involved polypharmacy, which accords with the high prevalence of polypharmacy in BD under a permissive criterion (2 or more core psychotropic drugs) worldwide. Notably, ≥ 80% of our sample received antipsychotics, which may indicate an increasing trend in antipsychotic use for BD treatment.

  12. Kubota C, Inada T, Lin SK, Avasthi A, Chee KY, Tanra AJ, et al.
    Hum Psychopharmacol, 2023 Mar;38(2):e2861.
    PMID: 36462184 DOI: 10.1002/hup.2861
    INTRODUCTION: Drug-induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychiatry. This study aimed to examine the factor structure of drug-induced extrapyramidal symptoms observed in patients with schizophrenia and assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS).

    METHODS: The participants were 1478 patients with a diagnosis of schizophrenia whose EPS was assessed using the DIEPSS in India, Indonesia, Japan, Malaysia, and Taiwan in the 2016 REAP AP-4 study. The records of the participants were randomly divided into two subgroups: the first for exploratory factor analysis of the eight DIEPSS items, and the second for confirmatory factor analysis.

    RESULTS: The factor analysis identified three factors: F1 (gait and bradykinesia), F2 (muscle rigidity and tremor), and F3 (sialorrhea, akathisia, dystonia, and dyskinesia).

    CONCLUSION: The results suggest that the eight individual items of the DIEPSS could be composed of three different mechanisms: acute parkinsonism observed during action (F1), acute parkinsonism observed at rest (F2), and central dopaminergic mechanisms with pathophysiology other than acute parkinsonism (F3).

  13. Chen CK, Yang SY, Park SC, Jang OJ, Zhu X, Xiang YT, et al.
    Asian J Psychiatr, 2023 Jul;85:103613.
    PMID: 37163943 DOI: 10.1016/j.ajp.2023.103613
    OBJECTIVE: Mood stabilizers are psychotropic drugs mainly used to treat bipolar disorder in the acute phase or for maintenance therapy to prevent relapse. In clinical practice, mood stabilizers are commonly prescribed for conditions other than bipolar disorder. This study investigated the distribution of mood stabilizer prescriptions for different psychiatric diagnoses and studied differences in the drugs, dosage, and plasma concentration in 10 Asian countries including Taiwan, South Korea, Malaysia, China, Thailand, India, Pakistan, Singapore, Indonesia, and Myanmar.

    METHODS: Patients prescribed mood stabilizers (lithium, carbamazepine, valproic acid, or lamotrigine) for a psychiatric condition other than bipolar disorder (codes F31.0-F31.9 in the International Classification of Diseases, 10th Edition, Clinical Modification) were recruited through convenience sampling. A website-based data entry system was used for data collection.

    RESULTS: In total, 1557 psychiatric patients were enrolled. Schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F20-F29, 55.8 %) was the most common diagnosis, followed by non-bipolar mood disorders (F30, F31- F39, 25.3 %), organic mental disorder (F00-F09, 8.8 %), mental retardation (F70-F79, 5.8 %) and anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders (F40-F48, 4.4 %). The most frequently targeted symptoms (>20 %) were irritability (48 %), impulsivity (32.4 %), aggression (29.2 %), anger (20.8 %), and psychosis (24.1 %). Valproic acid was the most frequently used medication.

    CONCLUSIONS: Clinicians typically prescribe mood stabilizers as empirically supported treatment to manage mood symptoms in patients with diagnoses other than bipolar disorders, though there is on official indication for these disorders. The costs and benefits of this add-on symptomatic treatment warrant further investigation.

  14. Shuy YK, Santharan S, Chew QH, Lin SK, Ouyang WC, Chen CK, et al.
    J Clin Psychopharmacol, 2024 01 16;44(2):117-123.
    PMID: 38230861 DOI: 10.1097/JCP.0000000000001813
    BACKGROUND: As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons.

    METHODS: We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 Asian sites and evaluated bivariate relationships of lithium treatment with clinical correlates followed by multivariate logistic regression modeling.

    RESULTS: In a total of 2139 BD participants (52.3% women) of mean age 42.4 years, lithium salts were prescribed in 27.3% of cases overall, varying among regions from 3.20% to 59.5%. Associated with lithium treatment were male sex, presence of euthymia or mild depression, and a history of seasonal mood change. Other mood stabilizers usually were given with lithium, often at relatively high doses. Lithium use was associated with newly emerging and dose-dependent risk of tremors as well as risk of hypothyroidism. We found no significant differences in rates of clinical remission or of suicidal behavior if treatment included lithium or not.

    CONCLUSIONS: Study findings clarify current prevalence, dosing, and clinical correlates of lithium treatment for BD in Asia. This information should support clinical decision-making regarding treatment of BD patients and international comparisons of therapeutic practices.

  15. Yoon JW, Kim E, Jeong N, Kang M, Kim HS, Lee S, et al.
    Asian J Psychiatr, 2024 Aug 30;101:104197.
    PMID: 39250855 DOI: 10.1016/j.ajp.2024.104197
    Lithium and mood stabilizers are considered effective augmentation agents of antidepressants for treatment-resistant depression. Thus, this study aimed to estimate the network structure of depression symptom criteria among unipolar depression patients with mood stabilizers, using data from the Research on Asian Psychotropic Prescription Patterns for mood stabilizers (REAP-MS). We estimated a network of the 9 depression symptom criteria among 411 unipolar depression patients in Asia. Each of the depression symptom criteria was considered to be a dichotomous categorical variable. Suicidality (suicidal ideation or attempt) was the most centrally situated within the network of depression symptoms, followed by depressed mood, loss of energy, anhedonia and weight loss or gain. Contrastingly, concentration problem was the least interconnected. The depression symptom criteria were organized into 4 clusters by the community detection method. The findings suggest that suicidality may be one of the significant therapeutic target symptoms in unipolar depression patients with mood stabilizers.
  16. Tang CT, Chua EC, Chew QH, He YL, Si TM, Chiu HF, et al.
    Asia Pac Psychiatry, 2020 Dec;12(4):e12393.
    PMID: 32468725 DOI: 10.1111/appy.12393
    INTRODUCTION: Patterns of clinical use of long-acting injectable (LAI) antipsychotic drugs in many countries, especially in Asia, for treatment of patients diagnosed with chronic psychotic disorders including schizophrenia are not well established.

    METHODS: Within an extensive research consortium, we evaluated prescription rates for first- (FGA) and second-generation antipsychotic (SGA) LAI drugs and their clinical correlates among 3557 subjects diagnosed with schizophrenia across 15 Asian countries and region.

    RESULTS: Overall, an average of 17.9% (638/3557; range: 0.0%-44.9%) of treated subjects were prescribed LAI antipsychotics. Those given LAI vs orally administered agents were significantly older, had multiple hospitalizations, received multiple antipsychotics more often, at 32.4% higher doses, were more likely to manifest disorganized behavior or aggression, had somewhat superior psychosocial functioning and less negative symptoms, but were more likely to be hospitalized, with higher BMI, and more tremor. Being prescribed an FGA vs SGA LAI agent was associated with male sex, aggression, disorganization, hospitalization, multiple antipsychotics, higher doses, with similar risks of adverse neurological or metabolic effects. Rates of use of LAI antipsychotic drugs to treat patients diagnosed with schizophrenia varied by more than 40-fold among Asian countries and given to an average of 17.9% of treated schizophrenia patients. We identified the differences in the clinical profiles and treatment characteristics of patients who were receiving FGA-LAI and SGA-LAI medications.

    DISCUSSION: These findings behoove clinicians to be mindful when evaluating patients' need to be on LAI antipsychotics amidst multifaceted considerations, especially downstream adverse events such as metabolic and extrapyramidal side effects.

  17. Lim WK, Chew QH, He YL, Si TM, Chiu FH, Xiang YT, et al.
    Hum Psychopharmacol, 2020 11;35(6):1-7.
    PMID: 32738085 DOI: 10.1002/hup.2752
    OBJECTIVE: Studies examining coprescription and dosages of mood stabilizers (MSs) with antipsychotics for psychotic disorders are infrequent. Based on sparse extant data and clinical experience, we hypothesized that adjunctive MS use would be associated with certain demographic (e.g., younger age), clinical factors (e.g., longer illness duration), and characteristics of antipsychotic treatment (e.g., multiple or high antipsychotic doses).

    METHODS: Within an Asian research consortium focusing on pharmaco-epidemiological factors in schizophrenia, we evaluated rates of MS coprescription, including high doses (>1000 mg/day lithium-equivalents) and clinical correlates.

    RESULTS: Among 3557 subjects diagnosed with schizophrenia in 14 Asian countries, MSs were coprescribed with antipsychotics in 13.6% (n = 485) of the sample, with 10.9% (n = 53) on a high dose. Adjunctive MS treatment was associated (all p < 0.005) with demographic (female sex and younger age), setting (country and hospitalization), illness (longer duration, more hospitalizations, non-remission of illness, behavioral disorganization, aggression, affective symptoms, and social-occupational dysfunction), and treatment-related factors (higher antipsychotic dose, multiple antipsychotics, higher body mass index, and greater sedation). Patients given high doses of MSs had a less favorable illness course, more behavioral disorganization, poorer functioning, and higher antipsychotic doses.

    CONCLUSIONS: Schizophrenia patients receiving adjunctive MS treatment in Asian psychiatric centers are more severely ill and less responsive to simpler treatment regimens.

  18. Loo LWJ, Chew QH, Lin SK, Yang SY, Ouyang WC, Chen CK, et al.
    PMID: 37068038 DOI: 10.1097/JCP.0000000000001693
    BACKGROUND: Pharmacoepidemiological studies of clozapine use to treat bipolar disorder (BD), especially in Asia, are rare, although they can provide insights into associated clinical characteristics and support international comparisons of indications and drug dosing.

    METHODS: We examined the prevalence and clinical correlates of clozapine treatment for BD in 13 Asian countries and regions (China, Hong Kong SAR, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, and Thailand) within an Asian Prescription Patterns Research Consortium. We compared BD patients treated with clozapine or not in initial bivariate comparisons followed by multivariable logistic regression modeling.

    RESULTS: Clozapine was given to 2.13% of BD patients overall, at a mean daily dose of 275 (confidence interval, 267-282) chlorpromazine-equivalent mg/day. Patients receiving clozapine were older, more likely males, hospitalized, currently manic, and given greater numbers of mood-stabilizing and antipsychotic drugs in addition to clozapine. Logistic regression revealed that older age, male sex, current mania, and greater number of other antipsychotics remained significantly associated with clozapine treatment. Clozapine use was not associated with depressed mood, remission of illness, suicidal risk, or electroconvulsive treatment within the previous 12 months.

    CONCLUSIONS: The identified associations of clozapine use with particular clinical features call for vigilance in personalized clinical monitoring so as to optimize clinical outcomes of BD patients and to limit risks of adverse effects of polytherapy.

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