Pharmacoepidemiology and Clinical Correlates of Lithium Treatment for Bipolar Disorder in Asia.

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.

Disability and its correlates among persons with bipolar disorder: Exploratory findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

Aim: This study aimed to evaluate the disability and its correlates in persons with Bipolar Disorder during the remission phase. Materials and Methods: As part of the multicentric study, 773 patients with bipolar disorder, currently in clinical remission, were evaluated for disability on the Indian Disability Assessment Evaluation Scale. Results: About one-fifth of the participants had some level of disability in the domain of self-care, one-third had some level of disability in the interpersonal domain, one-fourth had some level of disability in communication and understanding, and a maximum proportion (43.7%) had some disability in the domain of work. Overall, about one-fifth (18.4%) were considered to have a benchmark disability (i.e., disability >40%). In terms of correlates, those with a disability had a short duration of current remission, a higher number of manic and mixed episodes, a higher mean number of total episodes, spent more time in the episodes, had lower severity of the depressive episodes, higher residual depressive and manic symptoms, had overall higher manic affective morbidity, had a higher level of cognitive deficits, and had poorer insight. Conclusion: A significant proportion of patients with bipolar disorder have disability in work domain, and the presence of residual symptoms of either polarity are associated with higher level of disability.

Insight in patients with bipolar disorder: Findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

Background: There are limited number of studies evaluating insight among patients with bipolar disorder (BD). Aim: This study aimed to examine insight and its correlates in BD using the data from the multicenter BD course and outcome study from India (BiD-CoIN). The additional aim was to evaluate the insight in patients with BD using different scales and understand the correlates of insight. Materials and Methods: 773 BD patients presently in clinical remission were evaluated on the Insight Scale for Affective Disorders (ISAD), insight items of the Hamilton Depression Rating Scale (HDRS), and the Young Mania Rating Scale (YMRS). Results: The assessment scales influenced the prevalence of poor insight. Poorer insight irrespective of the assessment scale was consistently associated with higher residual depressive and manic symptoms, and a higher level of cognitive impairment and disability. Poor insight as assessed by ISAD was associated with a higher number of episodes in the lifetime, shorter duration of current remission, a higher number of depressive episodes, a higher amount of time spent in depressive episodes, higher depressive affective morbidity, a higher number of manic episodes, and higher residual depressive and manic symptoms. Conclusion: Poor insight in BD is consistently associated with higher residual depressive and manic symptoms and a higher level of cognitive impairment and disability. However, in terms of course variables, the correlates vary depending on the assessment method.

Prevalence of mixed features in patients with first-episode depression: An exploratory multicentric study.

Background and Aim: There is limited literature on the prevalence of mixed features in patients with depression, especially from countries in Asia. Our aim was to evaluate the prevalence of "mixed features" in patients with first-episode depression. Materials and Methods: Patients with first-episode depression were evaluated for the presence of mixed features as per the Diagnostic and Statistical Manual (DSM)-5 criteria. They were additionally evaluated on Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS). Results: About one-sixth (16%) of the patients fulfilled the DSM-5 criteria for the mixed features specifier. The most common manic/hypomanic clinical feature was increased talkativeness or pressure of speech, followed by elevated expansive mood (12.5%), and inflated self-esteem or grandiosity was the least common feature (8.7%). Those with mixed features had higher prevalence of comorbid tobacco dependence and psychotic symptoms. In terms of frequency of depressive symptoms as assessed on HDRS, compared to those without mixed features, those with mixed features had higher frequency of symptoms such as depressed mood, insomnia during early hours of morning, work and activities, agitation, gastrointestinal somatic symptoms, genital symptoms, hypochondriasis, and poorer insight. Conclusion: Mixed features specifier criteria were fulfilled by 16% patients with first-episode depression. This finding suggests that the extension of this specifier to depression can be considered as a useful step in understanding the symptom profile of patients with depression.

Subjective cognitive deficits and its correlates among patients with bipolar disorder: Findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

Aim: This study aimed to evaluate the prevalence of subjective cognitive complaints and their association with clinical variables, insight, and disability. Methodology: Seven hundred and seventy-three subjects with bipolar disorder (BD), recruited across 14 centers, currently in the euthymic phase were cross-sectionally evaluated on Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA). Results: The mean total COBRA score was 9.79 (SD: 6.99), and 322 (41.7%) of the participants were found to have subjective cognitive complaints when the cut-off of >10 was used. Compared to those without cognitive complaints, those with cognitive complaints more often had depression as the first episode in their lifetime, had a higher prevalence of alcohol dependence, a higher number of depressive episodes (first five years of illness, lifetime, and per year of illness), a higher number of manic episodes in the first five years of illness, more often had depressive or indeterminate predominant polarity, lower prevalence of at least one-lifetime episode with psychotic symptoms, higher severity of residual symptoms, spent more time in the episodes in the lifetime, had poorer insight and higher disability. Conclusion: The present study suggests subjective complaints complaints are associated with more severe illness, higher levels of residual symptoms, poor insight, and higher disability.

Clinical use of mood stabilizers beyond treatment for bipolar disorder: The REAP-MS study.

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.

Clozapine Use for Bipolar Disorder: An Asian Psychotropic Prescription Patterns Consortium Study.

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.

Factors associated with lifetime suicide attempts: findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

AIM: To evaluate the risk factors associated with lifetime suicide attempts in bipolar disorder (BD) patients. METHODOLOGY: 773 BD patients with a duration of illness of at least ten years, currently in clinical remission, were evaluated for suicidal attempts in their lifetime. Those with and without lifetime suicide attempt(s) were compared for various demographic and clinical risk factors. RESULTS: 242 (31.3%) patients had a history of at least one lifetime suicide attempt. Compared to those without lifetime suicide attempts, those with suicidal attempts were less educated, were more often females, spent more time in episodes, and had a significantly more number of total episodes (in the lifetime, first five years of illness, and per year of illness), had significantly more number of total depressive episodes (in the lifetime, first five years of illness, and per year of illness), spent more time in depressive episodes, had more severe depressive episodes, more often had depression as the first episode in the lifetime, spent more time in mania/hypomania/mixed episodes, had higher residual depressive and manic symptoms, more often had rapid cycling affective disorder pattern in the lifetime, use of cannabis in dependence pattern, had poorer insight into their illness and had a higher level of disability (especially in three out of the four domains of Indian disability evaluation assessment scale). CONCLUSIONS: About one-third of the patients with BD have at least one-lifetime suicidal attempt, and those with suicide attempts usually have a poorer course of illness.

The factor structure of extrapyramidal symptoms evaluated using the Drug-Induced Extrapyramidal Symptoms Scale in patients with schizophrenia: Results from the 2016 REAP AP-4 study.

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).

Prevalence and association of comorbid substance dependence on the course and outcome of bipolar disorder: Findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

Aim: To evaluate the prevalence of substance use disorder (SUD) and its association with the course and outcome of bipolar disorder (BD). Materials and Methods: A total of 773 patients with BD were recruited from 14 centers in different parts of India, and they were evaluated for the prevalence of comorbid substance dependence, course and outcome, subjective cognitive functioning, and disability. Results: About one-fourth (22.9%) of the participants had one or more substance dependence. In terms of specific substance of abuse, 136 (17.6%) had nicotine dependence, 80 (10.3%) patients had alcohol dependence, 13 (1.7%) had cannabis dependence, and nine (1.2%) had opioid dependence. Compared to those without comorbid substance dependence, those with a dual diagnosis (i.e., using at least one substance in a dependent pattern) were less educated, more often males, more often currently single, more often employed, had a lower number of depressive episodes per year of illness, had a higher number of manic and mixed episodes per year of illness in the first 5 years of illness, had a higher level of disability, and more often had a history of hospitalization and a history of receiving electroconvulsive therapy (ECT); also, a higher proportion of them had manic predominant polarity, more often had recurrent mania course, and were more often receiving a combination of lithium and valproate. Conclusion: About one-fourth of BD patients have comorbid SUDs, and presence of SUD has a negative impact on the course and outcome of BD.

Psychiatric and neuropsychiatric issues in persons with COVID-19 infection: A case-control online study from India-Neorealist study.

Background: Many studies across the globe have evaluated the adverse mental health consequences of COVID-19 in patients who suffered from COVID-19 infection. However, a comparative study of persons who suffered from COVID-19 infection and those who witnessed the COVID-19 infection in their close relatives is lacking. Aims and Objectives: This study aims to compare the psychiatric morbidity in persons who suffered from COVID-19 infections, and those who witnessed the illness in one of their close relatives. Methods: In this cross-sectional online survey, 2,964 adult participants completed the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) Scale, Fear of COVID-19 Scale (FCS-19), Brief Resilient Coping Scale (BRCS), The Brief Resilience Scale (BRS) and a self-designed questionnaire to evaluate other neuropsychiatric complications. Results: Compared to the close relatives who had witnessed COVID-19 infection, participants who developed COVID-19 infection had a significantly higher prevalence of depression (34.6%), anxiety disorder (32.3%), and fear of COVID-19 infection (18.8%), which was significantly higher than that noted in close relatives. However, BRS coping score was not significantly different between the two groups. Overall, about one-third of the participants who developed COVID-19 infection had depression and one-third had anxiety disorders. One-fifth of the participants reported high fear, post-traumatic symptoms, and obsessive-compulsive symptoms, whereas one-sixth reported other neuropsychiatric manifestations. Conclusion: Patients who suffered from COVID-19 have a higher prevalence of depression, anxiety, and fear as compared to those to witnessed COVID-19 in relatives.

Surface-based brain morphometry in schizophrenia vs. cannabis-induced psychosis: A controlled comparison.

BACKGROUND & AIM: We examined group differences in cortical thickness and surface-parameters among age and handedness--matched persons with cannabis-induced psychosis (CIP), schizophrenia with heavy cannabis use (SZC), and healthy controls (HC). METHODS: We recruited 31 men with SZC, 28 with CIP, and 30 with HC. We used the Psychiatric Research Interview for Substance and Mental Disorders to differentiate between CIP and SZC. We processed and analyzed T1 MR images using the Surface-based Brain Morphometry (SBM) pipeline of the CAT-12 toolbox within the statistical parametric mapping. After pre-processing, volumes were segmented using surface and thickness estimation for the analysis of the region of interest. We used the projection-based thickness method to assess the cortical thickness and Desikan-Killiany atlas for cortical parcellation. RESULTS: We observed the lowest cortical thickness, depth, and gyrification in the SZC, followed by CIP and the control groups. The differences were predominantly seen in frontal cortices, with limited parietal and temporal regions involvement. After False Discovery Rate (FDR) corrections and post-hoc analysis, SZC had reduced cortical thickness than HC in the middle and inferior frontal, right entorhinal, and left postcentral regions. Cortical thickness of SZC was also significantly lower than CIP in bilateral postcentral and right middle frontal regions. We found negative correlations (after FDR corrections) between the duration of cannabis use and cortical thickness in loci of parietal and occipital cortices. CONCLUSION: Our study suggested cortical structural abnormalities in schizophrenia, in reference to healthy controls and cannabis-induced psychosis, indicating different pathophysiology of SZC and CIP.

White Matter Microstructure and Gray Matter Volume in Cannabis-Induced Psychosis and Schizophrenia With Cannabis Use.

OBJECTIVE: This study explored the differences in white matter (WM) microstructural integrity and gray matter (GM) volume between cannabis-induced psychosis (CIP) and schizophrenia with cannabis use (SZC). METHODS: This cross-sectional study with convenience sampling involved three groups of 20 participants each (CIP, SZC, and a control group without substance use), matched on age, handedness, and education. CIP and SZC were diagnosed with the Psychiatric Research Interview for Substance and Mental Disorders. Diffusion tensor and kurtosis imaging were done, and fractional anisotropy (FA), mean diffusivity, and mean kurtosis were estimated. GM volume was measured with voxel-based morphometry. RESULTS: Group comparisons revealed comparable age at initiation and duration and frequency of cannabis use between participants in the SZC and CIP groups. Participants with SZC had lower FA than controls in the anterior and retrolenticular internal capsule limbs, cingulate gyrus hippocampal formation, fornix, and superior fronto-occipital fasciculus (all p<0.05). Participants with CIP had lower FA than controls in the left fornix and right superior fronto-occipital fasciculus but higher FA than those with SZC in the left corticospinal tract (all p<0.05). On morphometry, participants with CIP had greater cerebellar GM volume than those with SZC and greater inferior frontal gyrus volumes than controls (all p<0.05). CONCLUSIONS: Widespread WM microstructural abnormalities were observed in participants with SZC, and fewer but significant WM disruptions were observed in those with CIP. Better WM integrity in some WM fiber tracts and greater GM volumes in crucial brain areas among those with CIP may have prevented the transition to schizophrenia.

A Machine-Learning-Algorithm-Based Prediction Model for Psychotic Symptoms in Patients with Depressive Disorder.

Psychotic symptoms are rarely concurrent with the clinical manifestations of depression. Additionally, whether psychotic major depression is a subtype of major depression or a clinical syndrome distinct from non-psychotic major depression remains controversial. Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, we developed a machine-learning-algorithm-based prediction model for concurrent psychotic symptoms in patients with depressive disorders. The advantages of machine learning algorithms include the easy identification of trends and patterns, handling of multi-dimensional and multi-faceted data, and wide application. Among 1171 patients with depressive disorders, those with psychotic symptoms were characterized by significantly higher rates of depressed mood, loss of interest and enjoyment, reduced energy and diminished activity, reduced self-esteem and self-confidence, ideas of guilt and unworthiness, psychomotor agitation or retardation, disturbed sleep, diminished appetite, and greater proportions of moderate and severe degrees of depression compared to patients without psychotic symptoms. The area under the curve was 0.823. The overall accuracy was 0.931 (95% confidence interval: 0.897-0.956). Severe depression (degree of depression) was the most important variable in the prediction model, followed by diminished appetite, subthreshold (degree of depression), ideas or acts of self-harm or suicide, outpatient status, age, psychomotor retardation or agitation, and others. In conclusion, the machine-learning-based model predicted concurrent psychotic symptoms in patients with major depression in connection with the "severity psychosis" hypothesis.

Network analysis of psychiatric symptoms in schizophrenia: Findings from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP).

AIMS: Schizophrenia is a major mental disorder with a wide range of psychiatric symptoms. This study explored the structure of psychiatric symptoms of schizophrenia using network analysis in a large representative Asian sample based on a survey of clinical features and treatment used in schizophrenia patients across 15 countries/territories in Asia. METHODS: Data on the demographic characteristics and psychiatric symptoms in schizophrenia patients were extracted from the dataset of the fourth Research on Asia Psychotropic Prescription for Antipsychotics (REAP-AP) project. The presence of the following psychiatric symptoms including delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms, social/occupational dysfunction, verbal aggression, physical aggression, and affective symptoms were analyzed. RESULTS: A total of 3681 patients were included. The network analysis revealed that verbal aggression, hallucinations, and social/occupational dysfunction were the most central symptoms, while the connections between social/occupational dysfunction and verbal aggression, and between hallucinations and disorganized speech were the two strongest edges. There were significant gender differences in the network structure based on the network structure invariance test (M=0.74, P = 0.03) and invariant edge strength test. The positive correlation between verbal aggression and hallucinations was significantly stronger in the female network than that in the male network (P = 0.03), while a negative correlation between affective symptoms and negative symptoms was found in the female, but not the male network (P < 0.01). CONCLUSION: Central symptoms including verbal aggression, hallucinations, and socio-occupational dysfunction should be addressed in developing targeted treatment strategy for schizophrenia patients.

Current telepsychiatry practice in India - An online survey of psychiatrists.

Context: Telemedicine Practice Guidelines and Telepsychiatry Operational Guidelines released in 2020 have provided legal backing for telepsychiatry practice. Aims: To understand the current telepsychiatry practices in India. Settings and Design: An online survey was conducted after ethics approval by the IPS Ethics Review Board. All psychiatrists, who are members of the Indian Psychiatric Society and whose email address was available with the society, were sent the survey link by email. Methods and Material: Information about existing telepsychiatry consultation practices in India was collected between June and July 2020. Statistical Analysis Used: Frequency, percentages, mean, and standard deviation were calculated. Results: 340 responses were analyzed. Nearly three-fourths of the responders used smartphones (n = 260, 76.47%) for audio consultations (n = 196, 57.65%). Among those who were using a dedicated software (n = 36), one-third used the Zoom software (n = 12, 33.33%). Nearly three-fourths (n = 218, 73.4%) provided prescriptions with their registration number on a letterhead in the form of an email or text message. Two-thirds of the responders (n = 228, 67.06%) felt that in-person consultation is better. Many preferred a combination of voice, video, and text including emails (n = 134, 42.01%). Conclusions: This online survey showed that the use of technology has caught up with the practicing psychiatrists. Many are practicing telepsychiatry either formally or informally in India and are comfortable and satisfied with the telepractice.