Pharmacogenomics-assisted schizophrenia management: A hybrid type 2 effectiveness-implementation study protocol to compare the clinical utility, cost-effectiveness, and barriers.

OBJECTIVES: The response to antipsychotic therapy is highly variable. Pharmacogenomic (PGx) factors play a major role in deciding the effectiveness and safety of antipsychotic drugs. A hybrid type 2 effectiveness-implementation research will be conducted to evaluate the clinical utility (safety and efficacy), cost-effectiveness, and facilitators and barriers in implementing PGx-assisted management compared to standard of care in patients with schizophrenia attending a tertiary care hospital in eastern India. METHODS: In part 1, a randomized controlled trial will be conducted. Adult patients with schizophrenia will be randomized (2: 1) to receive PGx-assisted treatment (drug and regimen selection depending on the results of single-nucleotide polymorphisms in genes DRD2, HTR1A, HTR2C, ABCB1, CYP2D6, CYP3A5, and CYP1A2) or the standard of care. Serum drug levels will be measured. The patients will be followed up for 12 weeks. The primary endpoint is the difference in the Udvalg for Kliniske Undersøgelser Side-Effect Rating Scale score between the two arms. In part 2, the cost-effectiveness of PGx-assisted treatment will be evaluated. In part 3, the facilitators and barriers to implementing PGx-assisted treatment for schizophrenia will be explored using a qualitative design. EXPECTED OUTCOME: The study findings will help in understanding whether PGx-assisted management has a clinical utility, whether it is cost-effective, and what are the facilitators and barriers to implementing it in the management of schizophrenia. TRIAL REGISTRATION: The study has been registered with the Clinical Trials Registry-India (CTRI/2023/08/056210).

Prevalence and pattern of mental disorders in the state of West Bengal: Findings from the National Mental Health Survey of India 2016.

Background: West Bengal, situated in eastern India, comprising 19 districts as of 2016 and consisting of 9.13 crore population, had been one of the participating states in the National Mental Health Survey, 2015-16. Aim: To estimate the prevalence and pattern of mental disorders in a representative population in West Bengal. Materials and Methods: Based upon a multi-stage stratified random cluster sampling with probability proportionate to each stage, 2646 eligible individuals were interviewed. Standard validated instruments in Bengali like socio-demographic profiles and Mini International Neuropsychiatric Interview (MINI) version 6 were used by trained data collectors with quality monitoring as per a standardized protocol. Results: The current prevalence of mental illness in the state of West Bengal is 13.07% (12.9-13.24 95% CI), which is more than the current national average of 10.56% (10.51-10.61 95% CI). The prevalence of severe mental illness of 2.32% and suicide risk of 1.75% (1.68-1.81 95% CI) is higher than the national average. The common mental illness prevalence is 11.29 (11.13-11.45 95% CI), which is similar to the national weighted average. In West Bengal, severe mental illness is more concentrated in the rural areas in contrast to the national trend. Also, the prevalence of alcohol use disorder is 3.04 (2.96-3.13 95% CI) and epilepsy is 0.03 (0.27-0.29 95% CI), which is less than the national average. Conclusion: The prevalence of mental disorders in the state of West Bengal is higher than the national average, and for severe mental illness, the prevalence is the highest as compared to the national average.

Factors associated with medication non-adherence among patients with severe mental disorder - A cross sectional study in a tertiary care centre.

Background: Medications are an essential treatment modality of mental disorders. There is limited scientific literature on medication non-adherence among patients in Severe Mental Disorders with respect to patient-related factors. The current study explores the factors associated with medication non-adherence in such patients. Objectives: To study the relationship between socio-demographic, clinical, treatment related factors, self-stigma, patients' & caregivers' attitude towards psychotropic medications, doctor-patient communication and medication non-adherence in patients with severe mental disorders. Methods: A cross-sectional observation study, where patients with severe mental disorders attending Psychiatry Outpatient services, and their caregivers, were recruited. Sociodemographic and clinical variables were recorded using data collection form and illness-specific severity scales. Patients were administered Medication adherence rating scale (MARS), Internalised stigma of mental illness inventory (ISMI- 9), Attitude of patients towards psychotropic medication scale and Doctor-patient communication questionnaire (DPCQ). The Attitude of caregivers towards psychotropic medication scale was administered for caregivers. Results: Among 152 patients, 58 (38.16%) patients had a diagnosis of schizophrenia, 11 (7.24%) had delusional disorder, 32 (21.05%) patients were diagnosed with bipolar disorder type 1 - mania and 19 (12.50) with bipolar disorder type 2 - depression whereas 32 (21.05%) had major depressive disorder. Majority of the patients were non-adherent to medications (88.16%). MARS score was significantly higher among patients of middle socioeconomic class (p = 0.014), urban domicile (p = 0.033) and those with higher caregivers' age (p = 0.019) . Among 79.61% of patients, ISMI-9 score was minimal to mild. Most patients (76.97%) and caregivers (83.55%) had negative attitude towards psychotropic medications. MARS score negatively correlated with BPRS (p = 0.0001*), HAM-D (p = 0.0004*), YMRS (p = 0.0007*), ISMI-9 (p ≤0.0001*) and the attitude of the caregivers towards psychotropic medicationsnegative scale scores (p = 0.003*) . MARS score positively correlated with DPCQ scores (p ≤0.0001*) . Conclusion: Medication adherence was higher among patients belonging to uppermiddle socioeconomic status, urban domicile and higher caregiver age. Higher severity of illness, self-stigma and negative attitude of patients and caregivers towards psychotropic medications were associated with lower adherence whereas better doctor-patient communication was associated with higher adherence to medications.

Exploring the role of macular thickness as a potential early biomarker of neurodegeneration in acute schizophrenia.

OBJECTIVE: The retina has been investigated as a gateway to assess the neurodegenerative changes in the brain. Schizophrenia is also conceptualized as a neurodegenerative disorder like Alzheimer's and Parkinson's disease. The current literature suggests reduced retinal nerve fibre layer (RNFL) thickness and macular thickness (MT), as a marker of neurodegeneration, in patient suffering from chronic schizophrenia. This study aims to compare RNFL thickness and MT in acute schizophrenic patients with age and sex matched healthy controls. METHODS: Twenty acutely ill schizophrenic patients and 20 normal controls were included in the study after proper informed consent. RNFL thickness and MT was measured using spectral domain Optical Coherence Tomography after clinical psychological assessment and ocular examination. RESULTS: The two groups were comparable in terms of socio-demographic variables. The average RNFL thickness of patients and healthy controls was 102.11 ± 29.18 µm and 105.14 ± 27.35 µm, respectively. Central macular thickness was 181.12 ± 13.63 µm in patients and 234.58 ± 10.71 µm in controls. There was a statistically significant reduction in thickness of macula (p < 0.05) but not for RNFL (p = 0.339). CONCLUSION: The study concludes that macular thinning rather than reduced RNFL is an early manifestation in acute schizophrenia patients and can be considered as a potential early biomarker of neurodegeneration in schizophrenia.

Depression and anxiety associated with functional bowel disorders and its impact on quality of life: A cross-sectional study.

BACKGROUND: Functional bowel disorder (FBD) is conceptualized as a "biopsychosocial disorder." Psychological factors are important moderators of symptom severity and persistence, treatment seeking and response to treatment. We investigated psychological factors and quality of life (QOL) in patients with FBD. METHODS: Seventy patients visiting the department of medical gastroenterology diagnosed as FBD were included in the study. Severity of FBD was rated with FBD Severity Index. The Depression, Anxiety, and Stress Scale was applied and patients were divided into two groups, i.e., with moderate stress (Group A) and with severe stress (Group B). QOL in both the groups was assessed by WHOQOL-BREF Scale. Chi-square, t-test was done to compare the groups. Regression analysis was done to find predictors of poor QOL. P < 0.05 was taken as significant. RESULTS: Patients of Group B had a longer duration of illness and had higher prevalence of depressive disorder (P = 0.03) in comparison to patients in Group A, who had higher prevalence of anxiety disorders (P = 0.06). Severity of FBD was positively correlated with depression (r = 0.8; P = 0.02). Physical and psychological QOL was significantly impaired in Group B patients having depression (P = 0.02; P = 0.03). Regression analysis showed a positive trend for presence of depressive disorder (P = 0.05), anxiety disorder (P = 0.08) and severity of FBD (P = 0.09) as predictors of poor QOL. CONCLUSION: In our study, the high prevalence of stress, anxiety and depression in patients with FBD indicates the need for routine screening of such symptoms along with a collaborative and holistic treatment approach. Several etiological perspectives explaining the complex gut-brain interaction are also provided.

A cross-sectional study of psychiatric morbidity and quality of life among participants utilizing the preventive health-care services of a tertiary hospital.

BACKGROUND: The burden of mental disorders has been increasingly recognized and 450 million people globally are suffering from mental illness. Mental-physical comorbidity has adverse effects on the overall outcome. Research is scarce with regard to mental health screening in the context of "preventive health care" in India. Thus, the study aimed to identify the prevalence of mental illness and the effect on quality of life (QOL) among participants attending preventive health-care unit (PHCU). SETTINGS AND DESIGN: This was a cross-sectional study conducted in PHCU of a tertiary hospital in Puducherry. MATERIALS AND METHODS: All consecutive participants (>18 years) attending PHCU were included in the study. The Standard for Clinicians' Interview in Psychiatry (SCIP) screening module, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Level 1 Cross-Cutting Symptom Measure, Mini-Cog, and Quality of Life Enjoyment and Satisfaction Questionnaire were administered. Relevant diagnostic modules of SCIP were applied to participants who screened positive on SCIP. Data analysis was performed using SPSS (version 17.0). RESULTS: The mean age of participants was 43.38 ± 13.99 years. Of 203 participants enrolled, 28.1% screened positive and 26.1% were confirmed to have psychiatric disorder. About 4% screened positive for cognitive impairment. Most commonly diagnosed disorders were alcohol use disorder and major depressive disorder. The prevalence of depressive disorder was higher in patients with physical disorder. Participants with psychiatric disorder alone or with both psychiatric and physical disorders had significantly poorer QOL (F = 27.13; P < 0.001). CONCLUSION: One-fourth of the participants attending preventive health-care services were found to have psychiatric disorders. The presence of psychiatric disorder was associated with significantly poorer QOL. This highlights the importance of routine mental health screening in this setting.

Effect of adjunct yoga therapy in depressive disorders: Findings from a randomized controlled study.

BACKGROUND: Depression causes significant burden both to the individual and to society, and its treatment by antidepressants has various disadvantages. There is preliminary evidence that adds on yoga therapy improves depression by impacting the neurotransmitters involved in the regulation of mood, motivation, and pleasure. Our study aimed to find the effect of adjunctive yoga therapy on outcome of depression and comorbid anxiety. MATERIALS AND METHODS: A randomized controlled study involving patients with major depressive disorder (n = 80) were allocated to two groups, one received standard therapy (antidepressants and counseling) and the other received adjunct yoga therapy along with standard therapy. Ratings of depression and anxiety were done using Montgomery-Asberg Depression Rating Scale and Hospital Anxiety and Depression Scale at baseline, 10th and 30th day. Clinical Global Impression (CGI) Scale was applied at baseline and 30th day to view the severity of illness and clinical improvement. RESULTS: By the 30th day, individuals in the yoga group had significantly lower scores of depression, anxiety, and CGI scores, in comparison to the control group. The individuals in the yoga group had a significant fall in depression scores and significant clinical improvement, compared to the control group, from baseline to 30th day and 10th to 30th day. In addition, the individuals in the yoga group had a significant fall in anxiety scores from baseline to 10th day. CONCLUSION: Anxiety starts to improve with short-term yoga sessions, while long-term yoga therapy is likely to be beneficial in the treatment of depression.

Effect of Olanzapine on Clinical and Polysomnography Profiles in Patients with Schizophrenia.

Acute and short-term administration of olanzapine has a favorable effect on sleep in schizophrenia patients. This study aimed to clarify the effect of olanzapine on polysomnographic profiles of schizophrenia patients during the acute phase of illness after controlling for previous drug exposure. Twenty-five drug-naïve or drug-free schizophrenia patients were assessed at baseline and after six weeks of olanzapine treatment on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), and Udvalg for Kliniske Undersogelser (UKU) side-effect rating scale and a whole-night polysomnography; fifteen patients completed the study. There was a significant reduction in all psychopathological variables with maximum reduction in PANSS total, BPRS total, and PANSS positive scores. A significant increase in total sleep time (TST), sleep efficiency (SE), nonrapid eye movement (NREM) stage 1 duration, stage 3 duration, stage 4 duration, and stage 4 percentage of TST, number of rapid eye movement (REM) periods, REM duration, and REM percentage of TST was observed. REM latency at baseline inversely predicted the reduction in BPRS total and PANSS total and positive scores. In summary, short-term treatment with olanzapine produced significant improvement in clinical and polysomnography profiles of patients with schizophrenia with shorter REM latency predicting a good clinical response.

Higher Impulsivity and HIV-Risk Taking Behaviour in Males with Alcohol Dependence Compared to Bipolar Mania: A Pilot Study.

To study the association of impulsivity, high-risk behaviours and incidence of HIV infection in patients with alcohol dependence and bipolar mania. This was a cross-sectional hospital-based pilot study and the sample consisted of male patients divided into three groups: 25 patients with alcohol dependence and 25 with bipolar mania as per ICD-10 Diagnostic Criteria for Research and 25 normal controls. Severity of Alcohol Dependence Questionnaire (SADQ) and Young Mania Rating Scale (YMRS) were administered on alcohol dependent and bipolar patients, respectively. All three groups were rated on Barrett's Impulsivity Scale (BIS) and HIV Risk-taking Behaviour Scale (HRBS). None of the patients tested positive for either HIV 1 or 2. BIS motor impulsivity, BIS total score and HRBS total score were significantly higher in alcohol dependent patients as compared to bipolar mania patients. In the Alcohol dependent group, BIS score significantly correlated with education years, age of onset of alcohol use and SADQ, whereas, HRBS total score significantly correlated with SADQ scores. In the bipolar mania group, BIS significantly correlated with YMRS, and total number of episodes, whereas, there was no significant correlation of HRBS total score with any clinical variable. The findings of this pilot study underscore the link between alcohol use disorder and the impulsive behaviours that can lead to HIV infection, and highlight that those risks are higher for individuals with alcohol dependency than for individuals with bipolar disorder.

Risk factors for the development of delirium in alcohol dependence syndrome: Clinical and neurobiological implications.

INTRODUCTION: Alcohol withdrawal delirium (AWD) or delirium tremens (DT) is associated with severe complications and high mortality. Prospectively identifying patients with increased risk of developing DT would have important preventive and therapeutic implications. Thus, the present study aimed to identify clinical risk factors predicting the development of DT. MATERIALS AND METHODS: The study was a cross-sectional quasi-experimental one with equivalent control group, conducted at a tertiary hospital from August 2014 to May 2015. Forty adult male inpatients, diagnosed with DT, were compared with forty age- and sex-matched inpatients in alcohol withdrawal state without delirium. Assessments were done using confusion assessment method, Clinical Institute Withdrawal Assessment of Alcohol Scale, and Mini-Mental Status Examination. For group comparisons, Pearson's Chi-square test and independent sample t-test were used; logistic regression was applied to identify predictors followed by receiver operating characteristic curve analysis. RESULTS: Heavy drinking (P = 0.005; odds ratio [OR]: 1.17, confidence interval [CI]: 1.05-1.31), continuous pattern of drinking (P = 0.027; OR: 4.67, CI: 1.19-18.33), past history of delirium (P = 0.009; OR: 552.8, CI: 4.88-625.7), alcohol-induced psychosis (P = 0.002; OR: 74.6, CI: 4.68-1190), and presence of cognitive deficits (P = 0.044; OR: 12.5, CI: 1.07-147.3) emerged as strong predictors of AWD. CONCLUSION: The risk factors found can be easily evaluated in a clinical setting for physicians to readily identify patients at risk for developing DT and plan intensive therapies for them. At a neurobiological level, patients with preexisting brain neurotransmitter disturbances are at greater risk for developing DT.

Multimodal Hallucinations in a Visually Impaired Elderly Female: Is it a Variant of Charles Bonnet Syndrome?

Charles Bonnet Syndrome (CBS) is a common cause of visual hallucinations seen in elderly people with visual impairment. Well-formed visual hallucinations in clear consciousness with preserved insight are commonly reported in literature. We report a case of CBS having multisensory hallucinations. An elderly patient with visual impairment fulfilling the criteria of CBS presents with various modalities of hallucinations viz. visual, auditory and tactile hallucinations improved completely with low dose of antipsychotics. Atypical features are common in CBS and thus often make it difficult to diagnose this condition.

A novel approach in the detoxification of intravenous buprenorphine dependence.

BACKGROUND: Opioid dependence remains a significant problem in India, and of late intravenous (IV) buprenorphine use has increased in India, especially in combination with antihistamines and benzodiazepines. Its usage has many serious consequences in the form of needle-transmitted hepatitis and HIV, which is showing an increasing trend. Buprenorphine is a partial agonist at µ-opioid receptors. In tablet form (and rarely as IV), it is widely used in the treatment of opioid detoxification. We assessed the safety and efficacy of transdermal patch of buprenorphine with week long duration of action in the treatment of detoxification of IV buprenorphine dependence in view of its many advantages. MATERIALS AND METHODS: Six consecutive patients with International Classification of Diseases diagnosis of Opioid Dependence Syndrome (IV buprenorphine) were given a buprenorphine patch for treatment of withdrawal symptoms after receiving consent. Severity of opioid dependence was assessed by using Severity of Opioid Dependence Questionnaire on the day of presentation. Subjective and objective rating for opioid withdrawal was done by subjective opiate withdrawal scale (SOWS) and objective opiate withdrawal scale (OOWS) prepatch and postpatch 3(rd) and 7(th) day. Buprenorphine side effect checklist was applied on a daily basis. RESULTS: The patients had a mean age of 30 years, of whom 83.3% are males. All were educated and 50% were currently employed. All of them had additional comorbid substance use as well as a comorbid psychiatric diagnosis. Each of them received a patch of varying dosage. The patch dose used initially was based on clinical considerations alone and was fairly adequate in controlling acute withdrawal symptoms. There is a significant improvement in SOWS and OOWS while comparing the baseline (prepatch) with 3(rd) and 7(th) day (postpatch) (P ≤ 0.05). None of the patients reported any side effect with the patch. CONCLUSION: This study shows that transdermal buprenorphine is safe, useful, and clinically effective, and a 7-day application may provide an alternative means of detoxification. However, the result of the study needs to be replicated in a larger sample in a clinical setting, and a control group receiving a conventional mode of treatment needs to be included.

A Cross-sectional Study of Prevalence and Implications of Depression and Anxiety in Psoriasis.

BACKGROUND: Physical and mental comorbidity is common and has significant implications for overall health outcomes. Psoriasis, a psychocutaneous disorder, is a classic example of mental-physical comorbidity. AIMS: In view of the impact of socio-cultural influences on mind-body interactions and the paucity of Indian research pertaining to psychiatric morbidity in psoriatic patients, this study was undertaken to measure the prevalence of anxiety and depression in patients with psoriasis, and to correlate these with severity of psoriasis and quality of life. MATERIALS AND METHODS: This cross-sectional study was conducted on 90 consecutive patients of psoriasis, over a period of 12 months, in a tertiary care centre. The Psoriasis Area and Severity Index was used to assess severity of psoriasis. PHQ-9, GAD-7 and the Perceived Stress Scale were used to screen for depression, anxiety and perceived stress respectively. The WHOQOL-BREF was used to determine the quality of life. STATISTICS ANALYSIS: All analysis was performed using Microsoft Excel software and Statistical Package for Social Sciences. RESULTS: A total of 71 (78.9%) subjects had depression and 69 (76.7%) had anxiety. Fifty one patients had significant stress. A significant positive correlation was established between psoriasis variables (severity and duration of psoriasis) and psychological variables (depression, anxiety and stress). Severity of psoriasis had a significant negative correlation with social relationships and environmental domains of WHOQOL. Quality of life was significantly worse in patients with psoriasis with comorbid anxiety/depression. CONCLUSION: Patients with psoriasis have a clinically significant prevalence of depression, anxiety and perceived stress. This study highlights the complex relationship between psoriasis, psychiatric comorbidity and quality of life and the need to simultaneously consider dermatological and psychological factors.

Comparison of anticraving efficacy of right and left repetitive transcranial magnetic stimulation in alcohol dependence: a randomized double-blind study.

The objective of this study was to compare the anticraving efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right versus left dorsolateral prefrontal cortex (DLPFC) in patients with alcohol dependence. Twenty patients with alcohol dependence syndrome were randomly allocated to receive either right or left rTMS over the right DLPFC (10 sessions at 10 Hz frequency; 20 trains per session; 4.9 seconds per train and intertrain interval 30 seconds) and were assessed on the Alcohol Craving Questionnaire (ACQ-NOW) to measure craving. Two-way repeated-measures analysis of variance for ACQ-NOW total score showed no main effect of group (F[1,18] = 0.0001 but significant main effect of time (F[1,18] = 185.91, p<0.0001, η(2) = 0.912). The interaction effect between group and time was not significant. There was significant reduction in craving scores in patients receiving either right or left rTMS with large effect size. However, there was no difference in anticraving efficacy between the two groups.

External ear abnormalities in existing scales for minor physical anomalies: are they enough?

The pattern of external ear abnormalities in patients with schizophrenia and bipolar disorder was studied. Sixty-seven male patients having schizophrenia (n=30) and bipolar disorder (n=37) were examined using a scale constructed for the study. Stepwise logistic regression analysis showed that 'prominent crux of helix' and 'ear lobe crease' could differentiate between schizophrenia and bipolar disorder. These external ear abnormalities need further characterization and consideration for possible inclusion in scales that assess minor physical anomalies.

Depressive disorders in school children of suburban India: an epidemiological study.

PURPOSE: There is a dearth of research on the prevalence of depressive disorders in children from suburban and rural areas in the Indian subcontinent. Therefore, the present study was aimed at assessing the prevalence of depressive disorders and the associated risk factors in the primary and secondary school children in suburban India. METHODS: This was a cross-sectional, school-based epidemiological study involving 1,851 children from standard I to VII age group. Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS-PL), a semi-structured interview was used to diagnose depression in this sample. RESULTS: Using K-SADS-PL, prevalence of depressive disorder was 3.13% (n = 58); major depressive disorder was diagnosed in 15 (0.81%), dysthymia in 28 (1.51%) and depressive disorder NOS in 15 (0.81%). Age (OR 1.396, CI 1.121-1.738), class attendance (OR 0.251, CI 0.103-0.613), family history of psychiatric illness (OR 0.204, CI 0.069-0.605) and birth complications (OR 0.128, CI 0.029-0.558) emerged as significant predictors of depression; the model explained 24.1-32.3% of the variance in this sample. CONCLUSION: The present study confirms the findings from previous studies that childhood depression is a distinct diagnostic entity affecting a significant number of children and adolescents.

Delayed onset of clozapine-induced leucopenia.

Clozapine has been reported to cause agranulocytosis, neutropenia, and leucopenia that usually occur within 18 weeks of initiation of treatment. We report a case of delayed onset leucopenia after 11 years of treatment with clozapine, which reversed within a few days after discontinuation of medication.

Add-on effect of Brahmi in the management of schizophrenia.

Brahmi(Bacopa monnieri), an Ayurvedic herb has primarily been used to enhance cognitive ability, memory and learning skills. We present a case study of schizophrenia in which add-on Brahmi extracts 500 mg/day for a period of one month resulted in reduction in psychopathology without any treatment-emergent adverse effect. Although preliminary, our case study suggests therapeutic efficacy of add-on Brahmi in schizophrenia, thus opening up a new dimension of its role in alternative medicines.