Augmentation strategies for clozapine resistance: a systematic review and meta-analysis.

BACKGROUND: Several augmentation strategies have been used to improve symptomatology in patients not adequately responding to clozapine. Several randomised controlled trials (RCTs) have evaluated the efficacy of different strategies to augment clozapine. This systematic review and meta-analysis reviewed the available RCTs that have evaluated the clinical efficacy of various pharmacological agents, non-pharmacological strategies (occupational therapy, cognitive behaviour therapy), and somatic treatment [electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation, etc.)] as augmenting agents to clozapine. METHODS: Data were extracted using standard procedures, and risk of bias was evaluated. Effect sizes were computed for the individual studies. RESULTS: Forty-five clinical trials were evaluated. The pooled effect size for various antipsychotic medications was 0.103 (95% CI: 0.288-0.493, p < 0.001); when the effect size was evaluated for specific antipsychotics for which more than one trial was available, the effect size for risperidone was -0.27 and that for aripiprazole was 0.57. The effect size for lamotrigine was 0.145, and that for topiramate was 0.392. The effect size for ECT was 0.743 (CI: 0.094-1.392). Risk of bias was low (mean Jadad score - 3.93). Largest effect sizes were seen for mirtazapine (effect size of 5.265). Most of the studies can be considered underpowered and limited by small sample sizes. CONCLUSIONS: To conclude, based on the findings of the present systematic review and meta-analysis, it can be said that compared to other treatment strategies, clozapine non-responsive patients respond maximum to mirtazapine followed by ECT.

How and What are Indians Drinking? Findings from the National Family Health Survey.

AIMS: To assess recent changes in the extent and pattern of alcohol use in India using the National Family Health Survey (NFHS) data. METHODS: We used unit-level data from both rounds of NFHS. The pattern of alcohol use was categorized as: 'almost every day', 'almost once a week' and 'less than once a week'. The information was segregated for the urban and rural settings. Information was also available on the type of alcoholic beverage used by the respondents. The z test for differences in proportions was carried out for the study variables. RESULTS: Findings suggest a 22.37 and 39.02% reduction in the proportion of men and women who reported alcohol use, respectively. The proportion of men reporting 'almost every day' and 'about once a week' consumption of alcohol increased by 24.19 and 7.14%, respectively. CONCLUSIONS: With the caveats of expected limitations of surveys, the findings suggest an overall decrease in alcohol use in India, though the proportion of men with more frequent alcohol has increased. There is a need to strengthen the investment in the initiatives targeted at the harms due to alcohol use.

Exploring the clinical variables among drug-dependent HIV-Positive patients: Implications for treatment strategies.

This study explored the profile of HIV positive patients seeking treatment at a tertiary care addiction treatment facility. A retrospective study was done to collet detailed information on clinical characteristics: drug use (type, age of initiation, duration), general medical condition and past treatment history. The study included 138 patients with mean (SD) age 30.2 (8.3) years. Opioid dependence with injecting drug use (IDU) was diagnosed in 97% of the patients. The median age of injecting onset was 24.5 years (IQR 20-31 years). The most frequently injected substances were pheniramine (60.1%) and buprenorphine (59.4%). Past treatment seeking was reported by 57% patients and interestingly they were less likely to present any medical condition (2 =69.611, p < 0.001). Variability in the age of onset of drug use indicates the need for broad based approach to prevent IDU and motivation to seek treatment may lead to better health conditions.

Efficacy of adjunctive D-Cycloserine for the treatment of schizophrenia: a systematic review and meta-analysis of randomized controlled trials.

D-Cycloserine is a partial agonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor. Results have been inconsistent in trials on the efficacy of D-Cycloserine in patients with schizophrenia. We examined the efficacy of D-Cycloserine against negative and cognitive symptoms (primary and co-primary outcomes). Secondary outcomes were efficacy of D-Cycloserine against positive symptoms and the examination of early treatment outcomes. A systematic literature search was carried out using following selection criteria: Population = Patients with Schizophrenia; Intervention = Trials using D-Cycloserine either as monotherapy or adjuvant therapy; Comparison = Placebo or active comparator; Outcome = Change in negative symptoms, cognitive symptoms and positive symptoms; Study design = Randomized controlled trials with parallel design. We used the Cochrane Collaboration tool for risk of bias for study quality appraisal. Effect sizes for trials were calculated separately for negative, positive and cognitive symptom dimensions using the DerSimonian-Laird random effects model. Seven studies (pooled N = 413) provided data for meta-analysis. The pooled Standardized Mean Difference (SMD) for negative, cognitive, and positive symptom change scores were - 0.32 (95% CI, - 0.75 to 0.11), - 0.05 (95% CI, - 0.91 to 0.81), and - 0.08 (95% CI, - 0.37 to 0.20), respectively. No significant improvement was noted with regard to early outcome. I2 values for heterogeneity were 61%, 67%, and 0% for studies assessing negative, cognitive, and positive symptom ratings, respectively. D-Cycloserine did not exhibit significant efficacy in treating negative, cognitive, or positive symptoms of schizophrenia at either study-defined endpoint (4-36 weeks) or at four weeks (early outcome).

Barriers and Facilitators to Substance Use Disorder Treatment in Low-and Middle-Income Countries: A Qualitative Review Synthesis.

BACKGROUND AND AIMS: One of the ways to address the treatment gap for substance use disorders is to understand the barriers and facilitators to treatment. This study aimed to synthesize the literature on barriers and facilitators of treatment in Low- and Middle-Income Countries (LMICs). METHODS: We search Medline electronic database to identify English language peer reviewed empirical studies, both qualitative and quantitative which reported barriers and/or facilitators of treatment of substance use disorders. RESULTS: Of 1389 titles, we selected 28 studies (14 were qualitative and 14 quantitative studies). The sample sizes of the qualitative studies ranged from 11 to 235. The majority of studies were from community or clinic settings. A wide range of barriers and facilitators were identified from the qualitative studies and were synthesized according to perceived susceptibility/seriousness, self-efficacy, perceived costs, perceived benefits, and cues to action. Most of the quantitative studies were community-based cross sectional-observational by design. Commonly identified barriers in these quantitative studies were perceived lack of problem or lack of need for treatment and low motivation whereas factors such as good family support and availability of effective treatment was found to facilitate substance use disorder treatment. CONCLUSION: There are a wide range of barriers that hinder the substance use disorder treatment as well as certain factors that facilitate the treatment. Addressing them can help to minimize the treatment gap, which in turn can help in reducing the familial and social burden due to substance use disorders.

What are the options to implement an undergraduate medical exit examination in India?

Medical education and assessment processes in India are expected to undergo a paradigm shift with the introduction of the National Medical Commission Act, 2019. The Government of India intends to introduce a national exit test (NEXT) which is supposed to act as a single examination for graduation from medical school, granting licence to practice modern medicine, and allocating postgraduate residencies. As the nature, scope and stakes of these are different, various options regarding the content and conduct of the examination require careful consideration. We explore the options for implementation of this examination on a national scale. These options include theoretical (multiple assessment methods) with clinical examinations, multiple-choice question (MCQ)-based examination with separate clinical examination, only an MCQ-based examination, and multistep examination including screening followed by mixed assessment methods and clinical evaluation. We discuss the possible strengths and challenges of different options of implementing NEXT, and the caveats of the options.

Neurological Soft Signs in Cannabis Use Disorder with or without Psychosis: A Comparative Study from India.

OBJECTIVE: The purpose of this study was to assess and compare neurological soft signs in patients of cannabis use disorder (CUD) with and without co-occurring psychosis in a treatment-seeking sample. METHODS: We included 30 right-handed male subjects aged 18-65 years diagnosed with CUD (as per DSM-5) without any co-occurring psychiatric disorder in group I and those with co-occurring non-affective psychosis in group II. Group III consisted of 30 age and sex-matched, right-handed, healthy subjects with no psychiatric or medical conditions. Neurological Evaluation Scale (NES) was applied to measure neurological soft signs across the groups. We also used the Severity of Dependence Scale (in CUD with or without co-occurring non-affective psychosis groups) and Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Barnes Akathisia Rating Scale, Abnormal Involuntary Movements Scale, and Simpson Angus Scale (in CUD with co-occurring non-affective psychosis group) . RESULTS: Our data suggested higher total NES mean scores in CUD with (20.53 ± 13.77) or without co-occurring non-affective psychosis groups (15.93 ± 9.86) as compared to healthy controls (6.20 ± 5.40) (χ2 = 23.12; p < .001). However, there were no differences between cannabis use disorder with or without co-occurring non-affective psychosis groups. The mean of subdomain scores of motor incoordination, sequencing of complex motor tasks, sensory integration, and others was significantly higher in CUD with or without co-occurring non-affective psychosis groups compared to healthy controls. CONCLUSION: Impairment in neurological soft signs is present in patients with CUD regardless of a co-occurring psychosis. Cannabinoids might be interacting with the brain circuits known to be involved in schizophrenia.

Yoga Therapy For Medically Unexplained Physical Symptoms.

Medically unexplained physical symptoms (MUPS) is a common, yet neglected disease with a prevalence of around 25% in primary care setting. These patients present with multiple physical and psychological symptoms, without an underlying diagnosis, hampering their functional and mental wellbeing. The management of these undiagnosed symptoms through conventional treatment has not been encouraging. Patients shuttle between different specialities, seeking a diagnosis for their symptoms, making them dissatisfied and increasing healthcare burden. Yoga, as an adjunct therapy has shown to be effective in the management of MUPS related disorders such as somatoform disorder, irritable bowel syndrome (IBS) and depression and anxiety. Thus, we suggest an integrated yoga module which might help in improving both physical and psychological variable in MUPS patients and improving their overall quality of life. Furthermore, the gap in the literature on the efficacy of yoga in improving MUPS, can be addressed by planning a randomised controlled trial based on the suggested yoga module.

Are the Patients Ready for the Change?: An Empirical Study to Evaluate the Impact of Change in Formulation of Buprenorphine-Naloxone on Prescription Pattern, Treatment Adherence, and Patient Satisfaction.

BACKGROUND: Therapeutic adherence is one of the most important determinants of the outcome with OST. There are no published studies that have explored the impact of change in tablet formulation of buprenorphine-naloxone from one brand to another among patients receiving OST. OBJECTIVES: The current study is aimed at evaluation of the impact of change in buprenorphine-naloxone formulation on prescription pattern, treatment adherence, and patient satisfaction with OST. METHODS: Our study was a cross sectional study based on a cohort of patients who were receiving OST at the study setting. Changes in prescription pattern, reports of subjective opioid withdrawal symptoms, or observation of objective opioid withdrawal symptoms were noted from the case records. The satisfaction and concerns of the patients with buprenorphine-naloxone formulations were assessed using a semi-structured proforma. RESULTS: An increase in dose of buprenorphine-naloxone was noted in 22 participants, since formulation change. Twenty participants reported that the color of the formulation was different from the previous one, the intensity of effect was reported to be different by 87% participants. Seventy-three percent participants endorsed that increase in dose can be a possible solution to address the perceived differences in the effects of two formulations. Changes in physical attributes of the formulation, perception among treatment seeking peers regarding such changes in treatment, and lack of sense of autonomy regarding one's treatment play a more important role in determining response of the patients to changes in formulation of buprenorphine-naloxone.

Can Tramadol be Used for Maintenance Treatment of Opioid Dependence?

BACKGROUND: Certain limitations of the existing opioid substitution therapies necessitate exploration of other options for maintenance of patients with opioid dependence. This study aimed to present the experience of use of tramadol for long-term treatment of patients with opioid dependence. METHODS: This was a cross-sectional interview-based observational study conducted in Uttar Pradesh state in India. Patients with opioid dependence who received oral tramadol treatment for a period of more than 6 months were recruited. Outcome was assessed in terms of self-reported abstinence on tramadol. RESULTS: A total of 102 participants were recruited in the study, with a mean age of 41.3 years. All the participants were males. Abstinence to extraneous opioids was reported by 58.8% of the sample, and the median dose of tramadol at which abstinence was achieved was 350 mg/d. Those who reported to be taking natural opioids (raw opium or poppy husk) at the time of seeking treatment had higher rates of achieving abstinence. CONCLUSIONS: Tramadol may be a possible option for the maintenance treatment among some opioid-dependent individuals. Further studies are required to establish its efficacy vis-à-vis other medications used in opioid substitution treatment.

Internalized stigma among patients with substance use disorders at a tertiary care center in India.

Internalized stigma among individuals with substance use disorders is a major barrier for accessing mental health services. This study aimed to assess internalized stigma among individuals with substance use disorders and to assess the relationship of internalized stigma with the quality of life. This cross-sectional study recruited 201 patients with a clinical diagnosis of at least opioid or alcohol use disorder according to Diagnostic and Statistical Manual 5 at a public-funded tertiary care center in India. The study participants were interviewed using a sociodemographic questionnaire, the Internalized Stigma of Mental Illness Scale (ISMIS), and the World Health Organization's Quality of Life (WHOQOL-Bref) questionnaire. Seven participants (3.5% of the sample) had mild stigma according to ISMI scores, 62 (30.8%) had moderate stigma, and 132 (65.7%) had severe stigma. The various quality-of-life domains generally had a negative correlation with the internalized stigma scores. Participants using opioids as the primary substance of use were more likely to have severe internalized stigma. The experience of internalized stigma and dissatisfaction with quality of life is quite high among people suffering with substance use disorders in India. These results emphasize the need for interventions to reduce internal perception of stigma and improve the quality of life of individuals with substance use disorders.

An Observational Study of Treatment Seeking Users of Natural Opiates from India.

BACKGROUND: The type of opioid used influences the severity and complications experienced. Natural opiates (opium and poppy husk) use is a socio-culturally accepted phenomenon reported in India. However, studies on their profile, quality of life, and addiction severity are limited. OBJECTIVES: The objective of this cross-sectional, observational study was to assess the socio-demographic profile, clinical profile, addiction severity, and quality of life of treatment-seeking natural opiate users. METHOD: Hundred subjects aged 18-65 years using opium or poppy husk seeking outpatient treatment at a tertiary addiction treatment center in India were interviewed to collect information on their socio-demography, natural opiate, and other substance use. Additionally, their addiction severity and quality of life were assessed using Addiction Severity Index-Lite and WHO Quality of Life-Bref instrument, respectively. RESULTS: All subjects were male with a mean age of 44.6 (±11.0) years. Majority (97%) used poppy husk daily orally. Curiosity/experimentation (63%) was the most common reason for starting opiate use. The past month rates of tobacco, alcohol, cannabis, and sedative-hypnotics use was 58%, 33%, 3%, and 12%, respectively. Only 4% injected any opioid. Inability to afford opiates (72%) was the most common reason for seeking treatment. Rates of medical, familial, social, psychological, and legal complications were low, while the WHOQOL-BREF scores fell between 40 and 50 across various domains. Conclusions/Importance: Natural opiate users may constitute distinct subgroup of opioid users with fewer/no complications despite long duration of uninterrupted use. These findings would be important in planning management strategies for people dependent on natural opiates.

Initial treatment dropout in patients with substance use disorders attending a tertiary care de-addiction centre in north India.

BACKGROUND & OBJECTIVES: Dropout from substance use disorders treatment is associated with poor outcomes. Although many factors have been associated with an early dropout of patients, the reasons for dropping out of treatment prematurely remain poorly understood particularly in the Indian context. This study was aimed to study socio-demographic and clinical variables predicting initial dropout of patients attending a tertiary care de-addiction treatment centre in north India. METHODS: Information was extracted from the records of consecutive newly registered patients from January 2011 to December 2014. The patients who did not come for follow up within 30 days of the first contact were defined as initial dropouts. RESULTS: Data of 7991 patients could be retrieved. Majority of the sample consisted of male, married and employed individuals. Of them, 4907 patients (61.3%) were considered initial dropouts. Multivariate analysis revealed that after controlling for other factors, greater age, being employed, lower educational status, lesser duration of substance use, use of alcohol, opiate, tobacco, cannabis or sedative-hypnotic use but the absence of multi-substance use predicted initial drop out. INTERPRETATION & CONCLUSIONS: This study identified some socio-demographic and clinical variables which might predict treatment attrition in substance use disorders. Clinician's awareness towards these factors and tailor-made intervention might improve initial treatment retention. Future research could be directed to find the validity of this assumption.

History of Lifetime suicide attempt in bipolar I disorder: its correlates and effect on illness course.

OBJECTIVES: To identify the prevalence and correlates of bipolar I patients with a lifetime history of suicide attempt. MATERIALS AND METHODS: Bipolar I disorder was diagnosed in 150 patients as per DSM-IV-TR criteria. Their lifetime suicide risk was assessed using the Columbia Suicide Severity Rating Scale. NIMH retrospective Life Chart Methodology was used to chart the illness course. Medication Adherence Rating Scale (MARS) and Pittsburgh Sleep Quality Index (PSQI) were used to assess the recent adherence and subjective sleep quality, respectively. The suicide attempters were compared with non-attempters on individual variables. RESULTS: Around 23% had a positive lifetime history of suicide attempt. They were predominantly female, had an index (first ever) episode of depression, spent more proportion of time being ill, especially in depressive or mixed episode phase. Comorbid substance use disorder along with suicidal attempts was seen only in males. Suicide attempters displayed poor medication adherence attitudes for medications taken during the past week and reported impaired sleep quality for the previous month. CONCLUSIONS: A positive history of lifetime suicide attempt was significantly associated with a worse course of bipolar I disorder. Effective treatment of depressive episodes, addressing non-adherence, substance use and sleep problems can reduce the suicide risk in such patients. Retrospective design of the study and recall bias are some of the limitations.

Intensive Care Unit delirium: A wide gap between actual prevalence and psychiatric referral.

BACKGROUND AND AIMS: The study aimed to assess the rates of delirium in an Intensive Care Unit (ICU) prospectively assessed with a delirium screening instrument and confirmed through psychiatrist evaluation. In addition, the referral rate to psychiatric consultation liaison services from the same ICU was assessed through the rates of psychiatric referral over the previous 10 years. MATERIAL AND METHODS: In the prospective part of the study, consecutive patients aged 16 years or more admitted to the ICU of a tertiary care hospital were assessed daily for delirium using confusion assessment method for the ICU, a validated instrument that can be used for both mechanically ventilated and nonventilated patient by trained heath care personnel. Retrospectively, records of patients referred to psychiatric referral team for delirium from the ICU over the last 10 years were drawn out and the referral rate was calculated. RESULTS: In the prospective study, 109 patients were recruited of which 43 patients remained comatose throughout their ICU stay and could not be assessed for delirium. Of the 66 assessable patients, 45 (68.2% prevalence rate) patients developed delirium. Incidence rate of delirium was 59.6%. In contrast, the retrospective study showed that only 53 cases out of 3094 admissions in ICU over 10 years (1.71%) were referred to psychiatry consultation liaison team for management of delirium. In the prospective study, hypoactive delirium was the most common subtype of delirium. CONCLUSION: There is a mismatch between the incidence and prevalence of delirium in ICU patients prospectively diagnosed with structured, validated instruments and the diagnosis of delirium in cases referred to psychiatry consultation-liaison services.

Relationship between matrix metalloproteinase-9 and oxidative stress in drug-free male schizophrenia: a case control study.

BACKGROUND: Deregulation of synaptic plasticity and oxidative stress are reported to play a crucial role in the pathogenesis of schizophrenia. Matrix metalloproteinase-9 (MMP-9) is an extracellular protease involved in regulation of synaptic plasticity. Malondialdehyde (MDA) is a marker of lipid peroxidation which is elevated in schizophrenia. Earlier studies have reported polymorphism of MMP-9 and its association with schizophrenia. The present study was designed to assess the serum levels of MMP-9, MDA and total antioxidant status (TAS) and their association in schizophrenia. METHODS: A total of 40 cases and 40 controls were included in the study. Serum MMP-9, MDA and TAS were estimated in all the subjects. Disease severity was assessed using Positive and Negative Syndrome Scale (PANSS). RESULTS: MMP-9 and MDA were significantly increased and TAS were significantly reduced in schizophrenia cases compared to controls. MMP-9 was positively correlated with MDA (r=0.353, p=0.025) and negatively correlated with TAS (r=-0.461, p=0.003). TAS was significantly correlated with total (r=0.322, p=0.043) and negative symptom scores (r=0.336, p=0.034). Higher MMP-9 levels were associated with previous exposure to antipsychotics (p=0.032). CONCLUSIONS: MMP-9 and oxidative stress were increased and correlate well with each other in schizophrenia cases. Though total oxidant status showed positive association with disease severity, MMP-9 and MDA were not associated with the severity of the disease.

What happens to episode duration and cycle length over the course of bipolar disorder?

OBJECTIVES: Published scientific literature on cycle acceleration over the course of bipolar disorder has been equivocal. The present analysis aimed to find whether episode duration and cycle lengths become shorter over the course of bipolar disorder with predominantly manic polarity. METHODS: The present study comprised 150 patients diagnosed with bipolar I disorder using SCID-I for DSM-IV TR. The course of illness was charted according to the NIMH Life Chart Methodology - Clinician Retrospective Chart (NIMH - LCM CRC). Spearman correlation was used to assess the relationship of episode duration and cycle length with the number of episodes. RESULTS: The mean age of the sample was 37.8 years and the average duration of illness was 13.4 years. Unipolar mania comprised 52.7% of the sample. The episode duration and the cycle length decreased with increasing number of episodes (r=-0.245, p<0.001 & r=-0.299, p<0.001 respectively). CONCLUSION: The present study suggests that over the course of bipolar I disorder, cycle length and episode duration become shorter.

Barriers to healthcare seeking among medical students: a cross sectional study from South India.

OBJECTIVE: To determine the barriers to seeking help from healthcare services reported by medical students at an Indian medical school, and to compare the barriers for using physical health services with those for using mental health services. METHODS: In 2014, we invited all medical students across the nine semesters of training at a government medical college in Puducherry, India, to complete a 28 item questionnaire about perceived barriers to seeking healthcare services. The questionnaire enquired about barriers to using physical and mental healthcare services separately. RESULTS: Completed responses were available from 461 of 509 students (response rate 90.6%). Stigma, confidentiality issues, lack of awareness about where to seek help and fear of unwanted intervention were more commonly reported for mental healthcare seeking (OR 4.21, 4.01, 3.19 and 2.43, respectively), while issues relating to cost, lack of time and fear of side effects were observed less frequently (OR 0.45, 0.46 and 0.57, respectively) compared with physical healthcare seeking. In comparison with physical health, students were more indifferent to their mental health issues and preferred self-diagnosis and informal consultations over formal documented care. CONCLUSIONS: Barriers to seeking healthcare services differ for mental and physical health issues. Many system based barriers such as stigma, confidentiality issues and poor awareness of service location were reported by students. Institutional programmes should use this information for improving the usage, satisfaction and effectiveness of healthcare delivery systems for medical students.

How Do Indian Substance Users Perceive Stigma Towards Substance Use Vis-A-Vis Their Family Members?

Perceived stigma towards substance use may determine family members' willingness to help in the treatment process of a substance user. This study aimed to compare the perceived stigma towards substance use among Indian substance users and their family members. Fifty dyads each of alcohol- and opioid-dependent men and their family members were recruited through purposive sampling. Perceived stigma was assessed using Perceived Stigma of Substance Abuse Scale (PSAS) in both the dependent men and the family members. PSAS scores of patients and the family members correlated with each other in both the alcohol- and opioid-dependent groups. Being currently employed predicted higher PSAS scores among patients, while being unmarried predicted higher PSAS scores among family members.