The definition of treatment resistance in anxiety disorders: a Delphi method-based consensus guideline.

Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials of innovative therapeutic interventions. However, an explicit definition of treatment-resistant anxiety disorders (TR-AD) informing such trials is currently lacking. We used a Delphi method-based consensus approach to provide internationally agreed, consistent and clinically useful operational criteria for TR-AD in adults. Following a summary of the current state of knowledge based on international guidelines and an available systematic review, a survey of free-text responses to a 29-item questionnaire on relevant aspects of TR-AD, and an online consensus meeting, a panel of 36 multidisciplinary international experts and stakeholders voted anonymously on written statements in three survey rounds. Consensus was defined as ≥75% of the panel agreeing with a statement. The panel agreed on a set of 14 recommendations for the definition of TR-AD, providing detailed operational criteria for resistance to pharmacological and/or psychotherapeutic treatment, as well as a potential staging model. The panel also evaluated further aspects regarding epidemiological subgroups, comorbidities and biographical factors, the terminology of TR-AD vs. "difficult-to-treat" anxiety disorders, preferences and attitudes of persons with these disorders, and future research directions. This Delphi method-based consensus on operational criteria for TR-AD is expected to serve as a systematic, consistent and practical clinical guideline to aid in designing future mechanistic studies and facilitate clinical trials for regulatory purposes. This effort could ultimately lead to the development of more effective evidence-based stepped-care treatment algorithms for patients with anxiety disorders.

Investigating the impact of adjunctive priming repetitive transcranial magnetic stimulation in late-life depression: a pilot single-blind randomized control study.

BACKGROUND: Conventional treatment methods have limited effectiveness in addressing late-life depression (LLD) that does not respond well. While a new approach called priming repetitive transcranial magnetic stimulation (rTMS) has shown promise in treating depression in adults, its effectiveness in LLD has not been explored. This study aimed to investigate the impact of priming rTMS on LLD. METHODS: This study investigated the effectiveness of priming rTMS in 31 patients with LLD who did not improve after an adequate trial of antidepressants. Patients were randomly assigned to receive either active priming rTMS or sham priming rTMS. Active priming rTMS was delivered over the right dorsolateral prefrontal cortex for 10 sessions, lasting 31 minutes each, over a period of 2 weeks. RESULTS: The group receiving active priming rTMS demonstrated greater improvements in scores on the Hamilton Rating Scale for Depression (p < 0.037; partial η2 0.141) and the Geriatric Depression Rating Scale (p < 0.045; partial η2 0.131) compared to the sham priming group, with a mild effect size. At the end of the second and fourth weeks, the priming rTMS group achieved a response rate of 50%, while the sham priming group had response rates of 26.7% and 6.7%, respectively. No adverse effects requiring intervention were observed. CONCLUSION: Priming rTMS is well-tolerated for the treatment of LLD and not only reduces the severity of depression but also maintains the achieved response over time.

Indian Psychiatric Society multicentre study: Diagnostic patterns, comorbidity and prescription practices for patients with Dementia.

Background: There are more than 5 million people with dementia in India. Multicentre studies looking at details of treatment for people with dementia In India are lacking. Clinical audit is a quality improvement process which aims to systematically assess, evaluate, and improve patient care. Evaluating current practice is the key to a clinical audit cycle. Aim: This study aimed to assess the diagnostic patterns and prescribing practices of psychiatrists for patients with dementia in India. Method: A retrospective case file study was conducted across several centers in India. Results: Information from the case records of 586 patients with dementia was obtained. Mean age of the patients was 71.14 years (standard deviation = 9.42). Three hundred twenty one (54.8%) were men. Alzheimer's disease (349; 59.6%) was the most frequent diagnosis followed by vascular dementia (117; 20%). Three hundred fifty five (60.6%) patients had medical disorders and 47.4% patients were taking medications for their medical conditions. Eighty one (69.2%) patients with vascular dementia had cardiovascular problems. Majority of the patients (524; 89.4%) were on medications for dementia. Most frequently prescribed treatment was Donepezil (230; 39.2%) followed by Donepezil-Memantine combination (225; 38.4%). Overall, 380 (64.8%) patients were on antipsychotics. Quetiapine (213, 36.3%) was the most frequently used antipsychotic. Overall, 113 (19.3%) patients were on antidepressants, 80 (13.7%) patients were on sedatives/hypnotics, and 16 (2.7%) patients were on mood stabilizers. Three hundred nineteen (55.4%) patients and caregivers of 374 (65%) patients were receiving psychosocial interventions. Conclusions: Diagnostic and prescription patterns in dementia which emerged from this study are comparable to other studies both nationally and internationally. Comparing current practices at individual and national levels against accepted guidelines, obtaining feedback, identifying gaps and instituting remedial measures help to improve the standard of care provided.

Aripiprazole as First-Line Therapy for Late-Life Depression: A Case Note Review.

BACKGROUND: Aripiprazole, structurally considered a third-generation antipsychotic agent, is an effective adjuvant strategy for managing treatment-resistant depression. It has been used successfully as an add-on agent in late-life depression (LLD), but there are no controlled trials on its use as first-line therapy, either alone or in combination with an antidepressant. METHODS: This is a case note review of aripiprazole prescribed to outpatients with LLD as a first-line therapy either in combination with an antidepressant or as a monotherapy. The local ethics committee approved the audit. Case notes of subjects with Hamilton Rating Scale for Depression scores of ≥11 and with at least 1 follow-up visit were included in the review. Remission was defined as the first occurrence of achieving a Hamilton Rating Scale for Depression score of <10. RESULTS: Case notes of 54 subjects (mean age, 68.6 ± 6.9 years) were included, 52 of whom had unipolar depression. Aripiprazole alone was prescribed in 21 subjects, and with an antidepressant in the remaining subjects. The overall remission rate was 59% over 21 weeks, and in the remitted subjects (n = 32), the cumulative remission rate increased from 22% at week 2 to 82% at week 10. No subject discontinued treatment because of poor tolerability or serious adverse events. CONCLUSIONS: Aripiprazole was found to be an effective first-line antidepressant in LLD. The remission rates in the present study were considerably higher than the published literature on antidepressant monotherapy in fresh episodes of LLD. This warrants controlled trials of aripiprazole as a first-line antidepressant for this disease entity.

Delirium Assessment and Management in Geriatric Psychiatry under Prevailing Indian Laws (MHCA 2017).

The Indian Mental Health Care Act of 2017 (the Act) focuses on the human rights of persons with mental illness. It is based on the individual's dignity, autonomy, and independence with a client-centered approach. Delirium is frequently seen in the hospitalized geriatric population, more commonly in medical and surgical wards, and much less frequently in psychiatry wards. Delirium is covered under the Act as a "substantial disturbance of thinking, mood, perception, orientation or memory that grossly impairs judgment, behavior, (and) capacity to recognize reality or ability to meet the ordinary demands of life." The Act provides provisions for capacity assessment, emergency treatment, supported admission, advance directive, and the role of nominated representative in such cases.

Metals toxicity and its correlation with the gene expression in Alzheimer's disease.

Alzheimer's disease is a common neurodegenerative disease in the elderly population and a leading cause of dementia. Genetics and environmental risk factors were considered to play a major role in the onset of the disease. This study aimed to examine the correlation between different metals levels and the gene expression in Alzheimer's patients with age-matched control subjects. Non- essential metals were measured in the whole blood due to its higher concentration in red blood corpuscles (RBCs) and essential biometals in the serum samples of Alzheimer's disease (AD) by using Inductively coupled plasma optical emission spectroscopy (ICP-OES) that allows the analysis and detection of the different elements at low levels. Gene expression level was performed by quantitative real-time PCR (qRT-PCR). In this study, the levels of Lead and Arsenic metals were not detected in the AD patient samples. Cadmium, Mercury, and Aluminum were found higher in cases as compared to controls with 0.009240 ± 0.0007707 (P = < 0.0001), 0.02332 ± 0.001041 (P = < 0.0001), and 0.09222 ± 0.02804 (P = 0.0087) respectively. Essential biometal like copper was higher 0.1274 ± 0.02453 (P = 0.0254) in cases, while iron 0.1117 ± 0.009599 (P = 0.0304) and zinc 0.03800 ± 0.003462 mg/L were found significantly lower as compared to controls. All targeted genes such as APP, PSEN1, PSEN2, and APOE4 were found up-regulated in AD patients. We concluded that there was no significant correlation between metals dyshomeostasis and gene expressions in this study.

Effect of psychoeducation on short-term outcome in patients with late life depression: A randomized control trial - Protocol.

BACKGROUND: This is the PhD thesis protocol of an ongoing study entitled 'Effect of Psychoeducation on short- term outcome in patients with Late Life Depression: A Randomized Control Trial'. Psychoeducation is a proof-based therapeutic intervention for patients and their caretakers/family members that provides plenty of information and support for better understanding and coping up with the illness, which is being diagnosed. AIM: The aim is to examine the effect of psychoeducation on short- term outcome in patients with late life depression. HYPOTHESIS: The hypothesis is that psychoeducation will improve outcome in patients with late life depression at 4 weeks. The sample size is 154. MATERIAL AND METHODS: The methodology is that patients aged 60 years and above coming to Out Patient Department (OPD) of the Department of Geriatric Mental Health, King George's Medical University and having the first episode of depression, which has been clinically diagnosed, will be taken. Then, Mini International Neuropsychiatric Interview (MINI) 6.0.0 will be applied for the confirmation of diagnosis. After confirmation, Hindi Mental Status Examination (HMSE) will be done to know the cognitive status, those scoring 24 and above on HMSE will be included in the study. The included patients will be evaluated on Hamilton Depression Rating Scale (HAM-D), Geriatric Depression Scale (GDS) and Knowledge Attitude Experience (KAE) Questionnaire. Next, the patients will be randomized in case group and control group. Case group will be given intervention of 'psychoeducation' through a video, and control group will be given 'placebo' through a video. For both the groups, the first follow up termed as 'booster session' will be at 2 weeks +/- 4 days from the baseline and second follow up will be at 4 weeks +/- 4 days from the baseline. STATISTICAL ANALYSIS: Data will be recorded on the spreadsheet and the results will be analyzed using the statistical software.

Sialic acid associated with oxidative stress and total antioxidant capacity (TAC) expression level as a predictive indicator in moderate to severe Alzheimer's disease.

BACKGROUND: Several studies have shown many risk factors associated with disease onset, but the sialic acid association with oxidative stress biomarkers may a key factor in the pathogenesis of Alzheimer's disease (AD). We aim to find out the most specific biomarker from the peripheral blood samples in moderate to severe Alzheimer's patients. METHODS: This study examined the level of sialic acid associated with oxidative stress biomarkers and total antioxidant capacity level (TAC) in the plasma samples. Different parameters of Oxidative stress and Total antioxidant capacity by the immunoassay method have been examined in AD patients as compared to controls. The Catalase (CAT), Superoxide dismutase (SOD), Lipid peroxidation (LPO), Glutathione peroxidase (GPx), Total Glutathione (GSH), and Protein carbonyl group levels were estimated in this study. RESULTS: Increased level of sialic acid is found associated with a higher level of reactive oxygen species parameters in the patients. The antioxidant parameter levels have been found significantly lower in AD, while Protein carbonyl group and lipid peroxidation were increased in cases as compared to controls with the area under the curve (AUC) 0.816, p < 0.0001 and 0.754, p < 0.0001. The Protein carbonyl group, Total antioxidant capacity (TAC), and Sigma-Aldrich TAC levels were higher in females as compared to males in AD patients. CONCLUSION: During AD pathology, sialic acid, protein carbonyl, and lipid peroxidation were found as the more sensitive marker that may be used as a diagnostic and prognostic biomarker.

A pilot study of MD (psychiatry) theses-based research.

INTRODUCTION: Undertaking a research project is mandatory for MD Psychiatry trainees. The present study was undertaken to assess the type of research activity being undertaken as part of MD Psychiatry dissertation, and its contribution to national and international literature. MATERIALS AND METHODS: Three medical colleges supplied the data about the topic, names of the supervisor and the candidate, collaboration, funding accrued, and publication details of MD-based research carried out between years 2000 and 2010 inclusive; 95 records were collected for the final analysis. The details of the publications provided were cross-checked on the internet, which would have taken care of missed publications as well. RESULTS: Most studies were single-point assessment clinical studies. Only 2 studies had been funded, 11 had collaboration with other departments within the same institute, and 5 had inter-institute collaborations. Majority of the studies were not published. Only 30 were published as full paper and 9 as abstracts. Of these 30 full publications, only 3 were published in journals having JCI impact factor values (1.4, 1.3, and 1.4, respectively). CONCLUSIONS: The main finding of this pilot study was that MD-based research has low contribution to the national and international literature, and those articles which are published are in low impact journals. Suggestions for modifying this state of affairs are discussed.

Single bright light exposure decreases sweet taste threshold in healthy volunteers.

INTRODUCTION: Bright light exposure can alter circulating serotonin levels, and alteration of available serotonin by acute selective serotonin reuptake inhibition significantly lowers sweet but not salt taste recognition thresholds. We tested the hypothesis that bright light exposure would increase sweet but not salt taste sensitivity in healthy adults. METHODS: Fourteen healthy volunteers were exposed to bright (10,000 lux) and dim (<20 lux) light for 30 min each, in counterbalanced order. Measures of taste perception (salt and sweet) and mood were determined at baseline, and before and after each light exposure period. RESULTS: Recognition thresholds for sucrose were significantly lower after bright but not dim light exposure. Thresholds for salt were unaffected by either condition. There were no significant changes in taste acuity, intensity or pleasantness for both the taste modalities and on visual analogue scales (VASs) for mood, anxiety, sleepiness and alertness, under either light condition. CONCLUSION: Brief bright light exposure reduces sweet but not salt taste recognition thresholds in healthy humans.

Recollection deficiencies in patients with major depressive disorder.

Neuropsychological research suggests that recognition memory (RM) and recall memory are impaired in patients with a major depressive disorder or a dysphoric mood state. This study examines the proposal that abnormalities in recollection (a form of recall) result from a breakdown in frontal strategic memory processes involved in encoding and retrieval, and executive functions linked to reality monitoring, planning, problem-solving, reasoning and decision-making. We investigated two predictions arising from this theory. Firstly, patients diagnosed with a major depressive disorder (MDD) will display a dissociation between (deficient) recollection and (preserved) familiarity. Secondly, if recollection impairments are indicative of a breakdown in prefrontal strategic memory processes which are dependent, at least in part, on executive processes, then an explicit correlational approach predicts that recollection will be positively associated with the severity of executive dysfunction in MDD patients. The remember/know paradigm was used to investigate RM for words and neutral faces in 16 MDD patients and 16 healthy volunteers, matched for age, gender and estimates of premorbid IQ. Measures of executive function included working memory, reasoning and decision-making. Applying the Dual Process Signal Detection interpretation of the remember/know data, the MDD group displayed significant impairments in RM and recollection rates for both verbal and neutral facial memoranda. In contrast, familiarity-aware rates were preserved. There was no evidence of executive dysfunction in the patient group, and little evidence that recollection rates correlated with executive function. Furthermore, a single process signal detection approach suggested that the MDD patients displayed a reduction in sensitivity for RM and remember rates but not know responses. The criteria for detecting studied from unstudied items, and remembering from knowing, were the same in both patient and healthy control groups. Taken together, these findings are consistent with the view that MDD is marked by a decline in RM, which is underpinned by an impairment in recollection rather than familiarity processes. The extent to which the recollection deficiencies arise from disruption of strategic memory and executive processes requires further investigation.

Antidepressant-induced jitteriness/anxiety syndrome: systematic review.

BACKGROUND: Early worsening of anxiety, agitation and irritability are thought to be common among people commencing antidepressants, especially for anxiety disorders. This phenomenon, which may be termed jitteriness/anxiety syndrome, is cited as an explanation for early treatment failure and caution in using selective serotonin reuptake inhibitors (SSRIs). However, we believe that it is inconsistently defined and that robust evidence to support the phenomenon is lacking. AIMS: To review systematically all evidence relating to jitteriness/anxiety syndrome to identify: constituent symptoms; medications implicated; disorders in which it was reported; incidence; time course; management strategies; relationship of this syndrome to therapeutic response; distinction between syndrome and akathisia; relationship between syndrome and suicide; and genetic predispositions. METHOD: A systematic search identified articles and these were included in the review if they addressed one of the above aspects of jitteriness/anxiety syndrome. RESULTS: Of 245 articles identified, 107 articles were included for review. No validated rating scales for jitteriness/anxiety syndrome were identified. There was no robust evidence that the incidence differed between SSRIs and tricyclic antidepressants, or that there was a higher incidence in anxiety disorders. Published incidence rates varied widely from 4 to 65% of people commencing antidepressant treatment. Common treatment strategies for this syndrome included a slower titration of antidepressant and the addition of benzodiazepines. Conclusive evidence for the efficacy of these strategies is lacking. There was conflicting and inconclusive evidence as to whether the emergence of this syndrome had a predictive value on the response to treatment. It appears to be a separate syndrome from akathisia, but evidence for this assertion was limited. The effect of jitteriness/anxiety syndrome on suicide rates has not been evaluated. Three studies examined genetic variations and side-effects from treatment, but none was specifically designed to assess jitteriness/anxiety syndrome. CONCLUSIONS: Jitteriness/anxiety syndrome remains poorly characterised. Despite this, clinicians' perception of this syndrome influences prescribing and it is cited to support postulated mechanisms of drug action. We recommend systematised evaluation of side-effects at earlier time points in antidepressant trials to further elucidate this clinically important syndrome.

Auditory recognition memory, conscious recollection, and executive function in patients with schizophrenia.

BACKGROUND: Dual-process models propose that recognition memory (RM) involves two processes: conscious recollection and familiarity-aware memory. Studies investigating RM in schizophrenia report a selective deficit in conscious recollection and intact levels of familiarity-driven RM for stimuli presented in the visual and olfactory domains. It has been suggested that abnormalities in conscious recollection result from a breakdown in frontal strategic memory processes involved in encoding and retrieval and executive functions linked to reality monitoring and decision making. We investigated three predictions arising from these proposals. Firstly, if conscious recollection abnormalities arise from a central impairment, then these abnormalities should not be domain specific. Secondly, if the deficits in conscious recollection arise from a breakdown in executive processes, deficiencies should be correlated with executive dysfunction. Finally, the conscious recollection deficiencies are likely to be more severe in schizophrenia, a condition associated with marked executive dysfunction relative to Major Depressive Disorder, Recurrent (MDDR), in which executive dysfunction is less marked. METHODS: The remember/know paradigm was used to investigate RM for voices in three groups: patients with schizophrenia (n = 14), patients with MDDR (n = 16), and normal controls (n = 16). Executive function was assessed using the Wisconsin Card Sorting Task. RESULTS: Patients with schizophrenia made significantly fewer remember responses than normal controls (p < 0.01), despite normal levels of discrimination and familiarity-driven auditory RM. Patients with MDDR did not differ significantly from either normal controls or patients with schizophrenia. Executive dysfunction was limited to the schizophrenia group and was not correlated with conscious recollection deficiencies. CONCLUSIONS: Patients with schizophrenia exhibit a deficit in conscious recollection for auditory RM of voices. These findings, when considered alongside remember/know data collected from the same set of patients for olfactory and visual RM, support proposals that abnormalities in conscious recollection stem from a breakdown in central rather than domain-specific processes.

A three-year naturalistic follow-up of patients receiving clozapine: Report from India.

INTRODUCTION: Clozapine is a first-line drug for treatment-resistant schizophrenia, but studies dealing with long-term outcome are lacking, so we decided to carry out such a study. METHODS: Patients with treatment-resistant schizophrenia who were recruited in an open-label study three years ago were re-evaluated using the same parameters: BPRS, PANSS and a side-effect rating checklist. RESULTS: Nineteen out of 25 patients who participated in the initial study were available for re-evaluation. Two patients had changed to conventional neuroleptic medication, and were excluded from the study. A significant reduction in psychopathology was observed in 85% of patients. An improvement in social functioning was evident, with seven patients pursuing a career independently, and another six working with their family members since being started on clozapine. All the patients were on clozapine monotherapy, and the average daily dose was 248.21 mg. No patient required hospitalization and there was no incidence of granulocytopenia. CONCLUSIONS: A significant improvement in the psychopathology and social functioning of patients was observed with much lower doses of clozapine than has been reported elsewhere. The doses used for maintenance were lower than those used in the acute phase of treatment. (Int J Psych Clin Pract 2002; 6: 167-171 ).