Search

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.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 of10.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.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.

Objective Priming stimulation, which involves high-frequency repetitive transcranial magnetic stimulation (rTMS) followed by low-frequency, has been shown to enhance neural response and is one of the novel paradigms found beneficial in adult patients with depression and has not been studied in late-life depression (LLD). This study aims to compare the effect of adjunctive priming vis-a-vis no priming rTMS over right dorso-lateral prefrontal cortex (DLPFC), on treatment of LLD. Methods This trial is registered in Clinical Trial Registry-India (CTRI) on www.ctri.nic.in. CTRI registration number: CTRI/2020/08/027230. Forty patients of LLD who are symptomatic after an adequate antidepressant trial will be randomized into 2 groups (active priming and sham priming rTMS); each receiving 10 sessions of rTMS over 2 weeks. Patients will remain blind to treatment allocation. Assessments will be done using Hamilton rating scale for depression, Geriatric Depression Scale, Hamilton rating scale for Anxiety, Somatic Symptom Severity Scale 8, Hindi Mental Status Examination, and Clinical Global Impression scale at baseline, week 1, 2, and 4. Side effect checklist will be applied after each session in both groups and at the end of 4 weeks. Result Data will be analyzed using statistical software Statistical Package for Social Sciences. Both the groups (active and sham groups) will be compared at the four given timepoints. Also, the baseline characteristics will be compared with the 3 follow-up points for any change. Conclusion The findings of the study will give an insight to the possible role of priming to augment the effect of low-frequency rTMS in LLD.

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.

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 =

Contribution to KGMU Journal of Physiology 2020. ISSN 2320-2777

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.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.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.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.

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.

The population of older adults is increasing rapidly due to global population aging in the background of increasing life expectancy and reducing mortality rate. This phenomenon is projected to be more rapid in developing countries like India in the next few decades. The increase in the population of older adults is also associated with increasing prevalence of chronic noncommunicable diseases including dementia. Dementia is a condition characterized by progressive cognitive decline with significant impairment in the ability to do functional activities independently. Dementia has multiple causes that contribute to the existence of several subtypes with varying clinical presentation and outcome. Alzheimer's disease (AD) is the most common subtype of dementia (50%–60%). Vascular dementia (VD), diffuse lewy body dementia (DLBD), frontotemporal dementia (FTD), and mixed dementia are some of the other important types of dementia. The recent revision of classification – Diagnostic Statistical Manual-V refers dementia as major neurocognitive disorder. Dementia is emerging as a major public health priority due to increasing prevalence, increased risk for mortality, high level of disability, caregiver burden, and cost burden. The current estimates of global prevalence of dementia are nearly 47 million with nearly 4.6 million patients with dementia in India. The incidence rate of dementia is also alarming with one new case estimated to occur every 3 seconds. The global prevalence of dementia is estimated to increase to 131 million in the year 2050. The global economic cost for care of persons with dementia is estimated to increase from 818 billion USD to 2 Trillion USD by the year 2050. Behavioral and psychological symptoms such as delusions, hallucinations, depression, and agitation are common in persons with dementia. They contribute to significant distress in patients as well as caregivers. They are also an important reason for institutionalization. The major concern in the care of persons with dementia is the lack of effective disease modifying drugs and modest efficacy of currently available symptomatic drug treatments. Considering the low awareness about dementia in India, there is huge treatment gap for even the diagnosis and pharmacological treatment of persons with dementia. The important focus of treatment in dementia is the improvement of the quality of life and well-being of patients as well as the caregivers. Psychosocial interventions such as cognitive therapy and family interventions have been evaluated in persons with dementia and their caregivers. However, there are important challenges in improving the access for psychosocial interventions for persons with dementia. This clinical guideline will discuss about the potential role for these psychosocial interventions in the management of persons with dementia particularly in Indian context.

IntroductionIn healthy volunteers, light acting through serotonin pathways, decreases the threshold for sweet, but not salt taste; similar to SSRI paroxetine. In depressive disorders, there is deficiency of serotonin throughput, which is remedied by SSRI medications, and results in improvement in symptoms of depression. Thus, we report on taste thresholds before and after SSRI treatment.ObjectivesTo study the variation in thresholds for sweet with SSRI treatment in depressed patients in short- and long-term.AimsTo compare the threshold for sweet (test) and salt (control) after 1 and 4 weeks of SSRI escitalopram therapy in depressed patients.MethodsThe project was approved by the institutional ethics committee. Following informed consent, depressed patients were initiated on escitalopram 10 mg/d (increased to 15 or 20 mg, if required after 1 week,). Taste recognition threshold, intensity and pleasantness were measured for sweet and salt. Each tastant was made −1 to −3 (100 mM–1 mM). Regional recognition thresholds were determined at the tip of the tongue using a cotton bud well soaked in the tastant.ResultsThree males and 4 females of mean ages 39.1 years completed the study. There was significant shift to the left for sweet thresholds between days 0 and 7, and 7 and 28 [F(Dfn, Dfd) = 9.242 (4.162) P < 0.0001]. A similar shift to the left was seen for salt but day 7 only [F(Dfn, Dfd) = 6.213 (4.162)].ConclusionThe increase in serotonin throughput as envisaged through SSRI treatment was paralleled by decrease in sweet thresholds.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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.

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.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.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.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 ).

BackgroundDiagnosis of Alzheimer disease is mainly clinical, based on longitudinal history and clinical criteria due to lack of specific biochemical tests and neuroimaging studies. Deficient central cholinergic activity of AD pathology is said to be reflected as decreased peripheral cholinergic activity. Assessing peripheral cholinergic function with pupillometer for diagnostic and prognostic purpose may be beneficial, as it may be a non-invasive, acceptable, and easily administered diagnostic tool if proven so.MethodThis is a single point case control pilot study with sample size of 45 (25 AD patient and 20 controls). CAMDEX-R based interview, HMSE, and DSM-IV criteria were used for detailed assessment and diagnosis. The pupillometric parameters (Horizontal and vertical diameters of pupil) were measured by Oasis Colvard pupillometer (SKU-0401A) under three conditions namely after 5 minute of dark adaptation in dark room (PD-5min-DA i.e. Baseline PD); after 5 minutes (PD-5min-T) and 15 minutes (PD-15min-T) of instillation of 2–3 drops of 1.0% Tropicamide.ResultsThere was no difference in baseline pupil diameter (horizontal + vertical) of AD patients and age matched healthy controls. 1% tropicamide induced significant increment in pupil diameters from baseline to after 5 (‘PD-5min-T’) and 15 minutes (‘PD-15min-T’) of its instillation in both AD patients and age matched healthy controls. But tropicamide induced increment in pupil diameters were approximately equal in cases and controls.ConclusionThe study did not find the role of 1% tropicamide induced pupillary hypersensitivity in AD patients for diagnostic purpose.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Background: A number of studies have established the entity of seasonal affective disorder (SAD) and delineated the presence of atypical depressive features of carbohydrate craving, hyperphagia and hypersomnia. Most literature has emanated from research carried out in temperate climates, and only few reports are available from tropical countries, especially India. Methods: Consecutive patients with recurrent mood disorder (who had at least 2 episodes of depression in the past) comprised the study sample. The diagnosis of mood disorder was made according to DSM-III-R criteria. The sample was divided into two groups – seasonal and non-seasonal according to the DSM-III-R criteria of seasonal pattern. The depressed patients were rated on SADD and HDRS, and manic patients on BRMRS. Results: Eighteen of 93 patients fulfilled the criteria of seasonal pattern; 7 of these seasonal patients, and 25 of the non-seasonal patients were currently in depressive phase. Males dominated the sample in both the groups. The seasonal and non-seasonal groups as regards symptomatology, differed only on a few items – decreased libido on SADD, and suicidal ideation and helplessness on HDRS. Atypical vegetative features were not seen in any of the seasonal patients. Conclusions: SAD is seen at lower latitudes also, although atypical vegetative features are not a prominent part of the symptomatology. Limitations: The study sampled was obtained from a very select population, and thus does not indicate the prevalence of SAD in India. Secondly, the small sample size precludes any categorical comments of the symptomatology. Moreover, winter and summer depressives were considered as one group. Clinical relevance : Emphasising the presence of SAD in a tropical country where there is relatively less variation in daylight periods, this report forms a base for future studies. It also raises the question of the role of variations in daylight in the aetiology SAD.

Delirium is defined by the acute onset of fluctuating cognitive impairment and a disturbance of consciousness with reduced ability to attend. It may occur at any age but is more common in older adults. By virtue of working in the psychogeriatric hospital (Department of Geriatric Mental Health, King George’s Medical University, Lucknow, India), authors experienced that many elderly patients with psychiatric illness develops delirium because of various reasons. Subsequently, we observed that psychiatric manifestations of the patients improved significantly following recovery from delirium. A series of such four cases (case 1- Depression with psychotic features, 2- Manic episode, 3- Bipolar affective disorder current episode mania and 4- Depressive episode) later developed delirium has been presented and discussed in this paper. ICD-10 criteria were used for the diagnosis of delirium and psychiatric illnesses. Average stay of these patients in the hospital was 10 days. We found that signs and symptoms of these psychiatric disorders disappeared almost completely following the recovery from delirium. Therefore, it can be assumed that delirium potentially acts similar to ECT. By reporting such case we open a new dimension of research for effective treatment of the psychiatric patients. Inducing delirium in a patient is unethical but understanding pathophysiology behind it will certainly open the door for better cure of the ailing psychiatric patients.

BackgroundEarly 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.AimsTo 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.MethodA systematic search identified articles and these were included in the review if they addressed one of the above aspects of jitteriness/anxiety syndrome.ResultsOf 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.ConclusionsJitteriness/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.

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.

Byline: Shrikant. Srivastava, Radhey. Gangwar, Ambrish. Kumar Sir, Response rates to first line antidepressant therapy are abysmally low, and more so in older adults. Ketamine has been used successfully in treatment-resistant depression (TRD), and in nongeriatric population, with response rates at 24 and 72 h postinfusion being 25−85% and 14−72%, respectively.[sup][1] The postulated mechanism of action is through antagonism of N-methyl-D-aspartate receptors.[sup][2] A 65-year-old retired civil servant, living with her husband had fourth episode of depressive illness. In the last 3 years, the illness showed increasing resistance to antidepressant medication(s) with each additional episode. The first episode remitted with escitalopram (10 mg/day), the second episode required higher dosage of escitalopram (40 mg/day), and later, augmentation with amisulpride 25 mg/day, and the third episode remitted with duloxetine (up to 60 mg/day) (as she had relapsed while on escitalopram) and amisulpride 100 mg/day. In the Inter-episode period, the patient had attended all follow-up appointments and continued with prescribed medication. In this episode, she had failed treatment with duloxetine + amisulpride, agomelatine, and agomelatine + amisulpride, respectively. Informed consent was obtained from the patient. Ketamine infusion (0.5 mg/kg diluted in 100 ml of normal saline) was given over 40 min, under the supervision of consultant anesthetist (RSG). Ratings of mood (Hamilton rating scale for depression [HAMD])[sup][3] and side effects (Clinician Administered Dissociative States Scale)[sup][4] were undertaken on morning of the infusion, and 1, 2, and 4 h following infusions, and on in between days of the infusion [labelled as postinfusion days in Table 1]. Four days after the 4[sup]th infusion (HAMD = 10), the patient feeling very much improved subjectively, the ketamine infusions were discontinued, with the provision that further infusions may be required if the depressive symptoms recurred. Agomelatine 50 mg/day was continued through the infusion period and in the follow-up phase.{Table 1} Remission (HAMD The side effects reported with the infusions were − alteration of passage of time (infusion 3, hours 1 and 2) and mild gaps in memory (infusion 4, hour 2). …

Although alcohol has been recognized as an agent of abuse since the 17th century, the disease model was accepted only in the last century. Alcoholism is defined as a chronic and progressive disease characterized by loss of control over the use of alcohol with subsequent social, legal, psychological and ethical consequences. Recently, monoamines were shown to have a predominant role in the etiology of alcoholism. Dopamine has been implicated by virtue of its actions on the reward center. Endogenous opioids which lessen stress and produce euphoria, are released upon alcohol intake, whereas increased serotonin facilitates tolerance and thereby fosters increased alcohol consumption. Alcohol has facilitative effects on inhibitory action of GABA, while the stimulatory effects of glutamate are decreased. Drugs used for treatment of alcohol dependence can be broadly classified into 4 groups: sensitizing drugs, opioid antagonists, drugs acting on serotonergic systems and acamprosate. Disulfiram has been shown to be most effective for patients who believe in its efficacy and remain compliant with the treatment. The opioid antagonist naltrexone lowers relapse rate, reduces drinking days and prolongs periods of abstinence, while serotonin reuptake inhibitors and serotonin antagonists at best have equivocal efficacy. Acamprosate restores the normal activity of glutamate and GABA systems. The treatment of alcoholism should not be restricted to pharmacotherapy alone but should also be supplemented with interventions addressing the psychological, medical and social needs of patients.

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 (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.