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Ravi Anand

Publications and source records attributed to Ravi Anand.

15 recordsLinked to original sources
PubMed2004

The international suicide prevention trial (interSePT): rationale and design of a trial comparing the relative ability of clozapine and olanzapine to reduce suicidal behavior in schizophrenia and schizoaffective patients.

Suicidal behavior in patients with psychotic disorders represents a seriously undertreated life-threatening condition. The International Suicide Prevention Trial (InterSePT) is the first large-scale, prospective study designed to evaluate the potential of antipsychotic medications to reduce suicidal behaviors in patients with schizophrenia or schizoaffective disorder who are known to be at high risk for suicide. The unique challenges to study design and the solutions identified for the InterSePT study are described. These challenges included defining suicidal behavior in patients with psychosis, endpoint selection, determination of analytic strategy, and development of scales to assess suicidal behavior. Given the life-threatening nature of suicidal behavior, ethical considerations required that the design minimize suicide attempts and deaths. While the study focused primarily on treatment of suicide, opportunities were used to collect data in related areas of interest, including suicide risk factors, other efficacy measures (e.g., Positive and Negative Syndrome Scale, Covi Anxiety Scale, Calgary Depression Scale), adverse events, pharmacoeconomics, and pharmacogenetics. Because of the complexity of the design issues, a steering committee, suicide monitoring board, and publication committee were established to assist with their management.

Adolescent↗
PubMed2003

The InterSePT scale for suicidal thinking reliability and validity.

BACKGROUND: The InterSePT Scale for Suicidal Thinking (ISST) is a 12-item instrument for the assessment of current suicidal ideation in patients with schizophrenia and schizoaffective disorders. We report the psychometric characteristics of this new scale based on two studies. METHOD: In Study 1, 22 inpatients with schizophrenia and schizoaffective disorders, who had recently attempted suicide or engaged in suicidal ideation, were rated by three trained independent raters to examine interrater reliability. In Study 2, a total of 980 patients with schizophrenia or schizoaffective disorder with a history of suicidal ideation in the past 36 months were enrolled in a 2-year industry-sponsored suicide prevention study. At baseline, these patients were administered the ISST and the Clinical Global Impression Scale for Severity of Suicidality (CGI-SS) by the Principal Investigator (PI) and by a blinded rater (BR), who also administered the Positive and Negative Symptom Scale (PANSS), the Calgary Depression Scale (CDS), and the Scale of Functioning (SOF). Indices of internal reliability, construct and discriminant validity were examined. RESULTS: The intraclass correlation coefficient (ICC) for the total ISST score for the 22 subjects in Study 1 was 0.90 and mean weighted item kappa coefficients ranged from 0.66 to 0.92. In Study 2, internal reliability (Cronbach alpha) was high, ranging from 0.86 to 0.89 for the individual items, and the overall Cronbach alpha coefficient for all items was 0.88. The ISST (PI) total score was highly correlated with the CGI-SS by the blind rater (r = 0.61, p < 0.0001). ISST total scores significantly differentiated the different levels of CGI-SS (F = 519.2; p < 0.0001). Results of construct and discriminant validity analyses are also presented. CONCLUSION: The ISST is a reliable and valid instrument for the assessment of current suicidal thinking in patients with schizophrenia and schizoaffective disorder by both clinicians and researchers.

Adolescent↗
PubMed2003

Predicting suicidal risk in schizophrenic and schizoaffective patients in a prospective two-year trial.

BACKGROUND: Enhanced ability to reliably identify risk factors for suicidal behavior permits more focused decisions concerning treatment interventions and support services, with potential reduction in lives lost to suicide. METHODS: This study followed 980 patients at high risk for suicide in a multicenter prospective study for 2 years after randomization to clozapine or olanzapine. A priori predictors related to diagnosis, treatment resistance, and clinical constructs of disease symptoms were evaluated as possible predictors of subsequent suicide-related events. RESULTS: Ten baseline univariate predictors were identified. Historical predictors were diagnosis of schizoaffective disorder, history or current use at baseline of alcohol or substance abuse, cigarette smoking, number of lifetime suicide attempts, and the number of hospitalizations in the previous 36 months to prevent suicide. Predictive clinical features included greater baseline scores on the InterSePT scale for suicidal thinking, the Covi Anxiety Scale, the Calgary Depression Scale (CDS), and severity of Parkinsonism. Subsequent multivariate analysis revealed the number of hospitalizations in the previous 36 months, baseline CDS, severity of Parkinson's, history of substance abuse, and lifetime suicide attempts. Clozapine, in general, was more effective than olanzapine in decreasing the risk of suicidality, regardless of risk factors present. CONCLUSIONS: This is the first prospective analysis of predictors of suicide risk in a large schizophrenic and schizoaffective population judged to be at high risk for suicide. Assessment of these risk factors may aid clinicians in evaluating risk for suicidal behaviors so that appropriate interventions can be made.

Adult↗
PubMed2003

Neurocognitive performance does not correlate with suicidality in schizophrenic and schizoaffective patients at risk for suicide.

BACKGROUND: Almost 50% of schizophrenic persons attempt suicide at some time in their lives and 9-13% of patients ultimately commit suicide. While numerous studies have elucidated the relationship between psychiatric symptomatology and neurocognition in patients with schizophrenia, this is the first report, to our knowledge, to investigate the relationship between suicidal behavior and neurocognition in schizophrenia and schizoaffective disorder. METHODS: A subgroup of 188 patients participating in the InterSePT trial was assessed at baseline with an extensive neurocognitive battery and measures of suicidality and psychiatric symptomatology. RESULTS: Measures of suicidality did not significantly correlate with neurocognitive performance. Confirmatory analyses between patients currently judged to be at high and low risk for suicide also revealed no neurocognitive differences. Consistent with previous studies, poor neurocognitive performance tended to be modestly correlated with the Positive and Negative Syndrome Rating Scale (PANSS) negative symptom scale. The relationship between suicidality and neurocognitive performance was similar for schizoaffective and schizophrenic patients. CONCLUSIONS: The findings suggest that suicidality in patients with schizophrenia and schizoaffective disorder is not correlated with cognition and may, in fact, be a separate domain worthy of investigation and intervention.

Adult↗
PubMed2003

Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT).

BACKGROUND: Approximately 50% of patients with schizophrenia or schizoaffective disorder attempt suicide, and approximately 10% die of suicide. Study results suggest that clozapine therapy significantly reduces suicidal behavior in these patients. METHODS: A multicenter, randomized, international, 2-year study comparing the risk for suicidal behavior in patients treated with clozapine vs olanzapine was conducted in 980 patients with schizophrenia or schizoaffective disorder, 26.8% of whom were refractory to previous treatment, who were considered at high risk for suicide because of previous suicide attempts or current suicidal ideation. To equalize clinical contact across treatments, all patients were seen weekly for 6 months and then biweekly for 18 months. Subsequent to randomization, unmasked clinicians at each site could make any interventions necessary to prevent the occurrence of suicide attempts. Suicidal behavior was assessed at each visit. Primary end points included suicide attempts (including those that led to death), hospitalizations to prevent suicide, and a rating of "much worsening of suicidality" from baseline. Masked raters, including an independent suicide monitoring board, determined when end point criteria were achieved. RESULTS: Suicidal behavior was significantly less in patients treated with clozapine vs olanzapine (hazard ratio, 0.76; 95% confidence interval, 0.58-0.97; P =.03). Fewer clozapine-treated patients attempted suicide (34 vs 55; P =.03), required hospitalizations (82 vs 107; P =.05) or rescue interventions (118 vs 155; P =.01) to prevent suicide, or required concomitant treatment with antidepressants (221 vs 258; P =.01) or anxiolytics or soporifics (301 vs 331; P =.03). Overall, few of these high-risk patients died of suicide during the study (5 clozapine vs 3 olanzapine-treated patients; P =.73). CONCLUSIONS: Clozapine therapy demonstrated superiority to olanzapine therapy in preventing suicide attempts in patients with schizophrenia and schizoaffective disorder at high risk for suicide. Use of clozapine in this population should lead to a significant reduction in suicidal behavior.

Adolescent↗
PubMed2002

A pilot, randomized, open-label trial assessing safety and pharmakokinetic parameters of co-administration of rivastigmine with risperidone in dementia patients with behavioral disturbances.

BACKGROUND: The majority of patients with Alzheimer's disease (AD) or vascular dementia display, in addition to cognitive impairment, various degrees of behavioral disturbances. As the use of cholinesterase inhibitors for the treatment of cognitive impairment in dementia becomes widespread, many of these patients will be treated concomitantly with cholinesterase inhibitors and with anti-psychotic drugs to ameliorate behavioral disturbances. Despite the widespread use of this combination in clinical practice, the safety and tolerability of such combination therapy has not been evaluated in controlled clinical trials. This pilot study examined the effects of addition of risperidone 0.5-2 mg/day to patients on rivastigmine 3-12 mg/day, and vice versa. METHODS: 65 patients suffering from AD, 10 from vascular dementia, and 15 from both were randomized to open label rivastigmine and risperidone, alone or in combination, for 20 weeks. Adverse events caused by co-administration were assessed. RESULTS: No clinically relevant adverse interactions were observed. CONCLUSIONS: These preliminary results indicate that rivastigmine and risperidone can be safely co-administered. Confirmation of these results in large clinical trials studies is warranted.

Aged↗
PubMed2002

Long-term effects of rivastigmine in moderately severe Alzheimer's disease: does early initiation of therapy offer sustained benefits?

Goals of the study included evaluating the long-term efficacy of rivastigmine in Alzheimer's disease (AD) patient categories stratified by baseline dementia severity, and post hoc investigation of particular benefits of early initiation of rivastigmine treatment in moderately severe AD. Both rivastigmine-treated groups (originally randomized to 1-4 or 6-12 mg/day) experienced significantly smaller declines in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores from baseline than the projected placebo group after 52 weeks. Patients receiving rivastigmine from Day 1 experienced significantly less decline compared with patients originally receiving placebo and then initiating rivastigmine treatment after a 6-month delay. Furthermore, cognitive benefits were more robust in patients with moderately severe disease compared with previous reports in mild to moderately severe AD. Findings suggest that early treatment with rivastigmine 6-12 mg/day is associated with sustained long-term cognitive benefits in patients with moderately severe AD. The results support the value of early treatment of AD patients, particularly those with moderately severe AD.

Aged↗
PubMed2002

Impact of Alzheimer's disease and rivastigmine treatment on activities of daily living over the course of mild to moderately severe disease.

OBJECTIVES: To investigate the relationship between activities of daily living (ADL) impairment and Alzheimer's disease (AD) severity in mild to moderately severe AD patients receiving the cholinesterase (ChE) inhibitor rivastigmine. METHODS: ADLs were evaluated using the Progressive Deterioration Scale (PDS). Disease severity was assessed with the Global Deterioration Scale (GDS). Patients were participants in one of three double-blind, placebo-controlled trials with rivastigmine. RESULTS: Baseline PDS scores differed significantly (P<.001) by disease severity. At Week 26, PDS declines from baseline for placebo patients were significantly different at all disease stages. Specific ADL affected were disease stage-dependent. Rivastigmine treatment (6-12 mg/day) resulted in total PDS scores being significantly improved compared with placebo at all disease stages, although the effect on individual items differed by severity. CONCLUSIONS: ADL impairment differs across the stages of AD. Greater impairment in total ADL scores is observed with increasing severity of illness. However, the stage of illness determines the type of ADLs lost. Treatment response to rivastigmine occurs with mild, moderate and moderately severe AD, with the largest effect in patients with advancing severity of disease.

Activities of Daily Living↗
PubMed2002

Barriers to drug discovery and development for Alzheimer disease.

Alzheimer disease (AD) is a neurodegenerative condition leading to progressive, irreversible loss of cognitive and behavioral function. Despite considerable investments in neuroscience research, only four drugs, all cholinesterase inhibitors, have been approved for the symptomatic management of AD in the United States. Although basically safe and modestly effective, these drugs are far from ideal, being neither universally efficacious nor disease modifying. AD exacts a considerable toll in direct medical costs, quality of life, and caregiver burden for persons and society. In addition to the obvious clinical benefit, therapeutic agents for AD and related dementias represent a considerable market opportunity for the pharmaceutical and biotechnology industries. There are currently 8-10 million AD sufferers in the seven major pharmaceutical markets. The market will grow rapidly in coming decades, as the developed world experiences an enormous increase in its elderly population. Given the great need for new therapeutic agents to manage and prevent AD, the Institute for the Study of Aging and the Fidelity Foundation organized a workshop, "Barriers to the Discovery and Development of Drugs for Alzheimer's Disease," to examine ways to expedite drug discovery and development. The identified barriers and potential solutions will be discussed here and in the accompanying articles in more detail.

Alzheimer Disease↗
PubMed2002

Barriers to Alzheimer disease drug discovery and drug development in the pharmaceutical industry.

The drug development process in the pharmaceutical industry has evolved from separate programs, specific for each country, into one coordinated, global development scheme. As a result, such a development program must meet regulatory requirements for all countries in which approval for the new drug will be sought. Barriers to Alzheimer disease (AD) drug discovery and development in the pharmaceutical industry can be categorized as (1) regulatory, (2) logistical, and (3) drug development issues. Some of the regulatory barriers could be overcome by international harmonization of guidelines for the development of antidementia drugs. The logistical issues can be reduced through international collaboration in the conduct of clinical studies, and the developmental issues can be addressed by using an expedited drug development plan that not only can reduce the time but also the resources required to develop the drug.

Alzheimer Disease↗
PubMed2002

A PET study of the pathophysiology of negative symptoms in schizophrenia. Positron emission tomography.

OBJECTIVE: Positron emission tomography (PET) was used to compare cerebral metabolic patterns in schizophrenic subjects with predominantly negative symptoms (alogia, affective flattening, avolition, and attentional impairment) and in those with predominantly positive symptoms. METHOD: Fourteen right-handed male subjects with DSM-IV schizophrenia were assigned to groups with predominantly negative or predominantly positive symptoms on the basis of their post-drug-washout scores on the Positive and Negative Syndrome Scale. The patients were compared to seven age- and gender-matched normal volunteers. PET scans with [(18)F]fluorodeoxyglucose were obtained during a degraded Continuous Performance Task to measure absolute glucose metabolic rates. Statistical parametric mapping was used to estimate the regional metabolic differences between groups. RESULTS: The subjects with predominantly negative symptoms had significant differences in glucose metabolic rates, compared to both the subjects with predominantly positive symptoms and the normal subjects. Negative symptom subjects had a lower glucose metabolic rate in the right hemisphere, especially in the temporal and ventral prefrontal cortices, compared to the other groups, and higher metabolic rates in the cerebellar cortex and in the lower deep cerebellar nuclei. Negative symptom subscale scores were negatively correlated with glucose metabolic rates for most of the brain areas that differentiated subjects with predominantly negative symptoms from those with predominantly positive symptoms. CONCLUSIONS: Schizophrenic subjects with predominantly negative symptoms have greater metabolic abnormalities than subjects with predominantly positive symptoms, particularly in frontal, temporal, and cerebellar circuitry. These results are consistent with abnormalities in corticocortical, corticobasal ganglia, mesocortical dopamine, and cerebellar-thalamic-prefrontal circuits, which may underlie the negative symptoms of schizophrenia.

Adult↗
PubMed2002

Electrocardiographic effects of rivastigmine.

The electrocardiographic (ECG) effects of rivastigmine treatment were assessed in mild to moderately severe Alzheimer's disease (AD) by analysis of four 26-week, double-blind, multicenter, placebo-controlled, phase III clinical trials. Of an initial 2791 patients, 77% completed treatment. Seventy-one percent required at least one concomitant medication for conditions other than AD, with 34% requiring cardiovascular medications. Safety assessments included ECGs, adverse events, vital signs, and clinical laboratory parameters. Pooled 12-lead ECG data were analyzed by an independent cardiologist blinded to treatment group and clinical information. Heart rate, PR, QRS, and QTc intervals did not differ significantly between treatment and placebo groups. Percentage change from baseline for PR, QRS, and QTc intervals was also no different. In conclusion, rivastigmine appears not to produce adverse effects on cardiac function assessed by ECG.

Aged↗
PubMed2000

Rivastigmine for Alzheimer's Disease: Improvement Versus Reduced Worsening.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in later life. It is manifested by gradual and progressive decline in cognitive function and ability to perform activities of daily living (ADL) and the development of behavioral disturbances. Progressive reduction in functional ability reduces independence and quality of life and adversely affects caregivers and society. Therefore, benefit from any AD therapy may be obtained not only from improved function but also from stabilization or reduced worsening of function. METHOD: This retrospective study of pooled data from 3 randomized, placebo-controlled trials (N = 2126) compared the incidence of different levels of worsening between 2 rivastigmine treatment groups and a placebo group at week 26 for cognition, using the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog); global functioning, using the Clinicians' Interview-Based Impression of Change-Plus (CIBIC-Plus); and ADL, using the Progressive Deterioration Scale (PDS). Categories of worsening analyzed for each scale were as follows: ADAS-Cog: any decline, >/= 4-point decline, >/= 7-point decline; CIBIC-Plus: stabilized/worsened (rating = 4, 5, 6, or 7), any worsening (rating = 5, 6, or 7); PDS: any worsening, >/= 10% worsening. RESULTS: Patients treated with rivastigmine, 6-12 mg/day, showed significantly less decline in cognition, global functioning, and ADL for all categories of worsening examined compared with patients who received placebo. The reduction in decline compared with placebo was greater in the group receiving 6-12 mg/day of rivastigmine compared with the treatment group receiving 1-4 mg/day of rivastigmine. CONCLUSION: Rivastigmine reduces the amount of worsening observed in cognition, global functioning, and ADL in a 6-month trial period.

Journal Article↗
PubMedDate not supplied

Impact of study design and patient population on outcomes from cholinesterase inhibitor trials.

The authors conducted a comparative review of study designs and patient populations used in pivotal trials investigating various cholinesterase inhibitors (tacrine, donepezil, rivastigmine, galantamine, controlled-release physostigmine, and metrifionate) and their impact on outcomes reported. Study design parameters that were investigated included patient selection, definitions of adverse dropouts and serious adverse events, effective doses used, dosing flexibility (fixed versus flexible), forced titration, and titration rate. Population characteristics included medical comorbidity and disease severity. Data suggest that differences in study designs and patient populations affect outcomes. Therefore, caution should be taken before making decisions on relative efficacy, safety, and tolerability, because clinical studies are not always directly comparable.

Aged↗