PubMed Health⌕ Search

Biomedical subjects

Ranga Krishnan

Publications and source records attributed to Ranga Krishnan.

11 recordsLinked to original sources
PubMed2006

Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial.

BACKGROUND: Psoriasis has substantial psychological and emotional effects. We assessed the effect of etanercept, an effective treatment for the clinical symptoms of psoriasis, on fatigue and symptoms of depression associated with the condition. METHODS: 618 patients with moderate to severe psoriasis received double-blind treatment with placebo or 50 mg twice-weekly etanercept. The primary efficacy endpoint was a 75% or greater improvement from baseline in psoriasis area and severity index score (PASI 75) at week 12. Secondary and other endpoints included the functional assessment of chronic illness therapy fatigue (FACIT-F) scale, the Hamilton rating scale for depression (Ham-D), the Beck depression inventory (BDI), and adverse events. Efficacy analyses were based on the allocated treatment. Analyses and summaries of safety data were based on the actual treatment received. This study is registered with with the identifier NCT00111449. FINDINGS: 47% (147 of 311) of patients achieved PASI 75 at week 12, compared with 5% (15 of 306) of those receiving placebo (p<0.0001; difference 42%, 95% CI 36-48). Greater proportions of patients receiving etanercept had at least a 50% improvement in Ham-D or BDI at week 12 compared with the placebo group; patients treated with etanercept also had significant and clinically meaningful improvements in fatigue (mean FACIT-F improvement 5.0 vs 1.9; p<0.0001, difference 3.0, 95% CI 1.6-4.5). Improvements in fatigue were correlated with decreasing joint pain, whereas improvements in symptoms of depression were less correlated with objective measures of skin clearance or joint pain. INTERPRETATION: Etanercept treatment might relieve fatigue and symptoms of depression associated with this chronic disease.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Effects of antidepressant medication on morbidity and mortality in depressed patients after myocardial infarction.

BACKGROUND: Depression after myocardial infarction (MI) is associated with higher morbidity and mortality. Although antidepressants are effective in reducing depression, their use in patients with cardiovascular disease remains controversial. OBJECTIVE: To undertake a secondary analysis to determine the effects of using antidepressants on morbidity and mortality in post-MI patients who participated in the Enhancing Recovery in Coronary Heart Disease study. DESIGN: Observational secondary analysis. SETTING: Eight academic sites. PATIENTS: The Enhancing Recovery in Coronary Heart Disease clinical trial randomized 2481 depressed and/or socially isolated patients from October 1, 1996, to October 31, 1999. Depression was diagnosed using a structured clinical interview. This analysis was conducted on the 1834 patients enrolled with depression (849 women and 985 men). INTERVENTION: Use of antidepressant medication. MAIN OUTCOME MEASURES: Event-free survival was defined as the absence of death or recurrent MI. All-cause mortality was also examined. To relate exposure to antidepressants to subsequent morbidity and mortality, the data were analyzed using a time-dependent covariate model. RESULTS: During a mean follow-up of 29 months, 457 fatal and nonfatal cardiovascular events occurred. The risk of death or recurrent MI was significantly lower in patients taking selective serotonin reuptake inhibitors (adjusted hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.38-0.84), as were the risk of all-cause mortality (adjusted HR, 0.59; 95% CI, 0.37-0.96) and recurrent MI (adjusted HR, 0.53; 95% CI, 0.32-0.90), compared with patients who did not use selective serotonin reuptake inhibitors. For patients taking non-selective serotonin reuptake inhibitor antidepressants, the comparable HRs (95% CIs) were 0.72 (0.44-1.18), 0.64 (0.34-1.22), and 0.73 (0.38-1.38) for risk of death or recurrent MI, all-cause mortality, or recurrent MI, respectively, compared with nonusers. CONCLUSIONS: Use of selective serotonin reuptake inhibitors in depressed patients who experience an acute MI might reduce subsequent cardiovascular morbidity and mortality. A controlled trial is needed to examine this important issue.

Antidepressive Agents↗
PubMed2005

Effects of paroxetine and venlafaxine XR on heart rate variability in depression.

Depressed patients may exhibit reduced heart rate variability (HRV), and antidepressants which block norepinephrine uptake may also lower HRV. This study compared paroxetine (PAR) and venlafaxine XR (VEN-XR) on HRV. Outpatients were randomly assigned to double-blind treatment with PAR up to 40 mg or VEN-XR up to 225 mg daily. HRV measures of parasympathetic control consisted of change in R-R interval during forced 10-second breaths and respiratory sinus arrhythmia (RSA) during paced breathing. Ex vivo estimates of serotonin and norepinephrine transporter occupancy were obtained before and after treatment, as were measures of depression, anxiety, and resilience. Plasma drug concentrations were measured at end point. Forty-nine patients entered treatment; 44 of whom were evaluable (n = 22 per group). Significant within-group reductions were noted in R-R interval variation and in RSA after VEN-XR only. Between-group analyses showed significant group-by-time interaction, with greater reduction in R-R interval variation and in RSA for VEN-XR compared with PAR. Improvement in resiliency correlated significantly with norepinephrine transporter occupancy for VEN-XR. Further comparisons of selective serotonin reuptake inhibitor and serotonin and norepinephrine reuptake inhibitor drugs on HRV are warranted.

Adult↗
PubMed2005

The case for practical clinical trials in psychiatry.

OBJECTIVE: Clinical trials in psychiatry frequently fail to maximize clinical utility for practicing clinicians, or, stated differently, available evidence is not perceived by clinicians (and other decision makers) as sufficiently relevant to clinical practice, thereby diluting its impact. To attain maximum clinical relevance and acceptability, researchers must conduct clinical trials designed to meet the needs of clinicians and others who are making decisions about patients' care. The authors present the case for psychiatry's adoption of the practical clinical trials model, which is widely used in research in other areas of medicine. METHOD: The authors outline the characteristics and scope of practical clinical trials, give examples of practical clinical trials, and discuss the challenges of using the practical clinical trials model in psychiatry, including issues of funding. RESULTS: Practical clinical trials, which are intended to provide generalizable answers to important clinical questions without bias, are characterized by eight key features: a straightforward clinically relevant question, a representative sample of patients and practice settings, sufficient power to identify modest clinically relevant effects, randomization to protect against bias, clinical uncertainty regarding the outcome of treatment at the patient level, assessment and treatment protocols that enact best clinical practices, simple and clinically relevant outcomes, and limited subject and investigator burden. CONCLUSIONS: To implement the practical clinical trials model in psychiatry will require stable funding for network construction and maintenance plus methodological innovation in governance and trial selection, assessment, treatment, data management, site management, and data analytic procedures.

Adolescent↗
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↗
PubMed2004

Estimating suicidality as an outcome measure in clinical trials of suicide in schizophrenia.

A Suicide Monitoring Board (SMB) evaluated putative events of suicidal behavior to determine whether they should be counted as outcome data (endpoints) in the International Suicide Prevention Trial (InterSePT) study. The InterSePT study compared clozapine and olanzapine prospectively, on reduction of suicidality in schizophrenia and schizoaffective disorder. SMB members, blinded to patient identification, evaluated packages of clinical information and the forms used to summarize the putative events and their context. The SMB members met regularly by international teleconference to discuss ratings they found problematic and to achieve consensus. Exactly 243 of the 980 patients enrolled (24.8%) were considered to have experienced 577 suicidal events. Of these events, 483 (83.7%) were confirmed by the SMB as real or valid endpoints. Before the consensus discussions, acceptable levels of agreement (K = 0.52) were reached among the SMB members regarding ratings considered as valid suicidal events; agreement increased (K = 0.64) when consensus ratings and those of on-site psychiatrists also blinded to treatment were also included. This article discusses our experience of evaluating schizophrenia patients for suicidality in general and in particular from reviewing chart information. The process of making clinical judgments regarding the seriousness of suicidal behavior in schizophrenia patients and their suicidal risk warrants further study.

Adult↗
PubMed2004

The Child and Adolescent Psychiatry Trials Network (CAPTN).

OBJECTIVE: The current generation of clinical trials in pediatric psychiatry often fails to maximize clinical utility for practicing clinicians, thereby diluting its impact. METHOD: To attain maximum clinical relevance and acceptability, the Child and Adolescent Psychiatry Trials Network (CAPTN) will transport to pediatric psychiatry the practical clinical trials model widely used in other areas of medicine. RESULTS: CAPTN, a collaborative effort of the Duke Clinical Research Institute and the American Academy of Child and Adolescent Psychiatry, will conduct large, simple "practical" trials that provide generalizable answers to important clinical questions without bias. "Large" in this case means the random allocation of thousands of patients in hundreds of clinical centers to different treatments as they are delivered in community settings. "Simple" means that the number and type of data elements (and, hence, subject and investigator burden) is small and straightforward so as not to discourage provider or patient participation and to maximize the number of subjects per dollar spent. CONCLUSION: With 200 to 400 child and adolescent psychiatrists each participating in two or three practical clinical trials over 4 years, CAPTN promises to advance both the evidence base and research capacity in child and adolescent psychiatry.

Adolescent↗
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↗
PubMed2003

Evidence-based decision-making in psychopharmacology.

hen evaluating patients and making treatment decisions, physicians do not always have all the information necessary and may have to make judgments using limited information. This judgment is often intuitive in nature. The processes by which these judgments are made is of great theoretical and practical interest. In the 1960s, Amos Tversky and Daniel Kahnemann revolutionized the concept of human judgment. They introduced the notion that when individuals make judgments under uncertainty they use a limited number of cognitive processes. These processes are efficient and generally accurate, but can sometimes lead to errors or biases. In this review we discuss the nature of these processes and their potential effects on decision making.

Decision Making↗