Biomedical subjects

Larry Alphs

Publications and source records attributed to Larry Alphs.

7 recordsLinked to original sources

PubMed2006

An industry perspective on the NIMH consensus statement on negative symptoms.

Negative symptoms of schizophrenia remain an area of substantial unmet clinical need. By convening a consensus conference in January 2005, the NIMH has taken a leading role in stimulating a resurgence of interest in methodological considerations related to development of new medications for treating negative symptoms. One audience for this work is clinical researchers in industry. They must take ideas, like those emerging from this consensus meeting, and determine whether they can be applied to their global trials in order to meet the needs of a broad group of customers, which include patients, clinicians, regulators, and payers. This article takes the ideas that surfaced from the NIMH consensus work and interprets them in terms of issues that industry faces for its clinical trials. Particular emphasis is given to addressing hurdles to study design and analysis that come when developing broad-spectrum or adjunctive agents that may be effective for negative symptoms.

Antipsychotic Agents↗

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

Awareness of disorder and suicide risk in the treatment of schizophrenia: results of the international suicide prevention trial.

OBJECTIVE: Schizophrenia is characterized by high suicide risk and low awareness of disorder. Although awareness has benefits for medication compliance and clinical outcome, it is unclear how it may relate to suicide risk in this population. METHOD: This multicenter investigation assessed awareness and suicide-related behavior in 980 patients with schizophrenia or schizoaffective disorder. Patients were followed over 2 years and assessed by blinded raters for suicide-related events. RESULTS: Awareness of psychiatric condition at baseline was associated with increased risk of suicide events over the follow-up. This effect was mediated by depression and hopelessness levels. By contrast, changes in awareness associated with treatment decreased the risk of suicide. CONCLUSIONS: Although some patients may become depressed after acknowledging the clinical handicaps of their disorder, treatment-related changes in awareness are generally associated with a positive outcome relative to suicide risk. The complex interactions and mediation effects of these clinical variables require careful monitoring.

Adult↗

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↗