Baseline Positive And Negative Syndrome Scale Scores Research Articles

The Association of Dropout and Outcome in Trials of Antipsychotic Medication and Its Implications for Dealing With Missing Data

The extent to which noncompletion of a clinical trial relates to outcomes has implications for choosing the most appropriate method for contending with missing data due to dropout. We examined whether dropout relates to outcome in clinical trials of antipsychotic medication. Data from 5 large clinical trials of schizophrenia (n=3483) were examined separately. Patients were aggregated into groups based on their final study visit. Group mean Positive and Negative Syndrome Scale (PANSS) total scores for each visit were computed and graphed. Change from baseline to end point for each group was computed and examined using ANCOVA. Cox regression modeling was used to examine baseline PANSS total and change as predictors of time to dropout. In all 5 trials there was a statistically significantly relationship between time in trial and improvement. The longer the patients remained in the trial the more that they improved, with trial completers showing the most improvement at each time point. Higher baseline PANSS scores and symptom deterioration indicated by increased PANSS preceding the final study visit prior to dropout corresponded significantly with a greater likelihood of dropout. Dropout in clinical trials of antipsychotic medications corresponds with efficacy outcomes, the dynamics of symptom change and baseline symptom severity. Therefore, methods for statistical analysis should examine both efficacy and dropout and cannot assume that missing data due to dropout are completely at random.

Pharmacogenetics of treatment in first-episode schizophrenia: D3 and 5-HT2C receptor polymorphisms separately associate with positive and negative symptom response

We have been studying the pharmacogenetic correlates of side effects and early response to antipsychotic treatment in a series of Chinese Han first-episode drug-naïve patients with schizophrenia. Here, we report the association of three functional polymorphisms of receptor genes on initial symptom severity and outcome in these patients. We studied the dopamine D3 receptor ser9gly, the dopamine D2 receptor Taq IA and the 5-HT2C receptor promoter −759C/T polymorphisms in 117 patients who had symptoms assessed by Positive and Negative Syndrome Scale (PANSS) on admission and following 10-week antipsychotic treatment, primarily with risperidone or chlorpromazine. The D2 polymorphism was found not to be significantly associated with baseline levels or changes in total PANSS in these patients. The D3 genotype is associated with the change in total PANSS ( p<0.01), an effect reflecting positive and general (each p<0.01) but not negative symptom improvement. However, symptom improvement at 10 weeks strongly correlates with total PANSS score on admission, in which the greater improvement is seen with the more severe initial symptom score. The D3 genotype is also related to severity on admission, i.e. to total baseline PANSS ( p<0.05), including baseline PANSS score as a covariate, the association of the genotype to change over 10 weeks remains significant for total PANSS ( p<0.05) and for positive and general, but not negative, symptom scores. The 5-HT2C promoter polymorphism was also associated with improvement in PANSS ( p<0.05), but reflecting effects on negative and general, but not positive, symptom scores. This polymorphism was not associated with PANSS score on admission, although after controlling for the effect of this parameter on 10-week outcome, a stronger association with change in total PANSS ( p<0.01) was apparent, again reflecting improvements in negative and general symptoms but not changes in positive symptoms.