Non-genetic traits as predictors of variation in response to pharmacological interventions in ASD need to be identified for better management. This review aims to identify these non-genetic traits and the role of adjuvant medications in ASD. Electronic database searches in PUBMED and Cochrane libraries were conducted using MeSH search terms "Autism" and "Risperidone." Randomized or cross-over trials comparing the efficacy of ‘risperidone plus placebo’ vs. ‘risperidone plus adjuvant medications’ using Aberrant Behavior Checklist-Community Version (ABC-CV) scores in ASD patients of any age group were included in the analysis. The quantity of reduced irritability (ABC-I) sub-score was the primary outcome measure analyzed.In contrast, the reduction in remaining ABC-CV sub-scores at the end of 10 weeks were the secondary outcome measures analyzed. All the outcome measures were estimated by calculating the Mean Difference (MD) values and their 95% Confidence Intervals (CI) by both fixed and random effect models using Revman 5.4.1 software. A total of 13 trials were found to be eligible and included in the quantitative synthesis of efficacy. A small but significant decrease in the ABC irritability sub-score was evident in the ‘risperidone plus adjuvants’ group (MD: -3.19, 95% CI:-3.82, -2.56, N=658). The meta-analysis results attributed the highest decrease in ABC-irritability sub-scores to adjuvant topiramate. There is a possibility of bias and minimal impact of adjuvants in alleviating irritability symptoms of ASD. Baseline severity of irritability symptoms and the dose/medication regimen appear to be possible non-genetic traits responsible for variation in response to pharmacological intervention.
Chemotherapy-induced nausea and vomiting (CINV) is a complication of highly emetogenic chemotherapy (HEC) agents. The present meta-analysis was conducted to quantify and analyze the efficacy and safety of adding olanzapine to a Neurokinin Receptor Antagonist (NKRA) based triple-drug regimen in preventing HEC-induced CINV. Electronic database searches in PUBMED and Cochrane library was conducted using MeSH search terms “olanzapine” and “chemotherapy-induced nausea and vomiting.” Randomized or cross-over trials comparing the efficacy of “olanzapine + NKRA based triple-drug regimen” vs. “placebo + NKRA based triple-drug regimen” in patients of age > 18 years with any malignancy receiving HEC were considered under inclusion criteria. Complete Response (CR) for the delayed (25–120 h) phase of CINV in patients receiving HEC agents was the primary outcome measure analyzed. Outcome measures were estimated by calculating the Risk Difference (RD) values and their 95% Confidence Intervals (CI). The Mantel-Haenszel method and both fixed and random effect models were used in the analysis by Revman 5.4.1 soft- ware. An additional 14% (RD: 0.14, 95% CI: 0.09 to 0.19) of patients treated with olanzapine + triple-drug regimen had a statistically significant higher CR in the delayed phase when compared to placebo + NKRA-based triple-drug regimen. Adding olanzapine at 10mg to the triple-drug regimen significantly improves delayed phase CR rates by 16% and delayed phase ‘no significant nausea’ rates by 30%. Results need to be interpreted cautiously in the background of response variations and limited trials included in our analysis
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