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.

Background: Two new classes of drugs approved by USFDA for the treatment of acute migraine are non-peptide Calcitonin Gene-Related Peptide (CGRP) receptor antagonists (rimegepant and ubrogepant) and 5-HT1F receptor agonist lasmiditan. There are no clinical trials comparing these two classes of newer drugs. Aim and Objectives: The present network meta-analysis was conducted with the objective to compare the efficacy of orally administered lasmiditan versus CGRP-receptor antagonists (rimegepant and ubrogepant) in the treatment of acute migraine. Materials and Methods: Electronic database search in PUBMED and Cochrane library was conducted using MeSH search terms “Lasmiditan” AND “Migraine” for articles on lasmiditan; while MeSH terms “Ubrogepant” AND “Migraine;” “Rimegeapnt” AND “Migraine” were used for articles on CGRP-antagonists. Randomized or cross-over studies comparing efficacy of oral lasmiditan and two FDA approved CGRP-antagonists (rimegepant, and ubrogepant) versus other active treatment or placebo in adults with acute attack of migraine were included in the analysis. Incidence of 2 h pain-free event was the primary outcome measure while the incidence of 24 h pain-free was the secondary outcome measure compared. Both frequent and Bayesian network meta-analysis were conducted by CRSU MetaInsight software. Results: In 12 eligible studies, seven interventions were compared with total 13795 patients analyzed in the network. Higher treatment ranking for 2 h and 24 h pain-free events was observed for lasmiditan 200 mg and rimegepant 150 mg, respectively. Conclusions: There is strong evidence to conclude that lasmiditan at 200 mg is better drug for immediate (2 h) headache freedom. There is limited evidence to support rimegepant for sustained effect (beyond 24 h).

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