There is a substantial unmet need for effective and patient-acceptable drugs to treat severe mental illnesses such as schizophrenia (SZ). Computational analysis of genomic, transcriptomic, and pharmacologic data generated in the past 2 decades enables repurposing of drugs or compounds with acceptable safety profiles, namely those that are U.S. Food and Drug Administration approved or have reached late stages in clinical trials. We developed a rational approach to achieve this computationally for SZ by studying drugs that target the proteins in its protein interaction network (interactome). This involved contrasting the transcriptomic modulations observed in the disorder and the drug; our analyses resulted in 12 candidate drugs, 9 of which had additional supportive evidence whereby their target networks were enriched for pathways relevant to SZ etiology or for genes that had an association with diseases pathogenically similar to SZ. To translate these computational results to the clinic, these shortlisted drugs must be tested empirically through randomized controlled trials, in which their previous safety approvals obviate the need for time-consuming phase 1 and 2 studies. We selected 2 among the shortlisted candidates based on likely adherence and side-effect profiles. We are testing them through adjunctive randomized controlled trials for patients with SZ or schizoaffective disorder who experienced incomplete resolution of psychotic features with conventional treatment. The integrated computational analysis for identifying and ranking drugs for clinical trials can be iterated as additional data are obtained. Our approach could be expanded to enable disease subtype-specific drug discovery in the future and should also be exploited for other psychiatric disorders.

To design a meditation protocol and test its feasibility, acceptability and efficacy in conjunction with yoga training (YT) for persons with schizophrenia (SZ).

The meditation protocol consisted of Anapana (observing normal respiration) and Yoga Nidra (supine, restful awareness). In a single-blind randomised controlled trial, medicated and clinically stable outpatients diagnosed with SZ were randomised to receive treatment as usual (TAU), TAU augmented with YT or TAU augmented with meditation and yoga training (MYT) for 3 weeks (N = 145). Acceptability, clinical, social and cognitive functions were assessed after 3-week and 3-month post-randomisation using within-group and between-group analyses with repeated measures multivariate tests.

No group-wise differences in compliance, study discontinuation, major/serious side effects or adverse events were noted. For six assessed clinical variables, the direction of changes were in the desired direction and the effect sizes were greater in the MYT group compared with the TAU group at both time points. Changes in social function variables were greater at 3 months than at 3 weeks. Nominally significant improvement in individual cognitive domains were noted in all groups at both time points. All effect sizes were in the small to medium range.

MYT is feasible and acceptable and shows modest benefits for persons with SZ. MYT can also improve quality of life and clinical symptoms. Larger studies of longer duration are warranted.