So far, genetic studies of treatment response in schizophrenia, bipolar disorder, and major depression have returned results with limited clinical utility. A gene × environment interplay has been proposed as a factor influencing not only pathophysiology but also the treatment response. Therefore, epigenetics has emerged as a major field of research to study the treatment of these three disorders. Among the epigenetic marks that can modify gene expression, DNA methylation is the best studied. We performed a systematic search (PubMed) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines for preclinical and clinical studies focused on genome-wide and gene-specific DNA methylation in the context of schizophrenia, bipolar disorders, and major depressive disorder. Out of the 112 studies initially identified, we selected 31 studies among them, with an emphasis on responses to the gold standard treatments in each disorder. Modulations of DNA methylation levels at specific CpG sites have been documented for all classes of treatments (antipsychotics, mood stabilizers, and antidepressants). The heterogeneity of the models and methodologies used complicate the interpretation of results. Although few studies in each disorder have assessed the potential of DNA methylation as biomarkers of treatment response, data support this hypothesis for antipsychotics, mood stabilizers and antidepressants.

Objective: To determine the adverse drug reaction (ADR) profile of risperidone and their association with dopamine (DRD2 − 141 C Ins/Del/rs1799732) and serotonin receptor (5HTR2C −759 C>T/rs3813929) gene polymorphisms in patients with schizophrenia. Materials and Methods: The study was conducted among 289 patients who were diagnosed with schizophrenia and were on treatment with risperidone (4–8 mg/day)-based therapy for a minimum of 4 weeks. Genotyping was carried by real-time quantitative polymerase chain reaction. All the patients were observed for the occurrences of ADRs during the study. Changes in prolactin levels and body weight were analyzed for a subgroup of 102 and 97 patients, respectively. Results: Risperidone-induced extrapyramidal symptoms (EPSs) were seen in 36.7% of patients. Among them, tremors were the most common symptom 31.8%. Risperidone-induced hyperprolactinemia and weight gain were seen in 87.2% and 53.6% in subgroup patients. Adverse effects such as sedation, gastrointestinal effects, and amenorrhea were seen in 9.7% (28/289), 5.1% (15/289), and 6.1% (7/114), respectively. Occurrence of DRD2 − 141 Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels in response to risperidone (odds ratio [OR] = 10.45; 95% confidence interval = 1.29–84.89,P = 0.004). No such association was observed with 5HTR2C (−759 C>T) polymorphism. Weight gain and EPS were not associated with the above genetic polymorphisms. Conclusion: Hyperprolactinemia, weight gain, and EPSs (>36.7%) were common adverse effects of risperidone. DRD2 – 141C Ins/Del and Del/Del polymorphisms were significantly associated with increased prolactin levels (OR = 10.45) in response to risperidone.

As the world population ages, there will be an increasing need for effective therapies for aging‐associated neurodegenerative disorders, which remain untreatable. Dementia due to Alzheimer's disease (AD) is one of the leading neurological diseases in the aging population. Current therapeutic approaches to treat this disorder are solely symptomatic, making the need for new molecular entities acting on the causes of the disease extremely urgent. One of the potential solutions is to use compounds that are already in the market. The structures have known pharmacokinetics, pharmacodynamics, toxicity profiles, and patient data available in several countries. Several drugs have been used successfully to treat diseases different from their original purposes, such as autoimmunity and peripheral inflammation. Herein, we divulge the repurposing of drugs in the area of neurodegenerative diseases, focusing on the therapeutic potential of antineoplastics to treat dementia due to AD and dementia. We briefly touch upon the shared pathological mechanism between AD and cancer and drug repurposing strategies, with a focus on artificial intelligence. Next, we bring out the current status of research on the development of drugs, provide supporting evidence from retrospective, clinical, and preclinical studies on antineoplastic use, and bring in new areas, such as repurposing drugs for the prion‐like spreading of pathologies in treating AD.

Background Autophagy activation contributes to chemotherapy resistance in several cancers, including ovarian cancer. Hydroxychloroquine (HCQ) is an autophagy inhibitor inhibiting the fusion of the autophagosome with the lysosome and has been repurposed as an anti-cancer agent. In this randomized phase II study, we used HCQ in combination with standard chemotherapy in platinum sensitive relapsed ovarian cancer (PSROC) patients. Methods Patients were randomized in a 1:1 ratio to receive standard chemotherapy (carboplatin with paclitaxel/gemcitabine) with or without HCQ. Those randomized to receive HCQ received additional HCQ 200mg orally twice daily. The primary endpoint was the overall response rate (ORR). Other endpoints included survival outcomes, changes in autophagy biomarkers, toxicity, and quality of life. Results A total of 59 patients were enrolled- chemotherapy + HCQ (N = 28), chemotherapy alone (N = 31), and 56 were evaluable ( received ≥ 3 cycles treatment). The ORR was not superior with the addition of HCQ [85% (22/26) in the experimental arm as compared to 80% (24/30) in the control arm, chi-square test, P = 0.65]. The median progression-free survival was 12 (95% CI, 9.75–14.24) months for the experimental arm and 11 (95% CI, 5.25–16.74) months for the control arm (P = 0.56) , and the median overall survival was 16 (95% CI, 8.54–23.45) months vs. 21 (95% CI, 11.70–30.59 ) months (P = 0.49) respectively. HCQ was well tolerated, with no excess adverse events [21 (75%) in the experimental arm vs. 22 (71%) in the control arm]. There were no substantial differences in the reduction of autophagy biomarker levels and QOL between the control and experimental arms. Conclusion Adding HCQ to chemotherapy failed to improve response rates or survival in patients with PSROC. Conducting biomarker-stratified clinical trials might show the potential benefit of HCQ. Trial registration number (TRN): The trial was registered in the Clinical Trial Registry of India (www.ctri.nic.in; CTRI/2020/06/025790) on 17th June 2020.