A significant proportion of patients with treatment-resistant depression do not attain functional recovery despite administration of multiple steps of pharmacotherapeutic strategies. This highlights the elusiveness of meeting unmet needs in existing pharmacotherapies for treatment-resistant depression. There is accumulating evidence that antidepressant agents involving the glutamatergic system such as brexpiprazole and esketamine/ketamine have more rapid onset of action and potentially improved effectiveness as an augmentation therapy in treatment-resistant depression. This case series aimed to report five complex cases of unipolar and bipolar treatment-resistant depression where conventional treatment strategies were inadequate in managing high risk suicidal behavior and achieving functional recovery. We discussed further the possible synergistic mechanisms of the novel combination strategy of brexpiprazole and esketamine/ketamine, clinical and patient factors that influenced treatment response, challenges with this combination strategy and implications for future practice and research.

The internet has become an important medium for learning and communication during the COVID-19 pandemic, particularly for university students. Nevertheless, an increase in internet usage could predispose people to internet addiction (IA) and internet gaming (IG). Equally, there is concern that anxiety levels have increased during the pandemic. The aim of this study is to determine the prevalence of IA and IG, and their associations with anxiety among medical students during the pandemic. Data were collected during the second wave of the “Conditional Movement Control Order” (CMCO) in Malaysia between 12 November and 10 December 2020. A total of 237 students participated through proportionate stratified random sampling in this cross-sectional study. They completed a set of online questionnaires which consisted of a sociodemographic profile, the Malay version of the internet addiction test (MVIAT), the Malay version of the internet gaming disorder short form (IGDS9-SF) and the Malay version of the depression, anxiety and stress scale (DASS-21). The prevalence of IA and internet gaming disorder (IGD) were 83.5% and 2.5%, respectively. A multiple logistic regression showed that those in pre-clinical years had a greater risk of anxiety than those in clinical years [(AOR) = 2.49, p-value 0.01, 95% CI = 1.22–5.07]. In contrast, those who scored high on IA were protected against anxiety [AOR = 0.100, p-value 0.03, 95% CI = 0.01–0.76)]. In conclusion, IA was highly prevalent during the COVID-19 pandemic and its high usage might serve as a protective factor against anxiety among the medical students in this study sample.