DNA methylation associations with cognitive function in early-stage hormone receptor-positive breast cancer patients.

Treatment-resistant depression (TRD) is a complex and chronic disorder that is defined by regulators as a failure of at least two antidepressants at an adequate dose and for an adequate time []. Various augmentation strategies have been utilized to improve patient outcomes; however, lithium and atypical antipsychotics appear to be among the most consistently recommended options []. TRD still poses a major challenge for the psychopharmacology of mood disorders []. In recent years, ketamine use has been repurposed due to its observed rapid-acting antidepressant properties []. Primarily used solely as an anaesthetic, it has gained wide recognition in mental disorders. In contrast to conventional monoaminergic antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), ketamine primarily exerts its therapeutic effects through modulation of glutamatergic neurotransmission. Alongside its S-enantiomer, esketamine, ketamine has demonstrated rapid-acting antidepressant properties, with clinical effects often observed within hours of administration. This distinct mechanism of action has generated considerable interest, particularly in the context of TRD, where traditional agents may require weeks to achieve therapeutic benefit []. Apart from its antidepressant profile, ketamine has demonstrated antisuicidal [] and antianhedonic []. While the results are encouraging, the racemic ketamine is an off-patent substance and consequently is not tightly regulated by a Risk Evaluation and Mitigation Strategy (REMS), which is in stark contrast to esketamine []. Therefore, the regulatory monitoring of ketamine use in mental disorders is not as strict and requires further attention. Classic antidepressants produce certain treatment-emergent adverse events (TEAEs) such as sleep disturbances, changes in appetite and weight or decreased energy [, ], or emotional blunting []. It might be assumed that ketamine possesses its distinct psychiatric safety profile. Hence, the aim of this paper is to retrospectively assess the frequency and clinical characteristics of psychiatric TEAEs in hospitalized patients with TRD within major depressive disorder (TRD-MDD) receiving short-term ketamine administration.