ABSTRACT
Ebselen is an organoselenium compound developed as an antioxidant and subsequently shown to be a glutathione peroxidase (GPx) mimetic. Ebselen shows some efficacy in post-stroke neuroprotection and is currently in trial for the treatment and prevention of hearing loss, Meniere's Disease and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In vitro screening studies show that ebselen is also an effective inhibitor of the enzyme inositol monophosphatase (IMPase), which is a key target of the mood-stabilising drug lithium. Further, in animal experimental studies, ebselen produces effects on the serotonin system very similar to those of lithium and also decreases behavioural impulsivity. The antidepressant effects of lithium in treatment-resistant depression (TRD) have been attributed to its ability to facilitate presynaptic serotonin activity; this suggests that ebselen might also have a therapeutic role in this condition. Human studies utilising magnetic resonance spectroscopy support the notion that ebselen, at therapeutic doses, inhibits IMPase in the human brain. Moreover, neuropsychological studies support an antidepressant profile for ebselen based on positive effects on emotional processing and reward seeking. Ebselen also lowers a human laboratory measure of impulsivity, a property that has been associated with lithium's anti-suicidal effects in patients with mood disorders. Current clinical studies are directed towards assessment of the neuropsychological effects of ebselen in TRD patients. It will also be important to ascertain whether ebselen is able to lower impulsivity and suicidal behaviour in clinical populations. The objective of this review is to summarise the developmental history, pre-clinical and clinical psychopharmacological properties of ebselen in psychiatric disorders and its potential application as a treatment for TRD.
ABSTRACT
Despite its severe adverse effects, such as agranulocytosis, clozapine is the primary treatment for treatment-resistant schizophrenia. The established clozapine monitoring system has contributed to reducing agranulocytosis incidence and mortality rates. However, the pandemic coronavirus disease 2019 (COVID-19) has caused changes in the monitoring system. This review aimed to assess the current evidence on the neutrophil changes in the patient on clozapine treatment and infected with COVID-19. Individual cases reported various absolute neutrophil count (ANC) levels, normal, reduced, or elevated. No agranulocytosis case was reported. One case had a borderline moderate-severe ANC level, but the patient was in the 18-week period of clozapine treatment. A cumulative analysis of case the series initially reported inconclusive results. However, a more recent study with a larger sample size reported a significant reduction in the ANC during COVID-19 infection. Nevertheless, this effect is transient as no significant difference was found between the baseline and the post-infection period in ANC levels. In conclusion, COVID-19 is associated with a temporary reduction in ANC levels. The results supported the recommendation to reduce the frequency of clozapine monitoring in the eligible candidates. However, more data are required to confirm the current findings given the limitations, including study design, sample size, and statistical analysis.