The new European Medicines Agency guideline on antidepressants: a guide for researchers and drug developers.

According to the World Health Organization (WHO), depressive disorders are currently considered as one of the most disabling medical conditions in the world with one of the highest disability-adjusted life years [1] and this situation has apparently been further worsened during the COVID-19 pandemic [2]. Up to two thirds of patients with major depressive disorders (MDD) do not achieve full remission following an adequate first line standard of care and/or experience residual symptoms such as anxiety, impaired cognition, fatigue, sleep disturbance, or anhedonia [3]. Several attempts are often needed to find the most suitable treatment [4].

The European Medicines Agency review of pitolisant for treatment of narcolepsy: summary of the scientific assessment by the Committee for Medicinal Products for Human Use.

On 31 March 2016, the European Commission issued a decision for a marketing authorisation valid throughout the European Union (EU) for pitolisant (Wakix) for the treatment of narcolepsy with or without cataplexy in adults. Pitolisant is an antagonist/inverse agonist of the human histamine H3 receptor. The dose should be selected using an up-titration scheme depending on individual patient response and tolerance and should not exceed 36 mg/day.

Signaling from blood vessels to CNS axons through nitric oxide.

Brain function is usually perceived as being performed by neurons with the support of glial cells, the network of blood vessels situated nearby serving simply to provide nutrient and to dispose of metabolic waste. Revising this view, we find from experiments on a rodent central white matter tract (the optic nerve) in vitro that microvascular endothelial cells signal persistently to axons using nitric oxide (NO) derived from the endothelial NO synthase (eNOS). The endogenous NO acts to stimulate guanylyl cyclase-coupled NO receptors in the axons, leading to a raised cGMP level which then causes membrane depolarization, apparently by directly engaging hyperpolarization-activated cyclic nucleotide-gated ion channels.