Agmatine as a novel candidate for rapid-onset antidepressant response

Major depressive disorder (MDD) is a disabling and highly prevalent mood disorder as well as a common cause of suicide. Chronic stress, inflammation, and intestinal dysbiosis have all been shown to play crucial roles in the pathophysiology of MDD. Although conventional antidepressants are widely used in the clinic, they can take weeks to months to produce therapeutic effects. The discovery that ketamine promotes fast and sustaining antidepressant responses is one of the most important breakthroughs in the pharmacotherapy of MDD. However, the adverse psychomimetic/dissociative and neurotoxic effects of ketamine discourage its chronic use. Therefore, agmatine, an endogenous glutamatergic modulator, has been postulated to elicit fast behavioral and synaptogenic effects by stimulating the mechanistic target of rapamycin complex 1 signaling pathway, similar to ketamine. However, recent evidence has demonstrated that the modulation of the NLR family pyrin domain containing 3 inflammasome and gut microbiota, which have been shown to play a crucial role in the pathophysiology of MDD, may also participate in the antidepressant-like effects of both ketamine and agmatine. This review seeks to provide evidence about the mechanisms that may underlie the fast antidepressant-like responses of agmatine in preclinical studies. Considering the anti-inflammatory properties of agmatine, it may also be further investigated as a useful compound for the management of MDD associated with a pro-inflammatory state. Moreover, the fast antidepressant-like response of agmatine noted in animal models should be investigated in clinical studies.     

Treat-to-target strategy in patients with rheumatoid arthritis: Audit of adherence from real world clinical data

IntroductionThe current paradigm of the management of rheumatoid arthritis (RA) recommends achieving a state of remission or low disease activity through the treat-to-target strategy. Our study assesses adherence to this strategy.MethodPatients with RA (ACR-EULAR 2010 criteria) were included. From each centre, 19 patients were randomly selected. Clinical histories (CH) were assessed by independent auditors, checking compliance with predefined quality criteria. The study was approved by ethics committees.ResultsWe included 856 patients (mean age 54 years; 71% women). The use of a combined index (CI) was recorded in 61% of cases. Visits were recorded every 4 weeks using a CI in 4% of CH while attempts were made to achieve remission. Monitoring of disease activity every 6–8 months after reaching the target was recorded in 73% of cases.ConclusionsThe implementation of the treat-to-target strategy is barely recorded in patients with RA in routine clinical practice.