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Abstract Background Major depressive disorder (MDD) patients not responding to two or more different antidepressant treatments are currently considered to suffer from treatment resistant depression (TRD). Recently, intranasal esketamine has been approved by both the American Food and Drug Administration and European Medicines Agency for TRD and, more recently, in moderate to severe episode of MDD, as acute short-term treatment for the rapid reduction of depressive symptoms, which, according to clinical judgement, constitute a psychiatric emergency. There is currently no indication for obsessive–compulsive disorder (OCD) although recently published studies have already shown a rapid and significant reduction of OCD-like symptoms following ketamine administration. The etiology of OCD has not yet been fully elucidated but there is a growing evidence that glutamate signaling dysfunction in the cortico-striatal–thalamo-cortical circuitry plays an essential role. This case report exemplifies possible clinical effects of esketamine on both depressive and OCD symptoms. Case presentation We present the case of a 39-year-old man suffering from TRD. During the first evaluation at our clinic, he also reported the presence of OCD spectrum symptoms, causing him to perform time-consuming mental rituals due to pathological doubts regarding the relationship with his wife as well as intrusive thoughts regarding his mental conditions. He underwent psychometric evaluations, therapeutic drug monitoring analysis, and pharmacogenomic tests. The overall results helped to explain patient’s treatment-resistance. Moreover, we observed a significant reduction in both depressive and OCD symptoms after administration of esketamine. Conclusion This case underlines the importance of pharmacogenomic tests in profiling TRD patients and confirms the possible use of esketamine in the treatment of comorbid OCD.

Background: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first‐line therapeutic options, resulting in treatment‐resistant bipolar depression (B‐TRD). Esketamine, the S‐enantiomer of ketamine, has recently been approved for treatment‐resistant depression (TRD), but no data are available on its use in B‐TRD. Objectives: To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B‐TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B‐TRD, focusing on the average risk of an affective switch. Methods: Thirty‐five B‐TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery‐Asberg Depression Rating Scale/MADRS, Hamilton‐depression scale/HAM‐D, Hamilton‐anxiety scale/HAM‐A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up. Results: A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B‐TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B‐TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment‐emergent affective switch. Conclusions: Our results supported the effectiveness and tolerability of esketamine in a real‐world population of subjects with B‐TRD. The low risk of manic switch in B‐TRD patients confirmed the safety of this treatment. [ABSTRACT FROM AUTHOR]

About a third of patients with major depressive disorder (MDD) do not have an adequate response to first-line antidepressant treatment, i.e., develop a treatment-resistant depression (TRD). The partial understanding of MDD pathophysiology currently constitutes the major barrier to clinical and research progress on this topic. However, recent advances in genome editing techniques as well as in induced pluripotent stem cells (iPSC) technology are offering unprecedented opportunities in both human disease modelling and drug discovery. These technology progresses have been enabling to set up disease-relevant patient-specific in vitro disease modeling for various mental disorders. The resulting models have the potential to significantly improve pathophysiologic understanding of MDD and then overcome some limitations inherent to animal and post-mortem models. More recently, psychiatry started to deal with the fast acting antidepressant ketamine and its derivates. Although ketamine appears to have the potential to transform the treatment of depression, its specific mechanisms of action are only partially known. Such knowledge is necessary to develop a model to understand the mechanisms behind fast-acting antidepressants, which may enable the discovery of novel glutamatergic compounds for the treatment of MDD. After discussing both the current understanding of ketamine's mechanisms of action, and the state of the art of human iPSC technology, the authors will introduce the implementation of a TRD model based on iPSC human technology and aimed at studying the ketamine's fast acting antidepressant mechanisms of action.

Delirium is a phenomenon classified within neuro-cognitive disorders in the DSM-5. It has several etiologies and it is often lethal. This contribute aims at analyzing clinical characteristics and diagnostic possibilities of delirium in patients affected by covid-19. Furthermore, some preliminary recommendations on the use of psychopharmacological treatment of delirium and their interactions with main drugs used to treat covid-19 are given, with a special attention to comorbidities like in immunocompromised patients, in those affected by diabetes and cancer, in pregnant women or in addicted clients.