Risks of Antidepressant induced psychotic events in patients with depression and psychosis

The aim of this ‘literature review’-based argumentative paper has been to find out the risks of developing psychotic and depressive disorders in patients having been treated with antidepressants. In order to reach a resounding supposition, this literature review-based argumentative study had taken an incisive look into previous research works and meta-analysis, which in effect had underscored the risks of antidepressant-induced psychotic and depressive disorders in patients with depression as well as psychosis even as the protagonists of antidepressant drug classes could not be undermined given their upscaled magnitude of benefits. While following a probing interpretation of past studies, this might be demystified that antidepressants could lead to psychotic events and depressive disorders in patients of all age groups with children and young adults being more susceptible to develop psychosis. The psychotic episodes could even be developed during initial phase of treatments in patients suffering from depressive and psychotic disorders such as bipolar mood disorder, unipolar depression, major depressive disorders, mania, OCD (Obsessive Compulsive Disorder), delusional depression (psychotic depression), schizophrenia, schizoaffective disorders alongside multiple somatic symptoms among others as well. Concomitantly, with efficaciousness of antidepressants in major depressive disorder still remaining a subject to utter dubitability, different antidepressant drug classes were found to be associated with a considerable scale of adverse effects after carrying out protracted arguments on findings of evidence-based past studies, meta-analysis of previous researches and relevant clinical cases. Therefore, following a systematized approach towards past studies, this argumentative research has reached a coherent conclusion that antidepressants are likely to cause psychotic events and exaggeration of depressive disorders up to some extent in several cases. Hence, there is a stipulation of individual risk-benefit assessment and intricate history taking in patients being contemplated for antidepressant drugs alongside a close observation and follow-up in patients of all age groups after introducing antidepressant medications.

Analysis of recreational psychedelic substance use experiences classified by substance

Rationale and objectives Differences among psychedelic substances regarding their subjective experiences are clinically and scientifically interesting. Quantitative linguistic analysis is a powerful tool to examine such differences. This study compared five psychedelic substance report groups and a non-psychedelic report group on quantitative linguistic markers of psychological states and processes derived from recreational use-based online experience reports. Methods Using 2947 publicly available online reports, we compared Ayahuasca and N,N-dimethyltryptamine (DMT, analyzed together), ketamine, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), psilocybin (mushroom), and antidepressant drug use experiences. We examined word frequencies related to various psychological states and processes and semantic proximity to psychedelic and mystical experience scales. Results Linguistic markers of psychological function indicated distinct effect profiles. For example, MDMA experience reports featured an emotionally intensifying profile accompanied by many cognitive process words and dynamic-personal language. In contrast, Ayahuasca and DMT experience reports involved relatively little emotional language, few cognitive process words, increased analytical thinking-associated language, and the most semantic similarity with psychedelic and mystical experience descriptions. LSD, psilocybin mushroom, and ketamine reports showed only small differences on the emotion-, analytical thinking-, psychedelic, and mystical experience-related language outcomes. Antidepressant reports featured more negative emotional and cognitive process-related words, fewer positive emotional and analytical thinking-related words, and were generally not similar to mystical and psychedelic language. Conclusion This article addresses an existing research gap regarding the comparison of different psychedelic drugs on linguistic profiles of psychological states, processes, and experiences. The large sample of experience reports involving multiple psychedelic drugs provides valuable information that would otherwise be difficult to obtain. The results could inform experimental research into psychedelic drug effects in healthy populations and clinical trials for psychedelic treatments of psychiatric problems.

Adverse Drug Reaction Monitoring of Antidepressant Drugs in a Mental Health Institute in Odisha

Introduction: Antidepressants are used primarily in the management of depressive and anxiety disorders. The occurrence of adverse drug reactions (ADRs) to antidepressants is a major challenge as it influences patient compliance. Aim: The aim of this study was to find out the ADR profile of antidepressant drugs in a mental health institute in Odisha. Materials and Methods: This is a cross sectional observational study conducted in Department of Pharmacology in collaboration with Mental Health Institute (Centre of Excellence) S.C.B Medical College and Hospital, Cuttack from September 2017 to September 2019. Patients who received at least one antidepressant drug were included in the study irrespective of age and sex. Data were collected by interviewing the patients or attendants and on detection of ADR, it was recorded on suspected ADR reporting form designed by PvPI. Causality, severity and preventability of ADRs were assessed by, WHO-UMC causality assessment, modified Hartwig-Siegel Scale and modified Schumock-Thornton criteria respectively. Results: Out of 180 patients taking antidepressants, ADRs were reported in 24% of patients, with either possible or probable causality. None were labelled as certain. ADRs were observed in 50% of patients who received TCAs and among 34.5% who received polytherapy. Insomnia (27%), fatigue (17%) and agitation (13%) were most common ADRs. Most of the ADRs were of mild severity (91%) and not preventable (84%). Conclusion: Insomnia, fatigue and agitation were among most common ADRs. There was increased chance of ADRs with polytherapy and use of TCAs. Most ADRs were mild and not preventable.

Antidepressant drug treatment protecting from COVID-19: one more piece in the repurposing puzzle

In the article Analysis of the impact of antidepressants and other medications on COVID-19 infection risk in a chronic psychiatric in-patient cohort, Catherine L. Clelland and colleagues for the first time suggest a protective effect of antidepressants against infection with coronavirus disease 2019 (COVID-19) itself. During the observation period of the first wave of the pandemic in New York, more than 50% of patients in the psychiatric hospital studied were infected. From retrospective analysis of the hospital medical records, the authors found a significantly lower risk for infection in patients with antidepressant medication compared to treatment with other psychiatric drugs. The findings of a reduced infection incidence in patients who were already on antidepressant drug therapy underlines a preventive efficacy of antidepressants against COVID-19. Taken together with the prior obtained data of efficacy against deterioration of COVID-19 disease, this study adds a piece of evidence to the positive benefit-risk of antidepressants in repurposing condition against COVID-19.

Low-Dose Fluvoxamine Modulates Endocytic Trafficking of SARS-CoV-2 Spike Protein: A Potential Mechanism for Anti-COVID-19 Protection by Antidepressants

Commonly prescribed antidepressants may be associated with protection against severe COVID-19. The mechanism of their action in this context, however, remains unknown. Here, I investigated the effect of an antidepressant drug fluvoxamine on membrane trafficking of the SARS-CoV-2 spike protein and its cell host receptor ACE2 in HEK293T cells. A sub-therapeutic concentration (80 nM) of fluvoxamine rapidly upregulated fluid-phase endocytosis, resulting in enhanced accumulation of the spike-ACE2 complex in enlarged early endosomes. Diversion of endosomal trafficking provides a simple cell biological mechanism consistent with the protective effect of antidepressants against COVID-19, highlighting their therapeutic and prophylactic potential.

Novel Insights Into the Neurobiology of the Antidepressant Response From Ketamine Research: A Mini Review

The serendipitous discovery of ketamine’s antidepressant effects represents one of the major landmarks in neuropsychopharmacological research of the last 50 years. Ketamine provides an exciting challenge to traditional concepts of antidepressant drug therapy, producing rapid antidepressant effects seemingly without targeting monoaminergic pathways in the conventional way. In consequence, the advent of ketamine has spawned a plethora of neurobiological research into its putative mechanisms. Here, we provide a brief overview of current theories of antidepressant drug action including monoaminergic signaling, disinhibition of glutamatergic neurotransmission, neurotrophic and neuroplastic effects, and how these might relate to ketamine. Given that research into ketamine has not yet yielded new therapies beyond ketamine itself, current knowledge gaps and limitations of available studies are also discussed.

Gene mining, codon optimization and analysis of binding mechanism of an aldo-keto reductase with high activity, better substrate specificity and excellent solvent tolerance

The biosynthesis of chiral alcohols has important value and high attention. Aldo–keto reductases (AKRs) mediated reduction of prochiral carbonyl compounds is an interesting way of synthesizing single enantiomers of chiral alcohols due to the high enantio-, chemo- and regioselectivity of the enzymes. However, relatively little research has been done on characterization and apply of AKRs to asymmetric synthesis of chiral alcohols. In this study, the AKR from Candida tropicalis MYA-3404 (C. tropicalis MYA-3404), was mined and characterized. The AKR shown wider optimum temperature and pH. The AKR exhibited varying degrees of catalytic activity for different substrates, suggesting that the AKR can catalyze a variety of substrates. It is worth mentioning that the AKR could catalytic reduction of keto compounds with benzene rings, such as cetophenone and phenoxyacetone. The AKR exhibited activity on N,N-dimethyl-3-keto-3-(2-thienyl)-1-propanamine (DKTP), a key intermediate for biosynthesis of the antidepressant drug duloxetine. Besides, the AKR still has high activity whether in a reaction system containing 10%-30% V/V organic solvent. What’s more, the AKR showed the strongest stability in six common organic solvents, DMSO, acetonitrile, ethyl acetate, isopropanol, ethanol, and methanol. And, it retains more that 70% enzyme activity after 6 hours, suggesting that the AKR has strong solvent tolerance. Furthermore, the protein sequences of the AKR and its homology were compared, and a 3D model of the AKR docking with coenzyme NADPH were constructed. And the important catalytic and binding sites were identified to explore the binding mechanism of the enzyme and its coenzyme. These properties, predominant organic solvents resistance and extensive substrate spectrum, of the AKR making it has potential applications in the pharmaceutical field.