Background: Fluvoxamine, a selective serotonin reuptake inhibitor is widely used in the treatment of depression, one of the most common disorders prevalent in Russia. However, studies demonstrating its efficacy and sa...Background: Fluvoxamine, a selective serotonin reuptake inhibitor is widely used in the treatment of depression, one of the most common disorders prevalent in Russia. However, studies demonstrating its efficacy and safety in routine settings in Russia are scarce. Methods: This prospective, uncontrolled, open-label study was conducted at 11 centers in Russia. Total 293 patients (aged ≥ 18 years), meeting DSM-IV criteria for depression and scoring ≥ 17 on 17-item Hamilton Rating Scale of Depression (HAMD-17) received fluvoxamine 50 - 300 mg for 6 weeks. Primary efficacy measures included change from baseline in the HAMD-17 and Clinical Global Impression (CGI) scores. Secondary efficacy measure was evaluation of sleep quality changes on HAMD-17 subscale. Safety was assessed by monitoring of adverse drug reactions (ADRs). Results: Mean age of patients was 42.7 years and the majority of them were women (72%). At the end of treatment (day 42), clinically significant reduction was observed in mean HAMD-17, CGI-severity of illness and HAMD-17 sleep sub-score from 23.1, 4.5 and 3.9 at baseline to day 42;change from baseline (Δ) was: Δ-17.3 [95% CI: -18.0;-16.7]), Δ-2.1 and Δ-3.4 [95% CI: -3.53;-3.20]), respectively. At day 42, 20.8% patients reported as normal (not at all ill) on the CGI-severity scale and 85% patients reported as “much improved” or “very much improved” on the CGI-change in severity and quality of life scores. Nausea (12.6%) and somnolence (5.1%) were the most frequently reported ADRs. No deaths or serious ADRs were reported but eight patients discontinued treatment due to ADRs. Conclusion: Treatment with fluvoxamine under routine settings showed marked improvement in Russian patients with depression as measured by HAMD-17 and CGI ratings and was thus efficacious as well as safe and well-tolerated.展开更多
The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functio...The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.展开更多
文摘Background: Fluvoxamine, a selective serotonin reuptake inhibitor is widely used in the treatment of depression, one of the most common disorders prevalent in Russia. However, studies demonstrating its efficacy and safety in routine settings in Russia are scarce. Methods: This prospective, uncontrolled, open-label study was conducted at 11 centers in Russia. Total 293 patients (aged ≥ 18 years), meeting DSM-IV criteria for depression and scoring ≥ 17 on 17-item Hamilton Rating Scale of Depression (HAMD-17) received fluvoxamine 50 - 300 mg for 6 weeks. Primary efficacy measures included change from baseline in the HAMD-17 and Clinical Global Impression (CGI) scores. Secondary efficacy measure was evaluation of sleep quality changes on HAMD-17 subscale. Safety was assessed by monitoring of adverse drug reactions (ADRs). Results: Mean age of patients was 42.7 years and the majority of them were women (72%). At the end of treatment (day 42), clinically significant reduction was observed in mean HAMD-17, CGI-severity of illness and HAMD-17 sleep sub-score from 23.1, 4.5 and 3.9 at baseline to day 42;change from baseline (Δ) was: Δ-17.3 [95% CI: -18.0;-16.7]), Δ-2.1 and Δ-3.4 [95% CI: -3.53;-3.20]), respectively. At day 42, 20.8% patients reported as normal (not at all ill) on the CGI-severity scale and 85% patients reported as “much improved” or “very much improved” on the CGI-change in severity and quality of life scores. Nausea (12.6%) and somnolence (5.1%) were the most frequently reported ADRs. No deaths or serious ADRs were reported but eight patients discontinued treatment due to ADRs. Conclusion: Treatment with fluvoxamine under routine settings showed marked improvement in Russian patients with depression as measured by HAMD-17 and CGI ratings and was thus efficacious as well as safe and well-tolerated.
基金funded by the Taylor Family Institute for Innovative Psychiatric Researchthe Bantly FoundationMH122379 from the National Institute of Mental Health (to YI)。
文摘The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.
