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
Fluvoxamine maleate is an excellent antidepressive drug. In the literatures, it was synthesized by the use of 4-（trifluoromethyl） aniline or 4-（trifluoromethyl） benzonitrile as starting materials and 5-methoxy-4＇...Fluvoxamine maleate is an excellent antidepressive drug. In the literatures, it was synthesized by the use of 4-（trifluoromethyl） aniline or 4-（trifluoromethyl） benzonitrile as starting materials and 5-methoxy-4＇-（trifluoromethyl-phenyl） valerophenone as a key intermediate. However, the methods in literatures have some disadvantages, such as the use of expensive materials, heavy pollution of environment, long reaction time and low yield of the product （only 30-40% overall yield）. We herein report an environmentally friendly synthetic method of fluvoxamine maleate, which used 4-（trifluoromethyl） benzoic acid and tetrahydrofuran as starting materials and FeCI3 as catalyst for the coupling of acid chloride with Grignard reagent. The fluvoxamine maleate was synthesized in 46% overall yield, through the oximation, etheration and salification of the intermediate successively.This method has some advantages, such as the use of commercially available materials, low cost, short production period （12-14 h）, high yield and light pollution.展开更多
Objectives: To estimate the cost effectiveness of fluvoxamine against desvenlafaxine in Chinese patients with major depressive disorder (MDD). Methods: A cost effectiveness of treating Chinese patients with MDD for 6 ...Objectives: To estimate the cost effectiveness of fluvoxamine against desvenlafaxine in Chinese patients with major depressive disorder (MDD). Methods: A cost effectiveness of treating Chinese patients with MDD for 6 months maintenance period has been estimated by a decision tree model. The relative effectiveness on relapse rates came from a recent network meta analysis by Kishi et al. (2023) along with local drug cost data based on WHO defined daily dose (DDD) and relapse cost for the 6 months estimated from various sources were used in the model. Based on the Quality Adjusted Life Years (QALY) gain reported by Sobocki et al. (2007), QALY loss from a relapse was estimated. Univariate sensitivity analyses were presented by a Tornado diagram and extensive probabilistic sensitivity analysis based on 10,000 simulations was performed. The most recent cost effectiveness threshold of 1.5 times GDP suggested by Cai et al. (2022) was applied. Results: Fluvoxamine dominated desvenlafaxine (cost savings of 4003 CNY and 0.01 QALY higher in 6 months). The most sensitive parameters were relapse rates followed by desvenlafaxine cost and utility loss of relapse. However, the default result of fluvoxamine dominance was not changed for any univariate sensitivity analysis. The probabilistic sensitivity result showed the cost effectiveness acceptability at 1.5 times GDP as 99.93%. Conclusions: The cost effectiveness of fluvoxamine against desvenlafaxine among Chinese patients with MDD in a 6-month maintenance period was cost saving with better effectiveness (i.e., dominating) with low uncertainty.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.
文摘Fluvoxamine maleate is an excellent antidepressive drug. In the literatures, it was synthesized by the use of 4-（trifluoromethyl） aniline or 4-（trifluoromethyl） benzonitrile as starting materials and 5-methoxy-4＇-（trifluoromethyl-phenyl） valerophenone as a key intermediate. However, the methods in literatures have some disadvantages, such as the use of expensive materials, heavy pollution of environment, long reaction time and low yield of the product （only 30-40% overall yield）. We herein report an environmentally friendly synthetic method of fluvoxamine maleate, which used 4-（trifluoromethyl） benzoic acid and tetrahydrofuran as starting materials and FeCI3 as catalyst for the coupling of acid chloride with Grignard reagent. The fluvoxamine maleate was synthesized in 46% overall yield, through the oximation, etheration and salification of the intermediate successively.This method has some advantages, such as the use of commercially available materials, low cost, short production period （12-14 h）, high yield and light pollution.
文摘Objectives: To estimate the cost effectiveness of fluvoxamine against desvenlafaxine in Chinese patients with major depressive disorder (MDD). Methods: A cost effectiveness of treating Chinese patients with MDD for 6 months maintenance period has been estimated by a decision tree model. The relative effectiveness on relapse rates came from a recent network meta analysis by Kishi et al. (2023) along with local drug cost data based on WHO defined daily dose (DDD) and relapse cost for the 6 months estimated from various sources were used in the model. Based on the Quality Adjusted Life Years (QALY) gain reported by Sobocki et al. (2007), QALY loss from a relapse was estimated. Univariate sensitivity analyses were presented by a Tornado diagram and extensive probabilistic sensitivity analysis based on 10,000 simulations was performed. The most recent cost effectiveness threshold of 1.5 times GDP suggested by Cai et al. (2022) was applied. Results: Fluvoxamine dominated desvenlafaxine (cost savings of 4003 CNY and 0.01 QALY higher in 6 months). The most sensitive parameters were relapse rates followed by desvenlafaxine cost and utility loss of relapse. However, the default result of fluvoxamine dominance was not changed for any univariate sensitivity analysis. The probabilistic sensitivity result showed the cost effectiveness acceptability at 1.5 times GDP as 99.93%. Conclusions: The cost effectiveness of fluvoxamine against desvenlafaxine among Chinese patients with MDD in a 6-month maintenance period was cost saving with better effectiveness (i.e., dominating) with low uncertainty.
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.
