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George I Papakostas - One of the best experts on this subject based on the ideXlab platform.
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dose increase of s adenosyl Methionine and escitalopram in a randomized clinical trial for major depressive disorder
Journal of Affective Disorders, 2020Co-Authors: Hitoshi Sakurai, George I Papakostas, Linda L Carpenter, Audrey R Tyrka, Lawrence H Price, Christina Dording, Albert Yeung, Cristina Cusin, Elizabeth Ludington, Richard BernardnegronAbstract:Abstract Background The optimal dose of S-Adenosyl Methionine (SAMe) for major depressive disorder (MDD) remains unclear. The objective of this analysis was to address whether a dose increase provided further improvement in cases of insufficient response using data from an existing randomized clinical trial. Methods Sixty-five patients with MDD who failed to respond to SAMe 1,600 mg/day, escitalopram 10 mg/day, or placebo for 6 weeks were treated with doubled doses of the allocated treatments for the following 6 weeks. Changes in 17-item Hamilton Depression Rating Scale, Inventory of Depressive Symptomatology-Self Rated, and Systematic Assessment for Treatment Emergent Events-Specific Inquiry were compared between the lower and higher dose treatments in each treatment group and among the higher dose treatments of SAMe, escitalopram, and placebo. Results Various depression severity scores decreased significantly for all three treatment arms during the higher dose treatment. No within-group and between-group differences were found in any of the efficacy measures when comparing the doses and treatments. There was a significant difference in reported abdominal discomfort among patients receiving the higher dose of SAMe (31.3%), compared to escitalopram (8.7%) and placebo (3.8%) (χ2=7.32, p = 0.026). Limitations The sample size was relatively small. The study duration for dose increase was relatively short. Conclusions Patients with MDD failing to respond to 1,600 mg/day of SAMe may improve after increasing the dose to 3,200 mg/day, but we cannot rule out the contribution of a placebo effect and time-related improvement. The risk of abdominal discomfort may be increased with higher doses of SAMe.
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s adenosyl Methionine same versus escitalopram and placebo in major depression rct efficacy and effects of histamine and carnitine as moderators of response
Journal of Affective Disorders, 2014Co-Authors: George I Papakostas, Maurizio Fava, Jerome Sarris, Ottavio V Vitolo, David MischoulonAbstract:Abstract Objective To assess the antidepressant efficacy of S-Adenosyl Methionine (SAMe), a naturally occurring methyl donor, versus the selective serotonin reuptake inhibitor (SSRI) escitalopram and a placebo control; and to determine whether serum histamine or carnitine levels modified treatment response. Methods We examined a subsample ( n =144) from one site of a two-site study of adults with diagnosed Major Depressive Disorder (MDD), recruited from 4/13/05 to 12/22/09, who consented to the additional blood draw for serum histamine and carnitine levels. After washout, eligible subjects were randomized to SAMe (1600–3200 mg/daily), escitalopram (10–20 mg/daily), or matching placebo for 12 weeks of double-blind treatment (titration at week 6 in non-response). Results On the primary outcome of the Hamilton Depression Rating Scale (HAMD-17), a significant difference in improvement was observed between groups from baseline to week 12 ( p =0.039). The effect size from baseline to endpoint was moderate to large for SAMe versus placebo ( d =0.74). SAMe was superior to placebo from week 1, and to escitalopram during weeks 2, 4, and 6. No significant effect was found between escitalopram and placebo or SAMe. Response rates (HAMD-17≥50% reduction) at endpoint were 45%, 31%, and 26% for SAMe, escitalopram, and placebo, respectively; while remission rates (HAM-D≤7) were 34% for SAMe ( p =0.003), 23% for escitalopram ( p =0.023), and 6% for placebo. No correlation between baseline histamine level and reduction of HAMD-17 score was found for either the SAMe or escitalopram groups. Baseline carnitine levels were also not found to moderate response to either treatment. Limitations While SAMe appears to be an effective antidepressant agent, the overall findings from the parent study (which showed no significant difference between groups due to site differences) must be taken into consideration. Conclusions These preliminary results provide encouraging evidence for the use of SAMe in the treatment of MDD. Histamine and carnitine serum level may not necessarily moderate response to SAMe.
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effects of s adenosylMethionine augmentation of serotonin reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder
Journal of Affective Disorders, 2012Co-Authors: Yechiel Levkovitz, Jonathan E Alpert, Carrie E Brintz, David Mischoulon, George I PapakostasAbstract:Abstract Background Major depressive disorder (MDD) is often accompanied by significant cognitive impairment, and there are limited interventions specific to this particular symptom. S-Adenosyl Methionine (SAMe), a naturally occurring molecule which serves as a major methyl-donor in human cellular metabolism, is required for the synthesis and maintenance of several neurotransmitters that have been implicated in the pathophysiology and treatment of cognitive dysfunction in MDD. Methods This study is a secondary analysis of a clinical trial involving the use of adjunctive SAMe for MDD. Forty-six serotonin-reuptake inhibitor (SRI) non-responders with MDD enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAMe were administered the self-rated cognitive and physical symptoms questionnaire (CPFQ), a validated measure of cognitive as well as physical symptoms of MDD, before and after treatment. Results There was a greater improvement in the ability to recall information (p = 0.04) and a trend toward statistical significance for greater improvement in word-finding (p = 0.09) for patients who received adjunctive SAMe than placebo. None of the remaining five items reached statistical significance. Conclusion These preliminary data suggest that SAMe can improve memory-related cognitive symptoms in depressed patients, and warrant replication.
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s adenosyl Methionine same augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder a double blind randomized clinical trial
American Journal of Psychiatry, 2010Co-Authors: George I Papakostas, Jonathan E Alpert, David Mischoulon, Irene Shyu, Maurizio FavaAbstract:ObjectiveDespite the progressive increase in the number of antidepressants, many patients with major depressive disorder continue to be symptomatic. Clearly, there is an urgent need to develop better tolerated and more effective treatments for this disorder. The use of S-Adenosyl Methionine (SAMe), a naturally occurring molecule that serves as a methyl donor in human cellular metabolism, as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development. MethodParticipants were 73 serotonin reuptake inhibitor (SRI) nonresponders with major depressive disorder enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAMe (target dose: 800 mg/twice daily). Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial. The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale (HAM–D). ResultsThe HAM–D response...
David Mischoulon - One of the best experts on this subject based on the ideXlab platform.
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s adenosyl Methionine and transmethylation pathways in neuropsychiatric diseases throughout life
Neurotherapeutics, 2018Co-Authors: David Mischoulon, Jin Gao, Catherine M Cahill, Xudong Huang, Joshua L Roffman, Stefania Lamonfava, Maurizio Fava, Jack T RogersAbstract:S-Adenosyl Methionine (SAMe), as a major methyl donor, exerts its influence on central nervous system function through cellular transmethylation pathways, including the methylation of DNA, histones, protein phosphatase 2A, and several catecholamine moieties. Based on available evidence, this review focuses on the lifelong range of severe neuropsychiatric and neurodegenerative diseases and their associated neuropathologies, which have been linked to the deficiency/load of SAMe production or/and the disturbance in transmethylation pathways. Also included in this review are the present-day applications of SAMe in the treatment in these diseases in each age group.
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s adenosyl Methionine same versus escitalopram and placebo in major depression rct efficacy and effects of histamine and carnitine as moderators of response
Journal of Affective Disorders, 2014Co-Authors: George I Papakostas, Maurizio Fava, Jerome Sarris, Ottavio V Vitolo, David MischoulonAbstract:Abstract Objective To assess the antidepressant efficacy of S-Adenosyl Methionine (SAMe), a naturally occurring methyl donor, versus the selective serotonin reuptake inhibitor (SSRI) escitalopram and a placebo control; and to determine whether serum histamine or carnitine levels modified treatment response. Methods We examined a subsample ( n =144) from one site of a two-site study of adults with diagnosed Major Depressive Disorder (MDD), recruited from 4/13/05 to 12/22/09, who consented to the additional blood draw for serum histamine and carnitine levels. After washout, eligible subjects were randomized to SAMe (1600–3200 mg/daily), escitalopram (10–20 mg/daily), or matching placebo for 12 weeks of double-blind treatment (titration at week 6 in non-response). Results On the primary outcome of the Hamilton Depression Rating Scale (HAMD-17), a significant difference in improvement was observed between groups from baseline to week 12 ( p =0.039). The effect size from baseline to endpoint was moderate to large for SAMe versus placebo ( d =0.74). SAMe was superior to placebo from week 1, and to escitalopram during weeks 2, 4, and 6. No significant effect was found between escitalopram and placebo or SAMe. Response rates (HAMD-17≥50% reduction) at endpoint were 45%, 31%, and 26% for SAMe, escitalopram, and placebo, respectively; while remission rates (HAM-D≤7) were 34% for SAMe ( p =0.003), 23% for escitalopram ( p =0.023), and 6% for placebo. No correlation between baseline histamine level and reduction of HAMD-17 score was found for either the SAMe or escitalopram groups. Baseline carnitine levels were also not found to moderate response to either treatment. Limitations While SAMe appears to be an effective antidepressant agent, the overall findings from the parent study (which showed no significant difference between groups due to site differences) must be taken into consideration. Conclusions These preliminary results provide encouraging evidence for the use of SAMe in the treatment of MDD. Histamine and carnitine serum level may not necessarily moderate response to SAMe.
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effects of s adenosylMethionine augmentation of serotonin reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder
Journal of Affective Disorders, 2012Co-Authors: Yechiel Levkovitz, Jonathan E Alpert, Carrie E Brintz, David Mischoulon, George I PapakostasAbstract:Abstract Background Major depressive disorder (MDD) is often accompanied by significant cognitive impairment, and there are limited interventions specific to this particular symptom. S-Adenosyl Methionine (SAMe), a naturally occurring molecule which serves as a major methyl-donor in human cellular metabolism, is required for the synthesis and maintenance of several neurotransmitters that have been implicated in the pathophysiology and treatment of cognitive dysfunction in MDD. Methods This study is a secondary analysis of a clinical trial involving the use of adjunctive SAMe for MDD. Forty-six serotonin-reuptake inhibitor (SRI) non-responders with MDD enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAMe were administered the self-rated cognitive and physical symptoms questionnaire (CPFQ), a validated measure of cognitive as well as physical symptoms of MDD, before and after treatment. Results There was a greater improvement in the ability to recall information (p = 0.04) and a trend toward statistical significance for greater improvement in word-finding (p = 0.09) for patients who received adjunctive SAMe than placebo. None of the remaining five items reached statistical significance. Conclusion These preliminary data suggest that SAMe can improve memory-related cognitive symptoms in depressed patients, and warrant replication.
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s adenosyl Methionine same augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder a double blind randomized clinical trial
American Journal of Psychiatry, 2010Co-Authors: George I Papakostas, Jonathan E Alpert, David Mischoulon, Irene Shyu, Maurizio FavaAbstract:ObjectiveDespite the progressive increase in the number of antidepressants, many patients with major depressive disorder continue to be symptomatic. Clearly, there is an urgent need to develop better tolerated and more effective treatments for this disorder. The use of S-Adenosyl Methionine (SAMe), a naturally occurring molecule that serves as a methyl donor in human cellular metabolism, as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development. MethodParticipants were 73 serotonin reuptake inhibitor (SRI) nonresponders with major depressive disorder enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAMe (target dose: 800 mg/twice daily). Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial. The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale (HAM–D). ResultsThe HAM–D response...
Maurizio Fava - One of the best experts on this subject based on the ideXlab platform.
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s adenosyl Methionine and transmethylation pathways in neuropsychiatric diseases throughout life
Neurotherapeutics, 2018Co-Authors: David Mischoulon, Jin Gao, Catherine M Cahill, Xudong Huang, Joshua L Roffman, Stefania Lamonfava, Maurizio Fava, Jack T RogersAbstract:S-Adenosyl Methionine (SAMe), as a major methyl donor, exerts its influence on central nervous system function through cellular transmethylation pathways, including the methylation of DNA, histones, protein phosphatase 2A, and several catecholamine moieties. Based on available evidence, this review focuses on the lifelong range of severe neuropsychiatric and neurodegenerative diseases and their associated neuropathologies, which have been linked to the deficiency/load of SAMe production or/and the disturbance in transmethylation pathways. Also included in this review are the present-day applications of SAMe in the treatment in these diseases in each age group.
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s adenosyl Methionine same versus escitalopram and placebo in major depression rct efficacy and effects of histamine and carnitine as moderators of response
Journal of Affective Disorders, 2014Co-Authors: George I Papakostas, Maurizio Fava, Jerome Sarris, Ottavio V Vitolo, David MischoulonAbstract:Abstract Objective To assess the antidepressant efficacy of S-Adenosyl Methionine (SAMe), a naturally occurring methyl donor, versus the selective serotonin reuptake inhibitor (SSRI) escitalopram and a placebo control; and to determine whether serum histamine or carnitine levels modified treatment response. Methods We examined a subsample ( n =144) from one site of a two-site study of adults with diagnosed Major Depressive Disorder (MDD), recruited from 4/13/05 to 12/22/09, who consented to the additional blood draw for serum histamine and carnitine levels. After washout, eligible subjects were randomized to SAMe (1600–3200 mg/daily), escitalopram (10–20 mg/daily), or matching placebo for 12 weeks of double-blind treatment (titration at week 6 in non-response). Results On the primary outcome of the Hamilton Depression Rating Scale (HAMD-17), a significant difference in improvement was observed between groups from baseline to week 12 ( p =0.039). The effect size from baseline to endpoint was moderate to large for SAMe versus placebo ( d =0.74). SAMe was superior to placebo from week 1, and to escitalopram during weeks 2, 4, and 6. No significant effect was found between escitalopram and placebo or SAMe. Response rates (HAMD-17≥50% reduction) at endpoint were 45%, 31%, and 26% for SAMe, escitalopram, and placebo, respectively; while remission rates (HAM-D≤7) were 34% for SAMe ( p =0.003), 23% for escitalopram ( p =0.023), and 6% for placebo. No correlation between baseline histamine level and reduction of HAMD-17 score was found for either the SAMe or escitalopram groups. Baseline carnitine levels were also not found to moderate response to either treatment. Limitations While SAMe appears to be an effective antidepressant agent, the overall findings from the parent study (which showed no significant difference between groups due to site differences) must be taken into consideration. Conclusions These preliminary results provide encouraging evidence for the use of SAMe in the treatment of MDD. Histamine and carnitine serum level may not necessarily moderate response to SAMe.
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s adenosyl Methionine same augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder a double blind randomized clinical trial
American Journal of Psychiatry, 2010Co-Authors: George I Papakostas, Jonathan E Alpert, David Mischoulon, Irene Shyu, Maurizio FavaAbstract:ObjectiveDespite the progressive increase in the number of antidepressants, many patients with major depressive disorder continue to be symptomatic. Clearly, there is an urgent need to develop better tolerated and more effective treatments for this disorder. The use of S-Adenosyl Methionine (SAMe), a naturally occurring molecule that serves as a methyl donor in human cellular metabolism, as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development. MethodParticipants were 73 serotonin reuptake inhibitor (SRI) nonresponders with major depressive disorder enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAMe (target dose: 800 mg/twice daily). Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial. The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale (HAM–D). ResultsThe HAM–D response...
Jerome Sarris - One of the best experts on this subject based on the ideXlab platform.
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s adenosyl Methionine same versus escitalopram and placebo in major depression rct efficacy and effects of histamine and carnitine as moderators of response
Journal of Affective Disorders, 2014Co-Authors: George I Papakostas, Maurizio Fava, Jerome Sarris, Ottavio V Vitolo, David MischoulonAbstract:Abstract Objective To assess the antidepressant efficacy of S-Adenosyl Methionine (SAMe), a naturally occurring methyl donor, versus the selective serotonin reuptake inhibitor (SSRI) escitalopram and a placebo control; and to determine whether serum histamine or carnitine levels modified treatment response. Methods We examined a subsample ( n =144) from one site of a two-site study of adults with diagnosed Major Depressive Disorder (MDD), recruited from 4/13/05 to 12/22/09, who consented to the additional blood draw for serum histamine and carnitine levels. After washout, eligible subjects were randomized to SAMe (1600–3200 mg/daily), escitalopram (10–20 mg/daily), or matching placebo for 12 weeks of double-blind treatment (titration at week 6 in non-response). Results On the primary outcome of the Hamilton Depression Rating Scale (HAMD-17), a significant difference in improvement was observed between groups from baseline to week 12 ( p =0.039). The effect size from baseline to endpoint was moderate to large for SAMe versus placebo ( d =0.74). SAMe was superior to placebo from week 1, and to escitalopram during weeks 2, 4, and 6. No significant effect was found between escitalopram and placebo or SAMe. Response rates (HAMD-17≥50% reduction) at endpoint were 45%, 31%, and 26% for SAMe, escitalopram, and placebo, respectively; while remission rates (HAM-D≤7) were 34% for SAMe ( p =0.003), 23% for escitalopram ( p =0.023), and 6% for placebo. No correlation between baseline histamine level and reduction of HAMD-17 score was found for either the SAMe or escitalopram groups. Baseline carnitine levels were also not found to moderate response to either treatment. Limitations While SAMe appears to be an effective antidepressant agent, the overall findings from the parent study (which showed no significant difference between groups due to site differences) must be taken into consideration. Conclusions These preliminary results provide encouraging evidence for the use of SAMe in the treatment of MDD. Histamine and carnitine serum level may not necessarily moderate response to SAMe.
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major depressive disorder and nutritional medicine a review of monotherapies and adjuvant treatments
Nutrition Reviews, 2009Co-Authors: Jerome Sarris, Niikee Schoendorfer, David J KavanaghAbstract:A literature review was conducted to examine the evidence for nutritional interventions in depression. It revealed a number of significant conclusions. Interestingly, more positive clinical trials were found to support adjuvant, rather than monotherapeutic, use of nutrients to treat depression. Much evidence exists in the area of adjuvant application of folic acid, S-Adenosyl-Methionine, omega-3, and L-tryptophan with antidepressants. Current evidence does not support omega-3 as an effective monotherapy to treat depression. However, this may be due, at least in part, to olive oil being used as the control intervention, some studies using docosahexaenoic acid alone or a higher docosahexaenoic acid to eicosapentaenoic acid ratio, and significant heterogeneity regarding depressive populations. Nevertheless, adjunctive prescription of omega-3 with antidepressants, or in people with dietary deficiency, may be beneficial. Inositol lacks evidence as an effective antidepressant and cannot be currently recommended. Evidence on the use of L-trytophan for depression is inconclusive, and additional studies utilizing a more robust methodology are required.
Karen H Vousden - One of the best experts on this subject based on the ideXlab platform.
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serine metabolism supports the Methionine cycle and dna rna methylation through de novo atp synthesis in cancer cells
Molecular Cell, 2016Co-Authors: Oliver D K Maddocks, Christiaan F Labuschagne, Peter D Adams, Karen H VousdenAbstract:Crosstalk between cellular metabolism and the epigenome regulates epigenetic and metabolic homeostasis and normal cell behavior. Changes in cancer cell metabolism can directly impact epigenetic regulation and promote transformation. Here we analyzed the contribution of Methionine and serine metabolism to methylation of DNA and RNA. Serine can contribute to this pathway by providing one-carbon units to regenerate Methionine from homocysteine. While we observed this contribution under Methionine-depleted conditions, unexpectedly, we found that serine supported the Methionine cycle in the presence and absence of Methionine through de novo ATP synthesis. Serine starvation increased the Methionine/S-Adenosyl Methionine ratio, decreasing the transfer of methyl groups to DNA and RNA. While serine starvation dramatically decreased ATP levels, this was accompanied by lower AMP and did not activate AMPK. This work highlights the difference between ATP turnover and new ATP synthesis and defines a vital function of nucleotide synthesis beyond making nucleic acids.