Hitoshi Sakurai1, Linda L Carpenter2, Audrey R Tyrka2, Lawrence H Price2, George I Papakostas3, Christina M Dording3, Albert S Yeung3, Cristina Cusin3, Elizabeth Ludington4, Richard Bernard-Negron3, Maurizio Fava3, David Mischoulon5. 1. Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan. 2. Butler Hospital, Department of Psychiatry and Human Behavior, Brown University School of Medicine, Providence, RI, USA. 3. Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. 4. Agility Clinical, Carlsbad, CA, USA. 5. Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. Electronic address: DMISCHOULON@mgh.harvard.edu.
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.
RCT Entities:
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.
Authors: M L Hardy; I Coulter; S C Morton; J Favreau; S Venuturupalli; F Chiappelli; F Rossi; G Orshansky; L K Jungvig; E A Roth; M J Suttorp; P Shekelle Journal: Evid Rep Technol Assess (Summ) Date: 2003-08
Authors: Anup Sharma; Patricia Gerbarg; Teodoro Bottiglieri; Lila Massoumi; Linda L Carpenter; Helen Lavretsky; Philip R Muskin; Richard P Brown; David Mischoulon Journal: J Clin Psychiatry Date: 2017-06 Impact factor: 4.384
Authors: Madhukar H Trivedi; Charles South; Manish K Jha; A John Rush; Jing Cao; Benji Kurian; Mary Phillips; Diego A Pizzagalli; Joseph M Trombello; Maria A Oquendo; Crystal Cooper; Daniel G Dillon; Christian Webb; Bruce D Grannemann; Gerard Bruder; Patrick J McGrath; Ramin Parsey; Myrna Weissman; Maurizio Fava Journal: Psychother Psychosom Date: 2018-08-15 Impact factor: 25.617