Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder
ABSTRACT Major depressive disorder (MDD) is often accompanied by significant cognitive impairment, and there are limited interventions specific to this particular symptom. S-adenosylmethionine (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.
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.
There was a greater improvement in the ability to recall information (P=0.04) and a trend towards 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.
These preliminary data suggest that SAMe can improve memory-related cognitive symptoms in depressed patients, and warrant replication.
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ABSTRACT: Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (eg, enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 11/2014; 13(10). · 2.70 Impact Factor
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ABSTRACT: Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric illness often accompanied of cognitive dysfunction which may persist even when patients achieve clinical remission. Currently, cognitive deficits emerge as a potential target because they compromise the functional outcome of depressed patients. The aim of this study was to review data for several potential pharmacological treatments targeting cognition in MDD, resulting from monotherapy or adjunctive treatment. An extensive and systematic Pubmed/Medline search of the published literature until March 2014 was conducted using a variety of search term to find relevant articles. Bibliographies of retrieved papers were further examined for publications of interest. Searches were limited to articles available in English language. We describe studies using modafinil, lisdexamfetamine, ketamine, lanicemine, memantine, galantamine, donepezil, vortioxetine, intranasal oxytocin, omega-3, s-adenosyl-methionine, scopolamine and erythropoietin. From these articles, we determined that there are a number of promising new therapies, pharmacological agents or complementary medicines, but data are just emerging. Drugs and therapies targeting cognitive dysfunction in MDD should prove effective in improving specific cognitive domains and functioning, while ruling out pseudospecificity. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 01/2015; DOI:10.1016/j.euroneuro.2014.12.004 · 3.68 Impact Factor
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ABSTRACT: S-adenosyl-methionine (SAMe) is a common add-on treatment used to counteract depressive symptoms in subjects with mild-to-moderate depression, who are low responders to other antidepressant drugs. However, there is some concern about the possible impact of SAMe therapy on homocysteine levels. Betaine is known both to counteract high level of homocysteine in plasma and to increase liquor and plasma levels of SAMe, thus potentiating its effect. To evaluate the role played by betaine, administered along with SAMe, in potentiating the antidepressive role played by SAMe administered as such. The study enrolled 46 subjects with a diagnosis of mild-to-moderate depression according to the Beck Depression Inventory Scale II. All the subjects had a suboptimal control of their symptoms. After randomization, they were treated with adjunctive treatment with either Samyr(®) (enteric-coated SAMe) or DDM Metile(®) (enteric-coated SAMe plus betaine) for 90 days. Both treatments acted similarly in improving symptoms such as anxiety, psychomotor agitation, feelings of helplessness and worthlessness, physical efficiency, and somatization, but treatment with DDM Metile(®) determined better statistically significant results following a 90-day therapy. Tolerability and compliance were overlapping in both the treatments. The association of SAMe plus betaine seemed to demonstrate more effectiveness than SAMe alone when administered as an add-on therapy to subjects, affected by mild-to-moderate depression, who were low responders to conventional antidepressants.Journal of Multidisciplinary Healthcare 01/2015; 8:39-45. DOI:10.2147/JMDH.S77766