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Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder

Published online by Cambridge University Press:  15 April 2020

Y. Levkovitz*
Affiliation:
Psychiatry Department, Shalvata Mental Health Center, Tel Aviv University, Hamargoa 4, POB 94, Tel Aviv, Israel The Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, 15, Parkman Street, Boston, MA 02114, USA
J.E. Alpert
Affiliation:
The Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, 15, Parkman Street, Boston, MA 02114, USA
C.E. Brintz
Affiliation:
The Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, 15, Parkman Street, Boston, MA 02114, USA
D. Mischoulon
Affiliation:
The Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, 15, Parkman Street, Boston, MA 02114, USA
G.I. Papakostas
Affiliation:
The Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, 15, Parkman Street, Boston, MA 02114, USA
*
*Corresponding author. Tel.: +972 9 7478644; fax: +972 9 7478643. E-mail address:[email protected]
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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.

Objectives

This study is a secondary analysis of a clinical trial involving the use of adjunctive SAMe for MDD.

Methods

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 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.

Conclusions

These preliminary data suggest that SAMe can improve memory-related cognitive symptoms in depressed patients, and warrant replication.

Type
Original articles
Copyright
Copyright © European Psychiatric Association 2012

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References

American Psychiatric Association Diagnostic and statistical manual of mental disorders. 4th edWashington, DCAmerican Psychiatric Association 1994.Google Scholar
Austin, M.P.Mitchell, P.Goodwin, G.M.Cognitive deficits in depression: possible implications for functional neuropathology. Br J Psychiatry. 2001; 178: 200206.CrossRefGoogle ScholarPubMed
Bottiglieri, T.Ademetionine (S-adenosylmethionine) neuropharmacology: implications for drug therapies in psychiatric and neurological disorders. Expert Opin Investig Drugs. 1997; 6: 417426.CrossRefGoogle ScholarPubMed
Bottiglieri, T.Laundy, M.Martin, R.Carney, M.W.et al.S-adenosylmethionine influences monoamine metabolism. Lancet. 1984; 2(8396): 224.CrossRefGoogle ScholarPubMed
Castaneda, A.E.Suvisaari, J.Marttunen, M.Perälä, J.et al.Cognitive functioning in a population-based sample of young adults with a history of non-psychotic unipolar depressive disorders without psychiatric comorbidity. J Affect Disord. 2008; 110: 3645.CrossRefGoogle Scholar
Chan, A.Tchantchou, F.Graves, V.Rozen, R.et al.Dietary and genetic compromise in folate availability reduces acetylcholine, cognitive performance and increases aggression: critical role of S-adenosyl methionine. J Nutr Health Aging. 2008; 12: 252261.CrossRefGoogle ScholarPubMed
Erb, C.Klein, J.Enhancement of brain choline levels by nicotinamide: mechanism of action. Neurosci Lett. 1988; 249: 111114.CrossRefGoogle Scholar
Fava, M.Graves, L.M.Benazzi, F.Scalia, M.J.et al.A cross-sectional study of the prevalence of cognitive and physical symptoms during long-term antidepressant treatment. J Clin Psychiatry. 2006; 67: 17541759.CrossRefGoogle ScholarPubMed
Fava, M.Iosifescu, D.V.Pedrelli, P.Baer, L.Reliability and validity of the Massachusetts general hospital cognitive and physical functioning questionnaire. Psychother Psychosom. 2009; 78: 9197.CrossRefGoogle ScholarPubMed
Fennig, S.Mottes, A.Ricter-Levin, G.Treves, I.et al.Everyday memory and laboratory memory tests: general function predictors in schizophrenia and remitted depression. J Nerv Ment Dis. 2002; 190: 677682.CrossRefGoogle ScholarPubMed
First, M.B.Spitzer, R.L.Gibbon, M.Williams, J.B.W.Structured clinical interview for DSM-IV axis I disorders - Patient Edition (SCID-I/P, Version 2.0). New York: Biometrics Research Department, New York State Psychiatric Institute; 1995.Google Scholar
Guy, W.ECDEU Assessment Manual for Psychopharmacology, revised. DHEW Pub. No. (ADM) 76-338. Rockville, MDNational Institute of Mental Health 1976 338376.Google Scholar
Hamilton, M.A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960; 23: 5662.CrossRefGoogle ScholarPubMed
Hammer, A.Ardel, G.Cognitive functioning in major depression – a summary. Front Hum Neurosci. 2009; 3(26): 17.Google Scholar
Hirata, F.Axelrod, J.Phospholipid methylation and biological signal transmission. Science. 1980; 209: 10821090.CrossRefGoogle ScholarPubMed
Jaeger, J.Berns, S.Uzelac, S.Davis-Conway, S.Neurocognitive deficits and disability in major depressive disorder. Psychiatry Res. 2006; 145: 3948.CrossRefGoogle ScholarPubMed
Kennedy, N.Foy, K.Sherazi, R.McDonough, M.et al.Long-term social functioning after depression treated by psychiatrists: a review. Bipolar Disord. 2007; 9: 2537.CrossRefGoogle ScholarPubMed
Mischoulon, D.Fava, M.Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr. 2002; 76: 1158S1161S.CrossRefGoogle Scholar
Mischoulon, D.Fava, M.Are nutritional supplements ready for prime time?. J Clin Psychiatry. 2008; 69: 14971498.CrossRefGoogle ScholarPubMed
Muccioli, G.Scordamaglia, A.Bertacco, S.Di Carlo, R.Effect of S-adenosyl-L-methionine on brain muscarinic receptors of aged rats. Eur J Pharmacol. 1992; 227: 293299.CrossRefGoogle ScholarPubMed
Panza, F.Frisardi, V.Capurso, C.D’Introno, A.et al.Possible role of S-adenosylmethionine, S-adenosylhomocysteine, and polyunsaturated fatty acids in predementia syndromes and Alzheimer's disease. J Alzheimers Dis. 2009; 16: 467470.CrossRefGoogle ScholarPubMed
Papakostas, G.I.Alpert, J.E.Fava, M.S-adenosyl-methionine in depression: a comprehensive review of the literature. Curr Psychiatry Rep. 2003; 5: 460466.CrossRefGoogle ScholarPubMed
Papakostas GI, Mischoulon D, Shyu I, Alpert JE, et al. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors (SRIs) for SRI-non-responders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry 2010;167:942–8.CrossRefGoogle Scholar
Pavia, J.Martos, F.Gonzalez-Correa, J.A.Garcia, A.J.et al.Effect of S-adenosyl methionine on muscarinic receptors in young rats. Life Sci. 1997; 60: 825832.CrossRefGoogle ScholarPubMed
Remington, R.Chan, A.Paskavitz, J.Shea, T.B.Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer's disease: a placebo-controlled pilot study. Am J Alzheimers Dis Other Demen. 2009; 24: 2733.CrossRefGoogle ScholarPubMed
Shea, T.B.Chan, A.S-adenosyl methionine: a natural therapeutic agent effective against multiple hallmarks and risk factors associated with Alzheimer's disease. Am J Alzheimers Dis. 2008; 13: 6770.CrossRefGoogle ScholarPubMed
Taylor Tavares, J.V.Drevets, W.C.Sahakian, B.J.Cognition in mania and depression. Psychol Med. 2003; 33: 959967.CrossRefGoogle ScholarPubMed
Tchantchou, F.Graves, M.Ortiz, D.Chan, A.et al.S-adenosyl methionine: a connection between nutritional and genetic risk factors for neurodegeneration in Alzheimer's disease. J Nutr Health Aging. 2006; 10: 541544.Google ScholarPubMed
Trivedi, M.H.Hollander, E.Nutt, D.Blier, P.Clinical evidence and potential neurobiological underpinnings of unresolved symptoms of depression. J Clin Psychiatry. 2008; 69: 246258.CrossRefGoogle ScholarPubMed
Williams, A.C.Ramsden, D.B.Nicotinamide homeostasis: a xenobiotic pathway that is key to development and degenerative diseases. Med Hypotheses. 2005; 65: 353362.CrossRefGoogle ScholarPubMed
Williams, A.L.Girard, C.Jui, D.Sabina, A.et al.S-adenosylmethionine (SAMe) as treatment for depression: a systematic review. Clin Invest Med. 2005; 28: 132139.Google ScholarPubMed
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