| MEDLINE abstracts on SAMe (S-Adenosyl-L-Methionine) |
| Research summaries |
The Annals of Pharmacotherapy:
Vol. 35, No. 11, pp. 1414–1425.
Efficacy of the Dietary Supplement S-Adenosyl-L-Methionine*
CW Fetrow and Juan R Avila
OBJECTIVE: To review existing published clinical evidence surrounding the
dietary supplement SAMe (S-adenosyl-L-methionine).
DATA SOURCES: The majority of information was obtained from primary published
literature identified through MEDLINE search (1966–February 2001). Information
was also obtained through secondary and tertiary sources when available.
STUDY SELECTION AND DATA EXTRACTION: All articles identified from data sources
were evaluated and all relevant information included in this review.
DATA SYNTHESIS: The majority of clinical trial evidence surrounds the
application of SAMe for various depressive disorders, osteoarthritis, and
fibromyalgia. Sample sizes of these trials and the dose employed have varied
considerably. Several reviews and at least two meta-analyses have examined the
available evidence surrounding SAMe in the therapy of depression for trials
completed prior to 1994 and concluded that SAMe was superior to placebo in
treating depressive disorders and approximately as effective as standard
tricyclic antidepressants. Much of this information exists in the form of
isolated case reports or solitary clinical trials. SAMe appears to be well
tolerated, with the majority of adverse effects presenting as mild to moderate
gastrointestinal complaints. However, it is apparent that this agent is not
without risk of more significant psychiatric and cardiovascular adverse events.
Information documenting drug or food interactions with SAMe is very limited.
CONCLUSIONS: Consumers should be instructed to avoid unmonitored consumption of
this dietary supplement until sufficient discussion has taken place with their
primary healthcare provider. Although there exists significant potential for
therapeutic application of SAMe, its uncertain risk profile precludes definitive
recommendation at this time. Healthcare providers and consumers should likely
temper their enthusiasm for this dietary supplement until sufficient information
becomes available.
Back to 'SAMe is Effective for Depression'
Int J Neuropsychopharmacol 2002
Dec;5(4):287-94
A double-blind, randomized parallel-group, efficacy and safety study of
intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus
imipramine in patients with major depressive disorder.
Pancheri P, Scapicchio P, Chiaie RD.
III Clinica Psichiatrica, Universita 'La Sapienza', Viale dell'Universita 30
(00185), Rome, Italy.
S-adenosyl-L-methionine (SAMe) is a natural substance which constitutes the most
important methyl donor in transmethylation reactions in the central nervous
system. Several clinical trials have shown that SAMe possesses an antidepressant
activity. This multicentre study was carried out to confirm both efficacy and
safety of SAMe in the treatment of major depression. SAMe was given
intramuscularly (i.m.) at a dose of 400 mg/d, double-blind, vs. 150 mg/d oral
Imipramine (IMI) in patients with a diagnosis of major depressive episode, with
a baseline score on the 21-item Hamilton Depression Rating Scale (HAMD) of
>/=18. A total of 146 patients received SAMe whereas 147 received IMI for a
period of 4 wk. The two main efficacy measures were endpoint HAMD score and
percentage of responders to Clinical Global Impression (CGI) at week 4.
Secondary efficacy measures were the final Montgomery-Asberg Depression Rating
Scale (MADRS) scores and the response rate intended as a fall in HAMD scores of
at least 50% with respect to baseline. The analysis of safety and tolerability
was conducted in all treated patients. SAMe and IMI did not differ significantly
on any efficacy measure, either main or secondary. Adverse events were
significantly less in patients treated with SAMe compared to those treated with
IMI. These data show 400 mg/d i.m. SAMe to be comparable to 150 mg/d oral IMI in
terms of antidepressive efficacy, but significantly better tolerated. These
findings suggest interesting perspectives for the use of SAMe in depression.
PMID: 12466028 [PubMed - in process]
Back to 'SAMe is Effective for Depression'
Am J Clin Nutr 2002 Nov;76(5):1158S-61S Related Articles, Links
Role of S-adenosyl-L-methionine in the treatment of depression: a review of the
evidence.
Mischoulon D, Fava M.
Harvard Medical School, Depression Clinical and Research Program, Massachusetts
General Hospital, Boston 02114, USA. dmischoulon@partners.org
Major depression remains difficult to treat, despite the wide array of
registered antidepressants available. In recent years there has been a surge in
the popularity of natural or alternative medications. Despite this growing
popularity, there is limited evidence for the effectiveness of many of these
natural treatments. S-adenosyl-L-methionine (SAMe) is one of the better studied
of the natural remedies. SAMe is a methyl donor and is involved in the synthesis
of various neurotransmitters in the brain. Derived from the amino acid L-methionine
through a metabolic pathway called the one-carbon cycle, SAMe has been
postulated to have antidepressant properties. A small number of clinical trials
with parenteral or oral SAMe have shown that, at doses of 200-1600 mg/d, SAMe is
superior to placebo and is as effective as tricyclic antidepressants in
alleviating depression, although some individuals may require higher doses. SAMe
may have a faster onset of action than do conventional antidepressants and may
potentiate the effect of tricyclic antidepressants. SAMe may also protect
against the deleterious effects of Alzheimer disease. SAMe is well tolerated and
relatively free of adverse effects, although some cases of mania have been
reported in bipolar patients. Overall, SAMe appears to be safe and effective in
the treatment of depression, but more research is needed to determine optimal
doses. Head-to-head comparisons with newer antidepressants should help to
clarify SAMe's place in the psychopharmacologic armamentarium.
Publication Types:
* Review
* Review, Tutorial
PMID: 12420702 [PubMed - indexed for MEDLINE]
Back to 'SAMe is Effective for Depression'
Am J Clin Nutr 2002 Nov;76(5):1172S-6S Related Articles, Links
Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine
1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison
with imipramine in 2 multicenter studies.
Delle Chiaie R, Pancheri P, Scapicchio P.
III Clinica Psichiatrica La Sapienza University, Rome, Italy. delle.chiaie@flashnet.it
BACKGROUND: S-Adenosyl-L-methionine (SAMe), a natural compound, is the most
important methyl donor in the central nervous system. In several clinical
trials, SAMe showed antidepressant activity. OBJECTIVE: Two multicenter studies
were conducted in patients with a diagnosis of major depressive episode
[baseline score on the 21-item Hamilton Depression Rating Scale (HAM-D) >or=18]
to confirm the efficacy and safety of SAMe in the treatment of major depression.
In the first study (MC3), 1600 mg SAMe/d was given orally; whereas, in the
second study (MC4), 400 mg SAMe/d was given intramuscularly. In both studies,
the effects of SAMe were compared with those of 150 mg imipramine/d given orally
in a double-blind design. DESIGN: In MC3, 143 patients received oral SAMe and
138 patients received imipramine for 6 wk. In MC4, 147 patients received SAMe
intramuscularly and 148 patients received imipramine for 4 wk. In both studies
the 2 main efficacy measures were the final HAM-D score and the percentage of
responders to Clinical Global Impression at the endpoint. Secondary efficacy
measures were the endpoint Montgomery-Asberg Depression Rating Scale scores and
the percentage of responders, responders being those patients showing a decrease
in HAM-D score of >or=50% from baseline. RESULTS: In both studies, the results
of SAMe and imipramine treatment did not differ significantly for any efficacy
measure. However, significantly fewer adverse events were observed in the
patients treated with SAMe. CONCLUSIONS: The antidepressive efficacy of 1600 mg
SAMe/d orally and 400 mg SAMe/d intramuscularly is comparable with that of 150
mg imipramine/d orally, but SAMe is significantly better tolerated.
Publication Types:
* Clinical Trial
* Multicenter Study
* Randomized Controlled Trial
PMID: 12418499 [PubMed - indexed for MEDLINE]
Back to 'SAMe is Effective for Depression'
Am J Clin Nutr 2002 Nov;76(5):1162S-71S
Electrophysiological neuroimaging of the central effects of S-adenosyl-L-methionine
by mapping of electroencephalograms and event-related potentials and
low-resolution brain electromagnetic tomography.
Saletu B, Anderer P, Di Padova C, Assandri A, Saletu-Zyhlarz GM.
Department of Psychiatry, University of Vienna, Austria. bernd.saletu@akh-wien.ac.at
BACKGROUND: S-Adenosyl-L-methionine (SAMe, or ademetionine) is a naturally
occurring molecule used as both a nutraceutical and a pharmaceutical to treat
depression. OBJECTIVE: The central mode of action of SAMe was investigated in 20
healthy volunteers by mapping of electroencephalograms (EEGs) and event-related
potentials (ERPs) and low-resolution brain electromagnetic tomography (LORETA).
DESIGN: In an acute and subacute, double-blind, placebo-controlled, crossover
study, subjects received in random order infusions of 800 mg SAMe and placebo
for 7 d, with a washout period of 3 wk between the 2 treatment periods. EEG
recordings were made 0, 1, 3, and 6 h after and ERP recordings were made 0 and 1
h after the drug infusions on days 1 and 7. RESULTS: Multivariate analyses of
variance and Hotelling T2 tests showed significant acute and subacute
encephalotropic effects of SAMe compared with placebo. Acute pharmaco-EEG
changes were typical of classic antidepressants of the thymoleptic type;
subacute alterations were typical of cognition enhancers. Regarding ERPs,
standard N1 and P2 latencies were shortened, and target P300 latencies were
lengthened. N1 amplitudes increased after subacute treatment, and
temporooccipital P300 amplitudes increased after the acute dose. Similar changes
were described for antidepressants. LORETA showed that the N2 source strength
increased in both the left and the right temporal lobes, whereas the P300 source
strength increased in the dorsolateral prefrontal regions and decreased in the
ventral limbic regions. CONCLUSION: EEG-ERP mapping identified SAMe as an
antidepressant. LORETA targeted brain regions crucial in the therapeutic
efficacy of antidepressants.
Publication Types:
* Clinical Trial
* Randomized Controlled Trial
PMID: 12418497 [PubMed - indexed for MEDLINE]
Back to 'SAMe is Effective for Depression'
Am J Clin Nutr 2002 Nov;76(5):1151S-7S
S-Adenosyl-L-methionine (SAMe): from the bench to the bedside--molecular basis
of a pleiotrophic molecule.
Bottiglieri T.
Baylor University Medical Center, Institute of Metabolic Disease, Dallas, TX
75226, USA. teodorob@baylorhealth.edu
S-Adenosyl-L-methionine (SAMe), a metabolite present in all living cells, plays
a central role in cellular biochemistry as a precursor to methylation,
aminopropylation, and transsulfuration pathways. As such, SAMe has been studied
extensively since its chemical structure was first described in 1952. Decades of
research on the biochemical and molecular roles of SAMe in cellular metabolism
have provided an extensive foundation for its use in clinical studies, including
those on depression, dementia, vacuolar myelopathy, liver disease, and
osteoarthritis. This article provides an overview of the biochemical, molecular,
and therapeutic effects of this pleiotrophic molecule.
Publication Types:
* Review
* Review, Tutorial
PMID: 12418493 [PubMed - indexed for MEDLINE]
Back to 'SAMe is Effective for Depression'
Neurosci Lett 2002 Mar 15;321(1-2):110-4 Related Articles, Links
S-adenosyl-L-methionine prevents 5-HT(1A) receptors up-regulation induced by
acute imipramine in the frontal cortex of the rat.
Bellido I, Gomez-Luque A, Plaza A, Rius F, Ortiz P, Sanchez de la Cuesta F.
Department of Pharmacology and Clinical Therapeutics, School of Medicine,
University of Malaga, Malaga, Spain. ibellido@uma.es
S-adenosyl-L-methionine (SAM) has shown efficacy in speeding the onset of the
antidepressant effect of imipramine in depressed patients. This effect may be
related to their interactions at the serotonin(1A) (5-HT(1A)) receptors. Acute
imipramine up-regulated the frontal cortex 5-HT(1A) receptors (B(max), 51.5 +/-
8.4 fmol/mg protein) vs. saline (B(max), 27.5 +/- 5.9 fmol/mg protein), and did
not show antidepressant effect. Acute SAM and imipramine+SAM did not modify
frontal cortex 5-HT(1A) receptors, and showed antidepressant effects (decrease
of the immobility response of 26%, P<0.01; and 47%, P<0.001) vs. saline. All the
chronic treatments showed antidepressant effects and up-regulated the
hippocampus 5-HT(1A) receptors. SAM prevents the 5-HT(1A) receptor up-regulation
induced by acute imipramine in the frontal cortex. This mechanism may contribute
to imipramine's antidepressant effect.
PMID: 11872268 [PubMed - indexed for MEDLINE]
Back to 'SAMe is Effective for Depression'
Neuroreport 2001 Dec 21;12(18):3939-42 Related Articles, Links
Influence of SAMe on the modifications of brain polyamine levels in an animal
model of depression.
Genedani S, Saltini S, Benelli A, Filaferro M, Bertolini A.
Department of Biomedical Sciences, Section of Pharmacology, University of Modena
and Reggio Emilia, Via G. Campi 287, 41100 Modena, Italy.
The mechanism(s) of the antidepressant activity of S-adenosyl-L-methionine (SAMe)
have not yet been elucidated. SAMe is essential for the synthesis of polyamines,
which have a key role in protein synthesis, cell proliferation, and neuronal
plasticity. On the other hand, accumulating data indicate that depression is
associated with a reduction in regional brain volume and that antidepressants
increase neurogenesis in defined brain regions and also influence neuronal
plasticity. Here we show that in a validated rat model of depression (chronic
unpredictable mild stress-induced anhedonia) there is a significant reduction of
putrescine, spermidine and spermine in the hippocampus, and of only putrescine
in the nucleus accumbens septi. SAMe, at a fully antidepressant dose (300 mg/kg
i.m., daily for 7 days), completely restores the levels of putrescine in the
nucleus accumbens, and restores in part the levels of both spermidine and
spermine in the hippocampus. These results may suggest (i) a role for brain
polyamines in depression and in reward processes, and (ii) that the
antidepressant effect of SAMe may be due, at least in part, to a normalization
of putrescine levels in the nucleus accumbens septi.
PMID: 11742215 [PubMed - indexed for MEDLINE]
Back to 'SAMe is Effective for Depression'
8: Ann Pharmacother 2001 Nov;35(11):1414-25 Related Articles, Links
Efficacy of the dietary supplement S-adenosyl-L-methionine.
Fetrow CW, Avila JR.
Pharmacy Services, University of Pittsburgh Medical Center, Passavant Hospital,
PA 15237-5842, USA. fetrowcw@ph.upmc.edu
OBJECTiVE: To review existing published clinical evidence surrounding the
dietary supplement SAMe (S-adenosyl-L-methionine). DATA SOURCES: The majority of
information was obtained from primary published literature identified through
MEDLINE search (1966-February 2001). Information was also obtained through
secondary and tertiary sources when available. STUDY SELECTION AND DATA
EXTRACTION: All articles identified from data sources were evaluated and all
relevant information included in this review. DATA SYNTHESIS: The majority of
clinical trial evidence surrounds the application of SAMe for various depressive
disorders, osteoarthrits, and fibromyalgia. Sample sizes of these trials and the
dose employed have varied considerably. Several reviews and at least two
meta-analyses have examined the available evidence surrounding SAMe in the
therapy of depression for trials completed prior to 1994 and concluded that SAMe
was superior to placebo in treating depressive disorders and approximately as
effective as standard tricyclic antidepressants. Much of this information exists
in the form of isolated case reports or solitary clinical trials. SAMe appears
to be well tolerated, with the majority of adverse effects presenting as mild to
moderate gastrointestinal complaints. However, it is apparent that this agent is
not without risk of more significant psychiatric and cardiovascular adverse
events. Information documenting drug or food interactions with SAMe is very
limited. CONCLUSIONS: Consumers should be instructed to avoid unmonitored
consumption of this dietary supplement until sufficient discussion has taken
place with their primary healthcare provider. Although there exists significant
potential for therapeutic application of SAMe, its uncertain risk profile
precludes definitive recommendation at this time. Healthcare providers and
consumers should likely temper their enthusiasm for this dietary supplement
until sufficient information becomes available.
PMID: 11724095 [PubMed - indexed for MEDLINE]
Back to 'SAMe is Effective for Depression'
Psychiatry Res 1995 Apr 28;56(3):295-7 Related Articles, Links
Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methionine.
Fava M, Giannelli A, Rapisarda V, Patralia A, Guaraldi GP.
Depression Research Program, Massachusetts General Hospital, Boston 02114, USA.
A possible method of reducing the delay in antidepressant response is to use S-adenosyl-L-methionine
(SAMe), a naturally occurring compound that appears to have a rapid onset of
effect in the treatment of depression. In this open, multicenter study, 195
patients were given 400 mg of SAMe, administered parenterally, for 15 days.
Depressive symptoms remitted after both 7 and 15 days of treatment with SAMe,
and no serious adverse events were reported. Further studies with a double-blind
design are needed to confirm this preliminary indication that SAMe is a
relatively safe and fast-acting antidepressant.
Publication Types:
* Clinical Trial
* Multicenter Study
PMID: 7568552 [PubMed - indexed for MEDLINE]
Back to 'SAMe is Effective for Depression'
Acta Psychiatr Scand 1990 May;81(5):432-6 Related Articles, Links
The antidepressant potential of oral S-adenosyl-l-methionine.
Rosenbaum JF, Fava M, Falk WE, Pollack MH, Cohen LS, Cohen BM, Zubenko GS.
Clinical Psychopharmacology Unit, Massachusetts General Hospital, Boston 02114.
S-adenosyl-l-methionine (SAMe), a naturally occurring brain metabolite, has
previously been found to be effective and tolerated well in parenteral form as a
treatment of major depression. To explore the antidepressant potential of oral
SAMe, we conducted an open trial in 20 outpatients with major depression,
including those with (n = 9) and without (n = 11) prior history of
antidepressant nonresponse. The group as a whole significantly improved with
oral SAMe: 7 of 11 non-treatment-resistant and 2 of 9 treatment-resistant
patients experienced full antidepressant response. Side effects were mild and
transient.
Publication Types:
* Clinical Trial
PMID: 2113347 [PubMed - indexed for MEDLINE]