S-adenosyl-L-methionine as an Antidepressant

Results of a MEDLINE Search by, Ivan Goldberg, MD

Psychiatry Res 1995 Apr 28;56(3):295-7 

Rapidity of onset of the antidepressant effect of parenteral

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
Acta Neurol Scand Suppl 1994;154:7-14 

S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical

Bressa GM

Department of Psychiatry, University Cattolica Sacro Cuore School of Medicine,
Rome, Italy.

INTRODUCTION--S-adenosyl-l-methionine (SAMe) is a naturally-occurring substance
which is a major source of methyl groups in the brain. MATERIAL AND METHODS--We
conducted a meta-analysis of the studies on SAMe to assess the efficacy of this
compound in the treatment of depression compared with placebo and standard
tricyclic antidepressants. RESULTS--Our meta-analysis showed a greater response
rate with SAMe when compared with placebo, with a global effect size ranging
from 17% to 38% depending on the definition of response, and an antidepressant
effect comparable with that of standard tricyclic antidepressants.
CONCLUSION--The efficacy of SAMe in treating depressive syndromes and disorders
is superior with that of placebo and comparable to that of standard tricyclic
antidepressants. Since SAMe is a naturally occurring compound with relatively
few side-effects, it is a potentially important treatment for depression.
Drugs 1994 Aug;48(2):137-52 

The clinical potential of ademetionine (S-adenosylmethionine) in neurological

Bottiglieri T, Hyland K, Reynolds EH

Metabolic Disease Center, Baylor Research Institute, Dallas, Texas.

This review focuses on the biochemical and clinical aspects of methylation in
neuropsychiatric disorders and the clinical potential of their treatment with
ademetionine (S-adenosylmethionine; SAMe). SAMe is required in numerous
transmethylation reactions involving nucleic acids, proteins, phospholipids,
amines and other neurotransmitters. The synthesis of SAMe is intimately linked
with folate and vitamin B12 (cyanocobalamin) metabolism, and deficiencies of
both these vitamins have been found to reduce CNS SAMe concentrations. Both
folate and vitamin B12 deficiency may cause similar neurological and
psychiatric disturbances including depression, dementia, myelopathy and
peripheral neuropathy. SAMe has a variety of pharmacological effects in the
CNS, especially on monoamine neurotransmitter metabolism and receptor systems.
SAMe has antidepressant properties, and preliminary studies indicate that it
may improve cognitive function in patients with dementia. Treatment with methyl
donors (betaine, methionine and SAMe) is associated with remyelination in
patients with inborn errors of folate and C-1 (one-carbon) metabolism. These
studies support a current theory that impaired methylation may occur by
different mechanisms in several neurological and psychiatric disorders.
Acta Neurol Scand Suppl 1994;154:15-8 

S-adenosylmethionine blood levels in major depression: changes with drug

Bell KM, Potkin SG, Carreon D, Plon L

University of California, Irvine Medical Center, Orange 92668.

INTRODUCTION--The relationship between plasma levels of S-adenosylmethionine
(SAMe), an endogenous methyl donor, and clinical response were studied in
patients with a DSM-III-R diagnosis of major depression. MATERIAL AND
METHODS--A double-blind randomized protocol comparing oral SAMe with oral
desipramine, involving a total of 26 patients, was employed. RESULTS--At the
end of the 4-week trial, 62% of the patients treated with SAMe and 50% of the
patients treated with desipramine had significantly improved. Regardless of the
type of treatment, patients with a 50% decrease in their Hamilton Depression
Scale (HAM-D) score showed a significant increase in plasma SAMe concentration.
CONCLUSION--The significant correlation between plasma SAMe levels and the
degree of clinical improvement in depressed patients regardless of the type of
treatment suggests that SAMe may play an important role in regulating mood.
Acta Neurol Scand Suppl 1994;154:19-26 

S-adenosylmethionine levels in psychiatric and neurological disorders: a

Bottiglieri T, Hyland K

Metabolic Disease Center, Baylor Research Institute, Dallas, TX 75226.

INTRODUCTION--S-adenosylmethionine (SAMe) is an important methyl donor in over
35 methylation reactions involving DNA, proteins, phospholipids and catechol-
and indole- amines. MATERIAL AND METHODS--This article reviews the studies that
have examined brain and blood levels of SAMe in several psychological,
neurological and metabolic disorders. RESULTS--Although studies have found no
consistent changes in whole blood SAMe levels in psychiatric patients, other
investigators have found low cerebrospinal fluid (CSF) SAMe levels in patients
with neurological disorders such as Alzheimer's dementia, subacute combined
degeneration of the spinal cord (SACD), and HIV-related neuropathies, as well
as in patients with metabolic disorders such as 5, 10-CH2-H4 folate reductase
deficiency. CONCLUSION--Intravenous or oral administration of SAMe thus
represents a possible treatment for these neurological and metabolic disorders.
J Psychiatry Neurosci 1993 Nov;18(5):235-44 

The use of diet and dietary components in the study of factors controlling
affect in humans: a review.

Young SN

Department of Psychiatry, McGill University, Montreal, Quebec, Canada.

Although one of the first biological treatments of a major psychiatric disorder
was the dietary treatment of pellagra, the use of diet and dietary components
in the study of psychopathology has not aroused much interest. This article
reviews three areas in which the dietary approach has provided interesting
information. The tryptophan depletion strategy uses a mixture of amino acids
devoid of tryptophan to lower brain tryptophan in order to study the symptoms
that can be elicited. One effect of tryptophan depletion is a lowering of mood,
the magnitude of which seems to depend on the baseline state of the subject.
Therefore, recovered depressed patients often undergo an acute relapse, while
normal subjects show more moderate changes of mood. Totally euthymic subjects
show no lowering of mood, but subjects with high normal depression scale scores
or subjects with a family history of depression show a moderate lowering of
mood. These data indicate that low serotonin levels alone cannot cause
depression. However, serotonin does have a direct effect on mood, and low
levels of serotonin contribute to the etiology of depression in some depressed
patients. Folic acid deficiency causes a lowering of brain serotonin in rats,
and of cerebrospinal fluid 5-hydroxyindoleacetic acid in humans. There is a
high incidence of folate deficiency in depression, and there are indications in
the literature that some depressed patients who are folate deficient respond to
folate administration. Folate deficiency is known to lower levels of
S-adenosylmethionine, and S-adenosylmethionine is an antidepressant that raises
brain serotonin levels. These data suggest that low levels of serotonin in some
depressed patients may be a secondary consequence of low levels of
S-adenosylmethionine. They also suggest that the dietary intake and
psychopharmacological action of methionine, the precursor of
S-adenosylmethionine, should be studied in patients with depression. Normal
meals have definite effects on mood and performance in humans. The composition
of the meal, in terms of protein and carbohydrate content, can influence these
behaviors. Because protein and carbohydrate meals can influence brain serotonin
in rats, these effects in humans have usually been interpreted in terms of
altered serotonin functioning. However, the current balance of evidence is
against the involvement of serotonin in the acute effects of protein and
carbohydrate meals in humans. The underlying mechanisms involved are unknown,
but there are a variety of possibilities.
Psychother Psychosom 1993;59(1):34-40 

Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed
postmenopausal women.

Salmaggi P, Bressa GM, Nicchia G, Coniglio M, La Greca P, Le Grazie C

Obstetrics and Gynecology Department, University La Sapienza School of
Medicine, Rome, Italy.

S-adenosyl-L-methionine (SAMe) is a naturally occurring substance which is a
major source of methyl groups in the brain and has been found in previous
studies to be an effective antidepressant. The aim of this study was to assess
the efficacy of oral SAMe in the treatment of depressed postmenopausal women in
a 30-day double-blind placebo-controlled randomized trial. During the course of
the study, 80 women, between the ages of 45 and 59, who were diagnosed as
having DSM-III-R major depressive disorder or dysthymia between 6 and 36 months
following either natural menopause or hysterectomy, underwent 1 week of
single-blind placebo washout, followed by 30 days of double-blind treatment
with either SAMe 1,600 mg/day or placebo. There was a significantly greater
improvement in depressive symptoms in the group treated with SAMe compared to
the placebo group from day 10 of the study. Side effects were mild and
J Basic Clin Physiol Pharmacol 1992 Jan-Mar;3(1):1-17 

Antidepressant activity of S-adenosyl-L-methionine in mice and rats.

Czyrak A, Rogoz Z, Skuza G, Zajaczkowski W, Maj J

Institute of Pharmacology, Polish Academy of Sciences, Krakow.

S-Adenosyl-L-methionine (SAM), main methyl donor, was tested in mice and rats
in several models which are predictive of possible antidepressant activity. In
the forced swimming test in rats the effect of SAM was compared with that of
the tricyclic antidepressant amitriptyline. SAM decreased dose-dependently
immobility time in the forced swimming test in mice and rats, these effects
being antagonized by haloperidol and prazosin (the latter only in rats).
Locomotor or exploratory activity in mice and rats was not increased by SAM.
D-Amphetamine-induced locomotor hyper-activity in rats was increased by
repeated (14 days, twice daily) treatment with SAM. Behavioral stimulation
induced by D-amphetamine or L-dopa (given with benserazide) in mice was not
changed by a single dose of SAM. The drug reduced hypothermia induced by
apomorphine in mice. Hypothermia induced by reserpine or clonidine in mice was
not antagonized. SAM increased the amplitude of the acoustic startle reflex.
The above results indicate that the psychopharmacological profile of SAM
resembles that of antidepressants in only some tests. The mechanism by which
SAM produces its antidepressant effect needs further investigation.
Psychiatry Res 1992 Dec;44(3):257-62 

Efficacy of S-adenosyl-L-methionine in speeding the onset of action of

Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H

Special Studies Clinic, Mexican Institute of Psychiatry, Tlalpan.

A double-blind clinical trial was carried out to evaluate the efficacy of
S-adenosyl-L-methionine (SAMe) in speeding the onset of action of imipramine
(IMI). SAMe is a naturally occurring substance that has been shown to possess
antidepressant activity with a rapid mode of onset and minimal side effects.
Sixty-three outpatients with moderate to severe depression were included in the
study. After an initial 1-week placebo period, only 40 patients entered the
active treatment phase. During the first 2 weeks of the trial, half of these
patients received 200 mg/day of SAMe intramuscularly, while the other half
received placebo. Simultaneously, oral IMI was administered to all patients at
a fixed dose of 150 mg/day. The onset of clinical response was determined by
evaluating patients every second day. By the end of week 2, the parenteral
treatment was suppressed and IMI was adjusted according to individual needs.
Depressive symptoms decreased earlier in the patients who were receiving the
SAMe-IMI combination than in those who were receiving the placebo-IMI
Am J Psychiatry 1990 May;147(5):591-5 

Oral S-adenosylmethionine in depression: a randomized, double-blind,
placebo-controlled trial.

Kagan BL, Sultzer DL, Rosenlicht N, Gerner RH

Department of Psychiatry, West Los Angeles VA Medical Center, CA.

Methylation has been implicated in the etiology of psychiatric illness.
Parenteral S-adenosylmethionine, a methyl group donor, has been shown to be an
effective antidepressant. The authors studied the antidepressant effect of oral
S-adenosylmethionine in a randomized, double-blind, placebo-controlled trial
for 15 inpatients with major depression. The results suggest that oral
S-adenosylmethionine is a safe, effective antidepressant with few side effects
and a rapid onset of action. S-Adenosylmethionine induced mania in a patient
with no history of mania. S-Adenosylmethionine may be useful for patients who
cannot tolerate tricyclic anti-depressants. These findings support a role for
methylation in the pathophysiology of depression.
Acta Psychiatr Scand 1990 May;81(5):432-6 

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
J Psychiatr Res 1990;24(2):177-84 

Neuroendocrine effects of S-adenosyl-L-methionine, a novel putative

Fava M, Rosenbaum JF, MacLaughlin R, Falk WE, Pollack MH, Cohen LS, Jones L,
Pill L

Clinical Psychopharmacology Unit, Massachusetts General Hospital, Harvard
Medical School, Boston 02114.

S-adenosyl-L-methionine (SAMe), a putative antidepressant, is a naturally
occurring substance whose mechanism of action is still a matter of speculation.
It has been recently postulated that SAMe may increase the dopaminergic tone in
depressed patients. Since dopamine inhibits both thyrotropin (TSH) and
prolactin secretion, we investigated the effects of treatment with SAMe on the
TSH and prolactin response to thyrotropin-releasing-hormone (TRH) stimulation
in 7 depressed outpatient women (mean age: 46.1 +/- 7.2 years) and 10 depressed
outpatient men (mean age: 38.0 +/- 10.0 years) participating in a six-week open
study of oral SAMe in the treatment of major depression. At the end of the
study, there was a significant reduction after treatment with SAMe in the
response of both prolactin and TSH to TRH stimulation in the group of depressed
men compared to pre-treatment values. On the other hand, in the group of
depressed women, the posttreatment prolactin response to TRH did not appear to
change when compared to pre-treatment and the TSH response to TRH challenge
tended even to augment slightly after treatment with SAMe. Our results, at
least in depressed men, seem to support the hypothesis of a stimulating effect
of SAMe on the dopaminergic system.
Drugs 1989 Sep;38(3):389-416 

S-adenosyl-L-methionine. A review of its pharmacological properties and
therapeutic potential in liver dysfunction and affective disorders in relation
to its physiological role in cell metabolism.

Friedel HA, Goa KL, Benfield P

ADIS Drug Information Services, Auckland, New Zealand.

S-Adenosyl-L-methionine (SAMe) is a naturally occurring molecule distributed to
virtually all body tissues and fluids. It is of fundamental importance in a
number of biochemical reactions involving enzymatic transmethylation,
contributing to the synthesis, activation and/or metabolism of such compounds
as hormones, neurotransmitters, nucleic acids, proteins, phospholipids and
certain drugs. The administration of a stable salt of SAMe, either orally or
parenterally, has been shown to restore normal hepatic function in the presence
of various chronic liver diseases (including alcoholic and non-alcoholic
cirrhosis, estrogen-induced and other forms of cholestasis), to prevent or
reverse hepatotoxicity due to several drugs and chemicals such as alcohol,
paracetamol (acetaminophen), steroids and lead, and to have antidepressant
properties. In all of these studies SAMe has been very well tolerated, a
finding of great potential benefit given the well-known adverse effects of
tricyclic antidepressants with which it has been compared in a few trials.
Thus, with its novel mechanisms of action and good tolerability, SAMe is an
interesting new therapeutic agent in several diverse disease conditions, but
its relative value remains to be determined in appropriate comparisons with
other treatment modalities in current use.
Psychopharmacol Bull 1989;25(2):238-42 

Parenteral S-adenosyl-methionine (SAMe) in depression: literature review and
preliminary data.

Janicak PG, Lipinski J, Davis JM, Altman E, Sharma RP
Actas Luso Esp Neurol Psiquiatr Cienc Afines 1988 May-Jun;16(3):201-3 

[S-Adenosyl-L-methionine. Latest results on its efficacy as an antidepressive
[Article in Spanish]

Ortiz P
Encephale 1988 May-Jun;14(3):113-8 

[Therapeutic indications of S-adenosyl methionine in neuropsychiatry].
[Article in French]

Tramoni AV, Azorin JM

Clinique de Psychiatrie et de Psychologie Medicale, C.H.U. Timone, Marseille.

Studies conducted by Italian and Anglo-saxon authors underline the
thymoanaleptic properties of a transmethylant biological substance, the
S-adenosyl methionine (SAMe). The authors discuss a review of literature
concerning the use of SAMe in neuro-psychiatry, particularly in the treatment
of affective disorders. The many physiopathological implications are subtended
by the biological inter-relations of SAMe with other biological substances.
Some hypotheses are proposed on the role played by phospholipid methylation,
the folate metabolism and the purinergic transmission in mental diseases.
Am J Psychiatry 1988 Sep;145(9):1110-4 

S-adenosylmethionine treatment of depression: a controlled clinical trial.

Bell KM, Plon L, Bunney WE Jr, Potkin SG

University of California, Irvine Medical Center, Orange 92668.

The antidepressant properties of S-adenosylmethionine, an endogenous methyl
donor, were studied in inpatients who met the DSM-III criteria for major
depression. Nine patients given intravenous S-adenosylmethionine and nine given
low oral doses of imipramine were compared in a double-blind design for 14
days. The S-adenosylmethionine produced superior results by the end of the
first week of treatment. By the end of the second week, 66% of the
S-adenosylmethionine patients had a clinically significant improvement in
depressive symptoms, compared to 22% of the imipramine patients. Side effects
appeared to be fewer with S-adenosylmethionine than with imipramine during the
last 5 days of the study.
Ala J Med Sci 1988 Jul;25(3):313-6 

Published erratum appears in Ala J Med Sci 1988 Oct;25(4):496

Rapid antidepressant response with SAMe. A double-blind study.

Potkin SG, Bell K, Plon L, Bunney WE Jr
Neurosci Biobehav Rev 1988 Summer;12(2):139-41 

S-adenosylmethionine in the treatment of depression.

Vahora SA, Malek-Ahmadi P

Texas Tech University, School of Medicine, Department of Psychiatry, Lubbock

The antidepressant property of S-adenosylmethionine (SAMe) has been supported
by several uncontrolled and controlled studies. Compared to standard
antidepressant agents, SAMe has fewer side-effects and shorter lag period.
Future studies to delineate SAMe-responsive depression are warranted.
Am J Med 1987 Nov 20;83(5A):95-103 

Neuropharmacology of S-adenosyl-L-methionine.

Baldessarini RJ

Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.

The metabolite S-adenosyl-L-methionine (SAMe), when prepared as the stable
p-toluene-sulfonate complex of its sulfate salt and given parenterally in high
doses, appears to have mood-elevating effects in depressed adults. The material
is remarkably well tolerated when given by injection or intravenous infusion
for this purpose, even in elderly or demented patients. Assuming that the
toluene sulfonate component is inert, SAMe appears to have central
neuropharmacologic effects after systemic injection in high doses.
Nevertheless, the functional consequences of these remain unclear and, indeed,
the ability of exogenous SAMe to reach the brain, and especially neuronal
cytoplasm, is limited. SAMe has small effects on monoamine metabolism and,
after injection, appears to have effects on the microviscosity of cell
membranes that may be related to stimulation of phospholipid synthesis. The
recent introduction of an orally administered form of SAMe for use in the
treatment of osteoarthritis promises to stimulate further study of SAMe in
disease-associated depression, major depressive disorder, and other
neuropsychiatric conditions.
Am J Med 1987 Nov 20;83(5A):104-6 

S-adenosylmethionine and affective disorder.

Carney MW, Toone BK, Reynolds EH

Department of Psychiatry, Northwick Park Hospital, Harrow, England.

Several open and double-blind studies suggest that SAMe may have an
anti-depressant effect, and further studies are indicated. SAMe may exert a
beneficial effect selectively on endogenous rather than neurotic depression.
SAMe crosses the blood-brain barrier. SAMe is involved in several central
enzyme pathways relating to transmethylation and folate and monoamine
metabolism as well as in membrane function and neuro-transmission. The
neuropharmacology of SAMe's effect on mood and the switch mechanism has yet to
be fully explored. The actions of SAMe on the dopaminergic system are as yet
unclear. SAMe is a physiologic substance that is non-toxic and relatively free
of severe side effects (with the exception of mania, which may be a
manifestation of the basic mood disorder.
Int Clin Psychopharmacol 1987 Apr;2(2):97-102 

The influence of S-adenosylmethionine (SAM) on prolactin in depressed patients.

Thomas CS, Bottiglieri T, Edeh J, Carney MW, Reynolds EH, Toone BK

Twenty subjects entered a double-blind placebo-controlled trial of SAM in
depression. Prolactin concentrations were measured before and after 14 days'
treatment. There was a highly significant fall in prolactin concentrations in
the SAM-treated group.
Biol Psychiatry 1986 Dec;21(14):1391-8 

Abnormalities of one-carbon metabolism in psychiatric disorders: study of
methionine adenosyltransferase kinetics and lipid composition of erythrocyte

Smythies JR, Alarcon RD, Morere D, Monti JA, Steele M, Tolbert LC, Walter-Ryan

Two independent lines of inquiry have implicated some disturbance of one-carbon
cycle metabolism in affective disorders. Folic acid deficiency commonly leads
to depression, and S-adenosylmethionine has been reported to have
antidepressant properties. Methionine adenosyltransferase has been reported to
be underactive in depression and schizophrenia and overactive in mania. This
study reports the effects on erythrocyte methionine adenosyltransferase (MAT)
kinetics (Vmax) of a 2-week treatment in a population of patients housed on a
psychiatric research ward. The drug-free schizophrenic patients and depressives
had, upon admission, low Vmax values, and the drug-free manic patients had high
Vmax values on admission. After 2 weeks of appropriate treatment, the values
for all three patient samples showed significant normalization (i.e., the
levels rose in schizophrenics and depressives and fell in manics). We have
further shown that pretreatment low levels of erythrocyte membrane
phosphatidylcholine in depressives and high levels in manics show statistically
significant normalization following 2 weeks of pharmacotherapy. The
significance of these results is discussed.
Clin Neuropharmacol 1986;9(4):379-85 

Affective illness and S-adenosyl methionine: a preliminary report.

Carney MW, Edeh J, Bottiglieri T, Reynolds EM, Toone BK

S-Adenosyl methionine may well have an antidepressant action beyond a placebo
effect but this is virtually confined to endogenous depression. This should be
subjected to further study. Our own double-blind placebo-controlled study is
still incomplete. The indications are that SAM specifically affects folate,
dopamine, and serotonin metabolism as well as activating and switching brain
mechanisms. This suggests exciting prospects for further investigations. SAM is
a nontoxic physiological metabolite virtually free of side effects.
J Affect Disord 1985 Nov;9(3):297-301 

One-carbon metabolism disturbances in affective disorders. A preliminary

Alarcon RD, Tolbert LC, Monti JA, Morere DA, Walter-Ryan WG, Kemp B, Smythies

Methionine adenosyltransferase (MAT) activity (Vmax) and the relative amount of
phosphatidylcholine (% PC) were measured in erythrocytes of up to 30 DSM-III
diagnosed manic, 17 unipolar depressed patients, and 28 normal controls. Manic
subjects had significantly higher and depressed subjects significantly lower
MAT Vmax than normals. The relative amount of PC was in the low range for the
depressives, and in the high range for the manics. Depressive patients present,
in these tests, similar abnormalities to those seen previously in schizophrenic
patients. Clinical and diagnostic implications of these findings are discussed.
Lancet 1984 Jul 28;2(8396):196-8 

Methylation and mood.

Reynolds EH, Carney MW, Toone BK

S-adenosylmethionine (SAM) has antidepressant properties. The commonest
neuropsychiatric complication of severe folate deficiency is depression. These
independent observations suggest that methylation in the nervous system may
underlie the expression of mood and related processes and may be implicated in
some affective disorders; suggest new biological approaches to the
understanding and treatment of some affective disorders; and may explain why
methionine sometimes aggravates schizophrenia.
Am J Psychiatry 1984 Mar;141(3):448-50 

Open trial of S-adenosylmethionine for treatment of depression.

Lipinski JF, Cohen BM, Frankenburg F, Tohen M, Waternaux C, Altesman R, Jones
B, Harris P

Nine depressed inpatients completed trials with S-adenosylmethionine. Seven
showed improvement or remission of their symptoms. As in European studies, no
side effects were seen except the apparent induction of mania in two patients
with bipolar disorder.
Minerva Med 1975 Nov 17;66(78):4098-101 

[Controlled double-blind study (SAMe-imipramine) in depressive syndromes].
[Article in Italian]

Mantero M, Pastorino P, Carolei A, Agnoli A

Thirty one patients were treated with either S-Adenosylmethionine or Imipramine
in a double-blind clinical trial comparing S-Adenosylmethionine (25 mg i.m.
three times daily) with Imipramine (25 mg i.m. three times daily) administered
for a period of three weeks. Hamilton Rating scores showed no significant
differences between treatments, but such slight differences as were observed
favored S-Adenosylmethionine.

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