S-adenosyl-L-methionine

S-adenosyl-L-methionine (SAMe) is a natural component of the human body. It is available over-the-counter and is more often used for the treatment of arthritis than of depression. 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 some antidepressant properties. A small number of clinical trials with 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 still higher doses. SAMe also helped the tricyclic imipramine work faster. SAMe is well tolerated and relatively free of adverse effects, although some cases of mania have been reported in bipolar patients.

Unfortunately, SAMe is quite expensive at the dosage levels found effective in the research studies. A common price is $1 for a 200 mg tablet meaning that $4-8 per day would be required for the dosages most often used. This would be $120-$240 per month or $1440-$2880 per year.

Folate and vitamin B12 are required both in the methylation of homocysteine to methionine and in the synthesis of S-adenosylmethionine. S-adenosylmethionine is then involved in numerous methylation reactions involving proteins, phospholipids, DNA, and neurotransmitter metabolism. Thus, folate or B12 deficiencies result in deficiencies of SAMe. Both folate and vitamin B12 deficiencies may cause similar neurologic and psychiatric disturbances including depression, dementia, and a demyelinating myelopathy. In one study, giving patients folate increased a measure of their bodies’ SAMe by 43%. Folate has repeatedly been found to be of value in treating depression and is much less expensive than SAMe.

Rather than spending large sums of money on SAMe, it seems much more sensible to take folate and B-12 for pennies a day, especially since they have also been proven to help prevent a number of other medical diseases. Perhaps, some day future research will examine whether SAMe has any additional benefit for patients already taking folate and B-12. Of course, I recommend all adults take folate and B12 every day whether they have problems with depression or not. Since SAMe helped the anti-depressant work faster in one trial, it is possible, even likely, that folate will help imipramine and other anti-depressants work faster as well.

Helpful in DB Trials: A 1994 Scandinavian review of 6 DB trials of 793 pts found comparable to standard anti-depressans and nearly devoid of S-E. Action in one week—claimed faster than standard or St. John’s. Maurizio Fana of MGH did some Italian studies. Sold in 200mg caps for $1 per cap. S-adenosylmethionine contributes to synthesis of breakdown of serotonin and dopamine. It’s a compound found in every human call. Studied since 1970s and 40 clin studies. Depressd people may have low levels. Consumer Reports 10/99. Review in ActA Neurol Scand Suppl ’94;154:7-14 by Bressa found a global effect size of 17%-38% with it said was similar to standard anti-depr Also, 154:15-18. 200-400mg/day po or im in most studies, but studies small and short and old. One MGH study by Fava of 32 pts DB placebo failed to find any benefit. Acta Psyc Scand ’92;86(1):42-5. 800mg/day po for 6 wk vs placebo in 44 fibromyalgia patients found benefit for pain, fatigue, am stiffness, and mood. Jacobsen, Scand J Rheum ’91;20(4):294-302. SAM low in severely depr and Alzheimer’s. J Neurol Neurosurg Psych ’90;53:1096. DB trial of 15 in-pt for depr in DB found p.o. effective for major depr. Can induce mania. Kagan, West LA VA, Am J Psych 5/90;147:591-5

SAM-e Side-Effects: Consumers report cases of temporary memory disfunction, diarrhea, loss of energy, migraines, heart palpitations, and not mixing well with alprazolam.

SAMe IM Used at MGH: 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. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methionine. Fava M, Giannelli A, Rapisarda V, Patralia A, Guaraldi GP. Psychiatry Res 1995 Apr 28;56(3):295-7

SAMe = Imipramine in Two DB: Two Italian DB 1600 mg SAMe/d orally and 400 mg SAMe/d given intramuscularly 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. HAM-D score and Clinical Global Impression. No difference except fewer side-effects with SAMe. 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. Am J Clin Nutr 2002 Nov;76(5):1172S-6S

SAMe = Desipramine in Small DB: 26 MDD 4 weeks rx SAMe or desipramine. 62% SAMe and 50% desipramine 50% improvement. Blood SAMe levels higher in responders regardless of treatment. S-adenosylmethionine blood levels in major depression: changes with drug treatment. UC Irvine, Bell KM, Potkin SG, Carreon D, Plon L. Acta Neurol Scand Suppl 1994;154:15-8

SAMe + Imipramine Faster than Imipramine in DB: 40 pt DB PC imipramine 150/d with or without SAMe 200mg IM. Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine. Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H. Psychiatry Res 1992 Dec;44(3):257-62

SAMe Open Trial Depression in Parkinson’s Disease: 13 patients, 10 had more than 50% improvement in HAM-D. 10 weeks, 800-3600mg/d. S-Adenosyl-Methionine improves depression in patients with Parkinson's disease in an open-label clinical trial. One mild nausea, two mild diarrhea resolving spontaneously. Albert Einstein, Di Rocco A, Rogers JD, Brown R, Werner P, Bottiglieri T. Mov Disord 2000 Nov;15(6):1225-9