S-Adenosylmethionine (SAMe)
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Look Up > Supplements > S-Adenosylmethionine (SAMe)  > Interactions
Interactions with S-Adenosylmethionine (SAMe)

Intraperitoneal administration of SAM-e (2.5 mmol/kg) within 1 to 5 hours of reduced the lethality of toxic doses of acetaminophen (APAP) (2 to 3 mmol/kg) in mice; lower doses of SAM-e (0.5 mmol/kg) did not reduce mouse mortality (Bray et al. 1992). SAM-e reduced the hepatotoxic effects of APAP by metabolizing the active moiety to glutathione. SAM-e may be a useful antidote, along with N-acetylcysteine, for the treatment of APAP poisoning.

Clomipramine; Imipramine

In a double-blind, placebo-controlled trial, 40 patients with moderate to severe depression received imipramine (titrated from 50 mg/day to 150 mg/day) with either SAM-e (200 mg/day IM) or placebo; improvements on the Hamilton Rating Score for Depression (HRSD) occurred as early as day 4 for patients treated with both SAM-e and imipramine (Berlanga et al. 1992). However, there is a case report of serotonin syndrome associated with the combination of tricyclic antidepressants and SAM-e (Iruela et al. 1993). Specifically, a 71-year-old female became increasingly anxious, agitated, and confused within 48 to 72 hours after ingesting a higher dose of clomipramine (75 mg/day) while she was taking SAM-e (100 mg/day IM). Patients should be cautioned about this possible interaction.


Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H. Efficacy of S-adeno-L-methionine in speeding the onset of action of imipramine. Psychiatry Res. 1992;44(3):257-262.

Bray GP, Tredger JM, Williams R. S-adenosylmethionine protects against acetaminophen hepatotoxicity in two mouse models. Hepatotol. 1992;15(2):297-301.

Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry. 1993;150:3.

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