A Case Report of a Manic Episode Triggered by S-Adenosylmethionine (SAMe)

Sir: As previously described in the Companion,¹ an ever-growing number of Americans seek alternative therapies for their medical problems. Among those alternative therapies is the use of herbal medicines, substances that can elicit changes in mood, cognition, and behavior.² S-adenosylmethionine (SAMe) is a natural substance found in all human cells that is involved in methylation reactions such as gene expression and neurotransmitter synthesis, among others.³ It was shown to have antidepressant effects in a 1988 controlled trial.⁴ Here, a case is reported in which a patient with no previous psychiatric history experienced a manic episode following a course of SAMe.

Case report. Ms. A is a 39-year-old woman who, 5 weeks prior to hospitalization, began to use SAMe on a daily basis to “boost” her mood. She had an unremarkable medical history and denied any history of head injury, seizure disorder, or recent illness. She also denied the use of alcohol or illicit substances. Ms. A was admitted to an inpatient psychiatric unit and diagnosed with bipolar I disorder, manic, using DSM-IV criteria.⁵ Results of all screening laboratory tests, including a complete blood count, chemistry panel, liver function, erythrocyte sedimentation rate, thyroid-stimulating hormone, rapid plasma reagin, human immunodeficiency virus, urinalysis, urine drug screen, and urine pregnancy test, were within normal limits or negative. The patient stabilized on a combination of risperidone and divalproex sodium extended release within 4 days. Once stable, Ms. A mentioned that for 1 month prior to her manic episode, she had been taking SAMe, 400 mg, on a daily basis. She also related that her mother had a history of bipolar disorder. She remains stable at 3 months.

Antidepressants are known to trigger mania at rates higher than those of placebo.⁶ However, in an open multicenter study, Fava et al.⁷ treated 195 patients with 400 mg/day of SAMe for 15 days with no reported serious adverse effects. In a smaller open trial of intravenous and oral SAMe treatment, though, Carney et al.⁸ reported that 9 of 11 known bipolar patients switched into an elevated mood. This switching was not seen in an even smaller study reported by Lipinski et al.⁹ in which 9 depressed patients were treated with SAMe. In a 1994 meta-analysis, Bressa¹⁰ found SAMe to be equally effective as tricyclic antidepressants, with a lower incidence of side effects and no report of SAMe inducing a switch into mania. Switching was not reported in a double-blind study conducted by Bell et al.¹¹ comparing SAMe with desipramine in a 4-week trial.

The patient described in this letter, who has a positive family history for bipolar disorder, may eventually have had a manic episode not triggered by SAMe, but there is a strong possibility that the episode reported here was triggered secondary to exposure to SAMe. It is imperative that clinicians continue to inquire about their patients' use of herbal medication due to the possibility of changes in mood and behavioral problems. Herbal use should also be considered in the differential diagnosis when primary care providers evaluate patients who present with mood and behavioral changes but have no previous psychiatric history.