S-adenosylmethionine (SAMe) and Magnesium Orotate as adjunctives to SSRIs in sub-optimal treatment response of depression in adults: A pilot study

Major depression is a prevalent mental health disorder and a proportion of patients do not respond adequately to standard treatment. The use of nutraceutical adjunctives with antidepressant medication such as high dose S-adenosylmethionine (SAMe) has proven beneficial in terms of initial symptom response but the effect on symptom maintenance and relapse is unknown. In this pilot study [n = 36], participants [26 evaluable subjects] with established sub-optimal response to treatment for major depressive disorder and who were prescribed Selective Serotonin Reuptake Inhibitor (SSRI) medication were randomly allocated to either 1600 mg or 800 mg daily of SAMe for 15 weeks duration to evaluate the efficacy on both symptom response and maintenance. A variety of validated psychiatric measures of symptoms and mood including clinician assessment and self-report measures were used to assess outcome measures. Both SAMe doses achieved similar results with a significant proportion of participants (35%) achieving significant symptom improvement at the end of 15 weeks supplementation as assessed by the Beck Depression Inventory (BDI), Outcome Questionnaire 45 (OQ45), and improved Quality of Life (QOL) scores. After a 2 week washout period, SAMe non-responders were then supplemented with 1600 mg of Magnesium Orotate for 8 weeks duration which resulted in significant clinical improvement as measured by BDI, OQ45 and QOL scores [n = 8]. We progress the SAMe-methylation and Orotate–uridine hypothesis and consider that the response to these novel compounds implicates the microbiome as an important agent for the adjunctive treatment of sub-optimal response to pharmaceutical medications.