Table 2.
Characteristics of included studies examining the role of SAMe in CNS Signs.
| First Author (Year) Study Design|Location N of Patients|Study Length |
Intervention (with Dose) and Comparator | Disease (Sign) | Measurement of Mood/Depression |
|---|---|---|---|
| Abeysundera (2018) [13] Case report|Australia n = 1|2 weeks prior to incident |
No dose given | Depression | Differential diagnosis and lab levels |
| Alpert (2004) [14] Open trial|United States n = 30|6 weeks |
SSRI/Venlafaxine + SAMe: Initial: 400 mg twice daily At 2 weeks: 800 mg twice daily Comparator: None |
Resistant Major Depressive Disorder |
HAM-D–17, MADRS, CGI-I, CGI-S, SQ |
| Anderson (2016) [15] Case report|Canada n = 1|~1 month |
SAMe: 400 mg twice daily Comparator: None |
Anxiety (and hypothyroidism) | Not discussed |
| Arnold (2005) [16] Pharmacodynamic|Europe n = 12|15 days each medication + washout periods |
SAMe: 1600 mg/day SAMe: 400 mg/day Comparator: placebo |
Mood | EEG mapping and psychometry |
| Bambling (2015) [17] RCT|Australia n = 36|15 weeks |
SAMe: 1600 mg/day SAMe: 800 mg/day |
Major Depressive Disorder | BDI, ICD-DSM MINI, DASS, SCID, OQ45, WBS, QOLS |
| Carpenter (2011) [18] SR/MA|United States n = 14 studies on SAMe|N/A |
SAMe: 500–1050 mg/day | Major Depressive Disorder | Varied |
| Chitiva (2012) [19] Case report|United States n = 1|4 days prior to event |
No dose stated | Depression/suicide attempt | Not applicable |
| Cuomo (2020) [7] SR/MA|N/A n = 8 articles (1011 patients)|N/A |
SAMe: 200–3200 mg/day | Major Depressive Disorder | Varied |
| De Berardis (2013) [20] Non-randomized experimental|Europe n = 25|8 weeks |
Existing medication + SAMe: 800 mg/day | Major Depressive Disorder | HAM-D, CGI-I, SHAPS, SDS |
| Di Pierro (2015) [21] Open-label, randomized, observational|Europe n = 64 (60 completed)|12 months |
Betaine 250 mg/day + SAMe: 500 mg/day Comparator: Amitriptyline 75 mg/day | Mild Depression | Zung Self-Rating Depression Scale |
| Djokic (2017) [22] RCT|Europe n = 60|3 months |
Vit B complex + SAMe: 200 mg/day Comparator: placebo |
Depression (mild to moderate) | HAM-D, CGI-S, CGI-I |
| Dolcetta (2013) [23] Non-randomized experimental|Europe n = 14|12 months |
SAMe: 400–1600 mg/day; up to 80 mg/kg, depending on body weight and renal function | Mood Lesch–Nyhan Disease |
N/A |
| Galizia (2016) [24] SR/MA|UK n = 8 studies (934 patients)|N/A |
SAMe: 200–3200 mg/day | Depression | Varies |
| Green (2012) [25] RCT|Israel n = 12|6 weeks |
SAMe: 400 mg/day titrated up to 1600 mg/day (800 mg twice daily) Comparator: placebo |
22q11.2 deletion syndrome: depressive disorder, ADHD, cognitive deficits | Wechsler test: IQ, PANSS, YMRS, CGI-I, CDRS-R, ADHD-RS |
| Jaggumantri (2015) [26] Case report|Canada n = 2|Not described fully |
SAMe: 50 mg/kg, with a safe and tolerable dose identified as 17 mg/kg/day | Creatine transporter (SLC6A8) deficiency | MRI Various assessments and questionnaires |
| Kalman (2015) [27] RCT|United States n = 34 in efficacy analysis (out of 42 enrolled)|8 weeks |
SAMe: 400 mg/day Comparator: UP165 250 mg/day |
Mild depression or anxiety | BDI-II, BAI, SOS-10 |
| Levkovitz (2012) [28] RCT Re-Analysis|United States n = 55|6 weeks |
SAMe Weeks 1–2: 800 mg/day Weeks 3–6: 1600 mg/day |
Major Depressive Disorder | CPFQ |
| Limveeraprajak (2024) [5] SR/MA|N/A 23 trials (n = 2183)|N/A |
SAMe: 200–1600 mg/day | Depressive symptoms | Varied |
| Mischoulon (2012) [29] RCT|United States n = 35|6 weeks |
SAMe: 800–1600 mg/day Comparator: placebo |
Major Depressive Disorder | HAM-D Plasma SAMe levels |
| Mischoulon (2014) [30] RCT|United States n = 189|12 weeks |
SAMe: 1600–3200 mg/day Escitalopram: 10–20 mg/day Comparator: placebo |
Major Depressive Disorder | HAM-D |
| Murphy (2014) [31] RCT|United States n = 20 (17 completed)|6 weeks |
SAMe: Week 1: 800 mg/day Week 2: 400 mg/day Week 3: 800 mg/day Week 4: 1600 mg (only 3/7 days of week) | Persistent Treatment-Refractory Bipolar Depression | HAM-D, MADRS, YMRS |
| Olsufka (2017) [32] Case Report|United States n = 1|~1 week |
SAMe: 400 mg/day for 3 days then increased to 800 mg/day (up to day 10) | Depression | Not applicable |
| Papakostas (2010) [33] RCT|United States n = 73 (55 completed)|6 weeks |
Antidepressant + SAMe: 800 mg/day (up to 1600 mg/day) Comparator: antidepressant + placebo |
Major Depressive Disorder | HAM-D, CGI-S |
| Peng (2024) [34] SR/MA|Taiwan n = 14 studies (1522 patients)|N/A |
SAMe: 200–3200 mg/day | Depression | Varies |
| Saccarello (2020) [35] RCT|Europe n = 89|6 weeks |
Lactobacillus plantarum + SAMe: 200 mg/day Comparator: placebo |
Mild-to-moderate depression | Zung Self-Rating Depression Scale |
| Sakurai (2020) [36] RCT|United States n = 189|6 weeks |
SAMe: 1600 mg/day for 6 weeks (non-responders: 3200 mg/day for 6 weeks) Escitalopram: 10 mg/day Comparator: placebo |
Major Depressive Disorder | HAM-D, IDS-SR, CGI-S, CGI-I |
| Sarris (2014) [40] RCT|Australia n = 144|12 weeks |
SAMe: 1600–3200 mg/day Escitalopram: 10 mg/day Comparator: placebo |
Major Depressive Disorder | HAM-D |
| Sarris (2015) [41] RCT Re-Analysis|United States n = 189|12 weeks |
SAMe: 1600–3200 mg/day Escitalopram: 10–20 mg/day Comparator: placebo |
Major Depressive Disorder | HAM-D |
| Sarris (2018) [37] RCT|Australia n = 107 (77 completed)|8 weeks |
SAMe: 800 mg/day Comparator: placebo |
Non-remittent Major Depressive Disorder | MADRS |
| Sarris (2019) [38] RCT|Australia n = 158 | 8 weeks |
SAMe 800 mg + folinic acid + Omega-3 fatty acids + 5-HTP + Zinc picolinate + relevant co-factors/day Comparator: placebo |
Major Depressive Disorder | MADRS |
| Sarris (2020) [39] RCT|Australia n = 49 (41 completed)|8 weeks |
SAMe: 800 mg/day Comparator: placebo |
Major Depressive Disorder with mild-to-moderate symptoms | MADRS |
| Shippy (2004) [42] Non-randomized experimental study|United States n = 20 (15 completed)|8 weeks |
1000 μg Vit B12 + 800 mg Folic Acid + SAMe: 400 mg/day (200 mg bid) increased to 1600 mg/day (800 mg bid) Comparator: None |
Major Depressive Disorder | HAM-D (Response: ≥50% reduction in scores; Remission: HAM-D ≤ 7) |
| Strous (2009) [43] RCT|Israel n = 18 (15 completed)|8 weeks |
SAMe: Week 1: 400 mg/day Weeks 2–8: 800 mg/day Comparator: placebo |
Schizophrenia | PANSS, SANS, CGI, OAS, LHA, QLS |
| Targum (2018) [44] RCT|United States n = 234|8 weeks |
SAMe:800 mg/day Comparator: placebo |
Major Depressive Disorder | HAM-D, MADRS, IDS-SR |
| Targum (2020) [45] RCT (re-analysis)|United States n = 336|8 weeks |
SAMe:800 mg/day Comparator: placebo |
Major Depressive Disorder | HAM-D, MADRS, IDS-SR, CGI-S |
| Ullah (2022) [46] RCT (Crossover)|Europe n = 80 (65 completed)|3 months each |
Crossover between: 200 mg/day SAMe + lactobacillus and placebo |
Subthreshold depression Mild-to-moderate depression |
HAM-D, PHQ-9 |
Scales: Hamilton Rating Scale for Depression (HAM-D), Beck Depression Inventory (BDI) and BDI Version II (BDI-II), Mini International Neuropsychiatric Interview (ICD-DSM MINI), Depression Anxiety Stress Scale (DASS), Structured Clinical Interview for DSM (SCID), Outcome Questionnaire 45 (OQ45), Warwick–Edinburgh Mental Well-being Scale (WBS), Quality of Life Scale (QOLS), Clinical Global Impression of Improvement (CGI-I), Clinical Global Impression–Severity scale (CGI-S), Kellner Symptom Questionnaire (SQ), Snaith–Hamilton Pleasure Scale (SHAPS), Sheehan Disability Scale (SDS), Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS), Children’s Depression Rating Scale–Revised (CDRS-R); ADHD Rating Scale IV (ADHD-RS), Beck Anxiety Inventory (BAI), Schwartz Outcome Scale (SOS-10), cognitive and physical symptoms questionnaire (CPFQ), Montgomery–Asberg Depression Rating Scale (MADRS), Inventory of Depressive Symptomatology–Self Rated (IDS-SR), Calgary Scale for Depression in Schizophrenia (SANS), Overt Aggression Scale (OAS), Life History of Aggression Scale (LHA), Quality of Life Scale (QLS), Patient Health Questionnaire-9 (PHQ-9) Other Acronyms: Systematic Review (SR), Meta-Analysis (MA), Randomized Controlled Trial (RCT), Attention Deficit/Hyperactivity Disorder (ADHD).