Authors Year Type n Effect Size Key Findings Perera et al Metaanalysis SMD = 0.54, 95% CI: 0.95, 0.13

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1 DS1 Section 5. Complementary and Alternative Medicine Treatments. Supplemental Online etables Supplemental etable 5.1. Evidence for light therapy. Perera et 2016 Metaanalysis Bauer et 2013 Systematic Dirmaier et 2012 Systematic Güleç 2011 Systematic Mårtensson et al 2015 Metaanalysis 20 SMD = 0.41, 95% CI: 0.64, 0.18 Superior to placebo/control as monotherapy or augmentation in non-seasonal NR Not reported Supports 2009 recommendations for seasonal NR Not reported Supports 2009 recommendations NR Not reported Supports 2009 recommendations; effective for seasonal and nonseasonal depression 10 n=714 SMD = 0.54, 95% CI: 0.95, 0.13 Generally effective for moderate seasonal, but evidence not unequivocal Pail et 2011 Systematic NR Not reported Supports 2009 recommendations for Lam et 2015 RCT d = 0.80; 95% CI: 0.28 to 1.31; p = d = 1.11; 95% CI: 0.54 to 1.64; p < Monotherapy superior to placebo for non-seasonal moderate 2. Augmentation superior to placebo for non-seasonal Martiny et 2012 RCT 75 OR = 2.8; 95% CI: , p = 0.04 Augmentation with chronotherapeutic techniques (LT, SD, wake therapy) superior to augmentation with exercise for mild to severe non-seasonal Martiny et 2015 RCT (follow-up) 75 OR = 2.6, CL: , p = 0.01 Superiority of chronotherapeutic techniques as augmentation maintained after 20 weeks of treatment for mild to severe nonseasonal Rohan et 2015a RCT 177 χ2 = and 1.06, p = 0.96 and 0.30 Rohan et 2015b RCT (naturalistic follow-up) 177 Fewer recurrences for CBT (27.3%) than light therapy (45.6%) Similar efficacy to CBT (as monotherapy or augmentation) for moderate seasonal CBT superior in relapse prevention at two-year follow-up for moderate seasonal 1

2 DS2 Supplemental etable 5.2. Evidence for sleep deprivation. Ravindran and da Silva 2013 Systematic 16 Not reported Supports use of SD as augmentation to antidepressants in mild to severe Kundermann et 2009 RCT 18 Not significant No significant clinical effect as augmentation to psychotherapy to moderate to severe Martiny et 2012 RCT 75 OR = 2.8; 95% CI: , p = 0.04 Augmentation to antidepressants with chronotherapeutic techniques (SD, LT, wake therapy) superior to augmentation with exercise for non-seasonal mild to severe Supplemental etable 5.3. Evidence for exercise. Cooney et 39 n=2, SMD = 0.62, 95% CI: 0.81 to 0.42; n=35 2. SMD = 0.03, 95% CI: 0.32 to 0.26, n=7 3. SMD = 0.11, 95% CI: 0.34 to 0.12, n=4 4. SMD = 0.33, 95% CI: 0.63 to 0.03; n=8 In mild to severe, 1. Superior to notreatment control conditions 2. Comparable to psychotherapy 3. Comparable to pharmacotherapy 4. Small effect for long-term benefits Josefsson et Krogh et 2014 Metaanalysis 2011 Metaanalysis 13 n= n= n=328 Hedges' g = 0.77, 95% CI: 1.14 to 0.41, p < SMD = 0.40, 95% CI: 0.66 to SMD = 0.01, 95% CI: 0.28 to 0.26 Superior to notreatment control conditions and comparable to psychotherapy or pharmacotherapy for mild to moderate unipolar depression For mild to moderate, 1. Effective as augmentation in shortterm 2. No beneficial effect for interventions longer than 10 weeks 2

3 DS3 Rosenbaum et Silveira et Danielsson et Nyström et Stanton and Reaburn Carneiro et 2014 Metaanalysis 2013 Systematic 2015 Systematic 2013 Systematic 20 n=1, n=758 SMD = 0.80, 95% CI: 0.47 to 1.13, p < SMD = 0.61, 95% CI: 0.88 to 0.33, p < SMD = 0.06, 95% CI: 0.36 to 0.23 Superior to TAU, waitlist, or placebo conditions for moderate to severe depressive symptoms Superior to control conditions for mild to moderate Comparable to pharmacotherapy for 12 Not reported Effective as monotherapy for 5 n=? Mean frequency = 3.8 sessions/wk; mean duration = 9.3 wks (4-12) 2015 RCT , 95% CI: to 1.45, p = Examined program variables only Exercise as augmentation superior to TAU for women with mild to moderate or dysthymia Supplemental etable 5.4. Evidence for Yoga. Cramer et 12 n=619 SMD = 0.69, 95% CI: 0.99, 0.39; p < Effective as augmentation, compared to TAU for mild to severe Supplemental etable 5.5. Evidence for acupuncture. Chan et 2015 Metaanalysis Smith et 2010 Systematic Zhang et 2010 Metaanalysis Wu et 2012 Systematic 13 n=1,046 SMD = 2.52, 95% CI: 4.12 to 0.92, p < 0.01 More effective in augmentation than medication alone for moderate to severe 30 Inconsistent findings No consistent beneficial effect compared with waitlist or sham controls for 20 n=1,998 WMD = 0.31, 95% CI: , p = 0.63; n=16 Acupuncture monotherapy as effective as medication alone, but not superior to sham for mild to severe Insufficient evidence for augmentation in 21 Not reported Beneficial as monotherapy and more effective in augmentation than medication alone, for mild to severe depression 3

4 DS4 MacPherson et Quah-Smith et 2013 RCT p = 0.41, 95% CI: 1.77 to d = 0.39, 95% CI: 0.58 to Reduction in mean depression scores = 1.55, 95% CI: 2.41 to 0.70 For moderate to severe, 1. Similar efficacy to counseling 2. Superior as augmentation to medication alone 3. Monotherapy and augmentation benefits sustained long-term 2013 RCT 47 p < Monotherapy superior to placebo for moderate to severe, but only on objective measures of depression Supplemental etable 5.6. Evidence for St. John s wort. Carpenter 2011 Systematic Rahimi et Mannel et Sarris et 17 M ES = 0.64 n=3, WMD = 0.32, 95% CI: 2009 Systematic , p = RCT d = p = 0.02; d = 0.61 Superior to placebo for mild to moderate Comparable to antidepressants for For mild to moderate, 1. Monotherapy superior to placebo 2. Particularly effective for moderate atypical depression 2012 RCT 124 p = 0.61 No difference between SJW, sertraline, and placebo for mild or subthreshold depression Supplemental etable 5.7. Evidence for Omega-3 Fatty Acids. Appleton et Bloch and Hannestad 2015 Metaanalysis 2012 Metaanalysis 25 n=1, n=731 SMD = 0.32, 95% CI: 0.12, 0.52 SMD = 0.11, 95% CI: 0.04, 0.26 Small-to-modest effect as adjunctive compared to placebo for severe No significant effect for monotherapy or augmentation in mild to moderate Grosso et 2014 Metaanalysis Sublette et 2011 Metaanalysis Rocha Araujo et 2010 Systematic Sarris et 2009 Systematic 11 n= n=916 SD = 0.47, 95% CI: 0.29, 0.66 SMD for EPA 60% = 0.558, 95% CI: 0.277, 0.838, p = Superior to placebo as monotherapy or augmentation for mild to severe EPA-dominant formulations superior to DHA-based formulations (as monotherapy or augmentation) for mild to severe 19 Not reported Mixed evidence for benefit in mild to severe NR Not reported Superior to placebo as augmentation for mild to severe 4

5 DS5 Sarris et 2010 Systematic 4 Not reported Superior to placebo as augmentation for moderate to severe Supplemental etable 5.8. Evidence for SAM-e. Carpenter 2011 Systematic 9 Mean effect size = 1.0 (range ) Monotherapy superior to placebo for mild to moderate De Berardis et 2015 Systematic 48 Not reported Monotherapy superior to antidepressants for mild Effective as augmentation in moderate to severe Sarris et 2010 Systematic NR Not reported Effective as augmentation in mild to severe Sarris et 2009 Narrative NR Not reported Effective as augmentation in moderate to severe Sarris et 2015 RCT (post-hoc analysis) 189 p = 0.034; d = 0.95 More effective than placebo in males, but not in females, for moderate to severe Supplemental etable 5.9. Evidence for Tryptophan. Sarris et 2010 Systematic 9 Not reported Mixed evidence for augmentation in mild to severe Sarris et 2009 Narrative 9 Not reported Insufficient evidence for monotherapy in Jangid et 2013 RCT 70 Not reported Similar efficacy to fluoxetine in moderate to severe Supplemental etable Evidence for Other Natural Health Products. Folate preparations Almeida et 2015 Metaanalysis Sarris et 2010 Systematic Fava and 2009 Narrative Mischoulon Papakostas et 2012 Narrative 11 n=2,204 1 long-term study: odds ratio (OR) = 0.33, 95% CI: 0.12, 0.94 Long-term use may reduce risk of relapse No effect for short-term augmentation in moderate 2 Not reported Effective as augmentation in moderate 10 Not reported Support for monotherapy or 11 Not reported Support for augmentation with several folate forms, particularly L- methylfolate, in moderate to severe 5

6 DS6 Ginsberg et 2011 Retrospecti ve analysis Inositol Mukai et 2014 Metaanalysis Iovieno et 2011 Systematic Sarris et 2010 Systematic Sarris et 2009 Narrative Acetyl-L-carnitine Wang et 2014 Narrative Crocus sativus Hausenblas et Dwyer 2011 Systematic Hausenblas et Lopresti and Drummond 2015 Systematic 2014 Systematic 242 p = 0.01 L-methylfolate augmentation superior to antidepressant monotherapy in moderate 9 n=242 Not significant No benefit as monotherapy or and premenstrual dysphoric disorder 6 Not reported No benefit as monotherapy or 3 Not reported Mixed evidence for monotherapy of 4 Not reported No benefit as monotherapy or 8 Not reported Monotherapy superior to placebo and comparable to fluoxetine and amisulpride for and dysthymia 5 n= M ES = 0.15, 95% CI: , p = 0.42; n=2 2. M ES = 1.62, 95% CI: , p < 0.001; n=3 For mild to moderate, 1. Effective as monotherapy 2. Similar efficacy to antidepressants 6 Not reported Effective as monotherapy for mild to moderate 6 Not reported Effective as monotherapy for mild to moderate 6 Not reported Effective as monotherapy for mild to moderate Talaei et 2015 RCT 40 p < Superior as augmentation to SSRIs vs. SSRIs alone for mild to moderate Lavandula Nikfarjam et 2013 RCT 80 p < 0.01 Lavandula combined with citalopram more effective than citalopram alone for moderate to severe Rhodiola rosea Mao et 2015 RCT p = OR = 1.39 ( ) For mild to moderate, 1. No difference between R. rosea, sertraline, and placebo 2. R. rosea superior to placebo in global improvement 6