Systematic review of non-pharmacological non-psychological augmentation strategies for the treatment of unipolar depression: Synthesis without meta-analysis (SWiM)
Restricted accessReview articleFirst published online 2026
Systematic review of non-pharmacological non-psychological augmentation strategies for the treatment of unipolar depression: Synthesis without meta-analysis (SWiM)
In 2021 depressive disorders were the fourth leading cause of Disability-Adjusted Life Years (DALYs) in Australia accounting for 926.92 DALYs per 100,000 people.1 This review aimed to identify which non-pharmacological non-psychological treatments are effective augmentation strategies in treating depression and which primary therapies they most effectively augment.
Methods
PubMed, CENTRAL, and PsycINFO were searched for randomised-controlled trials for non-pharmacological non-psychological augmentation strategies in adults with unipolar depression. The results were synthesised qualitatively following the Synthesis Without Meta-analysis (SWiM) guidelines. Risk of bias was assessed using the JBI critical appraisal tool.
Results
3609 studies were screened against title and abstract and 3505 irrelevant studies were excluded. 104 studies were assessed for full-text eligibility. 31 studies were included for analysis. Included studies investigated augmentation with photobiomodulation, neurostimulation, exercise therapies, probiotics and acupuncture.
Conclusion
Non-pharmacological non-psychological augmentation strategies can be useful for patients with suboptimal response to standard treatment; however, more high-quality large RCTs are needed to investigate the effectiveness of these treatments in augmenting specific therapies. Due to their low cost and favourable safety profiles bright light therapies and exercise should be considered to augment standard treatment in adults with depression. There is lower levels of evidence for acupuncture and probiotics.
World Health Organization. Global health estimates 2021: disease burden by cause, age, sex, by country and by region, 2000-2021. Geneva: World Health Organization, 2024.
SchofieldDCunichMShresthaR, et al.Indirect costs of depression and other mental and behavioural disorders for Australia from 2015 to 2030. BJPsych Open2019; 5(3): e40. https://doi.org/10.1192/bjo.2019.26
4.
SchuchFBVasconcelos-MorenoMPBorowskyC, et al.Exercise and severe major depression: effect on symptom severity and quality of life at discharge in an inpatient cohort. J Psychiatr Res2015; 61: 25–32. https://doi.org/10.1016/j.jpsychires.2014.11.005
5.
RossREVanDerwerkerCJSaladinME, et al.The role of exercise in the treatment of depression: biological underpinnings and clinical outcomes. Mol Psychiatr2023; 28(1): 298–328. https://doi.org/10.1038/s41380-022-01819-w
6.
ChenCShanW. Pharmacological and non-pharmacological treatments for major depressive disorder in adults: a systematic review and network meta-analysis. Psychiatry Res2019; 281: 112595. https://doi.org/10.1016/j.psychres.2019.112595
7.
LarsenAJTeobaldiGJeraldoRI, et al.Effectiveness of pharmacological and non-pharmacological interventions for treatment-resistant depression in older patients: a systematic review and meta-analysis. BMJ Mental Health2025; 28(1).
8.
PageMJMcKenzieJEBossuytPM, et al.The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. bmj2021; 372: n71. https://doi.org/10.1136/bmj.n71
9.
BarkerTHStoneJCSearsK, et al.The revised JBI critical appraisal tool for the assessment of risk of bias for randomized controlled trials. JBI Evid Synth2023; 21(3): 494–506. https://doi.org/10.11124/JBIES-22-00430
10.
CampbellMMcKenzieJESowdenA, et al.Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. bmj2020; 368: l6890. https://doi.org/10.1136/bmj.l6890
11.
Covidence systematic review software 2024 {software]. Veritas Health Innovation, Melbourne, Australia. Available at: https://www.covidence.org
12.
ArnedtJTSwansonLMDoppRR, et al.Effects of restricted time in bed on antidepressant treatment response: a randomized controlled trial. J Clin Psychiatr2016; 77(10): e1218–e1225. https://doi.org/10.4088/JCP.15m09879
13.
ChenIPHuangCCHuangHC, et al.Adjunctive bright light therapy for non-seasonal major depressive disorder: a randomized controlled trial. Int J Environ Res Publ Health2022; 19(19): 12430. https://doi.org/10.3390/ijerph191912430
14.
FregnaLAttanasioFColomboC. Evaluating the impact of adjunct bright light therapy on subjective sleep quality in major depressive disorder. J Affect Disord2024; 348: 175–178. https://doi.org/10.1016/j.jad.2023.12.057
15.
GuuTWCassanoPLiWJ, et al.Wearable, self-administered transcranial photobiomodulation for major depressive disorder and sleep: a randomized, double blind, sham-controlled trial. J Affect Disord2025; 372: 635–642. https://doi.org/10.1016/j.jad.2024.12.065
16.
LamRWLevittAJLevitanRD, et al.Efficacy of bright light treatment, fluoxetine, and the combination in patients with nonseasonal major depressive disorder: a randomized clinical trial. JAMA Psychiatry2016; 73(1): 56–63. https://doi.org/10.1001/jamapsychiatry.2015.2235
17.
LovingRTKripkeDFShuchterSR. Bright light augments antidepressant effects of medication and wake therapy. Depress Anxiety2002; 16(1): 1–3. https://doi.org/10.1002/da.10036
18.
MartinyKLundeMUndenM, et al.Adjunctive bright light in non‐seasonal major depression: results from clinician‐rated depression scales. Acta Psychiatr Scand2005; 112(2): 117–125. https://doi.org/10.1111/j.1600-0447.2005.00574.x
19.
AustSBrakemeierELSpiesJ, et al.Efficacy of augmentation of cognitive behavioral therapy with transcranial direct current stimulation for depression: a randomized clinical trial. JAMA Psychiatry2022; 79(6): 528–537. https://doi.org/10.1001/jamapsychiatry.2022.0696
20.
KumariBSinghAKarSK, et al.Bifrontal-transcranial direct current stimulation as an early augmentation strategy in major depressive disorder: a single-blind randomised controlled trial. Asian J Psychiatry2023; 86: 103637. https://doi.org/10.1016/j.ajp.2023.103637
21.
PapakostasGITrivediMHSheltonRC, et al.Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial. Mol Psychiatr2024; 29(8): 2287–2295. https://doi.org/10.1038/s41380-024-02468-x
22.
YinBWYangL. Comparative efficacy of augmenting escitalopram with modified electroconvulsive therapy or high-frequency repetitive transcranial magnetic stimulation on depressive symptoms, quality of life, and cognitive function in treatment-resistant depression. Tohoku J Exp Med2024; 262(3): 191–199. https://doi.org/10.1620/tjem.2023.J103
23.
ZhouJLiDYeF, et al.Effect of add-on transcranial alternating current stimulation (tACS) in major depressive disorder: a randomized controlled trial. Brain Stimul2024; 17(4): 760–768. https://doi.org/10.1016/j.brs.2024.06.004
CarneiroLSFonsecaAMVieira-CoelhoMA, et al.Effects of structured exercise and pharmacotherapy vs. pharmacotherapy for adults with depressive symptoms: a randomized clinical trial. J Psychiatr Res2015; 71: 48–55. https://doi.org/10.1016/j.jpsychires.2015.09.007
26.
DanielssonLPapouliasIPeterssonEL, et al.Exercise or basic body awareness therapy as add-on treatment for major depression: a controlled study. J Affect Disord2014; 168: 98–106. https://doi.org/10.1016/j.jad.2014.06.049
27.
HaussleiterISBolsingerBAssionHJ, et al.Adjuvant guided exercise therapy versus self-organized activity in patients with major depression. J Nerv Ment Dis2020; 208(12): 982–988. https://doi.org/10.1097/NMD.0000000000001240
28.
HoCWChanSCWongJS, et al.Effect of aerobic exercise training on Chinese population with mild to moderate depression in Hong Kong. Rehabilitation Research and Practice2014; 2014(1): 627376. https://doi.org/10.1155/2014/627376
29.
LavretskyHAlsteinLLOlmsteadRE, et al.Complementary use of tai chi chih augments escitalopram treatment of geriatric depression: a randomized controlled trial. Am J Geriatr Psychiatr2011; 19(10): 839–850. https://doi.org/10.1097/JGP.0b013e31820ee9ef
30.
LavretskyHMililloMMKilpatrickL, et al.A randomized controlled trial of Tai Chi Chih or health education for geriatric depression. Am J Geriatr Psychiatr2022; 30(3): 392–403. https://doi.org/10.1016/j.jagp.2021.07.008
31.
LegrandFDNeffEM. Efficacy of exercise as an adjunct treatment for clinically depressed inpatients during the initial stages of antidepressant pharmacotherapy: an open randomized controlled trial. J Affect Disord2016; 191: 139–144. https://doi.org/10.1016/j.jad.2015.11.047
32.
MoraesHSSilveiraHSOliveiraNA, et al.Is strength training as effective as aerobic training for depression in older adults? A randomized controlled trial. Neuropsychobiology2020; 79(2): 141–149. https://doi.org/10.1159/000503750
33.
Mota-PereiraJSilverioJCarvalhoS, et al.Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder. J Psychiatr Res2011; 45(8): 1005–1011. https://doi.org/10.1016/j.jpsychires.2011.02.005
34.
PiluASorbaMHardoyMC, et al.Efficacy of physical activity in the adjunctive treatment of major depressive disorders: preliminary results. Clin Pract Epidemiol Ment Health2007; 3(1): 8. https://doi.org/10.1186/1745-0179-3-8
35.
TavaresVDSchuchFBde SousaGM, et al.Effectiveness of an affect-adjusted, supervised, multimodal, online and home-based exercise group protocol for major depression: a randomized controlled trial. Psychol Sport Exerc2025; 76: 102729. https://doi.org/10.1016/j.psychsport.2024.102729
36.
AbdollahiALeBouthillierDMNajafiM, et al.Effect of exercise augmentation of cognitive behavioural therapy for the treatment of suicidal ideation and depression. J Affect Disord2017; 219: 58–63. https://doi.org/10.1016/j.jad.2017.05.012
37.
YiLHuiFYaliM, et al.Effect of soothing-liver and nourishing-heart acupuncture on early selective serotonin reuptake inhibitor treatment onset for depressive disorder and related indicators of neuroimmunology: a randomized controlled clinical trial. J Tradit Chin Med2015; 35(5): 507–513.
38.
WuXTuMYuZ, et al.The efficacy and cerebral mechanism of intradermal acupuncture for major depressive disorder: a multicenter randomized controlled trial. Neuropsychopharmacology2025; 50(7): 1075–1083. https://doi.org/10.1038/s41386-024-02036-5
39.
ZhaoBLiZWangY, et al.Manual or electroacupuncture as an add-on therapy to SSRIs for depression: a randomized controlled trial. J Psychiatr Res2019; 114: 24–33. https://doi.org/10.1016/j.jpsychires.2019.04.005
40.
GhorbaniZNazariSEtesamF, et al.The effect of synbiotic as an adjuvant therapy to fluoxetine in moderate depression: a randomized multicenter trial. Arch. Neurosci2018; 5(2): e60507. https://doi.org/10.5812/archneurosci.60507
41.
SchaubACSchneiderEVazquez-CastellanosJF, et al.Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: a randomized controlled trial. Transl Psychiatry2022; 12(1): 227. https://doi.org/10.1038/s41398-022-01977-z
42.
McKenzieJEBrennanSE. Chapter 12: synthesizing and presenting findings using other methods, [last updated October 2019]. Cochrane Handbook for Systematic Reviews of Interventions Version2024; 6.
43.
KosanovicRBSagudMPivacN, et al.Illuminating the way: the role of bright light therapy in the treatment of depression. Expert Rev Neurother2023; 23(12): 1157–1171. https://doi.org/10.1080/14737175.2023.2273396
44.
StaudacherHMTeasdaleSCowanC, et al.Diet interventions for depression: review and recommendations for practice. Aust N Z J Psychiatr2025; 59(2): 115–127. https://doi.org/10.1177/00048674241289010
45.
ChristieLInmanJDavysD, et al.A systematic review into the effectiveness of occupational therapy for improving function and participation in activities of everyday life in adults with a diagnosis of depression. J Affect Disord2021; 282: 962–973. https://doi.org/10.1016/j.jad.2020.12.080
46.
VidaRGSághyEBellaR, et al.Efficacy of repetitive transcranial magnetic stimulation (rTMS) adjunctive therapy for major depressive disorder (MDD) after two antidepressant treatment failures: meta-analysis of randomized sham-controlled trials. BMC Psychiatry2023; 23(1): 1. https://doi.org/10.1186/s12888-023-05033-y
47.
FitzgeraldPBGillSBreakspearM, et al.Revisiting the effectiveness of repetitive transcranial magnetic stimulation treatment in depression, again. Aust N Z J Psychiatr2022; 56(8): 905–909. https://doi.org/10.1177/00048674211068788
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
