Systematic review of non-pharmacological non-psychological augmentation strategies for the treatment of unipolar depression: Synthesis without meta-analysis (SWiM)

Abstract

Objectives

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.

Keywords

depression augmentation behavioural and physical structured review

In Australia between 2020 and 2022 approximately 7.7% of adult females¹ and 5.6% of adult males were affected by a depressive episode or dysthymia.² The financial costs to individuals and government resulting from the direct and indirect effects of depression is substantial and increasing; it’s estimated that in Australia in 2015 individuals lost approximately $1062 million in income due to the impact of depressive disorders and this figure is projected to rise to $1539 million by 2030.³ The government is expected to face a 22% increase in social security payments and a 45% increase in lost tax revenue due to depression.³ Two-thirds of patients have an incomplete response to initial antidepressants, and 30% of patients with treatment-resistant depression continue to remain highly symptomatic despite receiving optimised treatment.^4,5 Augmenting treatment with non-psychological non-pharmacological therapies have the benefits of avoiding the adverse effects associated with adding or increasing drugs doses, and some forms may be cheaper and more accessible and acceptable to patients than psychological therapy.^5,6 Examples include neurostimulation, bright light therapies, dietary changes and exercise programs. The effectiveness of many of these therapies in treating depression has been well established, however it is a one-size-fits-all approach that is not individualised to the patient.^6,7 The existing evidence does not indicate which primary therapies are augmented best by other treatment modalities. For example, is it more beneficial for a patient on an SNRI with an incomplete response to add-on transcranial magnetic stimulation or exercise physiology? If on a tricyclic, is it better to engage in physical activity or receive bright light therapy? Generating the evidence needed to identify which patients will benefit the most from additional treatments may improve outcomes and can also justify their cost which is important in the current climate of increased government interest and spending on treating depressive disorders in Australia to reduce disability, suicide and economic burden. Prior to the inception of this review there were no systematic reviews of randomised-controlled trials evaluating the effectiveness of non-pharmacological non-psychological treatments in augmenting specific drugs and treatment modalities.

Table 1.

Eligibility criteria in PICO categories.

Population	Included:
	- Adults aged 18 and above diagnosed with unipolar depression
	Excluded:
	- Studies with participants with bipolar depression, psychotic depression, or substance-related depression.
Intervention	Included:
Intervention	- RCTs exploring non-psychological and non-pharmacological treatment implemented as an augmentation strategy for depression
Comparison	Included:
	- Another intervention or placebo
	- Treatment as usual
Outcome	Included:
Outcome	- Primary outcome was mean change in depression score at intervention end

Methods

A systematic review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA).⁸ Ethics approval was not required for this study.

Search strategy

Two reviewers independently searched PubMed, CENTRAL, and PsycINFO on the 25th March 2025 for English language studies published between 1st January 1980 and 25th March 2025. Supplemental file 1 contains the full search strategy for each database.

Study selection

The eligibility criteria were constructed to capture studies in which the intervention was implemented and investigated as an augmentation strategy to another primary treatment. Studies were included if they met the following criteria: (a) participants were adults aged 18 and above diagnosed with a unipolar depression, (b) study design was a prospective randomised-controlled trial, (c) primary outcome measure was change in depression score at intervention end, and (d) the augmentation strategy was a non-psychological non-pharmacological treatment (Table 1). The comparator could be another intervention or treatment as usual. Studies were excluded if the intervention was not implemented as an augmentation strategy, or if they included participants with bipolar depression, psychotic depression, or substance-related depression. Conference abstracts and pilot studies were excluded. The titles and abstracts of studies selected were screened independently by two reviewers to identify studies that potentially meet the selection criteria. The full text of the identified studies was assessed independently by two reviewers for inclusion. A third person resolved any discrepancies.

Data selection

Two reviewers independently extracted the data from each study which included study design and characteristics, number of participants, participant demographics, intervention and comparators characteristics, outcome measures, and results presented in tabular form.

Quality appraisal

Risk of bias in the studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal tool for randomised-controlled trials independently by two reviewers and a third person resolved any discrepancies.⁹ The overall risk of bias for each study is assessed as low, high, or unclear.

Data analysis

A meta-analysis was planned for this review however due to the high risk of bias and heterogeneity in the studies retrieved, a meta-analysis was not considered appropriate (see Table 3 risk of bias assessment). The results were summarised using qualitative synthesis and descriptive statistics following the Synthesis Without Meta-analysis (SWiM) guidelines.¹⁰

Results

On March 25th 2025 a total of 4624 articles were retrieved before removing 1015 duplicates, with 22 duplicates identified manually and 993 duplicates identified by Covidence.¹¹ 3609 studies were screened against title and abstract and 3505 irrelevant studies were excluded. 104 studies assessed for full-text eligibility. 31 studies were included for review (Figure 1). Most studies reported data as mean ± standard deviation, or mean with 95% confidence interval [CI], with significance level set at 0.05. Change in depression score was measured using scales where higher scores indicated more severe depression. In summarising the outcome of change in depression score the mean number of points change is given when reported. For studies where the rate of remission is reported the number needed to treat (NNT) for remission is given. Remission was defined by most studies as a greater than 50% improvement in score from baseline. NNT was calculated by these authors when not given by the paper.

Figure 1.

PRISMA flow diagram for study selection for systematic review. Generated with covidence.¹¹

Table 2 summarises the study characteristics and results. Studies were conducted in a variety of settings including both inpatient and community-based settings. For the augmentation strategies seven studies investigated photobiomodulation with five RCTs for bright light therapy (BLT), one for near-infrared and one sleep deprivation. Five RCTs augmented with neurostimulation including two for Transcranial Direct Current Stimulation (tDCS), two for repetitive Transcranial Magnetic Stimulation (rTMS), and one tACS (transcranial alternating current stimulation). Twelve RCTs investigated exercise as an augmentation strategy. Two RCTs investigated probiotics, and three investigated acupuncture. All studies with negative findings were inadequately powered to detect small to moderate effects. Supplemental file 2 contains an extended table with additional details for diagnostic criteria, participant demographics, and treatment details.

Table 2.

Summary of included studies with results grouped by type of augmentation strategy.

First author (year) and country	Subjects	Duration of intervention	Interventions and comparators	Outcome measures	Summary of findings	Risk of bias
Photobiomodulation (light therapies)
Arnedt et al. (2016)¹² USA	18–65 years n = 68	8 weeks	Group-1 n = 25 Fluoxetine + 6 h time-in-bed with 2 hr early rise Group-2 n = 24 Fluoxetine + 6 h time-in-bed with 2 hr bedtime delay Group-3 n = 19 Fluoxetine + 8 h time-in-bed (control)	HAMD-17	No statistically significant difference between the intervention and control groups in the change in HDRS scores at the end of the intervention period (p = .08). All groups improved. Study was underpowered to detect small-to-moderate effects.	High
Chen et al. (2022)¹³ Taiwan	Adults ≥20 years n = 43	4 weeks	Group-1 n = 22 *TAU (drug) + BLT 10,000 lux white light 30 min/day Group-2 n = 21 TAU (drug) + DRL 70 lux dim red light 30 min/day	HDRS, MADRS	No statistically significant improvement in either group and no difference between groups. Study was not powered to detect small-to-moderate effects. Both groups improved.	Low
Fregna et al. (2024)¹⁴ Italy	Adults n = 84	4 weeks	Group-1 n = 55 TAU (drug) + BLT 10,000 lux white light 30 min/day Group-2 n = 29 TAU (drug) only	HDRS	No statistically significant difference between the intervention and control group in the change in HDRS scores at the end of the intervention period. Both groups improved. Study was not powered to detect small-to-moderate effects.	High
Guu et al. (2025)¹⁵ Taiwan	Adults 18–75 years n = 48	8 weeks	Group-1 n = 25 TAU (drug) + near-infrared transcranial photobiomodulation Group-2 n = 23 TAU (drug) + sham	HDRS	No statistical difference between tPBM and sham. Both groups improved. Study was not powered to detect small-to-moderate effects.	Low
Lam et al. (2016)¹⁶ Canada	Adults 19–60 years n = 121	8 weeks	Group-1 n = 29 Bright white light 10,000 lux 30 min/day + fluoxetine 20 mg/day Group-2 n = 32 Bright white light 10,000 lux 30 min/day + placebo pill Group-3 n = 30 Deactivated (placebo) negative ion generator 30 min/day + fluoxetine 20 mg/day Group-4 n = 30 Deactivated (placebo) negative ion generator + placebo pill	MADRS	Augmentation with BLT demonstrated a clinically significant improvement in depression score. Both BLT groups were superior to placebo. BLT monotherapy was superior to fluoxetine monotherapy (p = .006). Combination therapy was superior to all groups (p < .001). The NNT for remission for combination compared to placebo was 4.	Low
Loving et al. (2002)¹⁷ USA	Adults 26–56 years n = 13	1 week	Group-1 n = 7 TAU + BLT 10,000 lux white light 30 min/day Group-2 n = 6 TAU + DRL 100 lux dim red light 30 min/day (placebo)	HDRS	No statistically significant improvement in the intervention group compared to control (p = .15) Study was underpowered.	Not clear
Martiny et al. (2005)¹⁸ Denmark	Adults 18 years+ n = 102	5 weeks	Group-1 n = 48 Sertraline 50 mg + BLT 10,000 lux white light 60 min/day Group-2 n = 54 Sertraline 50 mg + DRL 100 lux dim red light 60 min/day (placebo)	HDRS	The intervention group showed a greater improvement on the HDRS compared to the control group (p < .05). The intervention group HDRS scores improved from 22.4 (SD4.4) to 9.0 (4.4) compared to sertraline alone reducing from 22.1 (3.5) to 11.6 (4.3). The NNT for remission was 5.	Not clear
Neurostimulation
Aust et al. (2022)¹⁹ Germany	Adults 20–65 years n = 148	6 weeks	Group-1 n = 48 CBT + tDCS Group-2 n = 47 CBT + sham tDCS Group-3 n = 53 CBT alone tDCS = transcranial direct current Stimulation	MADRS	All groups improved, the addition of active tDCS to CBT did not produce a statistically significant greater reduction in depression scores at the end of the intervention period. Study was not powered to detect small to moderate effect sizes.	Low
Kumari et al. (2023)²⁰ India	Adults 18–60 years n = 50	4 weeks	Group-1 n = 26 Escitalopram 10 mg + bifrontal tDCS Group-2 n = 24 Escitalopram 10 mg + sham bifrontal tDCS	HDRS and BDI	No statistically significant difference on HDRS or BDI score reduction between groups at end of intervention (p = .52 and p = .41, respectively). Study was not powered to detect small effects.	Low
Papakostas et al. (2024)²¹ Canada and USA	Adults 18–80 years n = 260	8 weeks	Group-1 n = 70 TAU (drug) + rTMS (Repetitive transcranial magnetic Stimulation) Group-2 n = 92 TAU (drug) + aripiprazole Group-3 n = 98 Switch to venlafaxine or duloxetine	MADRS	Augmentation with rTMS did not show a statistically significant improvement in depression score compared to switching at the end of the intervention period (p = .234). Study was not powered to detect small-to-moderate effects. The rTMS group was not compared to the aripiprazole group.	High
Yin et al. (2024)²² China	Adults 18 years+ n = 90	12 weeks	Group-1 n = 30 Escitalopram + modified ECT Group-2 n = 30 Escitalopram + high-frequency rTMS Group-3 n = 30 Escitalopram only	HDRS-17	Both intervention groups had a statistically significant improvement in HDRS scores compared to control (both p < .05). There was no difference between the intervention groups. Escitalopram alone reduced depression score by 10 points (from 24.10 ± 3.49 at baseline to 14.37 ± 5.22 at 12 weeks), while both the modified ECT group and the rTMS group had an average reduction of 15 points (from 24.53 ± 3.32 to 10.27 ± 4.81, and 25.07 ± 3.74 to 10.77 ± 5.75, respectively).	High
Zhou et al. (2024)²³ China	Adults 18–55 years n = 66	4 weeks	Group-1 n = 33 tACS + escitalopram 5–20 mg Group-2 n = 33 Sham tACS + escitalopram 5–20 mg tACS = transcranial alternating current stimulation	HDRS	tACS group showed clinically meaningful improvement. The HDRS score in the intervention group reduced on average by 12.42 points (SD7.28) compared to 6.94 (6.65) for control (p < .002). To achieve a reduction in HDRS score more than 50% from baseline the NNT is 3.	Low
Exercise therapies
Murri et al. (2015)²⁴ Italy	Adults 65–85 years n = 121	24 weeks	Group-1 n = 42 Sertraline + progressive aerobic exercise Group-2 n = 37 Sertraline + non-progressive exercise (active control) Group-3 n = 42 Sertraline only	HDRS	Both sertraline-plus-exercise groups showed significantly greater decreases in HRSD scores over 24 weeks compared with sertraline alone (p < .01). There was no statistical difference in improvement between progressive and non-progressive exercise (active control). Study was powered to detect large effects only.	High
Carneiro et al. (2015)²⁵ Portugal	Adults 18–65 years n = 19	16 weeks	Group-1 n = 9 TAU (drug) + Aerobic exercise Group-2 n = 10 TAU (drug) only	BDI-II	Intervention group had greater improvement in depression scores on BDI-II compared to control (p = .031). Out of a total of 63 available points the intervention group reduced from 45.56 ± 9.65 to 34.89 ± 10.56, compared to the control group’s scores increasing from 46.10 ± 11.52 to 49.40 ± 16.72.	High
Danielsson et al. (2014)²⁶ Sweden	Adults 18–65 years n = 62	10 weeks	Group-1 n = 22 TAU (drug) + Aerobic exercise Group-2 n = 20 TAU (drug) + basic body Awareness therapy Group-3 n = 20 TAU (drug) + advice only (active control)	MADRS	There was statistically significant improvement in depression score for the aerobic exercise group compared to group 2 and 3 (p = .038). There was no statistical difference between BBAT and control. Out of 60 points on MADRS the intervention group improved by 10.3 ± 1.6 points compared to the control group improving by 5.8 ± 1.7.	High
Haussleiter et al. (2020)²⁷ Germany	Adults n = 76	6 weeks	Group-1 n = 36 TAU (drug) + supervised guided exercise therapy Group-2 n = 40 TAU (drug) + unsupervised self-organised exercise	HAMD-21	There was no statistically significant difference between intervention and control (p = .09). Study was likely underpowered to detect small-to-moderate effects.	High
Ho et al. (2014)²⁸ China	Adults 18–64 years n = 52	3 weeks	Group-1 n = 26 TAU (drug) + supervised aerobic exercise Group-2 n = 26 TAU (drug) + usual exercise (unsupervised)	MADRS	Intervention group showed a statistically significant improvement on MADRS than control (p = .003). Out of 60 points the scores in the intervention group improved by 10.08 ± 9.4 points compared to 4.69 ± 7.33 for control.	High
Lavretsky et al. (2011)²⁹ USA	Adults 60 years+ n = 73	10 weeks	Group-1 n = 36 Escitalopram + tai chi chih Group-2 n = 37 Escitalopram + health education (active control)	HDRS-24	Demonstrated statistically significant improvement in HSRD scores for the intervention group compared to control (p < .05) with the tai chi group reducing from 17.8 (2.0) to 5.1 (3.5) compared to the control group of 17.0 (1.6) to 6.7 (4.4).	High
Lavretsky et al. (2022)³⁰ USA	Adults aged 60 years+ n = 178	12 weeks	Group-1 n = 89 TAU (drug) + tai chi chih Group-2 n = 89 TAU + health education and wellness training (active control)	HDRS-24	Both groups improved HDRS scores but there was no significant difference between groups (p = .6). Study was powered to detect moderate to large effects only.	High
Legrand et al. (2016)³¹ France	Adults n = 35	10 days	Group-1 n = 14 TAU (drug) + aerobic exercise Group-2 n = 11 TAU (drug) + stretching (active control) Group-3 n = 10 TAU (drug)	BDI-II	Both the aerobic exercise and active control groups showed statistically significant improvement on BDI-II scores compared to treatment as usual (p < .001 and p = .011, respectively). There was no difference between the intervention group and active control.	High
Moraes et al. (2019)³² Brazil	Adults n = 25	12 weeks	Group-1 n = 9 TAU + aerobic training Group-2 n = 9 TAU + strength training Group-3 n = 7 TAU + low-intensity exercise (active control)	HDRS	Both the aerobic training group and the strength training group improved on HDRS scores compared to control (p = .005 and p = .007). No significant difference between the intervention groups.	High
Mota-Pereira et al. (2011)³³ Portugal	Adults 18–60 years n = 29	12 weeks	Group-1 n = 19 TAU (drug) + aerobic exercise Group-2 n = 10 TAU (drug) alone	BDI-II, HDRS	The intervention group showed a statistically significant improvement on both HDRS (p = .014) and BDI scores (p = .016). MADRS dropped by 6.84 (1.47) points compared to the control group which did not improve by intervention end (increased by 0.60 (0.96) points).	High
Pilu et al. (2007)³⁴ Italy	Adults 40–60 years n = 20	8 months	Group-1 n = 10 TAU (drug) + physical activity Group-2 n = 10 TAU (drug) only	HDRS	The intervention group did not show statistically significant improvement compared to control (p < .001). Study was underpowered.	High
Schuch et al. (2015)⁴ Brazil	Adults 18–60 years n = 50	Variable	Group-1 n = 25 TAU + aerobic exercise Group-2 n = 25 TAU only	HDRS	Intervention group HDRS scores improved compared to control at the end of intervention (p = .005). On discharge there was a 3.70 point difference favouring the intervention group. Mean scores were not reported.	High
Tavares et al. (2025)³⁵ Brazil	Adults 18–50 years n = 59	12 weeks	Group-1 n = 26 Escitalopram 10–15 mg + multimodal home exercise program Group-2 n = 33 Escitalopram 10–15 mg	MADRS	Both groups improved, no statistical difference between groups (p ≥ .50). Study was underpowered.	High
Abdollahi et al. (2017)³⁶ Iran	Adults n = 70	12 weeks	Group-1 n = 35 Group CBT + exercise Group-2 n = 35 Group CBT only	BDI-II	There was statistically significant improvement on BDI-II scores in the intervention group compared to control (p=<0.05). Depression score in the intervention group reduced from 20.89 (3.95) to 9.68 (2.91) compared to the control group 20.51 (4.39) to 14.48 (2.16).	High
Acupuncture
Yi et al. (2015)³⁷ China	Adults 18–60 years n = 120	6 weeks	Group-1 n = 60 SSRI + acupuncture Group-2 n = 60 SSRI only	MADRS	Intervention group had statistically significant improvement on MADRS scores compared to control at end of intervention (p < .01). Final change in score not reported on ITT analysis.	High
Wu et al. (2024)³⁸ China	Adults 18–60 years n = 120	6 weeks	Group-1 n = 40 SSRI + Intradermal acupuncture Group-2 n = 40 SSRI + Sham acupuncture Group-3 n = 40 SSRI only	HAMD-17	Intradermal acupuncture group showed a statistically significant improved in depression score compared to both control groups (p < .001). The intervention group reduced by 9.6 (SD4.9) points, the sham + SSRI group by 4.8 (4.6) points, and the SSRI only group by 4.6 (4.7) points.	Low
Zhao et al. (2019)³⁹ China	Adults n = 477	6 weeks	Group-1 n = 161 SSRI + manual acupuncture Group-2 n = 160 SSRI + electroacupuncture Group-3 n = 156 SSRI only	HDRS	Both intervention groups had statistically significant improvement on HDRS score than the control group (p < .05). There was no statistical difference between the two acupuncture groups. Study was powered to detect large effects.	High
Probiotics
Ghorbani et al. (2018)⁴⁰ Iran	Adults 18–55 years n = 40	10 weeks	Group-1 n = 20 Fluoxetine + synbiotic (probiotic) capsule Group-2 n = 20 Fluoxetine + placebo capsule	HDRS	Intervention group had statistically significant improvement on HDRS scores compared to placebo (p = .013). Intervention group’s HDRS score reduced by 19.25 (1.71) points compared to a reduction of 17.75 (2.05) points for control.	Low
Schaub et al. (2022)⁴¹ Switzerland	Adults 18 years+ n = 47	4 weeks	Group-1 n = 21 TAU (drug) + probiotic Group-2 n = 26 TAU (drug) + placebo	HDRS	Both groups improved. The probiotic group showed a statistically significant improvement compared to control only in the mITT analysis (p = <.05). Study was not powered to detect small effects.	Low

Outcome Acronyms: BDI-II = Beck’s Depression Inventory II, HDRS/HAMD-17 = Hamilton Depression Rating Scale 17 items, HDRS-21 = Hamilton Depression Rating Scale 21 items, HAMD-24 = Hamilton Rating Scale for depression 24 items, MADRS = Montgomery-Asberg Depression Rating Scale.

Intervention Acronyms: BLT = bright light therapy, CBT = Cognitive Behavioural Therapy, DRL = dim red light, rTMS = Repetitive Transcranial Magnetic Stimulation, SSRI = Selective Serotonin Reuptake Inhibitors, TAU = Treatment as Usual, tACS = Transcranial Alternating Current Stimulation, tDCS = Transcranial Direct Current Stimulation, tPBM = transcranial photobiomodulation.

Risk of bias assessment

A major problem among the included studies was related to lack of blinding and the inability to implement an effective control which led to a higher risk of bias in 21 out of 31 studies (see Table 3). All trials for exercise therapies had a high risk of bias due to being open label as participants and providers cannot be effectively blinded. The tDCS and tACS studies were low risk due to good sham controls and they also evaluated the effectiveness of their blinding. The majority of the light therapies and acupuncture trials also used a sham control. In some studies it may have been feasible to use a placebo or sham treatment but investigators did not implement a placebo-controlled condition for unclear reasons. Other problems were related to lack of clarity in reporting study data and for several studies the risk of bias could not be determined due to unclear methodology; the overall risk of bias for these studies was designated as unclear and treated as high risk. Intention-to-treat analysis was not reported in several studies. Overall, the studies were not amenable to meta-analysis due to high risk of bias in addition to variation in methodology and incomplete reporting.⁴²

Table 3.

Risk of bias assessment using JBI critical appraisal tool

	Risk of bias domain													Overall risk of bias
	1	2	3	4	5	6	7	8	9	10	11	12	13	Overall risk of bias
Abdollahi et al. (2017)³⁶	L	?	L	H	H	H	?	L	L	L	H	L	L	High
Arnedt et al. (2016)¹²	?	?	L	H	H	L	L	L	L	?	?	L	L	High
Aust et al. (2022)¹⁹	L	L	H	L	L	L	L	L	L	L	L	L	L	Low
Carneiro et al. (2015)²⁵	L	L	L	H	H	H	H	L	L	L	H	L	L	High
Chen et al. (2022)¹³	L	L	L	H	H	L	L	L	?	L	L	L	L	High
Danielsson et al. (2014)²⁶	L	L	L	H	H	L	L	L	L	L	L	L	L	High
Fregna et al. (2024)¹⁴	L	L	L	H	H	L	L	L	L	L	H	L	L	High
Ghorbani et al. (2018)⁴⁰	L	L	L	L	L	L	L	L	L	L	L	L	L	Low
Guu et al. (2025)¹⁵	L	L	L	L	L	L	L	L	L	L	L	L	L	Low
Haussleiter et al. (2020)²⁷	L	L	L	H	H	H	?	L	L	?	L	L	L	High
Ho et al. (2014)²⁸	L	L	L	H	H	H	L	L	L	L	L	L	L	High
Kumari et al. (2023)²⁰	L	L	L	L	H	L	H	L	L	L	L	L	L	Low
Lam et al. (2016)¹⁶	L	L	L	L	L	L	L	L	L	L	L	L	L	Low
Lavretsky et al. (2011)²⁹	L	L	L	H	H	L	L	L	L	L	L	L	L	High
Lavretsky et al. (2022)³⁰	L	L	L	H	H	L	?	L	L	L	?	L	L	High
Legrand et al. (2016)³¹	L	?	L	H	H	H	H	L	L	L	L	L	L	High
Loving et al. (2002)¹⁷	?	?	?	H	?	?	?	L	?	?	H	L	L	Unclear
Martiny et al. (2005)¹⁸	L	L	L	H	?	L	?	L	L	L	H	L	L	Unclear
Moraes et al. (2019)³²	?	L	L	H	H	?	L	L	L	L	H	L	L	High
Mota-Pereira et al. (2011)³³	?	?	H	H	H	L	L	L	L	L	H	?	L	High
Murri et al. (2015)²⁴	L	L	L	H	H	H	L	L	L	L	L	L	L	High
Papakostas et al. (2024)²¹	L	L	L	H	H	H	L	L	L	L	H	L	L	High
Pilu et al. (2007)³⁴	?	?	?	H	H	H	?	L	L	L	L	L	L	High
Schaub et al. (2022)⁴¹	L	?	L	L	L	L	L	L	L	L	L	L	L	Low
Schuch et al. (2015)⁴	L	L	L	H	H	H	L	L	L	L	L	L	L	High
Tavares et al. (2025)³⁵	L	L	L	H	H	?	H	L	L	L	L	L	L	High
Wu et al. (2024)³⁸	L	L	L	L	H	L	L	L	L	L	L	L	L	Low
Yi et al. (2015)³⁷	L	?	L	H	H	H	?	L	L	L	H	L	L	High
Yin et al. (2024)²²	L	L	L	H	H	H	?	L	L	L	?	L	L	High
Zhao et al. (2019)³⁹	L	L	L	H	H	H	L	L	H	L	?	L	L	High
Zhou et al. (2024)²³	L	L	L	L	H	L	L	L	L	L	L	L	L	Low

Key: L = Low risk, H = High risk, ? = Unclear.

Discussion

Bright light therapy may have a small effect on reducing depressive symptoms and should be considered as an adjunct to treatment because it has a great safety profile, is easy for patients to undertake in their own home, and is very affordable.⁴³ The evidence supports a regimen of exposure to 10,000 lux of bright white light for 30 min daily. Physical exercise may provide a small-to-moderate effect when implemented adjunctively and most types of exercise are suitable including aerobic exercise, strength training, and Tai Chi, and can be effective when undertaken both individually and in group formats. Most RCTs used structured supervised exercise programs which may be superior to self-organised exercise, however more evidence is needed. Acupuncture may demonstrate a mild reduction in depressive symptoms and also has a favourable safety profile. Of the neurostimulation techniques tDCS and tACS may offer small benefits. Probiotics may provide a small reduction in depressive symptoms however the evidence is not there to recommend any particular probiotic regimen. The only study on sleep deprivation included in this review found sleep deprivation ineffective. Other augmentation strategies not covered in this review include diet modification and occupational therapy, which the existing literature indicates may have a small effect on reducing depressive symptoms.^44,45 There is a large body of evidence supporting rTMS and ECT as primary treatments for depression and as such we have not included these in any further analysis.^7,46,47

Many studies included in this review did not use an adequate placebo, sham or active control, and this contributed to an overall high risk of bias. This limits the ability to recommend these interventions as augmentation strategies. Addressing this gap in the evidence base is important due to the ongoing high cost to the community of depression or partially treated depression, and clinicians require high-quality evidence to support treatment regimens.

Limitations

The eligibility criteria were constructed to capture studies in which the intervention was specifically investigated as an augmentation strategy to another primary treatment. As a consequence there were interventions included in this review that would normally be implemented as the primary treatment, including ECT and TMS, as the study investigators implemented these as adjunctive treatments in their clinical trials. This review accepted studies in which change in depression score at intervention end was the primary reported outcome and as a result there were several studies that were excluded due to only reporting the rate of remission as an outcome rather than change in depression score. This review did not investigate the rate of remission or the effect of interventions in accelerating response to treatment or consider follow up. Studies were limited only to articles published in English language.

Conclusions

Non-pharmacological non-psychological augmentation strategies have the potential to improve outcomes in patients with suboptimal treatment response without the burden of increased drug effects. However, more high-quality large placebo-controlled RCTs are needed to generate the evidence needed to support these interventions as augmentation strategies in individualising treatment for depression. The evidence is not yet there for being able to recommended specific augmentation strategies based on the primary treatment. The was limited evidence for acupuncture and probiotics, and improving evidence for bright light therapy and exercise.

Supplemental material

Supplemental material - Systematic review of non-pharmacological non-psychological augmentation strategies for the treatment of unipolar depression: Synthesis without meta-analysis (SWiM)

Supplemental material for Systematic review of non-pharmacological non-psychological augmentation strategies for the treatment of unipolar depression: Synthesis without meta-analysis (SWiM) by Hana Chapman, Rodney Blanch, Nishad Samad in Australasian Psychiatry

Supplemental material

Supplemental material - Systematic review of non-pharmacological non-psychological augmentation strategies for the treatment of unipolar depression: Synthesis without meta-analysis (SWiM)

Footnotes

Acknowledgements

Non-author contributors: • Emma White contributed to article screening and selection and risk of bias assessment. • Natalie Tam contributed to risk of bias assessment and manuscript editing.

ORCID iD

Hana Chapman

Ethical considerations

Ethics approval was not required for this study.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Use of AI declaration

Generative Artificial Intelligence (AI) was not used in the production of this paper.

Supplemental material

Supplemental material for this article is available online.

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