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The COVID-19 pandemic has created an epidemic of distress-related mental disorders such as depression, while simultaneously necessitating a shift to virtual domains of mental health care; yet, the evidence to support the use of virtual interventions is unclear.
The purpose of this study was to evaluate the efficacy of virtual interventions for depressive disorders by addressing three key questions: (1) Does virtual intervention provide better outcomes than no treatment or other control conditions (ie, waitlist, treatment as usual [TAU], or attention control)? (2) Does in-person intervention provide better outcomes than virtual intervention? (3) Does one type of virtual intervention provide better outcomes than another?
We searched the PubMed, EMBASE, and PsycINFO databases for trials published from January 1, 2010, to October 30, 2021. We included randomized controlled trials of adults with depressive disorders that tested a virtual intervention and used a validated depression measure. Primary outcomes were defined as remission (ie, no longer meeting the clinical cutoff for depression), response (ie, a clinically significant reduction in depressive symptoms), and depression severity at posttreatment. Two researchers independently selected studies and extracted data using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Risk of bias was evaluated based on Agency for Healthcare and Research Quality guidelines. We calculated odds ratios (ORs) for binary outcomes and standardized mean differences (SMDs) for continuous outcomes.
We identified 3797 references, 24 of which were eligible. Compared with waitlist, virtual intervention had higher odds of remission (OR 10.30, 95% CI 5.70-18.60; N=619 patients) and lower posttreatment symptom severity (SMD 0.81, 95% CI 0.52-1.10; N=1071). Compared with TAU and virtual attention control conditions, virtual intervention had higher odds of remission (OR 2.27, 95% CI 1.10-3.35; N=512) and lower posttreatment symptom severity (SMD 0.25, 95% CI 0.09-0.42; N=573). In-person intervention outcomes were not significantly different from virtual intervention outcomes (eg, remission OR 0.84, CI 0.51-1.37; N=789). No eligible studies directly compared one active virtual intervention to another.
Virtual interventions were efficacious compared with control conditions, including waitlist control, TAU, and attention control. Although the number of studies was relatively small, the strength of evidence was moderate that in-person interventions did not yield significantly better outcomes than virtual interventions for depressive disorders.
Prior to the COVID-19 pandemic, the lifetime prevalence of major depressive disorder (MDD) was over 20% for adults in the United States [
Prior systematic reviews and meta-analyses examined the evidence supporting the efficacy of computerized or virtual cognitive behavioral therapy (CBT) for MDD or depressive symptoms compared with no treatment or treatment as usual (TAU) (ie, referring participants to primary care providers or other health clinics in their local community to manage their depressive symptoms). Moreover, meta-analyses [
Information evaluating whether virtual care is an efficacious alternative to individual, face-to-face intervention with a therapist is needed for clinicians, health systems, payers, and policymakers. In addition, data to guide decisions about which existing virtual interventions are most efficacious for treating depressive disorder are lacking. In the absence of such data, common assumptions about the superiority of in-person treatment have guided clinical decisions and policies regarding depression treatment.
The purpose of this systematic review was to answer three clinically relevant key questions (KQs) for depressive disorders (ie, MDD, persistent depressive disorder, or dysthymia) based on studies conducted in the last 10 years.
KQ1: Does virtual intervention provide better clinical outcomes than no treatment, TAU, or attention control, defined as a rigorous control condition that simulates active treatment without the active ingredient (ie, does it work)?
KQ2: Does in-person intervention provide better outcomes than virtual intervention (ie, is in-person intervention better)?
KQ3: Does one type of virtual intervention provide better outcomes than another type of virtual intervention (ie, what works best)?
The KQs were structured based on Agency for Healthcare and Research Quality (AHRQ) guidance for decision-making related to best practices in treatment [
We used the Cochrane Handbook for Systematic Reviews of Interventions methods [
For this systematic review and meta-analysis, we searched the PubMed, EMBASE, and PsycINFO databases for trials published from January 1, 2010, to October 30, 2021, for MeSH (Medical Subject Headings) and major headings listed in Table A1 of
The study criteria were selected to inform clinical decision-making and policy in the United States. Eligible studies were randomized controlled trials (RCTs) of adults with a clinical diagnosis of MDD, dysthymic disorder, or persistent depressive disorder that tested a virtual psychological intervention for depression in at least one study arm, reported an outcome using a validated depression measure (see Table A2 of
References identified through searches were imported into Covidence Systematic Review software (Veritas Health Innovation, Melbourne, Australia). Two reviewers independently screened the titles and abstracts of all references according to the inclusion and exclusion criteria. Studies included by either reviewer were retrieved for full-text screening by two independent reviewers for eligibility. Discrepancies between reviewers were resolved through discussions and consensus.
One author extracted summary data from the included trials into standardized forms, and a second senior author (BNG, CES, or LL) checked the data for accuracy. Two authors independently rated the risk of bias across nine domains (see Table A4 in
Primary outcomes were rates of remission (ie, no longer meeting the clinical cutoff for depression), rates of response (ie, a clinically significant reduction in depressive symptoms), and depression severity at posttreatment. We calculated odds ratios (ORs) with 95% CIs for remission and response, and calculated standardized mean differences (SMDs, Cohen
To determine the appropriateness of quantitative analyses, the senior authors (BNG, CES, LL, AEB) assessed the clinical and methodological heterogeneity of studies under consideration [
Statistical heterogeneity in effects between studies included in each meta-analysis was assessed by calculating the
Database and manual searching yielded 3797 citations for consideration (
Study selection. *See Table A2 in
Participant characteristics in each included trial.
Referencea | MDDb diagnostic measurec | Average MDD severity at baseline | Intervention condition | Comparison condition | Age (years), mean (SD) | Women, n (%) | Some colleged, n (%) | |||
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Participants, n | Completed posttreatment assessment, n (%) | Participants, n | Completed posttreatment assessment, n (%) |
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Berger et al [ |
MINIf | Moderate | 25 | 22 (88) | 26 | 22 (85) | 39 (14) | 36 (70) | 32 (63) |
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Berger et al [ |
MINI | Moderate | 25 | 25 (100) | 26 | 22 (85) | 39 (14) | 36 (70) | 32 (63) |
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Carlbring et al [ |
SCIDg | Moderate | 40 | 40 (100) | 40 | 38 (95) | 44 (14) | 66 (83) | 61 (76) |
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Chan et al [ |
Clinical interview | Moderate | 167 | 109 (65) | 153 | 144 (94) | 27 (7) | 234 (73) | 288 (90) |
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Johansson et al [ |
SCID | Moderate | 27 | 25 (91) | 27 | 27 (100) | 39 (NRh) | 31 (57) | 23 (42) |
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Kenter et al [ |
CIDIi | Moderate | 136 | 96 (69) | 133 | 89 (67) | 38 (11) | 145 (54) | 110 (41) |
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Smith et al [ |
MINI | Moderate | 61 | 36 (59) | 68 | 55 (81) | 40 (13) | 106 (82) | 89 (69) |
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Vernmark et al [ |
SCID | Moderate | 30 | 29 (97) | 29 | 29 (100) | 37 (13) | 40 (68) | 48 (82) |
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Vernmark et al [ |
SCID | Moderate | 29 | 27 (93) | 29 | 29 (100) | 37 (13) | 39 (68) | 48 (82) |
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Dennis et al [ |
SCID | Moderate | 120 | 104 (87) | 121 | 100 (83) | 31 (6) | 241 (100) | 181 (75) |
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Forsell et al [ |
SCID | Moderate | 22 | 21 (95) | 20 | 18 (90) | 30 (5) | 42 (100) | 30 (71) |
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Hallgren et al [ |
MINI | Moderate | 317 | 273 (86) | 312 | 256 (82) | 43 (12) | 472 (75) | 390 (62) |
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Löbner et al [ |
ICD-10l | Mild to moderate | 320 | 259 (81) | 327 | 307 (94) | 44 (13) | 446 (69) | NR |
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Moreno et al [ |
MINI | Moderate | 80 | 74 (93) | 87 | 85 (98) | 44 (12) | 149 (89) | 28 (17) |
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Pfeiffer et al [ |
Medical record | Moderate | 167 | 109 (65) | 163 | 129 (79) | 52 (15) | 66 (20) | 281 (85) |
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Raevuori et al [ |
ICD | Moderate | 63 | 57 (90) | 61 | 51 (84) | 25 (NR) | 90 (73) | NR |
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Wozney et al [ |
SCID | Moderate to severe | 32 | 26 (81) | 30 | 24 (80) | 29 (5) | 62 (100) | 14 (22) |
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Flygare et al [ |
SCID | Moderate | 48 | 36 (74) | 14 | 11 (76) | 45 (12) | 47 (76) | NR |
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Johansson et al [ |
MINI | Moderate | 46 | 42 (91) | 46 | 46 (100) | 47 (14) | 64 (70) | 77 (84) |
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Ly et al [ |
MINI | Moderate | 40 | 36 (90) | 41 | 36 (88) | 36 (11) | 57 (70) | 51 (63) |
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Oehler et al [ |
MINI | Mild to moderate | 173 | 125 (72) | 174 | 127 (73) | 42 (12) | 274 (79) | 229 (66) |
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Reins et al [ |
SCID | Moderate | 65 | 49 (75) | 66 | 53 (80) | 42 (11) | 100 (76) | 94 (72) |
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Andersson et al [ |
SCID | Moderate | 36 | 33 (92) | 33 | 32 (97) | 42 (14) | 54 (78) | NR |
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Egede et al [ |
SCID | Moderate | 121 | 106 (88) | 120 | 108 (90) | 64 (5) | 5 (2) | NR |
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Mohr et al [ |
HAMDn | Moderate | 162 | 141 (87) | 163 | 151 (93) | NR (NR) | NR | NR |
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Thase et al [ |
SCID | Moderate | 77 | 67 (87) | 77 | 66 (86) | 46 (14) | 102 (66) | 152 (99) |
aEach row represents an intervention arm. Some references are listed more than once because they provided data from multiple intervention arms.
bMDD: major depressive disorder.
cParticipants of all trials were diagnosed with MDD.
dSome college means any self-reported level of educational attainment greater than high school or equivalent.
eKQ: key question.
fMINI: Mini International Neuropsychiatric Interview.
gSCID: Structured Clinical Interview for Axis-I Disorders.
hNR: not reported.
iCIDI: Composite International Diagnostic Interview.
jTAU: treatment as usual.
kAll participants were diagnosed with MDD with perinatal onset.
lICD-10: International Classification of Diseases, 10th revision.
mIncluded in systematic review but excluded from meta-analysis due to differences in methods from other studies.
nHAMD: Hamilton Rating Scale for Depression.
The characteristics of each trial, including the length of intervention, treatment modality and mode, provider type, and comparison condition, are summarized in
Risk of bias assessments across the nine individual domains and an overall summary is presented for each study in Table A4 of
Trial characteristics.
Referencea | Length of intervention (weeks) | Intervention condition | Comparison condition | |||||
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Modality | Mode | Provider type | Modality | Mode | Provider | |
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Berger et al [ |
10 | CBTc (Deprexis) | Online intervention, guided | Mental health specialist | Waitlist | NAd | None |
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Berger et al [ |
10 | CBT (Deprexis) | Online intervention, unguided | None | Waitlist | NA | None |
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Carlbring et al [ |
7 | ACTe/BAf | Online intervention, guided | Mental health specialist | Waitlist | NA | None |
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Chan et al [ |
6 | CBT-I | Smartphone intervention, unguided | None | Waitlist | NA | None |
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Johansson et al [ |
8 | CBT | Online intervention, guided | Mental health specialist | Waitlist | NA | None |
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Kenter et al [ |
8 | Problem-solving therapy | Online intervention, guided | Student | Waitlist | NA | None |
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Smith et al [ |
12 | CBT | Online intervention, guided | Mental health specialist | Waitlist | NA | None |
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Vernmark et al [ |
8 | CBT | Individualized email therapy | Mental health specialist | Waitlist | NA | None |
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Vernmark et al [ |
8 | CBT | Online intervention, guided | Mental health specialist | Waitlist | NA | None |
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Dennis et al [ |
12 | IPTh | Telehealth (telephone) | Nurses | TAU | In-person | Nurse |
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Forsell et al [ |
10 | CBT | Online intervention, guided | Mental health specialist | TAU | In-person | OBGYNi |
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Hallgren et al [ |
12 | CBT | Online intervention, guided | Mental health specialist | TAU | In-person | PCPj |
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Löbner et al [ |
6 | CBT (Moodgym)+TAU | Online intervention, self-guided | PCP | TAU | In-person | PCP |
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Moreno et al [ |
24 | Supportive therapy+medication | Telehealth (video) | Mental health specialist | TAU | In-person | PCP |
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Pfeiffer et al [ |
12 | CBT (Beating the Blues) | Online intervention, guided+TAU | Peer support specialist | TAU+depression workbook | In-person | VAk physician |
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Raevuori et al [ |
8 | CBT (Meru Health Program) | Smartphone intervention, guided | Mental health specialist | TAU | In-person | Mental health specialist |
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Wozney et al [ |
24 | CBT (MOM: Managing Our Mood) | Handbook and telephone coaching | Trained coach | TAU | In-person | PCP |
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Flygare et al [ |
8 | CBT | Online intervention, guided | Mental health specialist | Psychoedl | Online intervention, guided | Mental health specialist |
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Johansson et al [ |
10 | Psychodynamic therapy | Online intervention, guided | Mental health specialist | Psychoed | Online intervention, guided | Mental health specialist |
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Ly et al [ |
8 | BA | Smartphone, guided | Mental health specialist | Mindfulness | Smartphone, guided | Mental health specialist |
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Oehler et al [ |
6 | CBT (iFight Depression) | Online intervention, guided | Mental health specialist | Progressive muscle relaxation | Online intervention, guided | Mental health specialist |
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Reins et al [ |
6 | CBT (GET.ON Mood Enhancer) | Online intervention, guided | Mental health specialist | Psychoed | Online intervention, unguided | None |
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Andersson et al [ |
8 | CBT | In-person group,8 sessions (60 min) | Mental health specialist | CBT | Online intervention, guided | Mental health specialist |
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Egede et al [ |
8 | BA | In-person, 8 sessions (60 min) | Mental health specialist | BA | Telemedicine (video), 8 sessions (60 min) | Mental health specialist |
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Mohr et al [ |
18 | CBT | In-person, 18 sessions (45 min) | Mental health specialist | CBT | Telemedicine (telephone), 18 sessions (45 min) | Mental health specialist |
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Thase et al [ |
20 | CBT | In-person, 20 sessions (50 min) | Mental health specialist | CBT (Good Days Ahead) | Online intervention, guided (Good Days Ahead) | Mental health specialist |
aEach row represents an intervention arm. Some references are listed more than once because they provided data from multiple intervention arms.
bKQ: key question.
cCBT: cognitive behavioral therapy.
dNA: not applicable.
eACT: acceptance and commitment therapy.
fBA: behavioral activation.
gTAU: treatment as usual.
hIPT: interpersonal therapy.
iOBGYN: obstetrician/gynecologist.
jPCP: primary care provider.
kVA: Veteran’s Administration.
lPsychoed: psychoeducation.
mIncluded in systematic review but excluded from meta-analysis due to differences in methods from other studies.
Forest plots of virtual intervention compared with waitlist control clinical outcomes. ΔBDI: Change in Beck Depression Inventory Score; ΔPHQ: Change in Patient Health Questionnaire-9 Score; BDI: Beck Depression Inventory; CES-D: Center for Epidemiologic Studies Depression Scale; MADRS-SR: Montgomery–Åsberg Depression Rating Scale – Self-Report Questionnaire; MDD: Major Depressive Disorder; PHQ-9: Patient Health Questionnaire-9.
Forest plots of virtual intervention compared with treatment as usual (TAU) clinical outcomes. ΔMADRS: Change in Montgomery–Åsberg Depression Rating Scale Score; ΔMADRS-SR: Change in Montgomery–Åsberg Depression Rating Scale – Self-Report Questionnaire Score; BDI: Beck Depression Inventory; EPDS: Edinburgh Postnatal Depression Scale; MDD: Major Depressive Disorder; MADRS: Montgomery–Åsberg Depression Rating Scale Interview; MADRS-SR: Montgomery–Åsberg Depression Rating Scale – Self-Report Questionnaire; PHQ-9: Patient Health Questionnaire-9.
Forest plots for virtual intervention (internet-based cognitive behavioral therapy [iCBT]) compared with virtual sham intervention clinical outcomes. ΔBDI: Change in Beck Depression Inventory Score; BDI: Beck Depression Inventory; HAMD: Hamilton Depression Rating Scale; IDS-SR: Inventory for Depressive Symptomatology – Self-Report; MDD: Major Depressive Disorder; SCID: Semi-Structured Clinical Interview for DSM Disorders.
Forest plots for in-person intervention compared with virtual intervention clinical outcomes (key question 2). ΔBDI: Change in Beck Depression Inventory Score; ΔHAMD: Change in Hamilton Depression Rating Scale Score; ΔMADRS: Change in Montgomery–Åsberg Depression Rating Scale Score; BDI: Beck Depression Inventory; HAMD: Hamilton Depression Rating Scale; MDD: Major Depressive Disorder; SCID: Semi-Structured Clinical Interview for DSM Disorders.
Strength of evidence for each outcome organized by key question (KQ).
Outcome | Study design, duration, sample size (N), eventsa (n) | Effect size (95% CI) | Factors that affect the strength of evidence | Overall evidence strength and direction of effect | Findings | |
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Remission | RCTb (4 trials), 7-10 weeks, N=564, n=118 enrolled; N=619, n=126 analyzed due to 2 trials each having two intervention arms comparing to one control group | ORc 10.30 (5.70 to 18.60) | Low ROBd, imprecise estimatee but high effect (increase), direct consistent ( |
High; virtual intervention>waitlist | The SOEf is high that virtual interventions have 10 times higher odds of remission than waitlist |
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Response | RCT (2 trials), 10-12 weeks, N=195, n=74 enrolled; N=221, n=78 analyzed due to 1 trial having two intervention arms comparing to the same control group | OR 3.57 (0.86 to 14.78) | 1 Low, 1 moderate ROB (decrease),imprecise estimate (decrease), direct inconsistentg ( |
Low; no statistically significant difference | The SOE is low that there are no substantial differences in response between virtual interventions and waitlist |
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Depression severity | RCT (7 trials), 7-12 weeks, N=1180, n=1180 enrolled; N=1071, n=1071 analyzed due to 2 trials each having two intervention arms comparing to one control group | SMDh 0.81 (0.52 to 1.10) | 4 Low, 3 moderate ROB; precise estimate; direct inconsistent ( |
Moderate; virtual intervention>waitlist | The SOE is moderate that virtual interventions have greater reduction in depression severity compared with waitlist |
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Remission | RCT (4 trials), 10-24 weeks; N=512, n=285 | OR 2.27 (1.54 to 3.35) | Low ROB; imprecise estimate (decrease); direct consistent ( |
Moderate; virtual intervention>TAU | The SOE is moderate that virtual interventions have 2 times higher odds of remission than TAU |
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Response | RCT (3 trials), 10-24 weeks; N=450, n=238 | OR 2.95 (1.51 to 5.75) | Low ROB; imprecise estimate (decrease); direct consistent ( |
Moderate; virtual intervention>TAU | The SOE is moderate that virtual interventions have 3 times higher odds of response than TAU |
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Depression severity | RCT (7 trials), 8-24 weeks; N=1533, n=1533 | SMD 0.59 (0.13 to 1.05) | 5 Low, 2 Moderate ROB; precise estimate; direct inconsistent ( |
Moderate; virtual intervention>TAU | The SOE is moderate that virtual interventions have greater reduction in depression severity compared with TAU |
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Remission | RCT (2 trials), 6-8 weeks; N=226, n=99 | OR 1.92 (1.10 to 3.35) | 1 Low, 1 Moderate ROB (decrease); imprecise estimate (decrease); direct consistent ( |
Low; virtual CBTj>attention control | The SOE is low that virtual CBT has 2 times greater odds of remission than virtual psychoeducation |
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Response | RCT (2 trials), 6-8 weeks; N=226, n=79 | OR 1.68 (0.96 to 2.96) | 1 Low, 1 Moderate ROB (decrease); imprecise estimate (decrease); direct consistent ( |
Low; no statistically significant difference | The SOE is low there are no substantial differences in response between virtual CBT and virtual psychoeducation |
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Depression severity | RCT (3 trials), 6-8 weeks; N=573, n=573 | SMD 0.25 (0.09 to 0.42) | 2 Low, 1 Moderate ROB; precise estimate; direct consistent ( |
High; virtual CBT>attention control | The SOE is high that virtual CBT has greater reduction in depression severity compared with virtual psychoeducation |
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Remission | RCT (4 trials), 8-20 weeks; N=789, n=288, | OR 0.84 (0.51 to 1.37) | Low ROB; imprecise estimate (decrease); direct consistent ( |
Moderate; no statistically significant difference, noninferiority trialsf | The SOE is moderate that there are no substantial differences in remission between in-person and virtual interventions |
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Response | RCT (3 trials), 8-18 weeks; N=635, n=230 | OR 0.82 (0.44 to 1.54) | Low ROB; imprecise estimate (decrease); direct consistent ( |
Moderate; no statistically significant difference, noninferiority trials | The SOE is moderate that there are no substantial differences in response between in-person and virtual interventions |
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Depression severity | RCT (3 trials), 8-20 weeks; N=548, n=548 | SMD –0.04 (–0.30 to 0.23) | Low ROB; precise estimate; direct consistent ( |
Moderate; no statistically significant difference, noninferiority trials | The SOE is moderate that there are no substantial differences in posttreatment depression severity between in-person and virtual interventions |
aBased on risk of bias, precision of estimate, directness of comparison, and consistency.
bRCT: randomized controlled trial.
cOR: odds ratio.
dROB: risk of bias.
eImprecision is based on the number of events <300 events, or n=400 for continuous events or very wide confidence intervals; precision was the primary variable that influenced strength of evidence ratings given that most trials had low risk of bias and were direct and consistent.
fSOE: strength of evidence.
gInconsistent was based on I2>75%.
hSMD: standardized mean difference.
iTAU: treatment as usual.
jCBT: cognitive behavioral therapy.
The efficacy of virtual interventions compared with waitlist was assessed in seven double-blinded RCTs [
Remission was evaluated in four trials [
Efficacy of virtual interventions compared with TAU was evaluated in eight double-blinded RCTs [
Remission was evaluated in four trials [
Five trials compared a virtual adaptation of an evidence-based intervention (eg, CBT [
Remission and response were assessed in two trials [
Efficacy of in-person compared with virtual delivery of behavioral therapy, either CBT or BA, was evaluated in four RCTs [
Remission was evaluated in four trials [
Response was evaluated in three trials [
Depression severity was evaluated in all four trials [
No trials comparing the efficacy of one virtual intervention with another virtual intervention were identified in our searches that met our inclusion criteria.
Virtual intervention for individuals with mild to moderate depressive disorders resulted in higher remission rates and a lower severity of symptoms at posttreatment compared with waitlist, TAU, and attention control conditions. There was no consistent evidence that an in-person intervention is significantly more efficacious than a virtual intervention for depression. Two studies compared telehealth with in-person sessions, while two studies compared virtual behavior therapies with in-person sessions. Despite these methodological differences, heterogeneity between studies was low and sensitivity analyses showed no difference in results if any study was removed. Studies included individuals with mild to moderate depressive disorders across a number of patient populations, including primary care patients, veterans, perinatal women, and Spanish-speaking Latinx individuals, suggesting relatively broad generalizability to depressed populations in countries with a very high human development index. Of note, we found no eligible studies comparing the effectiveness of different active virtual interventions, which is an important research and clinical gap that should be addressed in future trials. Taken together, the results suggest that virtual therapy is an effective method of treatment for mild to moderate depressive disorders. The results further suggest a lack of clear evidence that in-person treatment is superior to virtual treatment for those with mild to moderate depressive disorders without significant comorbidity and living in countries with a very high human development index.
Given the significant limitations in access to evidence-based care in the United States, this represents a potential opportunity to increase access to effective and affordable treatment. Despite the finding that, on average, there is not reliable evidence that in-person treatment is superior to virtual treatment for depressive disorders, critical research to identify which patients benefit most from in-person and virtual treatment has not been done. Some patients may benefit more from in-person therapy than virtual treatment. Many people do not have access to high-speed internet, a private space for virtual sessions, or a home environment that is safe or conductive to engaging in therapy at home. None of the studies included in this review addressed these important individual differences that may differentially impact treatment feasibility, acceptability, and outcomes. As such, in-person therapy for mood disorders remains an important first-line treatment option. However, virtual therapy can be considered an additional first-line treatment option, particularly for those who prefer it and those without transportation, time, or geographical access to in-person treatment.
This systematic review and meta-analysis had important limitations. For some of the outcomes, a low number of events (ie, remission or response) observed across a small number of studies reduced the SOE, particularly in the case of response, which had the lowest number of observations of any outcome assessed and resulted in low to moderate SOE ratings across each key question. Our review was narrowly focused on depression intervention outcomes: all of the trials that met the inclusion criteria focused on interventions for MDD, and despite inclusion criteria of all depressive disorders, none examined other depressive disorders or other common co-occurring conditions such as anxiety disorders. Only one study included individuals with severe depressive symptoms, and therefore conclusions cannot be made regarding the utility of virtual therapy for those with more severe presentations. Interventions ranged in duration from 6 to 24 weeks. We evaluated immediate effects of the intervention on depression outcomes; however, due to variability in follow-up assessments, we did not examine long-term outcomes. Patient adherence to the intervention was not defined consistently across studies, and intervention fidelity was not assessed in most studies. Thus, neither variable could be evaluated as part of our risk of bias assessment. The studies included in KQ2 evaluated heterogeneous treatment populations (eg, veterans, primary care patients), and different in-person (eg, group therapy, individual therapy) and virtual (eg, telephone therapy, video therapy, virtual CBT) treatments. Although sensitivity analyses suggested that the results were the same when eliminating heterogeneous studies, additional studies are needed to have strong confidence in the results.
The results of this study were consistent with older meta-analyses establishing the efficacy of virtual CBT for depression and anxiety compared with no intervention [
Strengths of this systematic review included a multidimensional approach to assessing risk of bias, based on both the Cochrane risk of bias tool [
These results carry implications for health systems and mental health clinicians, policymakers, and researchers. Mental health clinics with long waitlists for evidence-based interventions and primary care clinics offering TAU could improve patient outcomes, reduce wait times, and reserve face-to-face sessions with therapists for those with the most severe symptoms by providing virtual interventions. With the rates of depression reaching epidemic proportions during the COVID-19 pandemic, existing efficacious technological solutions can help reduce the burden on the health care system, increase access to mental health care, and reduce the risk of COVID-19 transmission in health care settings. Implementation research is needed to determine when and for whom virtual interventions work best and when they may serve as an alternative to face-to-face therapy. Studies examining the efficacy of virtual adaptations of other evidence-based interventions for depression (eg, BA, acceptance and commitment therapy), optimal amount of guidance for virtual interventions (eg, regularly scheduled or as-needed coaching), optimal format for provider involvement (eg, telephone or email), and degree of provider training (eg, peer support, trained coaches, or licensed mental health providers) are needed to guide clinical decision-making. Nevertheless, our results suggest that virtual interventions provide an efficacious mechanism for scaling-up depression interventions to meet the growing demands created by the COVID-19 pandemic.
Supplementary information: Tables A1-A5; Figure A1.
Agency for Healthcare and Research Quality
behavioral activation
cognitive behavioral therapy
key question
major depressive disorder
Medical Subject Heading
odds ratio
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
randomized controlled trial
standardized mean difference
strength of evidence
treatment as usual
We thank our colleague, Nate Sowa, MD, for raising the important questions of whether virtual interventions work, whether in-person interventions work better, and which virtual interventions work best.
None declared.