Table 5 Overview of primary endpoints and study results (based on the intention-to-treat analyses)

Deprexis

t0 (Baseline)

t1 (3 months)^a

t2 (6 months follow-up)

Study 1 [17]

improvement of the state of health

depression severity

Patient Health Questionnaire-9 (PHQ-9)

0–27

higher scores indicate stronger symptoms

level of depression:

0–4 = minimal

5–9 = mild

10–14 = moderate

15–19 = moderately severe

20–27 = severe [35]

5-point reduction [35]

IG: M = 16.62 (3.44)

CG: M = 17.20 (3.86)

IG: M = 10.08 (6.37)

CG: M = 13.64 (6.14)

p  < 0.01

Cohens d = 0.57 [0.22, 0.92]

IG: M = 11.28 (6.04)

CG: M = 13.39 (6.59)

Cohens d = 0.33 [0.3, 0.69]

Study 2 [18]

IG: M = 10.23 (2.41)

CG: M = 10.34 (2.40)

IG: M = 7.54 (4.04)

CG: M = 9.15 (4.30)

Cohens d = 0.39 [0.13, 0.64]

IG: M = 7.31 (4.18)

CG: M = 8.69 (4.41)

Cohens d = 0.32 [0.06, 0.59]

Elevida [19, 36]

t0 (Baseline)

t1 (12 weeks) ^a

t2 (24 weeks follow-up)

improvement of the state of health

fatigue

Chalder Fatigue Scale

0–33

higher scores indicate stronger symptoms [37]

between

0.7 and 1.4 [37, 38]

IG: M = 21.58 (5.32)

CG: M = 21.17 (5.02)

Intergroup difference

-2.74 [-1.16, -4.32]

p  = 0.0007

Cohens d = 0.53

Intergroup difference

-2.19 [-0.57, -3.82]

p  = 0.0080

Hello Better

Diabetes and Depression [20, 21]

t0 (Baseline)

t1 (8 weeks) ^a

t2 (6 months follow-up 1)

t3 (12 months follow-up 2)

improvement of the state of health

depressive

symptom severity

Allgemeine Depressionsskala (ADS)

0–60

higher scores indicate stronger symptoms [39]

score of 23 or higher is indicative of clinically relevant depressive symptoms in

German populations [40]

standardized mean difference ≥ 0.24 [41]

IG: M = 32.22 (6.96)

CG: M = 31.55 (7.57)

IG: M = 20.86 (9.73)

CG: M = 29.1 (9.08)

MD = 8.07 (1.37)

p  < 0.001

Cohens d = 0.94 [0.62, 1.25]

IG: M = 20.09 (11.15)

CG: M = 27.13 (10.14)

MD = 5.78 (1.95)

p  < 0.001

Cohens d = 0.62 [0.21, 1.04]

IG: M = 19.88 (10.15)

KG: M = 26.73 (10.43)

MD = 5.57 (2.02)

p  = 0.002

Cohens d = 0.63 [0.18, 1.08]

Hello Better

Panik [22, 23]

t0 (Baseline)

t1 (8 weeks) ^a

t2 (6 months follow-up 1)

t3 (12 months follow-up 2)

improvement of the state of health

severity of panic and agoraphobia

symptoms

Panic Symptom Severity and Self-Rating (German: PAS)

0–52

higher scores indicate stronger symptoms

0–8 = no clinically relevant symptoms

9–28 = moderate

symptoms

 > 29 = severe level

of symptoms [42]

IG: M = 18.18 (6.54)

CG: M = 19.43 (5.49)

IG: M = 11.73 (6.90)

CG: M = 17.60 (8.86)

MD = 5.99 (1.86)

p  = 0.009

Cohens d = 0.78 [0.31, 1.26]

IG: M = 9.66 (7.65)

CG: M = 16.32 (7.13)

MD = 6.72 (1.97)

p  = 0.009

Cohens d = 1.00 [0.42, 1.58]

IG: M = 8.63 (6.33)

CG: M = 14.68 (7.65)

MD = 6.07 (1.90)

p  = 0.009

Cohens d = 0.96 [0.37, 1.56]

Hello Better

Stress and Burnout [24, 25]

t0 (Baseline)

t1 (7 weeks) ^a

t2 (6 months follow-up 1)

t3 (12 months follow-up 2)

improvement of the state of health

level of perceived stress

Perceived Stress Scale (PSS-10)

0–40

higher scores indicate stronger symptoms

0–13 = low

14–26 = moderate

27–40 = high perceived stress [43]

IG: M = 25.89 (3.85)

CG: M = 25.15 (3.96)

IG: M = 17.88 (6.17)

CG: M = 22.96 (6.07)

p  < 0.001

Cohens d = 0.83 [0.58–1.08]

IG: M = 16.08 (6.03)

CG: M = 22.10 (5.81)

p  < 0.001

Cohens d = 1.02 [0.76–1.27]

IG: M = 16.25 (6.35)

Hello Better

Vaginismus Plus [26, 27]

t0 (Baseline)

t1 (12 weeks) ^a

t2 (6 months follow-up)

improvement of the state of health

intercourse penetration behavior

Primary Endpoint Questionnaire (PEQ)

0 = not attempted or

attempted, but unsuccessful

1 = attempted and sometimes

successful or attempted and always successful [44]

IG: M = 0

CG: M = 0

IG = 31 (31%)

CG = 13 (13%)

Chi-Quadrat = 9.44

p  < 0.01

OR = 3.01 [1.46–6.18]

IG = 29 (29%)

CG = 20 (20%)

Chi-Quadrat = 2.19

p  = 0.19

OR = 1.63 [0.85–3.14]

Kalmeda [28]

t0 (baseline)

t1 (3 months) ^a

t2 (9 months) only IG

t3 (12 months) only CG

improvement of the state of health

tinnitus exposition

Tinnitus questionnaire according to Göbel and Hiller

0–84

higher scores indicate stronger symptoms

0–30 = mild

31–46 = medium

47–59 = severe

60–84 = severely [45]

IG: M = 37.14 (13.01)

CG: M = 37.46 (14.29)

IG: M = 23.43 (11.77)

CG: M = 24.76 (15.71)

p  < 0.0001

IG: M = 17.61 (10.21)

p  < 0.0001

CG: M = 20.27 (13.01)

p  < 0.0001

Selfapy

Depression [29]

t0 (Baseline)

t1 (6 weeks)

t2 (12 weeks) ^a

t3 (24 weeks follow-up)

improvement of the state of health

depressive symptoms

Beck-Depressions-Inventar II (BDI-II)

0–63

higher scores indicate stronger symptoms

0–8 = no depression

9–13 = minimal depression

14–19 = mild depression

20–28 = moderate depression

29–63 = severe depression [46, 47]

IG1: M = 30.09 (9.18)

IG2: M = 30.54 (8.53)

CG: M = 30.88 (10.74)

IG1: M = 20.71 (6.98)

IG2: M = 22.51 (7.83)

CG: M = 29.09 (6.39)

IG1 vs. IG2: Cohens d = 0.24 [0.02, 0.48]

IG1 vs. CG: Cohens d = 1.25 [0.99, 1.54]

IG2 vs. CG: Cohens d = 0.92 [0.65, 1.20]

IG1: M = 16.61 (9.55)

IG2: M = 18.49 (8.88)

CG: M = 30.26 (6.97)

IG1 vs. IG2: Cohens d = 0.20 [− 0.04, 0.45]

p  = 0.18

IG1 vs. CG: Cohens d = 1.63 [1.37, 1.93]

p  < 0.001

IG2 vs. CG: Cohens d = 1.47 [1.22, 1.73]

p  < 0.001

for the 24-week follow-up assessment only per protocol data were used

Somnio [30]

t0 (Baseline)

t1 (6 weeks) ^a

t2 (12 months follow-up)

improvement of the state of health

insomnia

Insomnia severity index (ISI)

0–28

higher scores indicate stronger symptoms

0–7 = normal

8–14 = sub-threshold insomnia

15–21 = moderate insomnia

 > 21 = severe clinical insomnia [48]

IG: M = 15.38 (3.74)

CG: M = 13.26 (3.29)

IG: M = 7.80 (4.94)

CG: M = 12.04 (3.86)

t = 5.06

p  < 0.001

Cohens d = 1.79

IG: M = 7.36 (5.38)

Cohens d = 1.98 [1.31, 2.66]

Velibra [31, 49]

t0 (Baseline)

t1 (9 weeks) ^a

t2 (6 months follow-up)

improvement of the state of health

depression,

anxiety and tension/stress

Depression Anxiety Stress Scales – Short Form (DASS-21)

0–120

higher scores indicate stronger symptoms [50]

Δ = 6.42 [51]

d = 0.24 [41]

IG: M = 58.2 (24.4)

CG: M = 55.8 (21.3)

IG: M = 40.9 (25.7)

CG: M = 52.7 (24.7)

p  < 0.01

Cohens d = 0.47 [0.13–0.81]

IG: M = 41.9 (30.0)

reduction of therapy-related efforts and strains for patients/their relatives

general psycho-

pathology

Brief Symptom Inventory (BSI)

Short version of the Symptom Checklist-90 (SCL-90)

IG: M = 1.34 (0.56)

CG: M = 1.27 (0.57)

IG: M = 0.94 (0.63)

CG: M = 1.18 (0.71)

p  < 0.001

Cohens d = 0.42 [0.08–0.75]

IG: M = 0.97 (0.77)

anxiety-related symptoms

Beck Anxiety Inventory (BAI)

0–63

higher scores indicate stronger symptoms

0–21 = low anxiety

22–35 = moderate anxiety

 > 36 = potentially concerning levels of anxiety [46]

IG: M = 34.9 (9.1)

CG: M = 33.3 (10.3)

IG: M = 27.8 (9.1)

CG: M = 31.4 (10.0)

p  < 0.001

Cohens d = 0.41 [0.07–0.74]

IG: 26.6 (9.4)

depressive symptoms

Beck Depression Inventory-II (BDI-II)

0–63

higher scores indicate stronger symptoms

0–8 = no depression

9–13 = minimal depression

14–19 = mild depression

20–28 = moderate depression

29–63 = severe depression [46, 47]

IG: M = 22.6 (10.6)

CG: M = 22.0 (11.0)

IG: M = 15.8 (12.4)

CG: M = 22.9 (12.6)

p  < 0.001

Cohens d = 0.61 [0.27–0.95]

IG: M = 16.3 (13.7)

quality of life

SF-12 Mental Health

0–100

higher scores indicate higher quality of life [52]

IG: M = 31.2 (8.8)

CG: M = 33.2 (9.5)

IG: M = 37.5 (11.8)

CG: M = 33.0 (9.2)

p  < 0.001

Cohens d = 0.49 [0.15–0.83]

IG: M = 39.9 (12.2)

SF-12 Physical Health

0–100

higher scores indicate higher quality of life [52]

IG: M = 48.5 (11.2)

CG: M = 48.3 (10.8)

IG: M = 48.3 (11.4)

CG: M = 47.2 (9.5)

p  = 0.19

Cohens d = 0.16 [− 0.17–0.50]

IG: M = 48.6 (11.1)

Vivira [32]

t0 (Baseline)

t1 (2 weeks)

t2 (6 weeks)

t3 (12 weeks) ^a

improvement of the state of health

back, knee and hip pain

visual numeric rating scale

difference in change from baseline = -2.34 [-2.84; -1.83]

p  < 0.0001

difference in change from baseline = -2.44 [-2.92; -1.95]

p  < 0.0001

Vorvida [33]

t0 (Baseline)

t1 (12 weeks) ^a

t2 (6 months)

improvement of the state of health

daily average consumption of pure alcohol in grams)

Quantity-frequency index: self-reported quantities of alcohol in g (last 30 days)

IG: M = 63.69 (61.84)

CG: M = 61.64 (58.84)

IG: mM = 40.8 (3.3)

CG: mM = 56.8 (3.3)

p  = 0.001

Cohens d = 0.278

IG: mM = 32.3 (2.1)

CG: mM = 44.1 (2.1)

p  < 0.001

Cohens d = 0.327

Timeline-Follow-Back: self-reported amount of alcohol in g (last 7 days)

IG: M = 52.91 (56.68)

CG: M = 46.82 (41.18)

IG: mM = 34.3 (1.3)

CG: mM = 43.7 (1.3)

p  < 0.001

Cohens d = 0.419

IG: mM = 25.7 (1.5)

CG: mM = 38.6 (1.4)

p  < 0.001

Cohens d = 0.540

Zanadio [34]

t0 (Baseline)

t1 (9 months) ^a

t2 (12 months)

improvement of the state of health

weight reduction of at least 5%

BMI

MD = -5.67%

p  = 0.001

95% CI [-7.32, -4.02]

MD = -7.75%

p  = 0.001

95% CI: [-9.61, -5.89]