JMIR FORMATIVE RESEARCH

Krämer et al

Original Paper

Efficacy of a Web-Based Intervention for Depressive Disorders:Three-Arm Randomized Controlled Trial Comparing Guided andUnguided Self-Help With Waitlist Control
Rico Krämer1; Lea Köhne-Volland2; Anna Schumacher3; Stephan Köhler1, Prof Dr
1

Department of Psychiatry and Neuroscience, Charité – Universitätsmedizin Berlin, Berlin, Germany

2

Department of Psychology, Technische Universität, Chemnitz, Germany

3

Department of Psychology, Sigmund-Freud Privat Universität, Berlin, Germany

Corresponding Author:
Stephan Köhler, Prof Dr
Department of Psychiatry and Neuroscience
Charité – Universitätsmedizin Berlin
Charitéplatz 1
Berlin, 10117
Germany
Phone: 49 15152515774
Fax: 49 30450517905
Email: stephan.koehler@charite.de

Abstract
Background: Digital health apps are efficacious treatment options for mild-to-moderate depressive disorders. However, theextent to which psychological guidance increases the efficacy of these apps is controversial.
Objective: We evaluated the efficacy of a web-based intervention, called Selfapy, for unipolar depression. We also investigateddifferences between psychotherapist-guided and unguided versions.
Methods: Selfapy is a cognitive behavioral therapy–based intervention for depressive disorders. Participants with mild-to-severe
depressive disorders were assigned randomly to participate in either guided (weekly 25-minute duration telephone calls) intervention,
unguided version, or waiting list (control group) for 12 weeks. We assessed depressive symptoms at the start of the study, midway
through the intervention (6 weeks), at the end of the intervention (12 weeks), and at follow-up (6 months). The main outcome
was difference in the Beck Depression Inventory score between the start of the study and the end of the intervention. Secondary
outcomes were the Quick Inventory of Depressive Symptomatology—Self Report, the Hamilton Rating Depression Scale, andthe Beck Anxiety Inventory.
Results: Of 401 participants, 301 participants (75.1%) completed the intervention. Changes in the Beck Depression Inventory
from baseline differed significantly between groups at the postintervention (F2,398=37.20, P<.001). The reductions in scores forboth guided and unguided intervention groups were greater than that for the control group, with large between-group effect sizes(guided vs control: d=1.63, 95% CI 1.37 to 1.93; unguided vs control: d=1.47, 95% CI 1.22 to 1.73) at postintervention. No
significant differences were found between guided and unguided intervention groups (P=.18). At follow-up (6 months), treatment
effects on the primary outcome were maintained for both intervention groups (guided: F1,194=0.62, P>.999; unguided: F1,176=0.13,
P>.999).
Conclusions: Both guided and unguided versions of the intervention were highly effective in reducing depressive symptoms.
Follow-up data suggest that these effects could be maintained. The guided version was not superior to the unguided version.
Trial Registration: German Clinical Trials Register DRKS00017191; https://tinyurl.com/2p9h5hnx
International Registered Report Identifier (IRRID): RR2-10.1186/s13063-021-05218-4(JMIR Form Res 2022;6(4):e34330) doi: 10.2196/34330

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KEYWORDS
major depressive disorder; online intervention; blended treatment; public health; routine practice; randomized controlled trial;
depression; disorder; intervention; treatment; efficacy; self-help; guidance

Introduction
Background
With more than 300 million people affected worldwide, unipolar
depression is a common mental disorder [1]. Depressive
disorders reduce quality of life for affected persons and arelinked to an increased prevalence of suicide and a shortened
lifespan [2,3]. However, access to treatment is limited, which
represents an obstacle in the care of people with depressive
disorders. Health care systems can only rarely give necessary
acute help, such as immediate access to a psychotherapist [4].
In Germany, it takes approximately 20 weeks to obtainoutpatient psychotherapeutic treatment [5].
In addition to evidenced-based treatments for depressive
disorders, such as psychotherapy and pharmacotherapy,
web-based interventions are becoming increasingly importantin the treatment of depressive disorders. Web-based
interventions based on cognitive behavioral therapy are suitable
due to their structured and standardized approach, their focus
on psychoeducation, and the homework tasks assigned
in-between treatment sessions [6]. Various forms of web-based
interventions exist, which differ in terms of the level of guidance
that they provide to the participant. The guided forms ofweb-based interventions can involve support from a
psychotherapist via email, chat, or telephone. Unguided forms
of web-based interventions usually do not include personal
contact.
The use of web-based interventions in the treatment ofdepressive disorders has been deemed efficacious in several
controlled studies [7-9] and meta-analyses [10-12]. In one
meta-analysis [10], self-guided web-based cognitive behavioral
therapy was found to be more effective than the control
treatment in reducing depressive symptoms severity (β=−0.21;
Hedges g=0.27) and treatment response (β=0.53; odds ratio
1.95, 95% CI 1.52 to 2.50). In a recent systematic review andindividual patient data network meta-analysis of 39 randomized
control trials, Karyotaki et al [12] made the distinction between
guided and unguided web-based cognitive behavioral therapy.
Both guided (PHQ-9 score: mean difference −1.7, 95% CI −2.3
to −1.1) and unguided (PHQ-9 score: mean difference −0.9,
95% CI −1.5 to −0.3) were more efficacious in reducing
depressive symptoms than treatment as usual, and both guided(PHQ-9 score: mean difference −3.3, 95% CI −3.9 to −2.6) andunguided (PHQ-9 score: mean difference −2.5, 95% CI −3.2 to−1.8) were more efficacious in reducing depressive symptoms
than waitlist control [12]; guided web-based cognitive behavioral
therapy was also more effective than unguided web-based
cognitive behavioral therapy postintervention (PHQ-9 score:mean difference −0.8; 95% CI −1.4 to −0.2), however, not at
follow-up at 6 or 12 months. Baseline severity of depressive
symptoms was a modifying factor, with better effects for guided
web-based cognitive behavioral therapy for patients withbaseline PHQ-9 scores greater than 9 [12]. However, Karyotaki
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et al [12] used varying definition of guidance between thestudies and only 6 trials included in the meta-analysis directlycompared guided to unguided web-based cognitive behavioral
therapy within a single trial.

Objectives
We aimed to evaluate the efficacy of guided and unguided
versions of a web-based intervention, called Selfapy, toinvestigate the effect of psychological guidance in web-based
interventions. In a randomized controlled trial, participants wereallocated to 3 treatment groups: guided, unguided, and control.

Hypotheses
We hypothesized that participants in the 3-month Selfapy
program would experience a greater reduction in depressive
symptoms than the control group, and we hypothesized thatparticipants in the guided version would experience a greater
reduction in depressive symptoms than participants in theunguided version.

Secondary Hypotheses
We hypothesized that a greater reduction in depressive
symptoms and anxiety symptoms would be present in bothintervention groups after the 3-month Selfapy program thanthat in the control group.

Methods
Recruitment
Participants with depressive symptoms were recruited via the
Selfapy website, advertisements in social media and numerous
information brochures from health insurance companies. The
recruitment took place throughout all of Germany. The central
recruiting tool was a study website through which interested
individuals could register their participation. This preregistered
trial was conducted according to the study protocol [13].

Ethical Standards
The study was approved by the ethics committee of the medical
faculty of the Charité University Medicine Berlin (EA/047/19).
All procedures contributing to this work comply with the ethicalstandards of the relevant national and institutional committees
on human experimentation and with the Helsinki Declarationof 1975, as revised in 2008 [14].

Inclusion and Exclusion Criteria
Potential participants were screened by telephone. Eligibility
for participation in our study was assessed by conducting adiagnostic interview using the Mini International
Neuropsychiatric Interview (MINI [15]), the Hamilton Rating
Depression Scale (HRSD-24) [16] (score ≥8), and by collecting
personal data. All MINI and HRSD-24 interviews wereconducted by trained interviewers (psychologists and medical
students, trained at the Charité Department of Psychiatry andPsychotherapy). The inclusion criteria were (1) age 18 to 65
years; (2) sufficient German-language skills to use and
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understand the web-based intervention (determined byinterviewers); (3) reliable internet access; (4) a Beck Depression
Inventory (BDI-II) [17] score ≥13; (5) willingness to provide
electronic data; and (6) diagnosis of a major depressive disorderor dysthymia based on the MINI, in accordance with theInternational Statistical Classification of Diseases tenth revision(ICD-10: F32, F33, F34).
Exclusion criteria were (1) diagnoses of a bipolar disorder or
schizophrenia; (2) acute psychotic symptoms; (3) current
substance dependence (within the past 6 months) or withdrawal
syndrome (ICD-10: F1x2, F1x3); (4) acute suicidality (assessedusing HRSD-24; individuals were excluded if they had a score≥3 on suicidality items). Individuals who were excluded fromthe study due to illness severity were advised to seek
professional help. Additional details have been previously
published [13].

Randomization and Blinding

Krämer et al
ratio (guided group: n=151, unguided group: n=150, control
group: n=100). Block randomization was performed by anindependent researcher using a random number assignment planwith a computer-controlled random number generator (Randlist,
version 1.2).
Participants either received immediate access to the guided
version of the program, immediate access to the unguided
version of the program, or delayed access (24 weeks) to theirchoice of the guided or unguided program (ie, control group).
Participants were informed via email about the result of theallocation process. Individuals in the intervention groups
received an email with a link and their unique access code toregister and start the intervention immediately. Individuals in
the control group also received an email with a link to theassessment material. Therefore, participants enrolled themselvesin the study. Diagnostic interviewers were blind to the assigned
group of individuals.

Participants meeting eligibility criteria were randomly allocatedto 3 groups (Figure 1). Participants were allocated in a 3:3:2

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Figure 1. Participant flowchart.

Intervention
The web-based intervention aimed to treat depressive symptoms
in individuals with mild-to-moderate depressive disorders, with
instructions on evidence-based methods and exercises in theareas of cognitive behavioral therapy, systemic therapy, andmindfulness training. The intervention consisted of 6 coremodules and 6 additional optional in-depth modules representing
different psychotherapeutic approaches (Multimedia Appendix
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depending on the user’s reading speed, interest, motivation, andindividual path through the program. The modules could beaccessed repeatedly during the intervention period. The course
was designed to engage the user in active exercises, provide
helpful and interesting content, and encourage self-reflection.
In addition, the intervention included short questionnaires toassess current mood, which allowed the mood trajectory to bevisualized over the course of therapy. Furthermore, individual
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goals could be set and reviewed. The program provided the user
with printable summaries and worksheets for each exercise.
Optionally, the user could receive reminder emails to use thecourse and reiterate program content.

24-week period, participants from the control group were given
access to the web-based intervention and allowed to choose
which type of program (guided or unguided) they wished toparticipate in.

Participants in both intervention groups used the same
web-based course for 12 weeks, and access to course content
was also available after the 12-week intervention period until
follow-up. Telephone or chat support was only offered during
the treatment period. Participants in the intervention and control
groups were not influenced or advised to change their existingtreatment patterns and were free to seek pharmacological or
psychological treatments to meet the reality of care.

Measurements

Guided GroupIn the guided version of Selfapy, the participants received
personal guidance by a psychotherapist-in-training (17 behavior
therapists and depth psychologists in training, registered atGerman institutes) for the entire duration of the program. The
topics discussed were in line with the course content(Multimedia Appendix 1). The therapists were able to set theirown focal points within the weekly topic and the associatedexercises. At the start of the program, thepsychotherapist-in-training and the participant got to know eachother, and psychotherapist-in-training and the participant had
weekly telephone calls (25 to 30 minutes duration) throughout
the intervention period. The telephone calls focused on
discussing and reflecting on the exercises of each module. Each
module addressed issues such as resources, behavioral
activation, self-esteem, and automatic thoughts. All therapists
who guided the participants received a 1-hour training sessionthat included: general information on the study; risks and their
mitigation; a discussion of the contingency plan; informationon handling and documenting dropouts; and information on thestandardization of telephone calls. The focus of the guided
version was to support web-based intervention use.

Unguided GroupIn the unguided version of Selfapy, the intervention was
independently followed. There was no option to have contact
with a psychotherapist-in-training via telephone. However, achat functionality allowed the participants to ask questions
regarding the correct use of the course. Active asynchronous
communication occurred only in the event of patient safetyconcerns. For an increase in acute symptoms or suicidality, aspecific protocol [13], for all study groups, was followed tosecure the safety of each participant.

Control Group
During the 24-week waiting period, the control group received
weekly standardized mindfulness exercises via email, with
content comparable to that of a self-help mindfulness guide. A
waitlist design with mood-stabilizing activities was chosen forthe control group to control for changes related to treatment
expectancy and to better mitigate loss of motivation comparedwith an untreated or passive waitlist control group [18]. These
exercises were only available for the control group so that there
was no content-related overlap between the intervention groups
and the control group. The control group was also free to accessother pharmacological and psychological treatments. After the
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Depressive symptoms were evaluated using the BDI-II (primary
outcome),
Quick
InventoryofDepressive
Symptomatology—Self Report (QIDS-SR-16) [19] and theobserver-rated HRSD-24. The Beck Anxiety Inventory (BAI)[20] was used to measure changes in the self-assessment ofanxiety symptoms (secondary outcome parameters). The primaryand secondary outcome parameters were measured at the startof the intervention (T1), 6 weeks after the start of theintervention (T2), at the end of the intervention (12 weeks after
the start of the intervention, T3), 24 weeks after the beginningof the intervention (follow-up, T4). All web-basedquestionnaires were completed independently by theparticipants.

Statistical Analyses
Consistent with CONSORT (Consolidated Standards ofReporting Trials recommendations) [21], we conducted (1)intention-to-treat (which comprised observed and imputed datafrom all randomized participants, regardless of whether theyused the intervention or activated their access vouchers to enter
the program), and (2) per protocol (which comprised data fromparticipants who completed pretreatment and postintervention
assessments) analyses (Multimedia Appendix 2).
The primary endpoint was the decrease in depressive symptoms
in the BDI-II between study entrance (T1) and the end of theintervention (T3). One-way analysis of variance (within-factor
group) was performed to analyze differences in the decrease ofdepressive symptoms between the intervention groups.
Repeated measures analysis of variance was used to evaluate
secondary endpoints and effects of group (guided vs unguided
vs control) and time interaction. If significant effects were found,pairwise comparisons were carried out by applying Bonferroni
correction (P<.016) for multiple testing. Results of the posthoccomparisons are presented as the mean with 95% CI and SD.
The Kolmogorov–Smirnov test was used to test for a normal
distribution. Values for the mean and SD of each variable were
calculated in addition to the Kolmogorov–Smirnov Z-value,
and the asymptomatic significance (for both intervention groups)
was specified. P<.05 indicated that the data did not have anormal distribution.
Independent 2-tailed t tests and chi-square tests were used toestimate the differences between groups in terms of
demographics and sample characteristics at baseline. Values
for the mean, 95% CI, and SD were calculated. Interim analyses
were not undertaken. Due to the high dropout rate from T3 to
T4, repeated measures analysis of variance was performed forthe follow-up-analysis, including only those who completed.
Moderator analysis was used to analyze the influence of various
sociodemographic variables on the primary outcome. Regression
analysis was directed at explaining the changes in the BDI-II(the difference between T3 and T1 was used as a criterion). The
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predictors used were the BDI-II at baseline as well as potential
moderators, assigned group, and sociodemographic variables(sex, age, relationship status, and number of children). Allvariables except age were dichotomous and coded as 0 or 1.
The moderator variables were generated by multiplying thez-standardized BDI-II score at baseline with the dichotomous
sociodemographic variables, the assigned group, and thez-standardized age. All dichotomous variables, assigned group,and z-standardized age were included as regressors.
Subsequently, we used hierarchical linear regression, which had
all predictors in the first block via the enter method and allmoderators in the second block via the stepwise method.
Furthermore, response rates (decrease of BDI-II score frombaseline of 50%), remission rates (postintervention BDI-II score≤10 [22]), and the minimal clinical important difference(decrease of 17.5% of the BDI-II score from baseline [23]) forthe primary outcome at postintervention were calculated andreported.
For the intention-to-treat analysis, missing values in the data
were replaced using multiple imputation by chained equations(with m=5 imputations). The pooled data (the mean of all 5
imputations) were calculated using the data imputed by linear
regression. Subsequently, scale values were determined fromthe imputed and existing values. After data imputation, imputed
and observed results were compared. The pooled imputed values
proved to be more conservative, therefore, the results of imputed
data set were used to evaluate the outcome of the web-based
intervention.

Krämer et alof variance with the factor group revealed no differences atbaseline (F2,398=0.23, P=.80). The mean age of participants was
37.1 years (SD 11.0).
For factor relationships, fewer participants (33/151, 22.0%)
reported themselves to be married or living with a partner inthe unguided group than in the control group (52/100, 52.0%;
χ21=8.25, P=.01), whereas no difference was shown between
the guided and control groups (χ21=1.56, P=.21) or between theguided and unguided groups (χ21=2.97, P=.08). Moreparticipants were employed in the guided group (82/151, 54.3%)
and the unguided group (86/150, 57.3%) compared to those in
the control group (57/100, 57.0%; guided vs control: χ21=9.12,
P=.01; unguided vs control: χ21=18.98, P<.001), while there
was no difference between the guided and unguided groups(χ21=1.76, P=.18). More participants in the control group(25/100, 25.0%) were trainees than those in the guided group(12/151, 7.9%; χ21=5.68, P=.01) or unguided group (6/150,
4.0%; χ21=12.62, P<.001), while there was no difference
between the guided and unguided groups (χ21=1.27, P=.26).
Lastly, more participants in the control group (14/100, 14.0%)
than in the unguided group (3/150, 2.0%; χ21=6.55, P=.05)
reported other occupations.
Analyses of the other sociodemographic variables did not reveal
a significant difference between groups (sex: P=.81, number ofchildren: P=.93).

Results

Being on waitlist (χ22=6.76, P=.03), use of antidepressantGeneralmedication both currently (χ22=7.31, P=.03) and in the year

Out of 401 participants, the number of dropouts at
postintervention (T3, end of the intervention) was 100 (24.9%)
for the BDI-II and the QIDS-SR-16, 128 (31.9%) for the
HRSD-24, and 103 (25.7%) for the BAI, respectively.

Characteristics
Upon study entrance, 353 out of 401 randomized participants(88.0%) fulfilled the diagnostic criteria for a current major
depressive episode (MINI interview), and 53 (13.2%) for
dysthymia (Multimedia Appendix 3). Data at baseline indicatedan average mild-to-severe level of depression in all participants(BDI-II: mean 30.5, SD 9.5, range 13-56). A one-way analysis

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before the intervention (χ22=10.25, P=.006) differed at baseline,with more participants in the guided group having taken
antidepressants than the unguided group in the year before theintervention (χ21=9.36, P=.002) and currently (χ21=6.56, P=.01).
There were no differences compared to the control group in theyear before the intervention (guided vs control: χ21=0.66, P=.42;
unguided vs control: χ21=3.2, P=.07) and currently (guided vscontrol: χ21=0.47, P=.49; unguided vs control: χ21=2.11, P=.15).
The groups did not differ with respect to current psychotherapy
at baseline (χ22=1.50, P=.47).

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Table 1. Sociodemographic characteristics of the study cohort at baseline.
Characteristic

Guided (n=151)

Unguided (n=150)

Control (n=100)

Total sample (n=401)

Female126 (83.4)

126 (84.0)

81 (81.0)333 (83.0)

Male

25 (16.6)

24 (16.0)

19 (19.0)

68 (17.0)

38 (10.7)

37 (10.8)

36 (11.9)

37 (11.0)

Married or living with a partner

54 (35.8)

33 (22.0)

52 (52.0)

139 (34.7)

Not living with a partner

19 (12.6)

8 (5.3)19 (19.0)

46 (11.5)

Single68 (45.0)

75 (50.0)26 (26.0)

169 (42.1)

Not reported

10 (6.6)

34 (22.7)

3 (3.0)47 (11.7)

Yes

31 (20.5)

33 (22.0)

11 (11.0)75 (18.7)

No

89 (58.9)

99 (66.0)

37 (37.0)

225 (56.1)

Not reported

31 (20.5)

18 (12.0)

52 (52.0)

101 (25.2)

Still in professional training

11 (7.3)

6 (4.0)16 (16.0)

33 (8.2)

Apprenticeship28 (18.5)

19 (12.7)

25 (25.0)

72 (18.0)

Master or vocational school

17 (11.3)

15 (10.0)

9 (9.0)41 (10.2)

University or university of applied sciences

39 (26.0)

45 (30.0)30 (30.0)

114 (28.4)

Without professional training

15 (9.9)

18 (78.7)

8 (8.0)41 (10.2)

Other professional training

2 (1.3)0 (0.0)8 (8.0)10 (2.5)

Not reported

39 (25.8)

47 (31.3)

4 (4.0)90 (22.4)

Employee

82 (54.3)

86 (57.3)

57 (57.0)

225 (56.1)

Self-employed

3 (2.0)4 (2.7)2 (2.0)9 (2.2)Trainee12 (7.9)

6 (4.0)25 (25.0)

43 (10.7)

Other

7 (4.6)3 (2.0)14 (14.0)

24 (6.0)

Not reported

47 (31.3)

51 (34.0)

2 (2.0)100 (24.9)

Sex, n (%)

Age (years), mean (SD)
Relationship status, n (%)

Children, n (%)

Professional qualification, n (%)

Occupation, n (%)

Usage Data
A total of 301 participants received the intervention after
baseline assessment. A mean of 9.4 (SD 2.3) modules werecompleted by each participant during the intervention period,and 254 participants (84.4%) completed the main course(Multimedia Appendix 3).

Primary Outcome
Descriptive statistics for the for each assessment point are shownin Table 2 for completer and intention-to-treat samples.
Kolmogorov-Smirnov tests did not reveal any violation of thenormal distribution for BDI-II scores. One-way analysis ofvariance revealed a significant interaction (factor group) in theintention-to-treat sample (F2,398=37.20, P<.001). Posthoc
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postintervention (T3) revealed a significant higher reduction in
depressive symptoms (BDI-II) in the guided group vs the control
group (P<.001) and the unguided group vs the control group(P<.001). There was no significant difference (P=.18) between
guided and unguided groups (Multimedia Appendix 4).
Within-group effect sizes for BDI-II (Table 3) were large bothfor the guided (d=1.44, 95% CI 1.21 to 1.68) and unguided(d=1.38, 95% CI 1.15 to 1.65) groups, whereas the control
group showed no effect (d=0.07, 95% CI −0.21 to 0.37).
Postintervention between-group effect sizes between the guided
and control groups (d=1.63, 95% CI 1.37 to 1.93) and between
the unguided and control groups (d=1.47, 95% CI 1.22 to 1.73)
were large, whereas effect sizes between the guided andunguided groups were negligible (d=0.20, 95% CI −0.04 to0.45).

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Table 2. Assessment scores.
Outcome and group

Per protocol
T1an

Intention to treat
T2b

T3c

T2

T3

Mean (SD)nMean (SD)nMean (SD)nMean (SD)nMean (SD)Beck Depression Inventory-II
Guided (n=151)

151

30.09 (9.18)

132

19.59 (6.60)

132

14.87 (8.77)

151

20.71 (6.98)

151

16.61 (9.55)

Unguided (n=150)

150

30.54 (8.53)

120

20.44 (7.22)

116

15.86 (8.03)

150

22.51 (7.83)

150

18.49 (8.88)

Control (n=100)

100

30.88 (10.74)

54

27.30 (7.05)

53

31.11 (8.30)

100

29.09 (6.39)

100

30.26 (6.97)

Quick Inventory of Depressive Symptomatology – Self Report
Guided (n=151)

151

17.41 (6.17)

132

11.14 (4.63)

132

6.53 (3.55)

151

11.62 (4.54)

151

7.33 (4.01)

Unguided (n=150)

150

19.36 (5.44)

120

11.00 (3.71)

116

6.84 (4.09)

150

12.09 (4.03)

150

7.99 (4.31)

Control (n=100)

100

18.55 (6.04)

54

17.17 (4.50)

53

20.15 (3.78)

100

16.90 (3.60)

100

17.88 (4.06)

Hamilton Rating Depression Scale
Guided (n=151)

151

23.23 (6.28)

N/Ad N/A

123

11.46 (6.81)

N/A

N/A

151

11.95 (6.50)

Unguided (n=150)

150

23.22 (6.75)

N/A

N/A

70

12.19 (6.57)

N/A

N/A

150

14.75 (5.88)

Control (n=100)

100

22.64 (6.76)

N/A

N/A

80

20.91 (8.78)

N/A

N/A

100

21.13 (8.20)

Guided (n=151)

150

32.46 (11.32)

132

23.36 (11.97)

128

14.45 (9.06)

151

24.65 (11.79)

151

17.25 (11.05)

Unguided (n=150)

150

34.09 (11.68)

120

20.43 (9.25)

118

16.22 (9.57)

150

23.27 (10.23)

150

19.98 (11.67)

Control (n=100)

100

31.83 (14.14)

52

37.92 (9.62)

52

31.02 (7.51)

100

37.56 (7.98)

100

34.91 (7.56)

Beck Anxiety Inventorya

T1 represents the start of the study.

b

T2 represents the midpoint of the intervention (6 weeks after the start of the study)cT3 represents the end of the intervention (12 weeks after the start of the study).

dN/A: not applicable. No data were available because the Hamilton Rating Depression Scale was not used at the midpoint assessment.

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Krämer et al

Table 3. Within- and between-group effect sizes for all groups in the intention-to-treat sample.
Measure and group

Within group, Cohen d (95% CI)

Between group (vs unguided), Cohen d(95% CI)

Between group (vs control), Cohen d(95% CI)T1a–T2b

T1–T3c

T2

T3

T2

T3

1.44 (1.21, 1.68)

0.24 (0.02, 0.48)

Beck Depression Inventory II
Guided

1.15 (0.91, 1.40)

0.20 (−0.04, 0.45)

1.25 (0.99, 1.54)

1.63 (1.37, 1.93)

dUnguided

0.98 (0.75, 1.25)

1.38 (1.15 1.65)——

0.92 (0.65, 1.20)

1.47 (1.22, 1.73)

Control

0.20 (−0.09, 0.47)

0.07 (−0.21, 0.37)

—

—

—

—

Quick Inventory of Depressive Symptomatology – Self Report
Guided1.07 (0.84, 1.33)

1.94 (1.68, 2.24)

0.11 (−0.10, 0.33)

0.16 (−0.06, 0.39)

1.29 (1.02, 1.53)

2.61 (2.28, 3.02)

Unguided

1.52 (1.28, 1.80)

2.32 (1.95, 2.72)——

1.26 (1.04, 1.53)

2.36 (1.98, 2.82)

Control

0.33 (0.05, 0.63)

0.13 (−0.14, 0.45)

—

—

—

—

Hamilton Rating Depression Scale
GuidedN/Ae

1.76 (1.50, 2.05)

N/A

0.45 (0.21, 0.70)

N/A

1.24 (0.93, 1.59)

Unguided

N/A

1.34 (1.10, 1.61)

—

—

N/A

0.89 (0.62, 1.21)

Control

N/A

0.20 (−0.08, 0.48)

—

—

—

—

Beck Anxiety InventoryaGuided

0.67 (0.44, 0.93)

1.35 (1.10, 1.64)−0.13 (−0.37, 0.11) 0.241 (0.01, 0.46)

1.28 (1.04, 1.55)

1.87 (1.61, 2.20)

Unguided

0.99 (0.73, 1.25)

1.21 (0.94, 1.51)——

1.56 (1.28, 1.86)

1.52 (1.25, 1.84)

Control−0.50 (−0.79, −0.22) −0.27 (−0.55, 0.01)

—

—

—

—

T1 represents the start of the study.

b

T2 represents the midpoint of the intervention (6 weeks after the start of the study)cT3 represents the end of the intervention (12 weeks after the start of the study).

d

No data.

e

Not available because the Hamilton Rating Depression Scale was not used at the midpoint assessment.

Response and Remission Rate
Response, defined as the percentage of participants that had areduction of depressive symptoms by 50% or more at
postintervention (T3), was reached by 34.9% of all participants(n=140/401). In the guided group, the response rate was 48.3%(73/151), 43.3% (65/150) in the unguided group, and 2.0%
(2/100) in the control group. Remission, defined as a
postintervention BDI-II score of 12 or less, occurred in 25.4%of all participants (102/401) of the intention-to-treat sample. In
the guided group, 39.7% of participants (60/151) reachedremission, with 28.0% (42/150) in the unguided group. No
participants in the control group reached remission.

Minimal Clinical Important Difference
Overall, 63.1% (253/401) of participants in the intention-to-treat
sample had depressive symptom reductions greater than theminimal clinical important difference, with 74.2% (n=112/151)
for the guided group, 70.7% (106/150) for the unguided group,and 35.0% (35/100) for the control group. In comparison, both
the guided group (χ21=36.44, P<.001) and the unguided group(χ21=29.61, P<.001) had significantly more occurrences ofsymptom improvement than the control group, whereas nodifference was found between the intervention groups (χ21=0.30,
P=.58).
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Moderator Analysis
The regression analysis was conducted using theintention-to-treat sample. The number of data sets that could
be used for the calculation was reduced to 279, due to missing
values in the sociodemographic variables. The regression
appeared to be unproblematic (Durbin-Watson-statistic 1.762
and collinearities <2.0). As the nonstandardized residuals hada mean of 0, homoscedasticity of the regression was indicated.
The Kolmogorov-Smirnov-test was asymptotically significant(P=.03). The skewed distribution lay within the 5% confidence
interval; the kurtosis lay slightly above. Based on the histogram,the normal distribution of residuals is accepted. In the first blockof the hierarchical multiple linear regression analysis, asignificant model was found (explained variance r2=0.592;
F6,272=65.9, P<.001). Notably, age influenced the treatment
outcome significantly—the older the participants, the greater
the improvement in the BDI-II score (b=0.103; β=0.087, t=2.25,
P=.02). In addition, a higher BDI-II score at T1 was associatedwith greater reduction in BDI-II score at T3 (b=−0.98,
β=−0.632, t=−15.93, P<.001). In addition, being assigned tothe control group was associated with a lower reduction in the
BDI-II score at T3 (b=11.6, β=0.34, t=8.52, P<.001). The othervariables (relationship status: P=.96; sex: P=.29; number ofchildren: P=.90) did not significantly predict the outcome
variables. In the second block of the hierarchical regression
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JMIR FORMATIVE RESEARCH
analysis, the moderators that are the interaction terms of thevariables from the first block at baseline were included using
the stepwise method. None was found to be significant, therefore
no moderation effect was indicated by the analysis.

Secondary Outcomes
Descriptive statistics of secondary outcomes are displayed inTable 2, and Table 3 shows within- and between-group effectsizes for all secondary outcome measures for theintention-to-treat sample. No violation of the normal distribution
was identified for any of the secondary outcomes.
Repeated measures analysis of variance revealed a significant
main effect for the factor time—QIDS-SR-16 (F3,1194=200.08,

Krämer et al
P<.001, η2=0.25), HRSD-24 (F2,796=152.26, P<.001, η2=0.19),
and BAI (F2,796=62.2 P<.001, η2=0.09). Additionally, we founda significant interaction (factors group × time) for all secondary
measurements in the intention-to-treat sample—QIDS-SR-16(F6,1194=33.2, P<.001, η2=0.10), HRSD-24 (F4,796=23.3, P<.001,
η2=.07), and BAI (F4,796=30.4, P<.001, η2=0.09) (Figure 2).
Bonferroni-adjusted posthoc analyses of the QIDS-SR-16(Figure 3) revealed a greater reduction of depressive symptoms
for both the guided group (P<.001) and the unguided group(P<.001) compared to the control group. However, no difference
between the guided and unguided groups was found (P=.50).

Figure 2. Change in depressive symptoms. BDI-II: Beck Depression Inventory-II.

Figure 3. Change in depressive symptoms. QIDS-SR-16: Quick Inventory of Depressive Symptomatology—Self Report.

Similarly, posthoc analyses of the HRSD-24 (Figure 4) revealed
a greater reduction of observer-rated depressive symptoms bothfor the guided group (P<.001) and the unguided group (P<.001)
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compared to the control group. A greater reduction in symptoms
was found for the guided group compared to the unguided group(P=.001).
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JMIR FORMATIVE RESEARCH
Finally, posthoc analyses of changes in BAI scores (Figure 5)
revealed significantly greater reductions in anxiety symptoms
in the guided (P<.001) and unguided groups (P<.001) compared

Krämer et al
to that of the control group. There was no significant difference
between the guided group and unguided group (P=.08).

Figure 4. Change in depressive symptoms. HRSD-24: Hamilton Rating Depression Scale.

Figure 5. Change in anxiety symptoms. BAI: Beck Anxiety Inventory.

Three-Month Follow-up
For the follow-up assessment 24 weeks after the start of theintervention (T4), repeated measures analysis of variances werecarried out using per protocol data for the BDI-II, the
QIDS-SR-16, and the HRSD-24. Data were available atfollow-up for 155 (38.7%) for the BDI-II, 156 (38.9%) for the
QIDS-SR-16, and 30 (7.5%) for the HRSD-24 out of all 401
participants (Table 4).
Repeated measures analysis of variance revealed a significant
interaction (factors group × time) for the BDI-II (F2,152=3.7,
P=.03, η2=0.02). Pairwise posthoc comparisons with
Bonferroni-correction at follow-up (T4) showed a significant
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difference between the guided group (P<.001) and the unguided
group (P<.001) compared to the control group, but not between
guided and unguided (P>.999) demonstrating a symptom
deterioration in the control group and maintenance of thetreatment effects in both intervention groups. Compared tobaseline (T1), the BDI-II scores at follow-up (T4) remained
significantly lower for both the guided group (d=1.58) and theunguided group (d=1.88). Moreover, the remission rate at T4
in the BDI-II was 29.2% for the guided group and 21.3% for
the unguided group. Repeated-measures analysis of variance
did not reveal a significant interaction effect (group × time) for
the QIDS-SR-16 (F2,153=3.32, P=.39, η2=0.02) or the HRSD-24(F2,19=0.27, P=.77, η2=0.15).
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Krämer et al

Table 4. Change from T3 to follow-up (T4) with completer data for depression outcomes.
Outcome and group

T3a
n

T4b

Test statistics (T3-T4)

Within group

Mean (SD)nMean (SD)F test (df1,df2)

P valueη2

T1−T4, Cohen d (95% CI)

Beck Depression Inventory-II
Guided132

14.87 (8.77)

64

15.92 (8.79)

0.62 (1,194)

>.999

.00

1.58 (1.29, 1.95)

Unguided116

15.86 (8.03)

62

16.29 (6.47)

0.13 (1,176)

>.999

.00

1.88 (1.59, 2.24)

Control

53

31.11 (8.30)

29

38.28 (9.88)

12.2 (1,80)

.002

.13

−0.72 (−1.35, −0.28)

Quick Inventory of Depressive Symptomatology – Self Report
Guided132

6.53 (3.55)

65

8.42 (4.80)

9.67 (1,195)

.006

.05

1.63 (1.31, 2.00)

Unguided116

6.84 (4.09)

62

8.85 (5.23)

8.05 (1,176)

.02

.04

1.97 (1.60, 2.45)

Control

53

20.15 (3.78)

29

18.76 (5.14)

1.96 (1,80)

.50

.02

−0.04 (−0.43, 0.37)

Hamilton Rating Depression Scalea

Guided123

11.46 (6.81)

17

12.24 (7.02)

0.19 (1,138)

>.999

.00

1.65 (0.94, 2.63)

Unguided70

12.19 (6.57)

6

9.83 (5.19)

0.73 (1,74)

>.999

.01

2.22 (1.81, 3.03)

Control

80

20.91 (8.78)

726.29 (4.15)

2.55 (1,85)

.342

.03

−0.65 (−1.35, −0.09)

T3 represents the end of the intervention (12 weeks after the start of the study).

b

T4 represents the follow-up point (24 weeks after the start of the study).

Discussion

the intervention group with guidance (d=1.42; control group:
d=0.65).

Principal Results

In our randomized controlled trial, the treatment effects of bothintervention groups were slightly higher than those in previous
studies [24,25]. In [25], the intervention duration was also 12
weeks, but therapeutic support was offered only upon request.
This approach might have stopped patients from seeking contact,
and therefore, may have hampered the overall effect. Moreover,
our interventions provided the option to contact a psychologist
in both intervention groups (guided group: telephone calls;
unguided group: standardized chat option) which, arguably, led
to a better outcome. Other than differences in study design, thecharacteristics of the participants may also be a reason for thehigh effect sizes. Compared with other web-based cognitive
behavioral therapy studies [24,26,27], the percentage of womenin our randomized controlled trial (333/401, 83%) was higher(74.4% [24]). In general, women tend to seek web-based
interventions more frequently than men [26,27]. Moreover,considerably more participants completed higher education, ie,university (28.4%) and vocational school (10.2%). A higheducation level is a predictor of high adherence to treatment[28] and a positive outcome of treatment [29] because
participants are better able to transfer the content of a particulartreatment to their life [30]. In individual patient data network
meta-analysis, Furukawa et al [31] found a higher baseline
severity of depressive symptoms associated with a better
response to web-based interventions and being unemployedwith a poorer outcome. Sex did not influence the response. We
also found that baseline severity, treatment, and age (higher age
with better outcome) were significant moderators of treatment
outcome.

We investigated the efficacy of a guided and unguided
web-based intervention for the treatment of depressive disorders
and found a significant improvement of depressive symptoms
in the BDI-II (primary outcome) and the HRSD-24 for bothintervention groups compared with those in the control groupin the intention-to-treat sample, with large pre- andpostintervention difference effect sizes observed for eachintervention (BDI-II: guided group, d=1.44; unguided group,d=1.38; HRSD-24: guided group, d=1.76; unguided group,d=1.34). Similarly, self-reported measures for depression andanxiety symptoms revealed a significant pre- andpostintervention difference intervention decrease in scores forboth intervention groups (QIDS-SR-16: guided group, d=1.94
and unguided group, d=2.32; BAI: guided group, d=1.35 andunguided group, d=1.21) compared with those in the control
group (QIDS-SR-16: d=0.13; BAI: d=−0.27).
In a similarly structured web-based intervention for depressive
disorders, Meyer et al [24] investigated an unguided web-based
cognitive behavioral therapy intervention for depressive
disorders and found the web-based intervention to be highly
efficacious (compared with waitlist control, pre- andpostintervention differences using PHQ-9: d=1.32), which iscomparable to our within-group effect sizes for the BDI-II.
In another trial with guided web-based intervention, Beiwinkel
et al [25] investigated the efficacy of a 12-week web-based
program for depression, with therapeutic support upon request(ie, psychologists gave feedback via telephone or email)compared with a waitlist control (which included unguided
internet-based psychoeducation only) and reported pre-and
postintervention BDI-II scores showed a significant reduction
in depressive symptoms with large within-group effect size forhttps://formative.jmir.org/2022/4/e34330

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The efficacy of the web-based intervention over waitlist control
is larger but consistent with previous literature on similarinterventions for both guided (between-group effect size d=0.55
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JMIR FORMATIVE RESEARCH[24]) and unguided (between-group effect size d=0.57 [25])web-based cognitive behavioral therapy. The response rate in
our control group was relatively low compared to that in otherweb-based intervention trials (within-group effect size in BDI-II:
d=0.07)—Meyer et al [24] found an average within-group effectsize (d=0.71) in the primary outcome (PHQ-9) for the control
group. Klein et al [32] reported for their control condition (careas usual alone) small effects in the pre- and postintervention
comparison (PHQ-9: d=0.39). In contrast, Berger et al [33],also did not find significant changes between pre- andpostintervention symptoms in their waiting list control group(BDI-II: d=0.14). Our results were similar. The low effects in
our control group could be explained by many different reasons.
Active waiting list condition, as in our control group, might
have nocebo effects compared to no treatment condition [34].
Additionally, specific interventions in the waiting list condition
may also have negative effects in internet interventions. For
example, Furukawa et al [31] reported that relaxation training
was even harmful compared to other components in web-based
cognitive behavioral therapy.
The effects of could be maintained at 3-month follow-up. BDI-II
scores remained significantly lower for the guided group(d=1.59) and unguided group (d=1.91) compared with baseline
scores. Our findings are similar to those from previous research,which found web-based interventions have positive long-term
effects [10].
We also investigated on the effects of guidance in web-based
interventions. We found in both groups with different guidanceas equally and highly effective to reduce depressive symptoms.
Completely unsupported web-based interventions have beensuggested to be less efficacious [8,12], associated with higher
attrition rates [35], and to carry greater risks than supported
interventions [34]. However, findings are to some extent
heterogeneous: Berger et al [33] compared an unguided
internet-based self-help program with the same intervention
supported by a therapist and waitlist control group. Our
comparison of guided and unguided did show differences,which, however, were not significant between the unguided
group and guided group (mean groups difference atpostintervention: d=0.24 in favor of guided self-help). In a recent
investigation, Zagorscak et al [36] compared web-based
cognitive behavioral therapy alone with therapy andKrämer et al
semistandardized email feedback from psychologists. Again,
between-group effects were nonsignificant across outcomes.
Regarding our study, the dose of psychological contact might
not vary sufficiently to elicit substantial differences between
the groups. Instead, both groups had contact with a therapist,
although the unguided group could only reach out for
non–content-related questions. Both groups also had a highmain course completion rate, especially compared to nonguided
web-based interventions in other studies [31]. Karyotaki et al[10] revealed that treatment adherence to web-based cognitive
behavioral therapy (session completion rate) influenced theoutcome. In contrast to the meta-analysis findings [12], we also
did not find severity of depression to be a predictor for better
outcome in the guided group.

Strength and Limitations
Our study has several strengths. We included self- and observer
ratings and included a follow-up assessment. Furthermore, we
compared different forms of guidance. We also consideredmultiple aspects in our evaluation, such as completion rate andsociodemographic factors. However, there are also some
limitations. First, using wide inclusion criteria, we acquired aheterogeneous study sample [37]. Second, the option to receive
additional treatment impeded the attribution of treatment effects
solely on the web-based intervention. Additional treatment (12people were in therapy and 70 were receiving psychiatrictreatment in both intervention groups) could have contributed
to the effects and possibly caused a reduction in internal validity.
Third, although conversations between psychotherapists andparticipants were standardized in the guided group, we had noinsights into the actual conversations and whether the structureof the predetermined content was followed. Last, our sample
size might have been too small to detect differences between
the guided and unguided groups.

Conclusions
The web-based intervention offers a highly efficacious andclinically relevant intervention for people with depressive
disorders. Contrary to our hypothesis, the efficacy of the guided
g and unguided intervention did differ. Our findings demonstrate
the value and applicability of the Selfapy web-based intervention
as a clinically significant treatment option for depressive
disorders.

Authors' Contributions
RK, LKV, AS, and SK contributed to the design of the study and coordinated recruitment and data collection. All authors drafted,
read, and approved the manuscript.

Conflicts of Interest
The study was funded by a commercial organization: Selfapy GmbH. RK worked for Selfapy as a student (November 2016 to
September 2017). SK, LKV, and AS have no relationship with Selfapy GmbH.

Multimedia Appendix 1
Course content.
[DOCX File , 21 KB-Multimedia Appendix 1]

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Krämer et alMultimedia Appendix 2
Diagnoses according to Mini International Neuropsychiatric Interview (MINI).
[PDF File (Adobe PDF File), 518 KB-Multimedia Appendix 2]

Multimedia Appendix 3Intervention usage data for the guided and unguided group.
[PDF File (Adobe PDF File), 507 KB-Multimedia Appendix 3]

Multimedia Appendix 4
Completer analysis.
[PDF File (Adobe PDF File), 514 KB-Multimedia Appendix 4]

Multimedia Appendix 5
CONSORT-EHEALTH checklist (V 1.6.2).
[PDF File (Adobe PDF File), 114 KB-Multimedia Appendix 5]

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Abbreviations
BAI: Beck Anxiety Inventory
BDI-II: Beck Depression Inventory-II
CONSORT: Consolidated Standards of Reporting Trials
HRSD-24: Hamilton Rating Depression Scale
ICD-10: International Statistical Classification of Diseases, tenth revision
MINI: Mini International Neuropsychiatric Interview
PHQ-9: Patient Health Questionnaire
QIDS-SR-16: Quick Inventory of Depressive Symptomatology—Self Report

Edited by A Mavragani; submitted 21.10.21; peer-reviewed by JP Klein, R Kessler, A Salamanca-Sanabria; comments to author
09.11.21; revised version received 28.01.22; accepted 01.02.22; published 04.04.22
Please cite as:
Krämer R, Köhne-Volland L, Schumacher A, Köhler S
Efficacy of a Web-Based Intervention for Depressive Disorders: Three-Arm Randomized Controlled Trial Comparing Guided andUnguided Self-Help With Waitlist Control
JMIR Form Res 2022;6(4):e34330
URL: https://formative.jmir.org/2022/4/e34330
doi: 10.2196/34330
PMID: 35105536©Rico Krämer, Lea Köhne-Volland, Anna Schumacher, Stephan Köhler. Originally published in JMIR Formative Research(https://formative.jmir.org), 04.04.2022. This is an open-access article distributed under the terms of the Creative Commons
Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction
in any medium, provided the original work, first published in JMIR Formative Research, is properly cited. The complete
bibliographic information, a link to the original publication on https://formative.jmir.org, as well as this copyright and license
information must be included.

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