Randomized trial of Internet-based relapseprevention for partially remitted depression

Introduction

It is well known that the long-term outcome afterremission frommajor depressive disorder (MDD) is

discouraging, and it has been estimated that half ofthe persons will relapse within 20 years in thegeneral population (1). In clinical populations, therisk is even higher (2), and in a recent meta-analysis,

Hollandare F, Johnsson S, Randestad M, Tillfors M, Carlbring P,Andersson G, Engstrom I. Randomized trial of Internet-based relapseprevention for partially remitted depression.

Objective: To investigate whether Internet-based cognitive behaviourtherapy (CBT) can prevent relapse in persons with partially remittedmajor depression after previous treatment.Method: Seventy-one women and 13 men (N = 84) with partiallyremitted major depression after treatment were randomly assigned toeither 10 weeks of Internet-based CBT or to a control group. Self-helpmaterial was used in combination with e-mail contact with a personaltherapist. Monthly self-ratings of depressive symptoms were made, anddiagnostic interviews were conducted before and after the treatmentperiod, as well as 6 months later.Results: Significantly fewer participants in the CBT group experiencedrelapse (4 ⁄ 38 or 10.5%) compared with those in the control group(14 ⁄ 37 or 37.8%). The difference in relapse rates between groupsoccurred early in the study period and was still apparent after6 months. A trend towards a larger reduction in depressive symptomswas observed at post-treatment in the participants who received CBTcompared with controls. Reduction in depressive symptoms reducedthe risk of relapse. A trend towards a higher remission rate was foundin the CBT group at the 6 month follow-up.Conclusion: Internet-based CBT seems promising in preventing relapsein persons with partially remitted major depression after previoustreatment.

F. Holl�ndare1, S. Johnsson2,M. Randestad2, M. Tillfors2,P. Carlbring3, G. Andersson4,5,I. Engstrçm1

1School of Health and Medical Sciences, PsychiatricResearch Centre, 2School of Law, Psychology and SocialWork, �rebro University, �rebro, 3Department ofPsychology, Ume� University, Ume�, 4Department ofBehavioural Sciences and Learning, Swedish Institute ofDisability Research, Linkçping University, Linkçping and5Department of Clinical Neuroscience, KarolinskaInstitutet, Stockholm, Sweden

Key words: depression; recurrence; Internet; self-care;cognitive behaviour therapy

Fredrik Holl�ndare, School of Health and Medical Sci-ences, Psychiatric Research Centre, �rebro University,Box 1613, 701 16 �rebro, SwedenE-mail: fredrik.hollandare@orebroll.se

Accepted for publication February 17, 2011

Significant outcomes

• Participants randomized to Internet-based cognitive behaviour therapy (CBT) suffered significantlyfewer relapses compared with those in the control group.

• There was a trend towards a group · time interaction effect, indicating a larger reduction in residualsymptoms in the CBT group compared with controls.

• Reduction in depressive symptoms was associated with lowered risk of relapse.

Limitations

• Diagnostic interviews were conducted over the telephone rather than in person, which could renderthem less valid.

• The sample size may have been too small to achieve the statistical power needed to detect treatmenteffects.

• The follow-up time was limited to 6 months.

Acta Psychiatr Scand 2011: 124: 285–294All rights reservedDOI: 10.1111/j.1600-0447.2011.01698.x

� 2011 John Wiley & Sons A/S

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51% experienced a relapse within 1 year afterwithdrawal from antidepressant medication(ADM) (3). In another meta-analysis, almost one-third suffered a relapse within 1 year after cognitivebehaviour therapy (CBT) (4).When a patient suffersfrom residual symptoms after treatment, the risk ofrelapse is even higher (5–7). Paykel and colleagues(8) showed that three of four patients with residualsymptoms suffered a relapse compared with onlyone of four of those without such symptoms, and ina recent review article, subclinical residual symp-toms are suggested as the strongest predictor ofanother episode (9). Furthermore, residual symp-toms are associated with lower levels of functioning(10) and a more chronic course of illness (11). Thegoal of depression treatment should be full remis-sion (12), and hence, treating the residual symptomsis a key component in the prevention of relapse.Because the prognosis for sustained improvement

after treatment is poor, especially in the presence ofresidual symptoms, attempts have been made toimprove the long-term outcome by using CBT orinterpersonal psychotherapy (IPT) (13) as mainte-nance treatment or as an adjunct to other treatment.This has been put forward in clinical practicerecommendations as effective relapse prevention(14) and has significantly reduced relapse rates inearlier studies. In one study, 158 persons withpartially remitted MDD were randomized to con-tinued medication or to 20 sessions of individualCBT plus continued medication. Adding CBTreduced the relapse rate significantly to 29% com-pared with 47% in the medication-only groupduring 68 weeks (15). In a smaller study, 40 patientswith partially remitted MDD were randomlyassigned to 10 sessions of individual CBT whiletapering ADM or to clinical management whiletapering ADM. Two years after withdrawal fromADM, 15% of the participants in the CBT grouphad suffered a relapse compared with 35% in theclinical management group (16); however, thisdifference was not significant. At the 4-year follow-upof the same sample, thedifferencebetween groupshad reached statistical significance, and the relapserates were 35% (CBT) vs. 70% (clinical manage-ment) (17). After 6 years, the relapse rates were 50%vs. 75% in favour of CBT, but only a trend towardssignificance could be observed (P = 0.06) (18).Several past episodes are also a known risk factor

for relapse (19), and apart from the mentionedstudies that show promising results for relapseprevention in partially remitted MDD, there is alsoevidence that CBT as an adjunct can reduce the riskof relapse in recurrent MDD when administeredbetween episodes. This has been demonstratedwhen ADM was tapered off and discontinued

during the CBT (20) and when continued cognitivetherapy was given to responders to acute phasecognitive therapy (CT) without any ADM at anystage of the study (21). A significantly higherprotective effect from CT has also been found inpersons with five or more past episodes, illustratedby a 46% relapse rate in major depression in the CTgroup and a 72% relapse rate in a group thatreceived treatment as usual (TAU) (22). Mindful-ness-based cognitive therapy (MBCT) (23) has beeninvestigated in three studies designed specifically forrelapse prevention for sufferers of recurrent depres-sion and is also administered during remission.MBCT seems to have a stronger effect in personswho have experienced several past episodes, e.g. inthe first study, a significant reduction in relapse wasfound only in the subgroup with three or more pastepisodes (24). This finding was later replicated inanother study by the same group, where 36% ofpatients with three or more episodes relapsed afterMBCT within 60 weeks compared with 78% afterTAU (25). In a third study, MBCT (with support totaper ADM) was as least as effective as ADM inpreventing relapse during 15 months (26). In arecent meta-analysis that included only the moremethodologically robust studies, the conclusionwas that CBT was effective for relapse prevention indepression (27).Although the above-mentioned results are prom-

ising, the clinical implications are limited becauseCBT as relapse prevention is relatively costly andin many places there are not enough therapists tomeet the demand. An Internet-based approach torelapse prevention could therefore be a comple-ment that could reach large numbers of patients.Earlier studies indicate that guided Internet-basedCBT is cost-effective (28) and can have moderate tolarge effects on depressive symptoms and stillrequire only 1.5–2 h of therapist time (29–31). Tothe best of our knowledge, no previous study hastested Internet-based CBT as relapse prevention inpartially remitted depression.

Aims of the study

The aim of the study was to test Internet-basedCBT as relapse prevention for people sufferingfrom partially remitted depression after previoustreatment.

Material and methods

Participants

The participants included in the study were at least18 years of age and had a history of at least one

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episode of MDD during the past 5 years, but didnot fulfil the criteria for MDD at the time ofrecruitment. They had all been treated for MDDwith psychotherapy and ⁄or ADM, and theirdepression was in partial remission. This wasdefined as a score no <7 and no higher than 19on the self-rated version of the Montgomery-Asberg Depression Rating Scale (MADRS-S)(32). Any psychotherapy should have ended30 days before recruitment and been performedby a licensed psychologist or licensed psychother-apist. An eventual ADM should have been stablefor 1 month or terminated 30 days before recruit-ment. Fifty per cent of the participants had ADMat the study start, and 50% had no ongoingtreatment. Baseline characteristics are presented inTable 1. Fluency in the Swedish language wasrequired for inclusion as well as having access to acomputer with an Internet connection. Reasons forexclusion were medicating against or reportinghaving being diagnosed with bipolar disorder orpsychosis as well as having an addiction problem.

Procedure

Participants were recruited through advertisementsin Swedish newspapers. The study was describedon a website where potential participants couldapply to take part and print out the consent form.Semi-structured interviews were conducted overthe telephone to diagnose current and past epi-sodes of major depression. The final decision aboutinclusion ⁄ exclusion was made at a diagnosticconference after a clinical psychologist and apsychiatrist had assessed all available materialtogether and reached consensus. The participants

were then randomized to Internet-based CBT or acontrol group by drawing numbers (each corre-sponding to a person) out of an opaque bowl. Overa 10-week period, participants in the treatmentgroup worked through CBT modules with guid-ance (via e-mail) from a personal therapist, afterwhich no guidance was received; however, theywere offered the remaining modules. During thewhole study period, participants in both groupsrated their depressive symptoms monthly withMADRS-S, and all such ratings resulted in feed-back by means of a graph showing their past andpresent scores. If a participant scored 19 or more,study staff interviewed her ⁄him over the telephoneto detect a possible relapse. Telephone interviewswere also conducted with all participants at the endof treatment and at the 6-month follow-up. Con-trol group participants had the possibility of e-mailcontact with a personal therapist; however, thecontent of the correspondence was restricted tonon-specific support. The study protocol wasapproved by the Regional Ethical Review Boardin Uppsala (No. 2007 ⁄335) (Fig. 1).

Outcome measures

The primary outcome measure was relapse, definedas fulfilling the DSM-IV criteria for MDD at anytime after the study start. This was established inthe telephone interviews, conducted by four clinicalpsychologists, using the questions about depressionin the Structured Clinical Interview for DSM-IVAxis I Disorders (SCID-I) (33). SCID-I has shownfair inter-rater agreement for diagnosing MDD(kappa value = 0.66) (34).The symptom levels of depression and anxiety as

well as self-reported quality of life were secondaryoutcomes. We used the MADRS-S to measure thedegree of depressive symptoms in the participants.It is a 9-item self-report measure and is the self-rated version of the original MADRS that wasespecially developed to be sensitive to change (35).A maximum of six on each item on the MADRS-Syields a 0–54 total score range, and remission wasdefined as having a score of 6 or less as suggestedfor the MADRS in a psychometric study (36).The Beck Depression Inventory – Second Edi-

tion (BDI-II) (37), a 21-item self-report measure ofdepressive symptoms, was also used in the study.BDI-II is a revised version of the original BDI andhas good psychometric properties, for example theinternal consistency has been reported to bea = 0.94 (alpha level) in one study (38) anda = 0.91 in another (39). For the calculation ofremission rates in the present study, we used a cut-off score of 10 or less as the definition of remission,

Table 1. Baseline characteristics

Total(N = 84)

Cognitive behaviourtherapy (n = 42)

Control(n = 42)

Age, mean (SD) 45.3 (12.8) 44.8 (13.9) 45.8 (11.9)Female gender, no. (%) 71 (84.5) 36 (85.7) 35 (83.3)ADM at recruitment, no. (%) 42 (50) 18 (42.8) 24 (57.1)Previous psychotherapy, no. (%) 52 (61.9) 28 (66.7) 24 (57.1)Previous episodes MDD,

mean (SD)5.96 (9.1) 4.17 (6.0) 7.8 (11.2)

Previous episodes MDD, median 3 3 4Marital status, no. (%)

Single 17 (20.2) 13 (30.9) 4 (9.5)Married or cohabiting 52 (61.9) 23 (54.8) 29 (69)Widowed 2 (2.4) 1 (2.4) 1 (2.4)Other 13 (15.4) 5 (11.9) 8 (19)

Highest education, no. (%)Senior high 12 (14.2) 9 (21.4) 3 (7.1)Vocational ed. 5 (5.9) 3 (7.1) 2 (4.8)University 67 (79.7) 30 (71.4) 37 (88.1)

ADM, Antidepressant medication; MDD, major depressive disorder.

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although this is lower and hence a more conserva-tive cut-off than 13 that is recommended in themanual (37). A cut-off of 10 has previously beenused in depression treatment trials (40, 41) and wasin one psychometric study (38) found to yield ahigh sensitivity for detecting depression.The Beck Anxiety Inventory (BAI), a 21-item

self-report measure of anxiety symptoms designedto overlap as little as possible with BDI, was alsoused in the study. A maximum of 3 on each itemyields a 0–63 score, and the internal consistencyhas been reported to be a = 0.92, and the test–retest reliability (1 week) is r = 0.75 (42).Quality of life (QOL) was measured using the

WHOQOL-BREF, which is a 26-item self-reportinstrument that measures four domains of QOL(43). It was designed to be applicable cross-culturally and has a reported test–retest reliabilityof r = 0.66 for physical health, r = 0.72 forpsychological QOL, r = 0.76 for social relation-ships and r = 0.87 for environment-related QOL(44).

All questionnaires were answered through theInternet. The self-report measures for depressivesymptoms and quality of life have been validatedfor online use, and the psychometric properties ofthe Internet versions have been shown to be largelyequivalent to those of the paper versions (45–47).

Internet-based CBT

We aimed at preventing relapse partly by treatingthe participants� residual symptoms with standardCBT components, such as behavioural activationand cognitive restructuring, and partly by provid-ing preventive strategies and skills (e.g. mindful-ness exercises). All participants had a personaltherapist who provided guidance, e.g. personalizedfeedback regarding homework and prompts wheninactive. Three of the therapists were clinicalpsychologists, two were M.Sc. clinical psychologystudents who had completed their clinical training,and all were supervised by an experienced CBTpsychotherapist during three group sessions. There

Assessedfor eligibility

(n = 323)

Excluded (n= 239)MADRS-S score >19 (176)MADRS-S score <7 (8)< 18 years of age (1)Ongoing psychotherapy (9)No previous treatment (2)Incomplete self-assessment (14)Current episode of MDD (18)No previous episode of MDD (1)Suspected psychosis (3)Suspected bipolar disorder (2)Risk consump on of alcohol (3)Physically caused dep. symptoms (1)Recent change in ADM dosage (1)

Randomized(n = 84)

Treatment

Droppedout, n = 3

Completed posttreatment

measurement, n = 39

Completed 6 monthfollow up, n = 35

Droppedout, n = 4

Droppedout, n = 4

Completed posttreatment

measurement, n = 38

Droppedout, n = 2

Completed 6 monthfollow up, n = 36

Internet-basedCBT, n = 42

Control condi onn = 42

Fig. 1. Flow of participants.

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were a total of 155 pages in the CBT materialcontaining text, exercises and worksheets. It con-sisted of nine basic modules that were mandatoryand had to be completed in a fixed order and sevenadvanced modules that were optional. See Table 2for the themes of the modules and their completionrates. The seven advanced modules covered alltopics except the first and the last and were moretheoretically advanced and contained moreexercises.

Analyses

A log-rank test was used to test the difference inrelapse rates between the two groups, and survivalcurves were calculated using the Kaplan–Meiermethod. Relapse rates were calculated by dividingthe number of relapses in each group by thenumber of participants who provided completedata until relapse or the 6-month follow-up. Coxregression was used to test whether symptomimprovement mediated relapse. Chi-square analy-ses were used to test differences in remission ratesbetween the two groups. Remission rates werecalculated by dividing the number of participantsbelow the cut-off score by the number whoprovided complete data at each measurementpoint as well as by dividing the number below thecut-off by the initial 42 in each group, treatingdropouts as non-remitters. Mixed models wereused to test differences in symptom levels betweenthe groups over time. This method is preferablewhen some data are missing (48) because it doesnot exclude any participants from the analysis, butrather uses all available data, which minimizes therisk of biasing the sample. This method also takesinto account the correlation between repeatedmeasurements within the same individual (49).Because it was reasonable to assume that correla-tions between scores from an individual�s repeatedmeasurements decrease as the time between them

increases, an autoregressive covariance pattern waschosen (AR1). All analyses were made with PASWStatistics 17.0, and effect sizes (Cohen�s d) werecalculated by dividing the difference in changescore by the pooled standard deviations. Effectsizes were calculated with the estimated meansfrom the mixed model and by the followingformula for converting standard error to standarddeviation: SD = SE · sqrt (n).

Results

Attrition

At post-treatment, complete data were collectedfrom 77 participants (91.7% of the 84 initiallyincluded; 38 in the CBT group and 39 controls)and at the 6-month follow-up from 71 participants(84.5% of 84) (36 in the CBT group and 35controls). The 13 (15.5% of 84) participants whofailed to provide full data sets did not differsignificantly from those who completed all assess-ments pertaining to age, number of previousepisodes, symptom levels at recruitment, level ofeducation, marital status, previous pharmacother-apy or the proportion of relapses. However, asignificantly higher proportion of those whodropped out or missed assessments had a historyof psychotherapy compared with those who com-pleted all assessments (P = 0.014, Fisher�s exacttest).

Adherence

Participants in the treatment condition completeda mean of 7.97 (SD 3.6) modules (range 1–16) outof a maximum of 16. A mean of 6.28 (SD 2.4) basicand 1.7 (SD 1.6) advanced modules were com-pleted. On average, 11.5 (SD 7.3) messages weresent from a CBT-group participant to her ⁄histherapist (range 0–36) compared with 1.2 (SD 1.5)in the control group (range 0–5). The mean numberof messages from a therapist to a CBT participantwas 15.3 (SD 6.3) (range 3–33) at an estimate of10 min ⁄message, resulting in approximately 2.5 hof total therapist time ⁄participant. The meannumber of messages from a therapist to a controlgroup participant was 3.7 (SD 1.6) (range 1–8) atan estimate of 10 min ⁄message, resulting inapproximately 37 min of total therapist time ⁄par-ticipant. CBT participants logged into the website29.2 times (SD 14.9) on average (range 1–62)compared with 5.8 times (SD 5.3) for controls(range 0–18). The mean number of monthly self-ratings completed was 5.38 (SD 2.69) in the CBTgroup and 5.67 (SD 2.38) in the control group, and

Table 2. Number (and percentage) of cognitive behaviour therapy (CBT) partici-pants that completed each basic and advanced module

Theme Basic Advanced

Introduction to CBT 41 (97.6) *Adding positively reinforced activities 40 (95.2) 10 (23.8)Handling negatively reinforced activities 35 (83.3) 7 (16.7)Cognitive restructuring 33 (78.6) 19 (45.2)Improving sleep 27 (64.3) 9 (21.4)Mindfulness 25 (59.5) 8 (19)Reducing anxiety 23 (54.8) 12 (28.6)Physical activity 12 (28.6) 3 (7.1)Long-term goals 11 (26.2) *

*Theme does not include advanced module.

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the difference was not significant (t82 = )0.515,P = 0.608).

Relapse rates

A log-rank test showed that Internet-based CBTsignificantly reduced the proportion of relapsecompared with the control group (v2 = 7.451,df = 1, P = 0.006). In the group that receivedInternet-based CBT, 10.5% (4 ⁄38) had experiencedrelapse at the 6-month follow-up, compared with37.8% (14 ⁄37) in the control condition. TheKaplan–Meier curves for the two groups arepresented in Fig. 2. A Cox regression showedthat the risk of relapse was mediated by theimprovement in depressive symptoms between thepre- and post-treatment measurements, Wald (1,N = 77) = 8.836, P = 0.003, hazard ratio =0.914 (95% CI = 0.861–0.970), and a five-pointimprovement on the MADRS-S reduced the risk ofrelapse by 36.2% compared with no improvement.

Remission rates

As shown in Table 3, there were no statisticallysignificant differences between the remission ratesamong those who provided complete data in thetwo groups. However, when measured by theMADRS-S, a trend towards a higher rate ofremission in the CBT group was found after6 months. When all dropouts were regarded asnon-remitters, we found a 40.5% remission rate for

CBT participants and 23.8% for controls(v2 = 2.674, df = 1, P = 0.102) at post-treat-ment, and a 40.5% remission rate for CBTparticipants compared with 21.4% for controls atthe 6-month follow-up (v2 = 3.565, df = 1,P = 0.059) (MADRS-S). Using the BDI, wefound a remission rate of 57.1% in the CBTgroup and 40.5% in the control group at post-treatment (v2 = 2.335, df = 1, P = 0.127), and47.7% (20 participants) in both groups after6 months when dropouts were regarded asnon-remitters.

Symptom reduction

We also investigated the actual change in self-reported residual symptoms of depression andanxiety, as well as self-rated quality of life, andfound a trend towards an interaction effectbetween group and time in the MADRS-S scores(P = 0.051), indicating that the CBT group had alarger reduction in symptoms over time. As shownin Table 4, there were also significant main effectsfor time as well as for group, and while thedifference between the groups was significant atpost-treatment, it had disappeared at the 6-monthfollow-up. With regard to BDI, we also found thegreatest difference between the groups at post-treatment. The between-group effect size frompretreatment to post-treatment was d = 0.33(95% CI = 0.11–0.55) for the MADRS-S andd = 0.29 (95% CI = 0.07–0.51) for the BDI-II.There were no significant interaction effects on themeasures of anxiety and quality of life.

Discussion

This study provides initial evidence for the effec-tiveness of guided Internet-based CBT in prevent-ing relapse in persons with partially remitted majordepression after other previous treatments. A clear

Weeks

Prop

orti

on fr

ee o

f rel

apse

403020100

1.0

0.8

0.6

0.4

0.2

0.0

CBT

Control

Fig. 2. Curves showing the proportion free of relapse in thecognitive behaviour therapy group and the control groupduring the 10 weeks of treatment and 26 weeks of follow-up.Vertical bars denote censored data.

Table 3. Remission rates in the two groups at post-treatment and at 6-monthfollow-up in participants who gave full data at each measurement point

Measure, time Group Remitters n Remission % v2 P

MADRS-S, post CBT 17 38 44.7 3.082 0.079Control 10 39 25.6

MADRS-S, 6 mo CBT 17 36 47.2 3.537 0.060Control 9 35 25.7

BDI-II, post CBT 24 38 63.2 2.960 0.085Control 17 39 43.6

BDI-II, 6 mo CBT 20 36 55.5 0.018 0.893Control 20 35 57.1

mo, months; MADRS-S, Montgomery-�sberg Depression Rating Scale – Self rated;BDI-II, Beck Depression Inventory – Second Edition; CBT, cognitive behaviourtherapy.

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difference in the survival curves is evident after the10-week intervention and is still present at the6-month follow-up. Internet-basedCBT reduced theresidual symptoms more rapidly than the controlcondition, and a trend suggests that more peoplewill enter remission after 10 weeks of Internet-based CBT. A reduction in the residual symptomsdecreased the risk of relapse significantly.This is the first study to investigate the possibil-

ity of using Internet-based CBT as relapse preven-tion and hence the first to demonstrate a significantdifference in relapse rates after such an interven-tion. The time · group interaction effect fordepressive symptoms failed to reach statisticalsignificance. However, a trend was observed(P = 0.051), which in combination with the morerapid drop in symptoms in the CBT group as wellas fewer relapses is in line with the established viewof residual symptoms as a risk factor for relapse. Itis also in line with a hypothesis, put forward byJudd et al. (6), predicting that the ability of CBT to

prevent relapse is directly related to its capacity toremove residual symptoms. One could, however,argue that as the interaction effect was not signif-icant, it might have been the more purelypreventive components (those aimed beyond treat-ment of symptoms) in the current study, e.g.physical exercise and mindfulness training, whichcaused or contributed the most to the prevention ofrelapse. This study does not directly investigatewhat part of the intervention actually preventedrelapse, so we have no clear answer to thisquestion. In the sample as a whole, however, wefound that a decrease in symptom levels reducedthe risk of relapse.Traditional CBT as an adjunct treatment has

already been found to have a preventive effect onrelapse in earlier studies, but its clinical use hasbeen limited, probably due to the costs involved. Ifour results from the current study can be repli-cated, an Internet-based approach would showpromising potential as a cost-effective (28) andacceptable (50) complement for partially remittedMDD sufferers as it has the potential to reach largenumbers of patients.The large reduction in the relapse rate (com-

pared with the control group) found in this studyindicates that Internet-based CBT as relapse pre-vention can be clinically important. One charac-teristic that might contribute to this is that thepatient has access to all the treatment material aswell the entire written correspondence after the endof the treatment period, possibly making it espe-cially useful for the prevention of relapse. The wayof working with Internet-based treatment alsoencourages patients to take more responsibilityfor their own treatment, which is another possibleadvantage. The rate of relapse in the control groupfound in this study was high (37.8% in 6 months)and can be compared with about 50% in 20 yearsin the general population (1). As we placedadvertisements seeking persons with partiallyremitted depression after treatment, we mighthave attracted a disproportionate rate of personsin a prodromal phase and thus perhaps recruited asample with a very high risk of relapse.The non-significant trend towards higher remis-

sion rates in the CBT group might be attributed toa lack of statistical power in the study, or alterna-tively, the intervention does not have the power toreduce symptoms below the remission threshold.The treatment of depressive symptoms by means ofInternet-based CBT has been successful in earliertrials, although no previous Internet-based studyhas included only participants suffering frompartially remitted MDD after other treatment.Nor has any previous study divided each theme of

Table 4. Estimated means (standard deviations), main and interaction effects,significant pairwise comparisons from the mixed effects model for each group atthe pre- and post-treatment self-report measurements as well as the 6-monthfollow-up

Measure

Treatment ControlMixed effect

model

M SD M SD F P

MADRS-S Pre 13.7 7.9 15.0 7.9 T:20.2 <0.001Post* 8.4 8.3 12.4 8.2 G:4.5 0.036

Follow-up 9.1 8.6 9.4 8.7 I: 3.0 0.051BAI Pre 10.7 8.9 10.8 8.9 T: 6.2 0.003

Post 7.9 9.1 9.5 9.1 G: 0.1 0.721Follow-up 8.5 9.4 8.0 9.5 I: 1.8 0.162

BDI-II Pre 17.0 11.5 17.7 11.5 T: 19.7 <0.001Post� 9.3 12.0 13.4 11.9 G:1.4 0.235

Follow-up 10.8 12.4 10.8 12.5 I: 2.4 0.090WHOQOL-BREF domains

Overall QOL Pre 3.2 1.2 3.4 1.2 T: 7.3 0.001Post 3.6 1.3 3.6 1.2 G: 0.4 0.546

Follow-up 3.6 1.3 3.7 1.3 I: 0.9 0.397Health Pre 2.8 1.3 2.9 1.3 T: 16.7 <0.001

Post 3.4 1.3 3.2 1.3 G: 0.0 0.930Follow-up 3.4 1.4 3.5 1.4 I: 2.2 0.116

Physical Pre 58.3 17.6 59.0 17.6 T: 20.3 <0.001Post 49.6 18.3 50.6 18.1 G: 0.0 0.977

Follow-up 50.8 18.9 49.0 19.0 I: 0.5 0.625Psychological Pre 46.5 18.4 48.9 18.4 T: 10.1 <0.001

Post 52.2 18.8 52.3 18.7 G: 0.1 0.728Follow-up 53.7 19.3 53.9 19.4 I: 0.5 0.584

Relationship Pre 47.0 25.3 50.4 25.3 T: 5.1 0.007Post 49.0 26.1 59.3 25.9 G: 3.7 0.057

Follow-up 52.3 26.9 57.7 27.1 I: 2.3 0.108Environment Pre 65.2 17.7 67.3 17.7 T: 7.9 0.001

Post 69.9 18.1 70.7 18.0 G: 0.5 0.466Follow-up 68.9 18.6 71.4 18.7 I: 0.4 0.662

*Significant between-group difference at post (F = 9.4, P = 0.002).�Significant between-group difference at post (F = 5.0, P = 0.026); T = time.G, group; I, interaction; QOL, quality of life; BDI, Beck Depression Inventory;MADRS-S, Montgomery-�sberg Depression Rating Scale – Self rated.

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the intervention into a basic and an advanced(optional) module, so one could argue that some ofthe participants in the current study gained asomewhat shallow understanding of CBT. On theother hand, the fact that so few advanced moduleswere completed could be because only the relevantones were chosen because the participants hadfairly few residual symptoms and therefore alimited number of problem areas.Traditional face-to-face CBT as relapse preven-

tion has shown long-term preventive effects inpersons with partially remitted MDD (15, 17), andin a sample mixing partially remitted and fullyremitted MDD (51), while the current study islimited by the short follow-up time. Anotherlimitation of this study was that, because ofgeographical distances, the diagnostic interviewswere conducted over the telephone rather than inperson, which could make them less valid. How-ever, this has been performed with valid results in aprevious study (52). In some interviews, treatmentallocation became obvious, and better measuresshould have been taken to conceal this. Thecapacity to detect relapse might have been limitedby only interviewing those with a MADRS-S score>19 in the monthly self-ratings. Interviews regard-less of MADRS-S score were only conducted atpost-treatment and at the 6-month follow-up.Face-to-face interviews every month would havebeen a more reliable way of establishing relapse.Because previous episodes of depression wereestablished by means of interviews, the answerscould be affected by memory bias. Patient recordscould be a more reliable source of informationabout past mental health. The generalizability ofthe results is limited by the relatively high educa-tional level of the participants. Other limitationswere the modest sample size and the fact that wedid not control for effects of all non-specific factorsor corrected for multiple comparisons. Strengths ofthe study design are that we included participantswith heterogeneous acute phase treatment andallowed stable medication at recruitment whichincreases the external validity.Individual CBT has previously been shown to

prevent relapse in partially remitted MDD (15, 17),and relapse in recurrent depression has beenprevented by individual (21) and group (22) CBT.In the current study, Internet-based CBT alsoprevented relapse in MDD, and thus, it seems thatthe specific CBT techniques can be delivered inmany forms and still prevent depressive relapse.There is a need for replication of these findings,

and future research should also investigate whatpatient characteristics predict a protective effect ofInternet-based CBT following other treatments

and also what components in the treatment mate-rial are most important for achieving this. It is alsoimportant to investigate the long-term effects ofthis approach to relapse prevention, in addition tothe role of therapist guidance. Other remainingresearch questions are whether these results couldbe generalized to persons with remitted recurrentdepression and whether the protective effect iscomparable to that of face-to-face CBT.Providing Internet-based CBT to sufferers from

partially remitted depression after other treatmentcould improve the course of illness for manypatients because it has the potential to preventrelapse.

Acknowledgements

This study was partly funded by the Swedish PsychiatryFoundation (Psykiatrifonden), the Capio Research Founda-tion and the National Association for Social and MentalHealth (RSMH).

Declaration of interest

None.

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