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Does Internet-based guided-self-help for depression cause harm? An individual participant data meta-analysis on deterioration rates and its moderators in randomized controlled trials

  • D. D. Ebert (a1), L. Donkin (a2) (a3), G. Andersson (a4) (a5), G. Andrews (a6), T. Berger (a7), P. Carlbring (a8), A. Rozenthal (a8), I. Choi (a9), J. A. C. Laferton (a10), R. Johansson (a4) (a5), A. Kleiboer (a3), A. Lange (a11), D. Lehr (a12), J. A. Reins (a12), B. Funk (a12), J. Newby (a13), S. Perini (a14), H. Riper (a3), J. Ruwaard (a3), L. Sheeber (a15), F. J. Snoek (a16) (a17), N. Titov (a18), B. Ünlü Ince (a3), K. van Bastelaar (a16), K. Vernmark (a4) (a19), A. van Straten (a3), L. Warmerdam (a3), N. Salsman (a20) and P. Cuijpers (a3)...



Almost nothing is known about the potential negative effects of Internet-based psychological treatments for depression. This study aims at investigating deterioration and its moderators within randomized trials on Internet-based guided self-help for adult depression, using an individual patient data meta-analyses (IPDMA) approach.


Studies were identified through systematic searches (PubMed, PsycINFO, EMBASE, Cochrane Library). Deterioration in participants was defined as a significant symptom increase according to the reliable change index (i.e. 7.68 points in the CES-D; 7.63 points in the BDI). Two-step IPDMA procedures, with a random-effects model were used to pool data.


A total of 18 studies (21 comparisons, 2079 participants) contributed data to the analysis. The risk for a reliable deterioration from baseline to post-treatment was significantly lower in the intervention v. control conditions (3.36 v. 7.60; relative risk 0.47, 95% confidence interval 0.29–0.75). Education moderated effects on deterioration, with patients with low education displaying a higher risk for deterioration than patients with higher education. Deterioration rates for patients with low education did not differ statistically significantly between intervention and control groups. The benefit–risk ratio for patients with low education indicated that 9.38 patients achieve a treatment response for each patient experiencing a symptom deterioration.


Internet-based guided self-help is associated with a mean reduced risk for a symptom deterioration compared to controls. Treatment and symptom progress of patients with low education should be closely monitored, as some patients might face an increased risk for symptom deterioration. Future studies should examine predictors of deterioration in patients with low education.

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Corresponding author

*Address for correspondence: D. D. Ebert, Ph.D., Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany. (Email:


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