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Background  Acceptance and Commitment Therapy (ACT) has been demonstrated to be effective in reducing depressive symptoms. However, little is known how and for whom therapeutic change occurs, specifically in web-based interventions. This study focuses on the mediators, moderators and predictors of change during a web-based ACT intervention.    Methods  Data from 236 adults from the general population with mild to moderate depressive symptoms, randomized to either web-based ACT ( n  = 82) or one of two control conditions (web-based Expressive Writing (EW;  n  = 67) and a waiting list ( n  = 87)), were analysed. Single and multiple mediation analyses, and exploratory linear regression analyses were performed using PROCESS and linear regression analyses, to examine mediators, moderators and predictors on pre- to post- and follow-up treatment change of depressive symptoms.    Results  The treatment effect of ACT versus the waiting list was mediated by psychological flexibility and two mindfulness facets. The treatment effect of ACT versus EW was not significantly mediated. The moderator analyses demonstrated that the effects of web-based ACT did not vary according to baseline patient characteristics when compared to both control groups. However, higher baseline depressive symptoms and positive mental health and lower baseline anxiety were identified as predictors of outcome across all conditions. Similar results are found for follow-up.    Conclusions  The findings of this study corroborate the evidence that psychological flexibility and mindfulness are distinct process mechanisms that mediate the effects of web-based ACT intervention. The results indicate that there are no restrictions to the allocation of web-based ACT intervention and that web-based ACT can work for different subpopulations.    Trial registration  Netherlands Trial Register  NTR2736 . Registered 6 February 2011.

How and for whom does web-based acceptance and commitment therapy work? Mediation and moderation analyses of web-based ACT for depressive symptoms