Background Psychotherapy is proven efficacious for the treatment of depression. However, the patient-perceived importance of its effect is not fully appreciated in the evidence base. The smallest worthwhile difference (SWD) represents the smallest beneficial effect of an intervention that patients deem worthwhile given the harms, expenses, and inconveniences associated with the intervention, and facilitates the interpretation of patient perceived importance of an intervention.

Methods The proposed study will estimate the SWD of the American Psychological Association recommended psychotherapies for depression treatment with English-speaking American and British respondents aged 18 and older. Respondents will be recruited using research participant crowdsourcing sites. The SWD will be estimated using the Benefit-Harm Trade-off Method, presenting survey respondents with variable, hypothetical magnitudes of psychotherapy outcomes to find the smallest acceptable effect over a no treatment alternative. The overall average SWD, and subgroup distributions by participant depression treatment experiences and depression symptomology will be described. Participant characteristics will be included in a regression model to explore associated variability in the SWD.

Expected Results We expect to find an estimate of the SWD for psychotherapy in the treatment of depression. Further, we expect that the SWD will vary between clinical subgroups based on depression symptomology and treatment experiences. We expect there to be variation between those who demonstrate depression symptoms consistent with a depressive disorder, based on PHQ-9 scores or self-reported diagnosis history. We think that the findings from this project will inform the treatment decision process about psychotherapy during the clinical consultation for people with depression.

TAF reports personal fees from Boehringer-Ingelheim, DT Axis, Kyoto University Original, Shionogi, SONY and UpToDate, and a grant from Shionogi, outside the submitted work; In addition, TAF has patents 2020-548587 and 2022-082495 pending, and intellectual properties for Kokoro-app licensed to Mitsubishi-Tanabe. ACi has received research, educational and consultancy fees from INCiPiT (Italian Network for Paediatric Trials), CARIPLO Foundation, Lundbeck and Angelini Pharma. He is the CI/PI of two trials about seltorexant in depression, sponsored by Janssen. In the last three years SL has received honoraria as a consultant and/or advisor and/or for lectures and/or for educational material from Alkermes, Angelini, Eisai, Gedeon Richter, Janssen, Lundbeck, Medichem, Medscape, Merck Sharpp and Dome, Mitsubishi, Neurotorium, NovoNordisk, Otsuka, Recordati, Roche, Rovi, Sanofi Aventis, TEVA. All the other authors declared no conflict of interest.

Funding was provided by the Kyoto University Graduate School of Medicine.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The ethics committee of Kyoto University Graduate School of Medicine gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors.