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Background: Gender minority populations experience an increased risk of depression and report significant barriers to accessing mental health services. While digital mental health (DMH) technologies may address barriers, it remains unclear how gender minority clients engage with DMH services and if DMH improves their clinical outcomes. Objective: This naturalistic study explored gender differences in 15-week clinical outcomes of clients receiving technology-mediated psychotherapy from a large DMH provider. Methods: This study used observational data of clients who signed up for Talkspace (Talkspace, Inc) between February 2017 and July 2021. The analytic sample included Talkspace clients (N=20,156) with a baseline 8-item Patient Health Questionnaire (PHQ-8) score ≥10. Participants completed at least 2 PHQ-8 assessments over 15 weeks of treatment. Multilevel linear models tested gender differences in depressive symptom trajectories over the course of treatment (model 1) while also controlling for baseline PHQ-8 scores (model 2) and treatment engagement indicators (model 3). Sensitivity analyses reestimated model 2 among clients who submitted a PHQ-8 survey during the week 15 assessment period and among those who discontinued treatment beforehand. Reasons for service cancellation were also described for the latter group. Gender differences in secondary clinical outcomes were examined via chi-square and Fisher exact tests. Results: In all models, there were significant week-by-gender interactions. When controlling for baseline PHQ-8 scores, rates of symptom change were significantly slower for gender-diverse participants (b=0.60; P<.001), nonbinary participants (b=0.81; P<.001), and transgender women (b=0.87; P=.007), but not for women (P=.98) or transgender men (P=.38) compared to men. By week 15, adjusted PHQ-8 scores declined 8.7 points for both men and women, versus 4.4-7.4 points for gender minority clients. Sensitivity analyses indicated attenuated symptom improvement among week-15 completers, with transgender women showing the slowest changes (b=0.76; P=.02). Among earlier dropouts, weekly symptom reductions were steep overall (eg, week 3: b=-4.06, P<.001; week 6: b=-2.31, P<.001) while certain gender minority subgroups worsened (eg, adjusted scores for transgender women increased from 15.41 at baseline to 16.08 at final week 3 PHQ-8 survey submissions). Cancellation data (3450/20,156, 17.12%) confirmed discontinuation reasons related to both symptom improvement (928/3691 reasons, 25.14%) and potential barriers to treatment engagement (eg, cost: 1431/3691, 38.77%; poor service fit or poor perceived effectiveness: 677/3691, 18.34%). Gender differences were observed in rates of treatment response (weeks 3-12; all P≤.02), symptom remission (weeks 3, 6, 9, and 15; all P≤.047), and clinically significant symptom reduction (all time points, all P≤.03). Symptom deterioration did not differ by gender (all P>.05). Conclusions: While clinical outcomes generally improved over time among clients engaged in technology-mediated psychotherapy, some gender minority populations experienced slower improvements. Future research may explore strategies to adapt DMH interventions to better meet the needs of diverse gender identities.
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