Stroboscopic Light Stimulation in Adults Reporting Depressive Symptoms: Safety, Tolerability, Feasibility, and Active-Comparator Development in a Staged Early-Phase Study

Stroboscopic light stimulation (SLS) is a candidate non-pharmacological intervention that induces transient visual and affective experiences, with potential application in depression. Before efficacy testing, clinical development requires safety, tolerability and feasibility data. We report a staged, single-site programme in adults reporting depressive symptoms. Work Package (WP) 1 tested 11 SLS parameter sets for safety and tolerability. An interim bridge study assessed whether a low-phenomenology SLS control reduced subjective visual effects while preserving session context. WP2 randomised 84 participants to four weekly supervised 31-minute sessions of the intervention or a low-phenomenology control. In WP1, 31 participants were analysed; no severe adverse reactions occurred, mean discomfort was low (0.49/10), and the highest session-level upper 80% confidence limit was 1.13/10, well below the prespecified threshold. The interim study supported experiential separation between intervention and control. In WP2, endpoint data were available for 70/84 participants (83.3%): 39/42 in the intervention arm and 31/42 in the control arm. Overall retention met the criterion, but lower control-arm retention remains a design issue; protocol adherence was high, discomfort remained low, and no serious SLS-attributable adverse events occurred. Exploratory depressive-symptom changes suggested a possible BDI-II signal, but do not establish efficacy. Supervised SLS met key safety, tolerability, and feasibility criteria, and a lower visual-phenomenology active control can be carried forward, while masking and comparator credibility remain to be established. The next step is a diagnostically defined, CTU-governed Phase 2a feasibility trial that pre-registers a locked protocol and tests masking, credibility, retention and endpoint precision.