A randomised double-blind placebo-controlled trial of topical menthol for pain relief during photodynamic therapy

Pain during conventional photodynamic therapy (PDT) for actinic keratoses remains a major limitation. We conducted a randomised double-blind placebo-controlled within-subject trial investigating whether 5% topical menthol cream reduced pain during conventional ALA-PDT for scalp and forehead actinic keratoses. Following a pre-specified interim analysis, the study was terminated early because pain scores remained high and no meaningful treatment difference was observed. Mean visual analogue scale pain scores immediately after PDT were 6.58 cm for menthol-treated sites and 6.31 cm for placebo (mean difference 0.27 cm; 95% CI -0.28 to 0.82; p = 0.30). Topical menthol did not provide clinically meaningful analgesia despite promising pre-clinical evidence. These findings support the need for caution with regards to translating experimental approaches into clinical PDT delivery in humans.