Choline Alfoscerate in the Treatment of Subthreshold Depression in the Elderly: A Pilot Study (CARTESIO)

Background: Subthreshold depression is a prevalent condition among the elderly and often remains untreated due to the limited efficacy and poor tolerability of standard antidepressants. Choline alfoscerate, a cholinergic precursor, is indicated for the treatment of a condition, pseudodepression in the elderly, that is currently clinically classified as subthreshold depression in older adults. Also, choline alfoscerate has shown neuroprotective and antidepressant-like effects. Objective: This pilot study aims to evaluate the efficacy and safety of choline alfoscerate in elderly patients with subthreshold depressive symptoms, using contemporary diagnostic criteria and standardized outcome measures. Methods: Seventeen patients aged ≥65 years were enrolled in an open-label, single-arm study and received 1200 mg/day of choline alfoscerate for 8 weeks. Clinical and neuropsychological assessments were performed at baseline, after 4 weeks, and at the study's end. Results: A statistically significant improvement was observed in depressive symptoms, as reflected by reductions in HAMD-17 (p < 0.001) and GDS-15 scores (p < 0.05), as well as in overall clinical severity assessed by the Clinical Global Impression-Severity scale (CGI-S, p < 0.05). No significant changes were noted in cognitive performance (MOCA) or apathy (AES-I). The treatment was well tolerated. Conclusions: Choline alfoscerate may represent a potentially safe and promising therapeutic option for subthreshold depression in older adults. However, given the exploratory nature of this open-label pilot study, these findings should be considered preliminary and hypothesis-generating and require confirmation in randomized controlled trials.