Beyond symptom control: The unseen effects of anticholinergic burden on executive functions and sleep quality in...

Adolescents with depression are frequently treated with antidepressants and antipsychotics, many of which possess anticholinergic properties that may influence cognitive functioning and sleep. While accumulating evidence in adults suggests an association between anticholinergic burden (ACB) and adverse neurocognitive outcomes, data in adolescents remain limited despite heightened developmental vulnerability during this period. This cross-sectional study included 105 adolescents aged 15-18 years diagnosed with unipolar depressive disorder according to DSM-5 criteria. The medicated group comprised 65 adolescents receiving antidepressant and/or antipsychotic treatment for at least six months with an ACB score ≥ 2, while the comparison group included 40 newly diagnosed, drug-naïve adolescents with an ACB score of 0. Executive functions were assessed using the Behavior Rating Inventory of Executive Function (BRIEF), sleep quality using the Pittsburgh Sleep Quality Index (PSQI), and depression severity using the Beck Depression Inventory (BDI). Partial correlation, regression, and receiver operating characteristic (ROC) analyses were performed to examine associations between ACB, executive functioning, and sleep quality while adjusting for age, sex, and depression severity. Higher anticholinergic burden was associated with poorer subjective sleep quality (PSQI total, p = 0.030) and greater difficulties in executive domains, particularly planning/organization (p = 0.033) and emotional control (p = 0.010). ROC analyses identified ACB thresholds of ≥3 for planning/organization impairment (OR = 3.40, p = 0.003) and ≥ 4 for emotional control impairment (OR = 2.52, p = 0.037), indicating modest discriminative ability. These associations remained statistically significant after adjustment for demographic factors and depression severity. Overall, the findings suggest that higher cumulative anticholinergic exposure is associated with poorer sleep quality and executive functioning in adolescents with depression. Although causal inferences cannot be drawn, the results highlight the potential relevance of considering anticholinergic burden in pharmacological decision-making during adolescence, a developmentally sensitive period for cognitive and emotional maturation.