Comparative analysis of anticholinergic burden scales to explain iatrogenic cognitive impairment and self-reported side effects in the euthymic phase of bipolar disorders: Results from the FACE-BD cohort

Bipolar disorders (BD) are characterized by cognitive impairment during the euthymic phase, to which treatments can contribute. The anticholinergic properties of medications, i.e., the ability of a treatment to inhibit cholinergic receptors, are associated with cognitive impairment in elderly patients and people with schizophrenia but this association has not been well characterized in individuals with remitted bipolar disorders. Moreover, the validity of anticholinergic burden scales designed to assess the anticholinergic load of medications has been scarcely tested in bipolar disorders. We aimed to test the concurrent validity of several scales by assessing their associations with objective cognitive impairment and subjective anticholinergic side-effects in BD. We hypothesized that the scale is valid if its association with cognitive impairment or self-reported anticholinergic side-effects is significant. A sample of 2,031 individuals with euthymic bipolar disorders was evaluated with a neuropsychological battery to identify cognitive impairment. Two scales among 27 were significantly positively associated with cognitive impairment in multiple logistic regressions, whereas chlorpromazine equivalents, lorazepam equivalents, the number of antipsychotics, or the number of treatments were not. The two scales significantly correlated with worse performance in processing speed and verbal memory. In addition, 14 scales showed good concurrent validity to assess self-reported peripheral anticholinergic side-effects and 13 were valid for evaluating self-reported central anticholinergic side-effects. Thus, we identified valid scales to monitor the anticholinergic burden in BD, which may be useful in assessing iatrogenic cognitive impairment in studies investigating cognition in BD.