Tardive dyskinesia and cognitive performances in late-life depression: a sex-stratified analysis

The relationship between baseline cognitive performance and tardive dyskinesia (TD) is poorly understood. The aim of the study was to evaluate the role of cognitive performance in the development of TD with a specific focus on sex differences.

We included 255 participants from the IRL-GRey trial treated with venlafaxine plus aripiprazole or placebo without baseline dyskinesia who had at least one post-baseline Abnormal Involuntary Movement Scale (AIMS) assessment. TD were considered as "present" using a highly sensitive but non-specific definition. Incident TD was assessed after Phase 1 (venlafaxine lead-in) in the full cohort (n = 255) and through the end of the randomized augmentation phase among non-remitters who entered randomization (n = 117). Incident TD was defined as AIMS item 8 ≥ 1 at the endpoint visit. A comprehensive neuropsychological battery was performed.

Sixteen of 255 participants (6.3%) developed TD by the end of Phase 1; all were non-remitters. By the end of randomized augmentation, 21 of 117 non-remitters randomized (17.9%) were TD+. No differences in depression severity nor neuropsychological performance were found between TD+ and TD-. In the exploratory sex-stratified analyses, males TD+ showed lower performance on selected neuropsychological measures of executive functioning and attention than males TD-.

In this late-life depression cohort, exploratory findings suggested a possible male-specific association between poorer executive and attentional functioning and subsequent TD development. However, given the small number of incident TD cases and the absence of correction for multiple comparisons, these results should be interpreted cautiously and need replication in larger studies.