Neuropsychological markers of antidepressant action: a secondary analysis of the ANTLER randomised controlled trial

BACKGROUND: Antidepressants have been proposed to act via their influence on emotional processing. We investigated the effect of discontinuing maintenance antidepressant treatment on positive and negative self-referential recall and the association between self-referential recall and risk of relapse. METHODS: The ANTLER trial was a large (N = 478) pragmatic double-blind trial investigating the clinical effectiveness of long-term antidepressant treatment for preventing relapse in primary care patients. Participants were randomised to continue their maintenance antidepressants or discontinue via a taper to placebo. We analysed memory for positive and negative personality descriptors, assessed at baseline, 12- and 52-week follow-up. RESULTS: The recall task was completed by 437 participants. There was no evidence of an effect of discontinuation on self-referential recall at 12 [positive recall ratio 1.00, 95% CI (0.90–1.11), p = 0.93; negative recall ratio 1.00 (0.87–1.14), p = 0.87] or 52 weeks [positive recall ratio 1.03 (0.91–1.17), p = 0.62; negative recall ratio 1.00 (0.86–1.15), p = 0.96; ratios larger than one indicate higher recall in the discontinuation group], and no evidence of an association between recall at baseline or 12 weeks and later relapse [baseline, positive hazard ratio (HR) 1.02 (0.93–1.12), p = 0.74; negative HR 1.01 (0.90–1.13), p = 0.87; 12 weeks, positive HR 0.99 (0.89–1.09), p = 0.81; negative HR 0.98 (0.84–1.14), p = 0.78; ratios larger than one indicate a higher frequency of relapse in those with higher recall]. CONCLUSIONS: We found no evidence that discontinuing long-term antidepressants altered self-referential recall or that self-referential recall was associated with risk of relapse. These findings suggest that self-referential recall is not a neuropsychological marker of antidepressant action.