Cognitive dysfunction in MDD represents one of the most frequent residual
symptoms persistently following the achievement of symptomatic remission.
Moreover, emerging evidence indicates that significant cognitive deficits occur early in
the course of the disorder and may persist during affective remission. Cognitive
impairment lowers the likelihood of achieving the functional recovery. Conventional
antidepressant treatments exert a beneficial yet unsatisfactory effect on cognitive
dysfunction in MDD. As a consequence, the recognition of treatments capable of
specific cognitive improvements is an unmet need. Vortioxetine, a multimodal
antidepressant, has cognitive enhancing properties that seem to occur independently of
affective improvement. Several routes of research are evaluating the potential of
several pharmacological and non-pharmacological interventions in improving cognitive
performance. Agents under investigation include lisdexamfetamine, glutamatergic
modulators, erythropoietin, anti-inflammatory agents as well as nutraceuticals, such as
omega-3-polyunsaturated fatty acids, S-adenosyl-methionine and melatonin. Moreover,
neuromodulatory, psychological and biobehavioural approaches provided preliminary
encouraging results. However, further investigations are warranted to confirm these
findings and to evaluate the potential pseudo-specificity of these approaches.
Keywords: Antidepressant, Anti-inflammatory agents, Cognitive deficits,
Cognitive dysfunction, Cognitive remediation, Erythropoietin, Ketamine,
Lisdexamfetamine, Major Depressive Disorder, Melatonin, Neuromodulation,
Omega-3-polyunsaturated fatty acids, Physical exercise, S-adenosyl-methionine,
Treatment, Vortioxetine.
