Cognitive remission: a novel objective for the treatment of major depression?

Beatrice Bortolato,Michael Berk,Brisa S Fernandes,André F Carvalho,Kamilla W Miskowiak,Michael Maes,Cristiano A Köhler

doi:10.1186/s12916-016-0560-3

Abstract

BackgroundCognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD.DiscussionConventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal antidepressant, has significant precognitive effects in MDD unrelated to mood improvement. Lisdexamfetamine dimesylate was shown to alleviate executive dysfunction in an RCT of adults after full or partial remission of MDD. Preliminary evidence also indicates that erythropoietin may alleviate cognitive dysfunction in MDD. Several other novel agents may be repurposed as cognitive enhancers for MDD treatment, including minocycline, insulin, antidiabetic agents, angiotensin-converting enzyme inhibitors, S-adenosyl methionine, acetyl-L-carnitine, alpha lipoic acid, omega-3 fatty acids, melatonin, modafinil, galantamine, scopolamine, N-acetylcysteine, curcumin, statins, and coenzyme Q10.SummaryThe management of cognitive dysfunction remains an unmet need in the treatment of MDD. However, it is hoped that the development of novel therapeutic targets will contribute to ‘cognitive remission’, which may aid functional recovery in MDD.

Highlights

Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention
It is hoped that the development of novel therapeutic targets will contribute to ‘cognitive remission’, which may aid functional recovery in MDD
We briefly review relevant clinical aspects pertaining to the assessment and effect of cognitive impairment in adults with MDD since we have critically evaluated these in a previous article [24]

Summary

Discussion

A significant body of evidence shows that individuals with MDD exhibit clinically significant cognitive impairment across multiple domains. Procognitive effects were suggested by a preliminary RCT that investigated vortioxetine treatment in non-demented subjects with recurrent MDD (n = 453) [71] These were secondary outcome measures, vortioxetinetreated individuals showed increased learning and memory performance (assessed by the Rey Auditory Verbal Learning Test; RAVLT) and higher processing speed (assessed by the Digit Symbol Substitution Test; DSST) compared with a placebo group, and the effects were independent of the reduction in depression severity (assessed by HDRS). One limitation of this study was the use of a self-report questionnaire to assess executive function since subjective ratings of cognitive deficits do not necessarily correlate with objective impairments [95] Another RCT with the primary objective of evaluating the effect of adjunctive LDX (20–50 mg/day) on residual symptoms and cognitive impairment in adults partially responsive to SSRIs or SNRIs is currently under way (ClinicalTrials.gov Identifier: NCT01148979).

Findings

Background