Elsevier

Journal of Affective Disorders

Volume 221, 15 October 2017, Pages 205-221
Journal of Affective Disorders

Review article
Treatment of neurocognitive symptoms in unipolar depression: A systematic review and future perspectives

https://doi.org/10.1016/j.jad.2017.06.034Get rights and content

Highlights

  • Cognitive dysfunction in major depressive disorder (MDD) is becoming a major concern.

  • We reviewed a broad number of interventions targeting cognitive symptoms of MDD.

  • Agents focusing on the glutamate system and neuroinflammation are being tested.

  • There are some promising pharmacological, physical and psychological therapies.

  • To date, there is no compelling data to draw any firm conclusion on this issue.

Abstract

Background

Cognitive symptoms in Major Depressive Disorder (MDD) are persistent and commonly entail neurocognitive impairment and a decline in quality of life. This systematic review gathers the current scientific evidence on therapeutic strategies for neuropsychological impairment in MDD.

Method

A systematic search on PubMed, PsycINFO and Clinicaltrials.gov was carried out on December 2016 according to PRISMA using Boolean terms to identify interventions for the treatment of cognitive dysfunction in MDD. Only English-written articles providing original data and focusing in adults with MDD were included with no time restrictions.

Results

A total of 95 studies reporting data on 40 pharmacological and non-pharmacological interventions were included. Interventions were grouped into the following categories: 1) Pharmacological Therapies (antidepressants, stimulants, compounds acting on NMDA receptors, compounds acting on the cholinergic system, compounds showing anti-inflammatory or antioxidant properties, other mechanisms of action), 2) Physical Therapies and 3) Psychological Therapies, 4) Exercise. There are some promising compounds showing a positive impact on cognitive symptoms including vortioxetine, lisdexamfetamine or erythropoietin.

Limitations

The studies included showed significant methodological differences in heterogeneous samples. The lack of a standardized neuropsychological battery makes comparisons between studies difficult.

Conclusion

Current evidence is not sufficient to widely recommend the use of procognitive treatments in MDD although promising results are coming to light.

Introduction

Major Depressive Disorder (MDD) is a chronic and multifactorial disease that presents with depressed mood, anhedonia and somatic symptoms such as lack of appetite or sleep disturbances (Otte et al., 2016). It affects more than 300 million people worldwide (WHO, 2012) and it is a leading cause of disability among young people (World Health Organization, 2014).

Neuroimaging studies have shown that MDD is associated with cerebral volume alterations and functional changes in brain networks related to emotional processing and cognition (Zhang et al., 2016). This is not merely a radiological finding, but it has important implications from a clinical point of view. Indeed, patients with MDD often present with cognitive dysfunction in domains like attention, executive functions, memory or psychomotor speed (Clark et al., 2016), which has been classically considered to be secondary to affective symptoms. Nowadays, however, this traditional view is changing since cognitive dysfunction has proved to be a central and lasting feature of MDD (Bartfai et al., 1991, Hammar et al., 2010), as previously seen in schizophrenia or bipolar disorder (BD) (Martinez-Aran et al., 2002). In addition, the cognitive impairment has been discarded as being exclusive of elderly depression and has been described in patients with first-episode depression (Lee et al., 2012).

Current treatments for MDD present remission rates around 30–40% (Trivedi et al., 2006). Moreover, patients with remitted depression show residual cognitive dysfunction (Hasselbalch et al., 2011), leading to impairment in psychosocial functioning (Al-Sukhni et al., 2015, Hasselbalch et al., 2011). Considering that one of the main targets in the treatment of MDD is achieving a functional recovery besides symptomatic recovery (Hasselbalch et al., 2011, Trivedi et al., 2006), there is growing interest about efficacious treatments for MDD and in particular for cognitive dysfunction in MDD.

The aim of this review is to systematically review current scientific evidence on therapeutic strategies for neuropsychological impairment in MDD.

Section snippets

Methods

With the aim of identifying all eligible peer-reviewed articles assessing treatments focused on residual cognitive symptoms on MDD we performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and guidelines from the Cochrane Collaboration (Higgins and Green, 2011). The systematic search was conducted on December 2016 using Pubmed, PsycINFO and ClinicalTrials.gov databases. The Boolean terms used were: ("major depression"

Antidepressants

The cognitive tolerability profile of selective serotonin reuptake inhibitors (SSRIs) in the long-term still remains to be clarified (Gorenstein et al., 2006, Popovic et al., 2015). In the short-term, their effects on cognition differ between young (Constant et al., 2005, Gudayol-Ferre et al., 2015, Herrera-Guzman et al., 2010, Wroolie et al., 2006) and elderly (Beheydt et al., 2015, Culang et al., 2009, Culang-Reinlieb et al., 2012, Marano et al., 2015, Marano et al., 2013, Martocchia et al.,

Discussion

This review aimed to offer an overview on the diverse interventions proposed for the management of cognitive dysfunction in MDD, both as monotherapy and adjuvant treatments. Given the correlation between cognitive impairment and poor functioning, there is a huge unmet need in finding effective treatments that might improve the outcome of MDD beyond the mere relief of mood symptoms. However, current evidence is insufficient to make any firm recommendation on their use. Most data are too

Conflicts of interest

Dr. I. Grande has received research Juan Rodés Contract JR15/00012 and grant Proyecto de Investigación en Salud PI16/00187 from the Instituto de Salud Carlos III, Spanish Ministry of Economy, Industry and Competitiveness and has served as a consultant for Ferrer and as a speaker for AstraZeneca, Ferrer and Janssen-Cilag.

Dr. Vieta has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, Actavis, Allergan, AstraZeneca, Bristol-Myers Squibb,

Role of funding sources

Supported by a Grant from the Spanish Ministry of Economy and Competitiveness (PI15/00283, PI12/00912, PI16/00187) integrated into the Plan Nacional de I+D+I and cofunded by el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER); CIBERSAM; and the Comissionat per a Universitats i Recerca del DIUE de la Generalitat de Catalunya (2014 SGR 398 to the Bipolar Disorder Group). IG is supported by a Juan Rodés Contract (JR15/00012) from Instituto de Salud Carlos

Acknowledgements

Authors thank the support of the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, CIBERSAM, the Spanish Ministry of Education and the Comissionat per a Universitats i Recerca del DIUE de la Generalitat de Catalunya to the Bipolar Disorders Group (2014 SGR 398).

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