title: Cognitive remission: a novel objective for the treatment of major depression?
abstract: BACKGROUND
  Cognitive 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.
  
  
  CONCLUSIONS
  Conventional 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. The 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.
authors.affiliation: Department of Neurosciences, University of Padova, Padova, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bortolato
authors.affiliation: Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Kamilla W
authors.initials: KW
authors.lastname: Miskowiak
authors.affiliation: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty Medicine, Federal University of Ceará, Rua Prof. Costa Mendes 1608, 4° andar, Fortaleza, CE, 60430-040, Brazil.
authors.forename: Cristiano A
authors.initials: CA
authors.lastname: Köhler
authors.affiliation: Deakin University, School of Medicine, IMPACT Strategic Research Centre, Geelong, Australia.|Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.affiliation: Deakin University, School of Medicine, IMPACT Strategic Research Centre, Geelong, Australia.|Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, UFRGS, Porto Alegre, Brazil.
authors.forename: Brisa S
authors.initials: BS
authors.lastname: Fernandes
authors.affiliation: Deakin University, School of Medicine, IMPACT Strategic Research Centre, Geelong, Australia.|Orygen, The National Centre of Excellence in Youth Mental Health, Department of Psychiatry and The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.affiliation: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty Medicine, Federal University of Ceará, Rua Prof. Costa Mendes 1608, 4° andar, Fortaleza, CE, 60430-040, Brazil. andrefc7@terra.com.br.
authors.forename: André F
authors.initials: AF
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001288:Attention / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy* / Q000523:psychology*; D006801:Humans; D008568:Memory / Q000187:drug effects; D015201:Meta-Analysis as Topic; D018697:Nootropic Agents / Q000627:therapeutic use*; D020127:Recovery of Function; D012074:Remission Induction
chemical_list: D000928:Antidepressive Agents; D018697:Nootropic Agents