Management of cognitive dysfunction in depression

Improving the treatment of depression to help patients achieve a full and lasting functional recovery is likely to require a combination of complementary approaches.

Despite the wide range of treatment options for patients with depression, improvement of cognitive dysfunction is often inadequate.

Functional recovery does not refer merely to the absence of low mood and negative thoughts, but rather also involves resolution of the cognitive problems patients have faced, and that these solutions continue into the long term.4,5

Current treatment options for cognitive dysfunction in depression

Effective treatment options for patients with depression include pharmacotherapy, psychological therapy, self-help and lifestyle changes such as exercise.6-9 While there is a wealth of research and evidence regarding the use of pharmacotherapies for depression, we are unable to discuss these on this website, in accordance with industry regulations. However, these medications are often prescribed in conjunction with psychological therapies, the effectiveness of which is also evidenced in the research literature, as summarised below.


Table: Non-pharmacological treatment options

Non-pharmacological interventions for the treatment of cognitive dysfunction in depressed patients.

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Cognitive behavioural therapy, interpersonal therapy, problem-solving therapy

Some evidence of benefit in depression10

Cognitive training

Limited evidence for its efficacy in depression11

Halting the administration of cognition-impairing medications

Limited evidence that some antidepressants impair cognitive functioning2


There is little current evidence for lifestyle changes such as exercise in improving cognitive dysfunction in depression.12 New neuropsychological models of treatment for depression suggest that combining pharmacotherapy with psychological therapies may improve long-term outcomes.3

There is a need to treat cognitive dysfunction in depression

Despite the wide range of treatment options for patients with depression, improvement of cognitive dysfunction is often inadequate, even in patients considered to be in remission.4,13-16

Furthermore, patients describe a range of indicators for recovery from depression beyond traditional symptom-based definitions, including behaviour, appearance and thoughts or feelings,17 and approximately half of patients in remission (HAM-D17 score of ≤7) do not consider themselves to be in remission.18

  1. Millan MJ. Dual- and triple-acting agents for treating core and co-morbid symptoms of major depression: novel concepts, new drugs. Neurotherapeutics 2009; 6: 53-77.
  2. Millan MJ, Agid Y, Brüne M, Bullmore ET, Carter CS, Clayton NS, Connor R, Davis S, Deakin B, DeRubeis RJ, Dubois B, Geyer MA, Goodwin GM, Gorwood P, Jay TM, Joëls M, Mansuy IM, Meyer-Lindenberg A, Murphy D, Rolls E et al. Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov 2012; 11: 141-168.
  3. Roiser JP, Elliott R, Sahakian BJ. Cognitive mechanisms of treatment in depression. Neuropsychopharmacology 2012; 37: 117-136.
  4. Greer TL, Kurian BT, Trivedi MH. Defining and measuring functional recovery from depression. CNS Drugs 2010; 24: 267-284.
  5. Conradi HJ, Ormel J, de Jonge P. Presence of individual (residual) symptoms during depressive episodes and periods of remission: a 3-year prospective study. Psychol Med 2011; 41: 1165-1174
  6. Gelenberg AJ. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. Available at: Last updated 2010. Accessed June 2015.
  7. Timonen M, Liukkonen T. Management of depression in adults. BMJ 2008; 336: 435-439.
  8. Coull G, Morris PG. The clinical effectiveness of CBT-based guided self-help interventions for anxiety and depressive disorders: a systematic review. Psychol Med 2011; 41: 2239-2252.
  9. Chalder M, Wiles NJ, Campbell J, Hollinghurst SP, Haase AM, Taylor AH, Fox KR, Costelloe C, Searle A, Baxter H, Winder R, Wright C, Turner KM, Calnan M, Lawlor DA, Peters TJ, Sharp DJ, Montgomery AA, Lewis G. Facilitated physical activity as a treatment for depressed adults: randomised controlled trial. BMJ 2012; 344: e2758.
  10. Barth J, Munder T, Gerger H, Nüesch E, Trelle S, Znoj H, Jüni P, Cuijpers P. Comparative efficacy of seven psychotherapeutic interventions for patients with depression: a network meta-analysis. PLoS Med 2013; 10: e1001454.
  11. Kruijt AW, Putman P, Van der Does W. A multiple case series analysis of six variants of attentional bias modification for depression. ISRN Psychiatry 2013; 2013: 414170.
  12. Rimer J, Dwan K, Lawlor DA, Greig CA, McMurdo M, Morley W, Mead GE. Exercise for depression. Cochrane Database Syst Rev 2012; 7: CD004366.
  13. Fava M, Graves LM, Benazzi F, Scalia MJ, Iosifescu DV, Alpert JE, Papakostas GI. A cross-sectional study of the prevalence of cognitive and physical symptoms during long-term antidepressant treatment. J Clin Psychiatry 2006; 67: 1754-1759.
  14. McClintock SM, Husain MM, Wisniewski SR, Nierenberg AA, Stewart JW, Trivedi MH, Cook I, Morris D, Warden D, Rush AJ. Residual symptoms in depressed outpatients who respond by 50% but do not remit to antidepressant medication. J Clin Psychopharmacol 2011; 31: 180-186.
  15. McDermott CL, Gray SL. Cholinesterase inhibitor adjunctive therapy for cognitive impairment and depressive symptoms in older adults with depression. Ann Pharmacother 2012; 46: 599-605.
  16. Herrera-Guzmán I, Herrera-Abarca JE, Gudayol-Ferré E, Herrera-Guzmán D, Gómez-Carbajal L, Peña-Olvira M, Villuendas-González E, Guàrdia-Olmos J. Effects of selective serotonin reuptake and dual serotonergic-noradrenergic reuptake treatments on attention and executive functions in patients with major depressive disorder. Psychiatry Res 2010; 177: 323-329.
  17. Johnson C, Gunn J, Kokanovic R. Depression recovery from the primary care patient’s perspective: ‘hear it in my voice and see it in my eyes’. Ment Health Fam Med 2009; 6: 49-55.
  18. Zimmerman M, Martinez JA, Attiullah N, Friedman M, Toba C, Boerescu DA, Rahgeb M. Why do some depressed outpatients who are in remission according to the Hamilton Depression Rating Scale not consider themselves to be in remission? J Clin Psychiatry 2012; 73: 790-795.
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