Fatigue in Patients with Major Depressive Disorder: Prevalence, Burden and Pharmacological Approaches to Management


Fatigue is a frequently reported symptom in major depressive disorder, occurring in over 90% of patients. Clinical presentations of fatigue within major depressive disorder encompass overlapping physical, cognitive and emotional aspects. While this review addresses the epidemiology, burden, functional impact and management of fatigue in major depressive disorder, the main focus is on available pharmacotherapy options and their comparative efficacies. Our review of the effects of pharmacological treatments on fatigue in major depressive disorder found that medications with dopaminergic and/or noradrenergic action such as modafinil, flupenthixol and atomoxetine were most effective in improving symptoms of fatigue and low energy. However, significant variation across studies in assessment tools and study inclusion/exclusion criteria may have contributed to inconsistent findings. The efficacy of non-pharmacological interventions is also discussed, including light therapy and exercise.

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Corresponding author

Correspondence to Sidney H. Kennedy.

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No funding was received for the preparation of this article.

Conflict of interest

Sidney H. Kennedy has received research funding or honoraria from the following sources: Abbott, Allergan, AstraZeneca, BMS, Brain Cells Inc., Brain Canada, Canadian Institutes for Health Research, Clera, Janssen, Lundbeck, Lundbeck Institute, Ontario Mental Health Foundation, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, St. Jude Medical, Sunovion and Xian-Janssen. Helia Ghanean and Amanda K. Ceniti have no conflicts of interest directly relevant to the content of this article.

Additional information

Helia Ghanean and Amanda K. Ceniti are joint first authors.

Appendix: Search Strategy for Review of Pharmacological Interventions for Fatigue in Major Depressive Disorder

Appendix: Search Strategy for Review of Pharmacological Interventions for Fatigue in Major Depressive Disorder

((fatigu*) OR (energy) OR (anerg*) OR (FSS) OR (Fatigue Severity Scale) OR (FAD) OR (Fatigue Associated with Depression) OR (MAF) OR (Multidimensional Assessment of Fatigue) OR (PFS) OR (Piper Fatigue Scale) OR (BFI) OR (Brief Fatigue Inventory) OR (MFS) OR (Mental Fatigue Scale) OR (MEI) OR (Motivation and Energy Inventory))


((MDD) OR (depression) OR (major depressive disorder))


((antidepress*) OR (SSRI) OR (selective serotonin reuptake inhibit*) OR (TCA) OR (tricyclic) OR (MAOI) OR (monoamine oxidase inhibitor) OR (SNRI) OR (serotonin norepinephrine reuptake inhibit*) OR (fluoxetine) OR (fluvoxamine) OR (paroxetine) OR (sertraline) OR (*citalopram) OR (duloxetine) OR (*venlafaxine) OR (amitriptyline) OR (nortriptyline) OR (*pramine) OR (maprotiline) OR (doxepin) OR (nomifensine) OR (protriptyline) OR (phenelzine) OR (moclobemide) OR (selegiline) OR (tranylcypromine) OR (isocarboxazid) OR (bupropion) OR (mirtazapine) OR (*zodone) OR (amoxapine) OR (reboxetine) OR (lithium) OR (carbamazepine) OR (lamotrigine) OR (benzodiazepine) OR (alprazolam) OR (*ketamine) OR (*milnacipran))

NOT (Review[ptyp])

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Ghanean, H., Ceniti, A.K. & Kennedy, S.H. Fatigue in Patients with Major Depressive Disorder: Prevalence, Burden and Pharmacological Approaches to Management. CNS Drugs 32, 65–74 (2018). https://doi.org/10.1007/s40263-018-0490-z

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