Depression--be it a formal diagnosis based on consensus clinical criteria, or a collection of symptoms revealed by a self-report rating scale--is common in patients with multiple sclerosis (MS) and adds substantially to the morbidity and mortality associated with this disease. This Review discusses the prevalence and epidemiology of depression in patients with MS, before covering aetiological factors, including genetics, brain pathology, immunological changes, dysregulation of the hypothalamic-pituitary-adrenal axis, and psychosocial influences. Treatment options such as antidepressant drugs, cognitive-behavioural therapy, mindfulness-based therapy, exercise and electroconvulsive therapy are also reviewed in the context of MS-related depression. Frequent comorbid conditions, namely pain, fatigue, anxiety, cognitive dysfunction and alcohol use, are also summarized. The article then explores three key challenges facing researchers and clinicians: what is the optimal way to define depression in the context of diseases such as MS, in which the psychiatric and neurological symptoms overlap; how can current knowledge about the biological and psychological underpinnings of MS-related depression be used to boost the validity of this construct; and can intervention be made more effective through use of combination therapies with additive or synergistic effects, which might exceed the modest benefits derived from their individual components?

Purpose:To promote understanding of cognitive impairment in multiple sclerosis (MS), recommend optimal screening, monitoring, and treatment strategies, and address barriers to optimal management.Methods:The National MS Society (“Society”) convened experts in cognitive dysfunction (clinicians, researchers, and lay people with MS) to review the published literature, reach consensus on optimal strategies for screening, monitoring, and treating cognitive changes, and propose strategies to address barriers to optimal care.Recommendations:Based on current evidence, the Society makes the following recommendations, endorsed by the Consortium of Multiple Sclerosis Centers and the International Multiple Sclerosis Cognition Society:Increased professional and patient awareness/education about the prevalence, impact, and appropriate management of cognitive symptoms.For adults and children (8+ years of age) with clinical or magnetic resonance imaging (MRI) evidence of neurologic damage consistent with MS:As a minimum, early baseline screening with the Symbol Digit Modalities Test (SDMT) or similarly validated test, when the patient is clinically stable;Annual re-assessment with the same instrument, or more often as needed to (1) detect acute disease activity; (2) assess for treatment effects (e.g. starting/changing a disease-modifying therapy) or for relapse recovery; (3) evaluate progression of cognitive impairment; and/or (4) screen for new-onset cognitive problems.For adults (18+ years): more comprehensive assessment for anyone who tests positive on initial cognitive screening or demonstrates significant cognitive decline, especially if there are concerns about comorbidities or the individual is applying for disability due to cognitive impairment.For children (<18 years): neuropsychological evaluation for any unexplained change in school functioning (academic or behavioral).Remedial interventions/accommodations for adults and children to improve functioning at home, work, or school.

Detecting clinically significant symptoms of depression and anxiety in medically ill patients using self-report rating scales presents a challenge because of somatic confounders. The Hospital Anxiety and Depression Scale (HADS) was developed with this in mind, but has never been validated for a multiple sclerosis population. Our objective was to validate the HADS for multiple sclerosis patients. Multiple sclerosis patients were interviewed for the presence of major depression (n = 180) and anxiety disorders (n = 140) with the Structured Clinical Interview for DSM-IV disorders. A receiver operating characteristic (ROC) analysis was undertaken to assess which HADS cut-off scores give the best yield with respect to diagnoses of major depression and all anxiety disorders defined by the Structured Clinical Interview for DSM-IV. A threshold score of 8 or greater on the HADS depression subscale provides a sensitivity of 90% and specificity of 87.3% (ROC area under the curve 0.938). The same cut-off score gives a sensitivity of 88.5% and a specificity of 80.7% on the anxiety subscale (ROC area under the curve 0.913), but for generalized anxiety disorder only. The study confirms the usefulness of the HADS as a marker of major depression and generalized anxiety disorder, but not other anxiety disorders, in multiple sclerosis patients.