Depression before exacerbations

#MSBlog: Do you get depressed, anxious or fatigued before a relapse?

Epub: Burns et al. Prospective Examination of Anxiety and Depression Before and During Confirmed and Pseudoexacerbations in Patients With Multiple Sclerosis. Psychosom Med. 2012 Nov.

Objective: This study was designed to determine whether pseudoexacerbations and confirmed MS exacerbations are preceded by or concurrent with increased anxiety or depressive symptoms.

Methods: This was a secondary analysis of 121 MSers who were observed for 48 weeks during a randomized controlled trial. Participants completed monthly self-reports on depressive and anxiety symptoms. MSer-reported exacerbations were assessed through a telephone-administered symptom checklist and neurologic examination.

Results: Both pseudoexacerbations and confirmed exacerbations were associated with concurrent somatic depressive (β = .16 and β = .33, respectively; p values < .05), affective depressive (β = .17 [p = .02] and β = .12 [p = .06]), and anxiety symptoms (β = .24 and β = .20, p values < .01), controlling for baseline symptoms. Preexisting somatic and affective depressive symptoms predicted amplified relationships between concurrent confirmed exacerbations and these symptoms (β = .19 and β = .20, respectively; p values < .01). A standard deviation increase in anxiety symptoms relative to baseline predicted subsequent onset of pseudoexacerbations (odds ratio = 1.54, p = .02), whereas increased somatic depressive symptoms predicted confirmed exacerbations (odds ratio = 1.59, p = .01).

Conclusions. MSers experiencing pseudoexacerbations or confirmed exacerbations should be assessed and monitored for depressive and anxiety symptoms, and confirmed exacerbations are particularly concerning in MSers with a history of depression. The psychological or psychiatric antecedents of MS exacerbations generate new hypotheses on etiologies of confirmed exacerbations and pseudoexacerbations. 


“The implications of this study are very important. Have any of you felt low or depressed prior to an exacerbation? A lot of MSers tell me that they know when they are about to have an exacerbation. May be the inflammatory mediators and/or cytokines that are produced within the central nervous system as part of a relapse affects how the brain functions and causes depression and anxiety. There is little doubt that when you are ill, for example with influenza, you feel low. Similarly  in other inflammatory conditions such as rheumatoid arthritis, psoriasis and inflammatory bowel disease active inflammation is associated with low mood. Anothe issue is fatigue; this is commonly associated with depression and anxiety and I have little doubt that it will also increase prior to a relapse. Many neurologists, myself included, have started to identify exacerbations of fatigue as a manifestation of disease activity.”

“The term pseudoexacerbation is a poor one; it simply refers to relapses that are not associated with objective changes on the neurological examination  Some MSers find this ridiculous as many MS attacks are not associated with changes on the examination, in particular sensory attacks. In trials we only count exacerbations that can be confirmed objectively.”


“To explore this further I have prepared a short survey. Please let us know if depression, anxiety and fatigue are prodromal symptoms of a relapse!”

2 thoughts on “Depression before exacerbations”

  1. These spells of fatigue or feeling that something is wrong when the doctor says all is ok – do they count when assessing Disease Activity Free status?

    1. I think a patient-related outcome measure or PRO (USA) or PROM (UK) will eventually make its way into the definition of DAF. Unfortunately, none of the current ones capture disease activity.

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