The team compared the risk of disability progression (assessed through the expanded disability status scale, or EDSS) and conversion to secondary progressive MS (SPMS) in MS patients with depression or bipolar disorder to that of patients without these conditions.

The study was based on the analysis of clinical data from 15,541 patients enrolled in the Swedish National MS registry (SMSreg). Among this sample, 1,320 had at least one diagnosis of depression, 271 had at least one diagnosis of bipolar disorder, and 4,921 had been prescribed selective serotonin reuptake inhibitors (SSRI), a commonly used class of antidepressant medications, at least once.

The analysis revealed that patients taking SSRIs were at a significantly higher risk of being increasingly disabled. Specifically, they were 1.4 times, 1.97 times, and 2.2 times more likely of reaching sustained EDSS scores of 3, 4 and 6 (the higher the score, the greater the disability level).

An EDSS score 3 is defined as “moderate disability in one functional system, or mild disability in three or four functional systems; no impairment to walking.” EDSS score 4 is “significant disability but self-sufficient and up and about some 12 hours a day; able to walk 500 meters without aid or rest.” EDSS score 6 is “requires a walking aid — cane, crutch, etc. — to walk about 100 meters with or without resting.”

MS patients diagnosed with depression were also at higher risk of reaching all three levels of disability — a risk 1.54 times higher to reach EDSS 3, 1.87 times for EDSS 4, and 2.1 times for EDSS 6. Also, they were at a 38% increased risk of converting to SPMS, and reached higher levels of incapacity more quickly. 

Specifically, MS patients with depression had a reduced median time to reach EDSS 3 by three years, EDSS 4 and 6 by six years, and the median time to convert to SPMS was reduced by three years, compared to MS patients without depression.

A group analysis looking at 261 patients diagnosed with depression prior to MS onset revealed that these patients reached an EDSS disability score of 3 and 4 three and seven years earlier, respectively, than MS patients without depression.

The risk of disability worsening was also greater for MS patients with bipolar disorder. Their likelihood of reaching EDSS 4 was 58% (0.58 times higher risk). The risk of reaching EDSS 3 and 6 was also greater but non-significant (0.34 times and 0.16 times greater, respectively).

Gender also affected the probability of having a worse disease course, with men showing the highest risk among those with depression or bipolar disorder.

“MS patients with depression or bipolar disorder have a significantly worse MS disease course, also in patients with a diagnosis of depression prior to MS onset,” the researchers wrote.

These results suggest that both disorders “are major risk factors for disability worsening,” Binzer said, adding that “the causal mechanisms of these associations need further investigation.”

Taken together, the results led the team to “hypothesize that a depressive state may render the central nervous system more sensitive to inflammation, a possibility that may warrant an increased focus on treatment of depressive symptoms in MS,” the team concluded.

Binzer emphasized that “early recognition and effective management of mood disorders should be incorporated into clinical care.”