Anxiety and Coping Strategy Changes in Multiple Sclerosis Patients Initiating Fingolimod: The GRACE Prospective Study

Abstract

The objective of this prospective study was to assess the changes in anxiety levels, and their relationship with coping strategies over the first four months of fingolimod treatment in patients with relapsing remitting multiple sclerosis (RRMS). Data were collected at the inclusion visit (Visit 1) and 4 months later (Visit 2). We used the Hospital Anxiety and Depression Scale (HADS) to assess the level of anxiety and the Coping Inventory for Stressful Situations scale to assess the coping strategies used when engaged with stressful situations. The HADS anxiety scores were compared between Visits 1 and 2, according to the preferred coping strategy. At Visit 1, half of the 198 patients included were considered to be anxious (doubtful or in a certain way). The same proportion preferentially used an avoidance-oriented strategy and one-third preferentially used an emotion-oriented strategy. The mean HADS anxiety score decreased significantly (p = 0.001) at Visit 2 (8.1 ± 4.0) compared to Visit 1 (8.8 ± 4.3), particularly in the group of patients who used an emotion-oriented strategy (p = 0.002). In conclusion, the initiation of fingolimod in patients with RRMS is followed by a decrease of anxiety levels which vary according to the coping strategy used.

Importin α5 Regulates Anxiety through MeCP2 and Sphingosine Kinase 1

“…The clear anxiolytic effects of fingolimod suggest that this pathway provides new targets for anxiety drug development and demonstrate the possibility of repurposing existing drugs to anxiety therapy. In this context, a prospective study described a decrease in anxiety levels in multiple sclerosis patients upon initiation of fingolimod treatment ( Moreau et al., 2017 ). Current therapies for anxiety disorders either directly affect neurotransmitter receptor systems or modulate neurotransmitter levels or availability, but their long-term use is limited by problematic side effects and suboptimal efficacy ( Griebel and Holmes, 2013 ).…”

Adverse psychiatric effects of disease-modifying therapies in multiple Sclerosis: A systematic review

“…A meta-analysis including the five studies which provided the necessary information also found that depression improved ( Fig. 4A, SMD [95%CI]; 1.18 [0.17, 2.19]) (Bayas et al, 2016;Hersh et al, 2017;Hunter et al, 2016;Moreau et al, 2017;Popova et al, 2017). High heterogeneity existed between estimates (I 2 99%; p = 0.0001).…”

“…Eight publications, representing six unique studies (2 observational, 4 RCTs) examined changes in depression symptoms following fingolimod treatment using various tools (Achiron et al, 2017;Bayas et al, 2016;Calkwood et al, 2014;Fox et al, 2014;Hersh et al, 2017;Hunter et al, 2016;Montalban et al, 2011;Moreau et al, 2017;Popova et al, 2017). In all studies, depression symptoms improved following fingolimod treatment.…”

“…Removing one study with a large effect substantially reduced the pooled estimate for the (SMD [95%CI]: 0.37 [0.11, 0.62], I 2 = 87%, Appendix 7). One study examined changes in anxiety symptoms, and showed a non-significant improvement (SMD: 0.17 [−0.03, 0.37]) (Moreau et al, 2017).…”

Sphingolipids as prognostic biomarkers of neurodegeneration, neuroinflammation, and psychiatric diseases and their emerging role in lipidomic investigation methods

“…Interestingly, fingolimod has been also shown to decrease anxiety [ 204 ] and improve depressive symptoms in MS treated patients [ 205 ]. Studies in mice further supported a protective role for fingolimod upon chronic stress exposure [ 206 ] in a neurogenesis dependent way [ 207 ], as a facilitator of fear memory extinction [ 208 ] and in reversing the anxiety-like behavior induced by the regional expression of α-importin 5 in the ventral hippocampus [ 209 ].…”