Effects of onabotulinumtoxinA treatment for chronic migraine on common comorbidities including depression and anxiety

Abstract

Objective: To assess the effects of onabotulinumtoxinA treatment for chronic migraine (CM) on comorbid symptoms of depression, anxiety, fatigue and poor sleep quality.

Methods: The Chronic Migraine OnabotulinuMtoxinA Prolonged Efficacy open-Label (COMPEL) study is a multicentre, open-label, prospective study assessing the long-term safety and efficacy of onabotulinumtoxinA 155 U over nine treatments (108 weeks) in adults with CM. The Patient Health Questionnaire (PHQ-9) and Generalised Anxiety Disorder (GAD-7) scales were used to assess the effects of onabotulinumtoxinA on comorbid symptoms of depression and anxiety, respectively. A clinically meaningful improvement was assessed by the percentage of patients experiencing a ≥1 severity category reduction in PHQ-9 and GAD-7. The effects of onabotulinumtoxinA on associated sleep quality and fatigue were assessed using the Pittsburgh Sleep Quality Index and Fatigue Severity Scale, respectively.

Results: OnabotulinumtoxinA treatment was associated with sustained reduction in headache days and PHQ-9 and GAD-7 scores in the analysis population (n=715) over 108 weeks. PHQ-9 and GAD-7 scores were significantly reduced at all time points in patients with clinically significant symptoms of depression and/or anxiety at baseline. By week 108, 78.0% and 81.5% had clinically meaningful improvement in depression and anxiety symptoms, respectively. Sleep quality and symptoms of fatigue also improved; however, less is understood about clinically meaningful changes in these measures. No new safety concerns were identified.

Conclusion: In addition to reducing headache frequency, onabotulinumtoxinA treatment for CM was associated with clinically meaningful reduction in symptoms of depression and anxiety, and improved associated symptoms of poor sleep quality and fatigue.

Trial registration number: NCT01516892.

Keywords: anxiety; comorbidities; depression; fatigue; onabotulinumtoxinA; sleep.

Conflict of interest statement

Competing interests: AMB has served on advisory boards for Allergan, Amgen, Alder, Teva, Supernus, Promius, Eaglet and Lilly, and has received funding for speaking from Allergan, Amgen, Pernix, Supernus, Depomed, Avanir and Promius. He holds patents for onabotulinumtoxinA in migraine assigned to Allergan. SJT is an employee of the Dartmouth-Hitchcock Medical Center and receives a salary from the American Headache Society (AHS). He also serves as a consultant for Acorda, Alder, Alexsa, Allergan, Amgen, ATI, BioVision, Cefaly, Charleston Laboratories, DeepBench, Dr Reddy’s, ElectroCore, Eli Lilly, eNeura, GLG, Guidepoint Global, Impax, Neurolief, Novartis, Scion Neurostim, Slingshot Insights, Supernus, Teva and Zosano, and has received royalties for books published by Springer. His employer receives research grants from Alder, Allergan, Amgen, ATI, Dr Reddy's, Scion Neurostim, Teva and Zosano. LDR has served as a speaker for Avanir, Pernix and Merck. AMA and AO are employees of Allergan, and AMA holds stock in the company. DCB has received grant support and honoraria from Allergan, Avanir, Amgen, Eli Lilly and Company, and Promius, and for work on the editorial board of Current Pain and Headache Reports. SDS has served as a consultant and/or advisory panel member and received honoraria from Alder BioPharmaceuticals, Allergan, Amgen, Avanir Pharmaceuticals, eNeura, ElectroCore Medical, Eli Lilly and Company, Medscape and Teva Pharmaceuticals, and grants from Amgen and Teva Pharmaceuticals. His employer has received research support from Allergan, Amgen, Cumberland Pharmaceuticals, ElectroCore Medical, Eli Lilly and Company, and Troy Healthcare.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Change in (A) PHQ-9 scores and (B) GAD-7 scores in the analysis population after treatment with onabotulinumtoxinA. *p

Figure 2

Change in (A) PHQ-9 scores from baseline and (B) the percentage of patients experiencing a ≥1 reduction in PHQ-9 severity category after treatment with onabotulinumtoxinA in patients with mild or worse depressive symptoms at baseline (PHQ-9 >5). PHQ-9, 9-Item Patient Health Questionnaire.

Figure 3

Change in (A) GAD-7 scores from baseline and (B) the percentage of patients experiencing a ≥1 reduction in GAD-7 severity category in patients with symptoms of anxiety at baseline after treatment with onabotulinumtoxinA. GAD-7, 7-Item Generalised Anxiety Disorder.

Figure 4

Mean change in (A) PHQ-9 and (B) the percentage of patients with a reduction of ≥1 severity category in PHQ-9 scores in those with depressive symptoms (PHQ-9 ≥5) at baseline, with or without a ≥25% decrease in headache days after treatment with onabotulinumtoxinA. *Significant change compared with baseline, p†Significant difference compared with non-responder group, p<0.001. PHQ-9, 9-Item Patient Health Questionnaire.

Figure 5

Mean change in (A) GAD-7 scores from baseline and (B) the percentage of patients with a reduction of ≥1 severity category in GAD-7 scores in those with clinically significant anxiety (GAD-7 ≥10) at baseline, with or without a ≥25% decrease in headache days after treatment with effect of onabotulinumtoxinA. *Significant change compared with baseline, p