Fremanezumab for Anxiety: Not a Treatment Option
Fremanezumab is not indicated for the treatment of anxiety—it is a migraine preventive medication that targets CGRP pathways and has no direct anxiolytic properties. However, if you are asking about using fremanezumab in patients who have both migraine and comorbid anxiety, the evidence strongly supports its use in this population.
Fremanezumab in Patients with Migraine and Comorbid Anxiety
Primary Indication and Mechanism
- Fremanezumab is a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide (CGRP) for migraine prevention, not anxiety treatment 1, 2.
- It is approved for preventive treatment of both episodic and chronic migraine in adults 3.
Efficacy in Patients with Psychiatric Comorbidities
Fremanezumab demonstrates robust effectiveness in migraine patients with comorbid anxiety and depression, with the added benefit of improving psychiatric symptoms as migraine burden decreases.
- In real-world studies of difficult-to-treat chronic migraine patients with psychiatric comorbidities (primarily anxiety and/or depression), fremanezumab achieved comparable response rates: 58.5% in patients with psychiatric comorbidities versus 66.6% without (p = 0.41) 4.
- Mean reduction in monthly headache days was significant in both groups: -8.9 days in patients with psychiatric comorbidities and -9.8 days without (both p < 0.001) 4.
- Notably, 43.1% of patients with baseline psychiatric comorbidities experienced de-escalation in severity or complete resolution of anxiety/depression symptoms after fremanezumab treatment 4.
Evidence in Comorbid Depression and Anxiety
- In patients with chronic migraine and moderate-to-severe depression (PHQ-9 score ≥10), fremanezumab reduced monthly headache days of at least moderate severity by -5.3 to -5.5 days versus -2.2 days with placebo (both p < 0.001) 5.
- Real-world data showed that 45.8% of patients with comorbid generalized anxiety disorder reported improvements in GAD severity after fremanezumab treatment 6.
- In the GAD subgroup, mean reduction in monthly migraine days at Month 6 was -9.5 days (66.4% reduction from baseline) 6.
Clinical Positioning for Patients with Anxiety
Recognition of anxiety as a comorbidity is crucial because it represents a risk factor for migraine chronification, but does not contraindicate fremanezumab use—in fact, it may strengthen the indication.
- Anxiety is a recognized risk factor for transformation from episodic to chronic migraine and should be identified during clinical evaluation 3.
- Approximately 50-60% of individuals with depression have comorbid anxiety disorders, with generalized anxiety being most prevalent 3.
- The presence of anxiety does not alter fremanezumab's efficacy profile and may improve as migraine burden decreases 6, 4.
Treatment Algorithm Considerations
For migraine patients with comorbid anxiety:
First-line options include beta-blockers (propranolol, metoprolol), valproate, venlafaxine, or amitriptyline—with amitriptyline potentially preferred for patients with both anxiety and sleep disturbances 3.
Second-line options include CGRP monoclonal antibodies like fremanezumab, particularly after failure of 2-3 first-line agents or when first-line agents are contraindicated 3.
Fremanezumab-specific advantages in anxious patients include:
Important Caveats
- The most common adverse events leading to discontinuation in clinical trials included anxiety (n=2) and depression (n=2), though these rates were very low 2.
- Cost remains a significant barrier, with annual treatment costs ranging from $7,071 to $22,790 compared to $67-$393 for first-line agents 3.
- Efficacy should be assessed after 3-6 months of treatment before determining success or failure 3.
- If anxiety is the primary concern requiring treatment, refer to appropriate psychiatric or psychological services for evidence-based anxiolytic interventions 3.