Person seeking relief from a migraine, represented by a swirling storm of colors around their head.

Migraine Treatment: What To Do When It's Not Working

Lena Voss in Health & Wellness November 2025 • 4 min read.

"Exploring Options for Initial Non-Responders to Galcanezumab"

Migraine, impacting both episodic and chronic sufferers, significantly diminishes quality of life through medical and psychiatric comorbidities, and substantial disability. Many resort to discontinuing treatments due to perceived lack of efficacy or intolerable side effects, underscoring the need for alternative strategies.

A recent study analyzes the effectiveness of continuing Galcanezumab treatment for those who initially don't respond. The goal is to determine the likelihood of improvement with continued use, to avoid premature treatment cessation, and also to limit unnecessary exposure when improvement is unlikely.

The study focuses on patients with episodic and chronic migraine who did not achieve significant early improvement with Galcanezumab, offering insights into whether persistence pays off or when it's time to explore other options.

Understanding Initial Non-Response: Why Isn't My Migraine Treatment Working?

Person seeking relief from a migraine, represented by a swirling storm of colors around their head.

Patients who experience migraine are often in search of reliable, effective treatments to manage their symptoms and reduce the frequency and intensity of attacks. Galcanezumab, a monoclonal antibody targeting the calcitonin gene-related peptide (CGRP), represents a significant advancement in migraine prevention. However, not every patient experiences immediate relief, leading to the critical question of whether to continue treatment or explore other options.

A post hoc analysis was conducted on data from the EVOLVE-1, EVOLVE-2, and REGAIN randomized, double-blind, placebo-controlled studies. These studies included patients with episodic (N = 879) and chronic (N = 555) migraine who did not achieve 'good' early improvement (≥50% reduction in migraine headache days [MHD] for episodic and ≥30% reduction for chronic) after the first month of Galcanezumab treatment.

Modest Improvement: >30% to <50% fewer MHD for episodic and >10% to <30% fewer MHD for chronic.
Limited Improvement: >10% to ≤30% fewer MHD (episodic migraine only).
Minimal/No Improvement: ≤10% fewer MHD to ≤10% more MHD.
Worsening: >10% more MHD.

The researchers categorized patients based on their level of improvement after one month and again after two months. This categorization helped to assess whether continued treatment could still lead to a positive outcome, even in those who initially did not respond well. The results shed light on the importance of evaluating individual responses and the potential benefits of sticking with a treatment plan.

Making Informed Decisions: What's the Next Step in My Migraine Treatment?

Deciding on the best course of action when initial migraine treatments don't work requires a collaborative effort between patient and physician. Factors such as the degree of early improvement, individual circumstances, and overall treatment goals should be carefully considered. Remember, effective migraine management often involves a combination of strategies tailored to your unique needs. Don't hesitate to explore all available options and maintain open communication with your healthcare provider to achieve the best possible outcome.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1111/head.13443, Alternate LINK

Title: Analysis Of Initial Nonresponders To Galcanezumab In Patients With Episodic Or Chronic Migraine: Results From The Evolve-1, Evolve-2, And Regain Randomized, Double-Blind, Placebo-Controlled Studies

Subject: Neurology (clinical)

Journal: Headache: The Journal of Head and Face Pain

Publisher: Wiley

Authors: Russell Nichols, Erin Doty, Sara Sacco, Dustin Ruff, Eric Pearlman, Sheena K. Aurora

Published: 2018-11-21

Everything You Need To Know

What is Galcanezumab, and how does it work to treat migraines?

Galcanezumab is a monoclonal antibody medication designed to prevent migraines. It works by targeting the calcitonin gene-related peptide (CGRP), a molecule involved in the development of migraine headaches. By blocking CGRP, Galcanezumab aims to reduce the frequency and severity of migraine attacks. It's important to understand that Galcanezumab is a preventive treatment, meaning it is designed to reduce the number of migraine days over time, rather than providing immediate relief during an active migraine attack.

If Galcanezumab doesn't immediately relieve my migraine, should I stop taking it?

Not necessarily. The text highlights the importance of evaluating continued Galcanezumab treatment even if there is not immediate relief. The studies analyzed patients with episodic and chronic migraine who did not show significant improvement in the first month. The research categorizes patient improvement to assess if continued treatment is beneficial. It's recommended to consult with your healthcare provider to determine the best course of action. They will consider factors such as the degree of early improvement, individual circumstances, and overall treatment goals. Prematurely stopping the medication could mean missing out on potential benefits, while continued use might not be effective for everyone.

What level of improvement in migraine symptoms is considered a 'good' response to Galcanezumab treatment?

According to the study, a 'good' early improvement with Galcanezumab is defined differently for episodic and chronic migraine. For patients with episodic migraine, a 'good' response is considered a reduction of 50% or more in migraine headache days (MHD). For patients with chronic migraine, a 'good' response is a reduction of 30% or more in MHD.

How were patients categorized based on their response to Galcanezumab?

Patients were categorized based on the level of improvement they experienced after one month of Galcanezumab treatment and then again after two months. The categories included: Modest Improvement (>30% to <50% fewer MHD for episodic and >10% to <30% fewer MHD for chronic), Limited Improvement (>10% to ≤30% fewer MHD for episodic migraine only), Minimal/No Improvement (≤10% fewer MHD to ≤10% more MHD), and Worsening (>10% more MHD). This categorization allowed researchers to assess if continuing treatment could still lead to a positive outcome, even in those who didn't initially respond well.

What should I do if Galcanezumab isn't working for me, and what other options are there?

If Galcanezumab is not effectively managing your migraines, the next step is a collaborative discussion with your healthcare provider. Factors such as the degree of early improvement, individual circumstances, and overall treatment goals should be considered. Effective migraine management often involves a combination of strategies. This may include exploring alternative preventive medications, such as other monoclonal antibodies or different classes of drugs, or adjusting the dosage or frequency of your current treatment. Additionally, non-pharmacological approaches, such as lifestyle modifications, stress management techniques, and identifying and avoiding triggers, can also play a crucial role in managing migraines.