A Review of Current Migraine and Cluster Headache Therapies

A review of the current treatment drugs and modalities demonstrated that the established hypothesis of the CGRP panel in the therapy of migraine headaches is short on their translational efficacy. A critical look into the Full Prescribing Information Contents demonstrates a lack of information about the mechanism of action of those drug molecules. All is to convince of the short-term safety of their drugs. Where is the main potential action tissue or cell?

The impact felt by market analysis is the continuous suffering from migraine headaches and further sales erosion throughout the industry, as patients and investors try to understand the long-term effects of biosimilar entry, particularly on the innocent pediatric population. A critical review of the literature revealed that, in the past 20 years, scientists and pharmaceutical manufacturers tried to convince the world of the new biosimilar CGRP monoclonal antibodies and receptor blockers, with no significant therapeutic value of these biologics and biosimilars.

In addition, this line of drugs made no difference from Triptans or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Effective marketing of daily flourishing new biosimilars on the market—in scientific journals, conferences, television, and radio—is far from the reality of effectively preventing and aborting migraine symptoms. Not even closer to a cure. Patients and physicians are astonished by the frequent modification of migraine headache treatments by defenders of the CGRP hypothesis and their blooming monoclonal antibody products in the migraine treatment market.

CGRP-related drugs do not demonstrate any action in the neuroinflammatory process, in neutralizing TNF-α inhibition, or in neutralizing activated NF-κB anywhere in the central and peripheral nervous system. Utilization of CGRP drug lines is not suitable for the eradication and relief of migraine and cluster headaches. CGRP drugs, by in-depth analysis of their results, are unfit for the marketed scientific expectations. Reality proved that CGRP drugs are not advantageous to NSAIDs or Triptans.

NSAIDs and Their Mechanism

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), such as aspirin and ibuprofen, are routinely marketed for headache relief and belong to a class of medications known as cyclooxygenase (COX) inhibitors. These agents inhibit the activity of COX-1 and COX-2 enzymes, which are pivotal in the biosynthesis of prostaglandins—lipid compounds that mediate inflammation, pain, and fever.

• COX-1: Constitutively expressed; involved in maintaining gastrointestinal and renal function.
• COX-2: Inducible; upregulated during inflammation and contributes to pain signaling.

By inhibiting these enzymes, aspirin and ibuprofen reduce prostaglandin synthesis. This leads to short-term analgesia and anti-inflammatory effects, particularly beneficial in conditions like craniofacial neuralgia, where localized inflammation in the vascular adventitia of neurons contributes to pain manifested in the brain center.

Scientific Premise vs. Disillusionment

In the past decade, we recognized the discouraging failure of the CGRP and vasodilation hypothesis of migraine headaches and subsequent drugs of monoclonal antibodies. Basically, this hypothesis and treatment modus failed because it did not provide the relief it pretended. It is eliminating itself by not supporting its purpose. The enthusiasm of paid research scientists at universities has flattened. There are no self-criticisms or revisions in this particular hypothesis on the horizon.

The Scientific Premise vs. Disillusionment

• Many patients report minimal or inconsistent relief despite high expectations and aggressive marketing.
• Real-world data, such as those from the VYEPTI® experience, show mixed outcomes: while some patients report improved quality of life, others continue to suffer frequent, debilitating attacks.
• Adverse effects like hypertension and Raynaud’s phenomenon have further eroded trust.

Physician Frustration

• Clinicians face pressure to prescribe CGRP therapies despite limited long-term data and variable patient responses.
• The hypothesis has arguably narrowed the therapeutic lens, sidelining other mechanisms and holistic approaches.

Media and Public Outcry

• Patients increasingly voice their dissatisfaction in public forums, questioning the scientific rigor and ethical transparency of pharma-led narratives.
• The disbelief stems not only from unmet expectations but also from the perception that industry-driven science has overshadowed patient-centered care.

The community’s response to the frequent introduction of new biosimilar products is filled with skepticism and disbelief. They look beyond the megalomaniac introduction of new routes of application and observe a decrease in the results of these biosimilars. This behavior is reflected in the reduced prescription of monoclonal antibodies by neurologists and primary care providers. The market has not been uniform across America and European countries.

Economic Impact and Humanitarian Approach

One primary reason each country’s economy has been deprived of billions of dollars in the common health budget each year over the past decades is the sophisticated advertisement of speculative drugs and new biosimilars in the field of migraine headaches. We live in real-time, and it is thoroughly challenging for consumers’ economies and productivity.

Yet, we believe in humanity more than industry. Ultimately, we decided to introduce our knowledge by teaching and opening our expertise and discoveries to all headache communities—to resolve migraines and cluster headaches without extravagant financial gain.

Our De-Novo Model offers something radically different: freedom from recurrence, not just relief from pain.

A Call for Change

Let’s stop experimenting with the lives of innocent people. Did we hurt anyone? Our apologies!

CURE MIGRAINE WORLDWIDE & RESEARCH, LLC.