Cluster Headache: A Distinct Approach to Management

Cluster headache, often called “suicide headaches,” is one of the most severe and disabling primary headache disorders, yet it continues to be overshadowed by migraine in awareness, research, and clinical management.¹ Addressing this imbalance, Stephanie J Nahas, MD, MSEd, FAHS, FAAN; Professor of Neurology and Assistant Director of the Headache Medicine Fellowship at Thomas Jefferson University, discussed evidence-based strategies to improve diagnosis and care during her presentation, “Treating Cluster in a Migraine World,” at the 2025 Clusterbusters Annual US Patient Conference.

Dr Nahas co-leads the Cluster Headache and Trigeminal Autonomic Cephalalgia Clinic, the newest dedicated clinic of its kind in the US, at The Jefferson Headache Center in Philadelphia. The center, which received the 2025 Healthcare Partner Award for advancing cluster headache care, represents a model of specialized, preparedness-based treatment that acknowledges the unique nature of cluster headache as distinct from migraine.

“For too long, we have been trying to fit managing cluster headache into a migraine framework,” Dr Nahas explained. “That simply does not work. Cluster headache requires an entirely different playbook — rapid, aggressive, and individualized.”

The Invisible Burden of Cluster Headache

Cluster headache is defined by the third edition of the International Classification of Headache Disorders as a primary headache disorder characterized by severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes. Attacks may occur from once every other day to 8 times per day, and are typically accompanied by ipsilateral autonomic symptoms such as lacrimation, nasal congestion, eyelid edema, or restlessness/agitation.²

Unlike migraine, cluster headache often goes undiagnosed for years. Patients experience unpredictable cycles of excruciating pain, typically with multiple attacks per day, yet the intermittent nature of the disorder can delay care.¹

“Cluster headache does not always show itself,” Dr Nahas said. “By the time a patient seeks medical attention, the cycle might be over, and they cancel the appointment.”

Even when patients do seek care, many encounter clinicians unfamiliar with the disorder. Attacks are brief but intense, often occurring in the middle of the night, and can be mistaken for sinus or dental problems. The resulting diagnostic delay contributes to prolonged suffering, frequent fruitless emergency department visits, and a profound psychological toll. This burden is compounded by stigma and misunderstanding.¹

“Many people — even within medicine — do not grasp that cluster headache can be an emergency,” Dr Nahas noted. “If a patient with a cluster headache calls, that can be a drop-everything situation. The acuity is on par with stroke or seizure.”

This level of acuity carries even greater significance for those whose work and lived experiences intensify both risk and burden. Among them, veterans and first responders face unique neurologic, circadian, and trauma-related exposures that may heighten the impact of cluster headache.

Cluster headache requires an entirely different playbook — rapid, aggressive, and individualized.

A Hidden Crisis: Veterans and First Responders

Veterans and first responders represent 2 of the most vulnerable yet overlooked groups in the headache community. A 2024 analysis of more than 10 years of national electronic health records identified approximately 24,000 veterans with a formal diagnosis of cluster headache within the Veterans Health Administration (VHA), the nation’s largest integrated health system.³ In that cohort, the 1-year period prevalence of cluster headache ranged from 0.08% to 0.10% in women and 0.10% to 0.18% in men, translating to a measurable population burden in a system that already manages hundreds of thousands of veterans with migraine and post-traumatic headache.³

Compared with the general population, veterans with cluster headache exhibit disproportionately high rates of depression, sleep apnea, and chronic pain. Suicidal ideation and attempts are also more common, affecting about 7% of the cohort overall and nearly 10% among women within the cohort.³ These patterns may stem from shared occupational and physiologic exposures, including traumatic brain injury, blast events, circadian disruption from deployment schedules, and chronic sleep deprivation, factors also linked to post-traumatic headache and migraine in post-service populations.⁴

Although empirical data for first responders remain limited, case narratives and advocacy reports describe similar diagnostic challenges and treatment barriers, particularly around access to high-flow oxygen therapy, which remains a first-line abortive for cluster headache.⁵

The Jefferson Headache Center’s model of preparedness-based care may also serve as a framework for collaboration with VHA Headache Centers of Excellence and occupational health programs for firefighters and police, initiatives that could help improve screening, expedite oxygen access, and enhance provider education on cluster headache.

Why Cluster Needs Its Own Playbook

Although cluster headache and migraine share some overlapping treatments, their management diverges sharply. Cluster attacks escalate within minutes and demand rapid-acting, high-intensity interventions rather than the gradual escalation typical of migraine care.

“In migraine, we say do not take triptans more than twice a week,” Dr Nahas explained. “But what do you tell someone having 8 cluster attacks a day? They cannot just pick 2.”

This urgency underscores the need for alternative routes of administration and repeated dosing, including subcutaneous or intranasal formulations. Oxygen therapy, which provides near-immediate relief when delivered as 100% oxygen at 10 L/min via non-rebreather for approximately 15 minutes, is effective for cluster headache but seldom used in migraine. Many patients, however, struggle to access oxygen due to payer restrictions and logistical barriers.¹

“Cluster care is about anticipation,” Dr Nahas said. “We build a ‘pre-game plan,’ so when the cycle starts, everything is ready: oxygen, triptans, transitional steroids, and a clear taper schedule.”

Jefferson provides each patient with a written “pre-game plan,” a concise action sheet listing oxygen setup instructions, triptan dosing, and emergency contact numbers to activate as soon as a new cycle begins.⁶

The Five-Pronged Approach to Cluster Headache Care

At Jefferson, clinicians operationalize what Dr Nahas describes as a 5-pronged model for cluster management, a structured yet flexible framework developed with colleague William B Young, MD, FAHS, FAAN, FACP; Professor of Neurology and Director of the Inpatient Program at the Jefferson Headache Center, and Michael J Marmura, MD, FAHS, FAAN; Professor of Neurology and Director of the Center. The 5-pronged model accounts for:

1. Available treatments^1,6
2. Daily attack frequency^1,6
3. Duration of the cycle/bout^1,6
4. Cluster-specific comorbidities (eg, testosterone deficiency, depression)^1,6
5. Duration of the remission period^1,6

“Once we laid it out explicitly, we realized we had been practicing it intuitively all along,” Dr Nahas expressed.

Preparedness is the cornerstone. During remission, patients work with clinicians to identify early warning signs, review medication supply, and pre-authorize oxygen delivery. Those with shorter cycles may rely on corticosteroid bursts and acute therapies alone, while longer or chronic cycles require preventive agents and closer monitoring to avoid cumulative steroid exposure.^1,6

Patients are also encouraged to maintain a cluster diary, noting cycle onset, daily attack counts, and potential triggers, which help to refine treatment plans and identify patterns over time.^1,6

“Corticosteroids are great, but they are not benign,” Dr Nahas cautioned. “They can cause Cushing syndrome, hyperglycemia, even avascular necrosis. We must be judicious, especially in patients needing multiple tapers per year.”

Treatment Landscape

Managing cluster headache often requires a layered approach, combining acute, transitional, and preventive strategies simultaneously. Compared with migraine, treatment demands greater therapeutic intensity, closer monitoring, and stronger patient advocacy.¹

Preventive therapy forms the backbone of long-term management. Verapamil is a first-line agent, typically prescribed at doses of 360 mg per day or higher and sometimes exceeding 1 g per day in divided doses. Because of potential PR-interval changes, electrocardiogram monitoring is required.¹ Lithium is another effective option, but it is used less frequently due to its narrow therapeutic window and the need for regular renal, thyroid, and electrolyte monitoring.¹ Galcanezumab, administered as 300 mg monthly subcutaneous injections during active bouts, is the only US Food and Drug Administration-approved preventive treatment for episodic cluster headache, though insurance coverage often limits access.¹

Acute therapies emphasize speed and reliability. Subcutaneous sumatriptan remains a cornerstone, despite dose limits and cardiovascular risk concerns. Alternatives such as intranasal sumatriptan or zolmitriptan, dihydroergotamine, and topical agents like lidocaine or capsaicin can provide adjunctive relief. Oxygen therapy is among the safest and most effective acute options, though access remains inconsistent.¹

Transitional therapies bridge the gap between acute and preventive phases. Longer corticosteroid tapers of 2 to 3 weeks, or greater occipital nerve blocks with both anesthetic and steroid can be useful but carry risks for tissue necrosis, alopecia, and hyperpigmentation with overuse.¹

For refractory or chronic cluster, Jefferson clinicians employ advanced approaches such as neuromodulation (eg, non-invasive vagus nerve stimulation), sphenopalatine ganglion blocks, inpatient infusions, and hormone-based interventions like clomiphene or testosterone therapy when deficiencies are identified.¹

“Cluster pushes us to be creative,” Dr Nahas said. “You cannot just follow a migraine algorithm and expect success.”

Beyond Pharmacology: Whole-Person Care

At the Jefferson Cluster Headache Center, medical treatment is only one aspect of recovery. The program integrates mental-health screening, suicide-risk assessment, and counseling referrals into every patient pathway.¹

“Suicidality rises dramatically during active cluster periods,” Dr Nahas explained. “We have to address mental health as aggressively as we do pain.”

Every patient receives crisis-resource information, including the 988 Suicide and Crisis Lifeline, reinforcing that mental health support is integral, not optional, in cluster management.^1,6

The center also incorporates occupational support, disability navigation, and education. Among first responders and veterans, groups often defined by stoicism and self-sacrifice, acknowledging personal vulnerability can present a significant barrier to care. Clinicians at Jefferson employ trauma-informed communication strategies that balance medical precision with compassionate engagement.^1,6

“Education is a form of therapy,” Dr Nahas added. “When patients understand what is happening in their brain, they regain a sense of control.”

Jefferson’s Role in Shaping the Future of Cluster Care

By establishing one of the newest US clinics devoted exclusively to cluster headache, Jefferson has created a model of comprehensive, individualized care that merges science, advocacy, and empathy.

In partnership with organizations like Clusterbusters and the American Headache Society, the center ensures that patient voices inform research priorities and insurance policy reform. Clinicians also connect patients with peer support and educational materials from these organizations to extend care beyond the clinic visit.

The center also leads professional education efforts aimed at improving early recognition, reducing diagnostic delays, and ensuring rapid referral for suspected cluster headaches.

“Every person with cluster headache deserves timely, compassionate, and informed care,” Dr Nahas said. “This center is proof that we can build systems around that principle.”

With the establishment of Jefferson’s new program, cluster headache care is beginning to look less like borrowed migraine management and more like its own discipline. The model that Dr Nahas and her colleagues have built, rooted in preparedness, rapid intervention, and advocacy, illustrates how specialized centers can change the trajectory of this disorder, once defined by crisis rather than control.