What is the Drug of Choice for Headaches? A Pharmacological Guide

October 10, 2025 •

4 min read

Headache disorders affect nearly half of the global adult population [1.4.3]. When pain strikes, many wonder: what is the drug of choice for headaches? The answer is not a single pill, but a personalized approach based on headache type, frequency, and severity.

Quick Summary

The ideal drug for a headache depends on its type. Over-the-counter NSAIDs are effective for tension-type headaches, while prescription medications like triptans and CGRP inhibitors are designed specifically for treating and preventing migraines.

Key Points

No Single Answer: The 'drug of choice' is determined by the specific headache type, such as tension, migraine, or cluster [1.2.5].
OTC as First-Line: Over-the-counter pain relievers like ibuprofen and naproxen are the primary treatment for most tension-type headaches [1.2.2].
Migraine-Specific Drugs: Prescription triptans are a standard for stopping active migraines, while newer CGRP inhibitors offer another targeted approach [1.2.4, 1.6.1].
Acute vs. Preventive: Acute (abortive) drugs stop an ongoing headache, while preventive (prophylactic) drugs are taken regularly to reduce attack frequency [1.5.1].
Risk of Overuse: Using acute headache medication more than 10-15 days per month can lead to medication-overuse headaches (MOH) [1.7.2].
Professional Consultation is Key: A proper diagnosis from a healthcare provider is essential for creating a safe and effective, personalized treatment plan [1.2.3].

Understanding Your Headache: The First Step to Relief

Before choosing a medication, it's crucial to identify the type of headache. The three most common primary headaches are tension-type, migraine, and cluster headaches, each responding to different treatments [1.2.5].

Tension-Type Headaches: The most common form, often described as a constant ache or pressure around the head, especially at the temples or back of the head and neck [1.2.5, 1.10.4].
Migraine Headaches: A neurological condition characterized by intense, throbbing pain, often on one side of the head. Migraines can be accompanied by nausea, vomiting, and extreme sensitivity to light and sound [1.2.4].
Cluster Headaches: A rare but severe type, causing excruciating, piercing pain on one side of the head, often around the eye. They occur in cyclical patterns or clusters [1.2.5].

Over-the-Counter (OTC) Medications: The First Line of Defense

For mild to moderate tension headaches and some mild migraines, OTC medications are the standard first-line treatment [1.2.2, 1.3.1]. These are readily available and effective for occasional use.

Simple Analgesics and NSAIDs

Acetaminophen (Tylenol): A pain reliever that is a common choice, though it may have fewer anti-inflammatory properties than NSAIDs [1.2.3].
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): This class includes ibuprofen (Advil, Motrin), naproxen sodium (Aleve), and aspirin. They work by reducing inflammation and are effective for tension headaches and mild migraines [1.2.3, 1.11.2].
Combination Products: Some OTC products, like Excedrin Migraine, combine acetaminophen, aspirin, and caffeine. The caffeine can enhance the pain-relieving effects of the other ingredients [1.2.2].

Prescription Medications: Acute and Abortive Treatments

When OTC options are not sufficient, or for moderate to severe migraines, prescription medications offer more targeted and powerful relief. These are known as acute or abortive therapies, designed to stop a headache or migraine attack as it is happening [1.5.1, 1.11.3].

Triptans: The Migraine Gold Standard

Triptans are a class of drugs specifically designed to treat migraines [1.11.3]. They work by activating serotonin receptors, which constricts blood vessels in the brain and blocks pain pathways [1.2.4]. Triptans are considered a first-line treatment for moderate to severe migraines and are not typically effective for tension headaches [1.2.4, 1.6.1].

Examples: Sumatriptan (Imitrex), Rizatriptan (Maxalt), and Zolmitriptan (Zomig) [1.2.4].
Formulations: They are available as oral tablets, dissolving tablets, nasal sprays, and injections, offering rapid relief [1.2.4, 1.11.3].

CGRP Inhibitors: A Newer Frontier

Calcitonin Gene-Related Peptide (CGRP) inhibitors are a newer class of drugs for both acute treatment and prevention of migraines [1.6.1]. CGRP is a protein involved in pain transmission in the brain, and levels are higher during a migraine attack [1.6.1, 1.6.2]. These drugs work by blocking CGRP or its receptor.

Acute Treatment (Gepants): Ubrogepant (Ubrelvy) and Rimegepant (Nurtec ODT) are oral tablets that can stop a migraine attack [1.2.2].
Advantages: They have a different mechanism than triptans and can be a suitable option for patients with cardiovascular risk factors who cannot take triptans [1.6.1, 1.8.1].

Preventive (Prophylactic) Medications

For individuals suffering from frequent or chronic headaches (15 or more headache days per month), preventive therapy is essential [1.7.2]. The goal is not to treat an active headache but to reduce the frequency, severity, and duration of future attacks [1.5.1].

Beta-Blockers: Medications like propranolol are often used to prevent migraines [1.2.2, 1.9.3].
Antidepressants: Certain antidepressants, such as amitriptyline, can be effective in preventing both migraines and frequent tension headaches [1.2.2, 1.11.3].
Anti-seizure Drugs: Topiramate and valproate can help reduce migraine frequency [1.2.2].
CGRP Monoclonal Antibodies: These are newer preventive treatments administered via injection (monthly or quarterly) or infusion. Examples include Erenumab (Aimovig), Fremanezumab (Ajovy), and Galcanezumab (Emgality) [1.2.2, 1.8.1].


Drug Class	Primary Use	Type (Acute/Preventive)	Common Examples	Common Side Effects
NSAIDs	Tension Headache, Mild Migraine	Acute	Ibuprofen, Naproxen	Gastrointestinal upset, bleeding, kidney damage (with overuse) [1.2.3]
Triptans	Moderate-Severe Migraine	Acute	Sumatriptan, Rizatriptan	Tingling, dizziness, chest tightness, nausea [1.8.2, 1.8.3]
Gepants (CGRP)	Migraine	Acute & Preventive	Rimegepant, Ubrogepant	Nausea, fatigue [1.2.2, 1.11.2]
Beta-Blockers	Migraine Prevention	Preventive	Propranolol, Metoprolol	Fatigue, dizziness, low blood pressure [1.2.2]
CGRP Antibodies	Migraine Prevention	Preventive	Erenumab, Fremanezumab	Injection site reactions, constipation [1.2.2, 1.8.1]

The Danger of Medication-Overuse Headache (MOH)

A critical consideration is the risk of medication-overuse headache (MOH), also known as rebound headache [1.7.4]. Regularly using acute headache medications for more than 10-15 days per month can ironically lead to more frequent and persistent headaches [1.7.2, 1.9.2]. It's crucial to limit the use of acute treatments and speak with a doctor if you find yourself needing them frequently [1.3.4, 1.7.3].

Conclusion: Personalized Treatment is Essential

There is no single "drug of choice for headaches." The optimal treatment is highly individualized. It depends on a proper diagnosis of the headache type, its frequency, and severity, as well as the patient's overall health and medical history [1.2.3, 1.3.3]. Over-the-counter NSAIDs are a great starting point for tension-type headaches, while prescription medications like triptans and CGRP inhibitors provide powerful, specific relief for migraines. For those with chronic headaches, a preventive strategy is key to long-term management. Always consult a healthcare professional to develop a safe and effective treatment plan tailored to your needs.

For more information on headache disorders, you can visit the National Institute of Neurological Disorders and Stroke.

Frequently Asked Questions

The most common and effective drugs for tension headaches are over-the-counter (OTC) nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Advil) and naproxen (Aleve) [1.2.3, 1.2.5].

Triptans are a class of prescription drugs used to treat active migraines. They work by activating serotonin receptors, which helps constrict blood vessels in the brain and block pain signals [1.2.4].

CGRP inhibitors are not necessarily 'better,' but they work differently and have different side effect profiles. They are a good alternative for patients who cannot take triptans due to cardiovascular risks or who do not respond well to them [1.6.1, 1.8.1].

Using acute pain relief medication for 10 or more days a month for over three months puts you at risk for developing medication-overuse headache (MOH), a condition where the medication itself causes more headaches [1.7.2, 1.7.4].

Abortive (or acute) medications, like triptans or ibuprofen, are taken during a headache to stop the symptoms. Preventive medications, like propranolol or CGRP antibodies, are taken regularly to reduce the frequency and severity of future headaches [1.5.1, 1.5.4].

While some OTC medications like Excedrin Migraine or ibuprofen can help with mild migraines, migraine-specific treatments like triptans and CGRP inhibitors require a prescription from a healthcare provider [1.3.1, 1.11.3].

Non-drug approaches can also be effective. These include resting in a quiet, dark room, applying a cold pack to your forehead, staying hydrated, and practicing relaxation techniques. For prevention, regular exercise and identifying triggers are helpful [1.11.4].