Migraine Medications Compared: Triptans, CGRP Inhibitors, and OTC Options

Migraine medication genuinely splits into two entirely different jobs: stopping an attack already underway and preventing future attacks from starting in the first place at all. Confusing the two, or expecting one single medication to reasonably do both at once, is a genuinely common source of frustration for many people living with migraine. This guide compares the real options for each job specifically: triptans, the newer CGRP inhibitors, and over-the-counter choices, including what actually has solid evidence behind it.

Triptans: The Standard Acute Treatment

Migraine itself is covered in depth on our conditions page, including diagnosis and the full symptom picture; this article focuses specifically on the medication landscape once migraine is confirmed.

Triptans work by narrowing dilated blood vessels around the brain and blocking the release of pain-signaling chemicals, including CGRP, and they remain the standard prescription option for stopping a moderate to severe migraine once it starts. Several triptans exist as a class, sumatriptan, rizatriptan, eletriptan, and others, and while research comparing them finds real differences in speed and consistency between individual drugs, all of them work through the same basic mechanism.

• Sumatriptan, the original and most widely prescribed triptan; available as a tablet, nasal spray, or injection; the tablet typically starts working within 30 minutes to an hour and works best when taken early in an attack rather than waiting. Roughly a third of people who respond well still see the migraine genuinely return within 24 hours, which is why a second dose, taken at least two hours after the first and within the daily maximum, is sometimes needed

• Dihydroergotamine, an ergot alkaloid rather than a triptan, for attacks that genuinely do not respond well to a triptan alone, or that come with significant nausea limiting how well oral medication is tolerated; it works through a broader, less selective mechanism, though it carries its own distinct side-effect profile and is generally reserved for more treatment-resistant cases. It is given as a nasal spray or injection, should not be used within 24 hours of a triptan, and is not safe during pregnancy or with certain drugs that block its breakdown, such as some antibiotics and antifungals

Read More: Chronic Pain, Inflammation, Arthritis, and Migraine: Symptoms, Causes, Diagnosis, and Treatment

CGRP Inhibitors: The Newer Preventive Option

CGRP inhibitors are the first drug class developed specifically to prevent migraine, rather than borrowed from another condition the way older preventives such as propranolol and topiramate were. They block calcitonin gene-related peptide, a protein genuinely central to migraine pain, and come in two forms: monthly or quarterly injections called monoclonal antibodies, and daily or every-other-day oral tablets called gepants.

The evidence behind this class is genuinely strong. A 2023 network meta-analysis of 19 separate clinical trials found that every approved CGRP inhibitor reduced monthly migraine days compared to placebo, and the American Headache Society now recommends the entire class as first-line preventive therapy for many patients.

OTC Options for Milder Attacks

For attacks that are mild to moderate in severity, an over-the-counter option is often sufficient on its own and does not require a prescription conversation at all. Naproxen, an NSAID, works by reducing inflammation and is a reasonable first try for someone who has not yet needed a triptan.

A combination of acetaminophen, aspirin, and caffeine, sold under several OTC brand names, is a specific, well-studied formulation rather than just a marketing claim. Clinical trial evidence has found the three-ingredient combination more effective than any single ingredient alone, since the caffeine both narrows dilated blood vessels and helps the other two be absorbed faster. Using simple pain relievers such as naproxen on 15 or more days a month, or combination products like acetaminophen-aspirin-caffeine on 10 or more days a month, risks medication overuse headache, a genuine pattern worth watching for rather than a minor caveat.

Prevention: Propranolol and Topiramate

For someone having frequent or genuinely disabling attacks, preventive medication taken daily, regardless of whether a migraine happens to be present that particular day, is usually the more effective long-term strategy than only ever treating each attack as it comes along one at a time. Guidelines generally suggest considering prevention once attacks reach four or more days a month, though the real decision depends heavily on how disruptive they genuinely are day-to-day, not the raw number alone.

• Propranolol, a beta-blocker, is one of the original and still most commonly used migraine preventives, despite being developed for blood pressure originally; it is generally avoided in people with asthma or a slow heart rate

• Topiramate, an anticonvulsant, works through a different mechanism and is often chosen when beta-blockers are not a good fit, though it carries its own distinct side-effect profile, including cognitive side effects that some people find bothersome enough to switch away from it; it also raises the risk of birth defects if taken during pregnancy and can reduce the effectiveness of hormonal birth control, so anyone who could become pregnant should discuss contraception with their prescriber

Where to Start

If a triptan genuinely works but the migraine keeps coming back within a day, that is a real pattern worth naming specifically to a prescriber rather than simply assuming the medication failed outright. If daily prevention has not been discussed at all despite genuinely frequent attacks, that is worth raising directly too, since it is easy for a conversation to stay focused on acute treatment alone without ever addressing prevention specifically, even when someone has been living with frequent migraines for years already. Triptans are not recommended for people with heart disease, a prior stroke, or uncontrolled high blood pressure, so a full cardiovascular history matters before starting one. A sudden, severe headache unlike any before, or a headache with weakness, confusion, vision loss, or fever and a stiff neck, needs emergency evaluation rather than a migraine medication.

Our conditions page covers migraine alongside chronic pain, arthritis, and inflammation more broadly.

Read More: Chronic Pain, Inflammation, Arthritis, and Migraine: Symptoms, Causes, Diagnosis, and Treatment