Headaches, sensitivity to light, nausea: Around ten percent of all people in Germany suffer from migraines. Researchers have now conducted a meta-analysis to investigate which medications are best for combating the pain attacks. In total, the studies included 17 different active ingredients and almost 90,000 participants. The result: The group of triptans works the fastest and most effectively against migraine headaches – significantly better than newer medications that dock onto the so-called CGRP receptor in the brain, for example. In addition to the triptans, the painkiller ibuprofen also proved to be effective against a flare-up of the pain. Paracetamol, on the other hand, performed the worst, barely being more effective than a placebo.
Migraine is one of the most common pain disorders worldwide, affecting more than a billion people. According to the Robert Koch Institute, in Germany almost 15 percent of women and six percent of men suffer from recurring migraine attacks. Typical symptoms are one-sided, often severe throbbing headaches, accompanied by nausea, sensitivity to light and exhaustion. In some cases, perceptual disturbances, known as auras, occur before an attack begins. A migraine attack can last for several hours, or in extreme cases for several days. During severe attacks, those affected are often no longer able to work and their quality of life suffers greatly. Whether a person suffers from migraines is partly genetic, and those affected also often show abnormalities in brain metabolism and anatomy between attacks. However, how often acute attacks occur usually depends on additional factors such as diet, stress or hormones.
17 preparations from five classes compared
But what is the best way to combat painful migraine attacks? Most sufferers still fight the pain with classic painkillers such as ibuprofen, acetylsalicylic acid or paracetamol. But there are a whole range of medications that work more specifically against migraines. Among them are the triptans, which act on the serotonin receptors in the brain and reduce both the headaches and the accompanying symptoms such as nausea and sensitivity. However, because they also constrict the blood vessels, they are only suitable to a limited extent for people with circulatory problems. This is one of the reasons why even more specific medications have been developed, the ditans, which only dock onto a certain serotonin receptor and do not constrict the veins. Also relatively new to the treatment of migraines are medications that act on another docking site involved in migraines, the CGRP receptor. These so-called gepant drugs inhibit the release of a certain peptide which, among other things, dilates the brain vessels during migraines and is involved in the development of migraine attacks.
“Given the wide range of medications available for acute migraine treatment, it is important for patients and doctors to know which is the best choice for those affected,” say William Karlsson from Copenhagen University Hospital and his colleagues. “But so far there is no agreement on which drugs from these different classes of active ingredients should be used primarily.” To create more clarity, the research team therefore carried out a so-called network meta-analysis. This evaluated 137 randomized and controlled studies with a total of 89,445 participants, which had examined the effectiveness of 17 drugs from the various classes of substances against a placebo. The comparison criteria were the reduction in pain two hours after taking the drug and the freedom from pain after 24 hours. The team also took into account the effect on concomitant symptoms and the side effects of the drugs.
Triptans are most effective
The evaluations showed that the triptans performed best in almost all criteria. “Eletriptan, rizatriptan, sumatriptan and zolmitriptan had the best efficacy profiles and were more effective than the newly marketed drugs lasmaditan, rimegepant and ubrogepant,” report Karlsson and his colleagues. The triptans helped above all to relieve acute migraine pain quickly and as effectively as possible, and were more effective than placebos, common painkillers and most newer preparations. In terms of pain relief after 24 hours, eletriptan and ibuprofen proved to be effective, as the researchers found. Paracetamol, on the other hand, is less effective: this painkiller performed only slightly better than a placebo, but also showed hardly any side effects, apart from the risk of liver damage in the event of an overdose.
Two of the newer active ingredients, however, had significantly more severe side effects: Lasmaditan frequently causes dizziness, tiredness and sensory disturbances, which is why the US Food and Drug Administration (FDA) advises against driving after taking it. Nausea was a common side effect of ubrogepant, the researchers report. “However, when it comes to side effects, it must be taken into account that symptoms such as nausea, tiredness or dizziness can also be complaints associated with the actual migraine attack, which are sometimes only noticed by those affected when the headache has improved as a result of the treatment,” says co-author Hans Christoph Diener from the University of Duisburg-Essen. With triptans, it should be noted that they should not be taken in the case of cardiovascular diseases due to their vasoconstricting effect.
In summary, the researchers conclude that triptans are likely to be the best choice for treating acute migraines in most cases. However, these active ingredients in particular have not been used in large numbers to date. “Despite their low cost and balanced effectiveness and tolerability, triptans are underused,” write Karlsson and his colleagues. In Europe, these drugs account for 3.4 to 22.5 percent of prescribed migraine medications. In Germany, according to the RKI, only around 7.3 percent of migraine sufferers take triptans. There is therefore still room for improvement in migraine therapy. “The most effective triptans should be considered the preferred acute treatment for migraines and should also be included in the WHO’s list of essential medicines,” states the research team.
Source: William Karlsson (Copenhagen University Hospital) et al., The BMJ, doi: 10.1136/bmj-2024-080107