What is the recommended dosage for Excedrin Migraine. How does the dosage differ for adults and children. What factors should be considered when determining the proper dosage. What are the potential risks of exceeding the recommended dosage. When might it be safe to take more than the recommended amount.

Understanding Excedrin Migraine: Composition and Recommended Dosage

Excedrin Migraine is a popular over-the-counter medication used to alleviate migraine symptoms. Its active ingredients include acetaminophen (250 mg), aspirin (250 mg), and caffeine (65 mg). These components work synergistically to reduce pain, inflammation, and enhance blood flow to the brain.

What is the recommended dosage for adults? For individuals 18 years and older, the standard recommendation is two tablets every six hours, with a maximum of six tablets in 24 hours. It’s crucial to adhere to these guidelines to ensure both efficacy and safety.

How does the dosage differ for children? Children between 12 and 17 years old should take one tablet every six hours, not exceeding four tablets in 24 hours. It’s important to note that Excedrin Migraine is not recommended for children under 12 years of age without medical supervision.

Factors Influencing Excedrin Migraine Dosage

Several factors can influence the appropriate dosage of Excedrin Migraine for an individual. These include:

• Age and body weight
• Severity and frequency of migraines
• Individual tolerance to the medication
• Presence of other medical conditions
• Concurrent use of other medications

How do these factors impact dosage? For instance, individuals with a lower body weight or those particularly sensitive to medications may require a lower dose. Conversely, those with more severe or frequent migraines might need the maximum recommended dose for effective relief.

Potential Risks of Exceeding Recommended Dosage

While Excedrin Migraine can be highly effective when used as directed, exceeding the recommended dosage can lead to serious health risks. What are the potential consequences of taking too much Excedrin Migraine?

• Liver damage due to excessive acetaminophen
• Stomach ulcers or bleeding from high doses of aspirin
• Increased risk of cardiovascular events
• Caffeine-related side effects such as insomnia, anxiety, and rapid heartbeat
• Rebound headaches from overuse

How can these risks be minimized? By strictly adhering to the recommended dosage and consulting a healthcare professional before increasing intake or using the medication for extended periods.

When to Consider Increasing Excedrin Migraine Dosage

In some cases, the standard recommended dosage may not provide sufficient relief. When might it be appropriate to consider increasing the dosage? This decision should never be made without consulting a healthcare professional, but some situations where it might be considered include:

• Persistent, severe migraines unresponsive to standard dosing
• Individuals with a higher body mass who may metabolize the medication more quickly
• Cases where the benefits of increased dosage outweigh potential risks, as determined by a doctor

What steps should be taken before increasing the dosage? Always consult with a healthcare provider who can assess your individual situation, consider potential drug interactions, and monitor for adverse effects.

Alternative Approaches to Migraine Management

While Excedrin Migraine can be an effective treatment, it’s not the only option for managing migraines. What are some alternative approaches that can complement or potentially replace medication?

• Lifestyle modifications (regular sleep schedule, stress management, diet changes)
• Trigger avoidance (identifying and avoiding personal migraine triggers)
• Non-pharmacological therapies (acupuncture, biofeedback, cognitive behavioral therapy)
• Preventive medications (prescribed by a healthcare provider for frequent migraines)
• Natural supplements (magnesium, riboflavin, CoQ10 – under medical supervision)

How can these alternatives be incorporated into a migraine management plan? Working with a healthcare provider to develop a comprehensive strategy that may include a combination of medication and alternative approaches can often yield the best results.

Recognizing and Managing Excedrin Migraine Side Effects

Like all medications, Excedrin Migraine can cause side effects in some individuals. What are the most common side effects to be aware of?

• Stomach upset or nausea
• Heartburn
• Nervousness or restlessness (due to caffeine)
• Sleep disturbances
• Ringing in the ears (with long-term use)

How can these side effects be managed? For mild side effects, taking the medication with food or reducing the dosage may help. However, if side effects persist or worsen, it’s crucial to consult a healthcare provider.

Serious Side Effects Requiring Immediate Attention

While rare, some side effects of Excedrin Migraine require immediate medical attention. These include:

• Signs of allergic reaction (rash, itching, swelling, severe dizziness)
• Black, tarry stools or vomit that looks like coffee grounds (signs of gastrointestinal bleeding)
• Unusual bruising or bleeding
• Persistent headache or migraine that doesn’t respond to medication
• Changes in vision or hearing

What should you do if you experience these symptoms? Seek immediate medical attention and discontinue use of the medication until you’ve been evaluated by a healthcare professional.

Long-Term Use of Excedrin Migraine: Benefits and Risks

For individuals with chronic or frequent migraines, long-term use of Excedrin Migraine may be tempting. However, it’s important to understand both the potential benefits and risks associated with prolonged use.

Potential Benefits of Long-Term Use

• Consistent pain relief for chronic migraine sufferers
• Improved quality of life and daily functioning
• Reduced reliance on prescription medications

Risks Associated with Long-Term Use

• Increased risk of medication overuse headaches
• Potential for liver damage due to long-term acetaminophen use
• Increased risk of gastrointestinal issues from aspirin
• Potential for caffeine dependence

How can the risks of long-term use be mitigated? Regular check-ins with a healthcare provider, periodic breaks from the medication, and exploring alternative or preventive treatments can help balance the benefits and risks of long-term Excedrin Migraine use.

Interactions of Excedrin Migraine with Other Medications and Substances

Understanding potential interactions between Excedrin Migraine and other medications or substances is crucial for safe use. What are some common interactions to be aware of?

• Blood thinners (increased risk of bleeding)
• Other NSAIDs (increased risk of gastrointestinal side effects)
• Certain antidepressants (increased risk of bleeding)
• Alcohol (increased risk of liver damage and gastrointestinal bleeding)
• Caffeine-containing products (potential for caffeine overdose)

How can you ensure safe use of Excedrin Migraine with other medications? Always inform your healthcare provider about all medications, supplements, and substances you’re using. They can advise on potential interactions and adjust your treatment plan accordingly.

Special Considerations for Certain Medical Conditions

Individuals with certain medical conditions may need to exercise extra caution when using Excedrin Migraine. These conditions include:

• Liver disease
• Kidney disease
• Stomach ulcers or a history of gastrointestinal bleeding
• High blood pressure
• Heart disease
• Asthma

What should individuals with these conditions do before taking Excedrin Migraine? Consult with a healthcare provider to determine if the medication is safe for them and if any dosage adjustments are necessary.

Proper Storage and Disposal of Excedrin Migraine

Proper storage and disposal of Excedrin Migraine are important for maintaining its effectiveness and preventing accidental ingestion. How should Excedrin Migraine be stored?

• Keep in a cool, dry place away from direct sunlight
• Store at room temperature (between 20-25°C or 68-77°F)
• Keep out of reach of children and pets
• Store in its original container with the lid tightly closed

What is the best way to dispose of expired or unused Excedrin Migraine? The FDA recommends mixing the medication with an unpalatable substance like used coffee grounds or cat litter, sealing it in a plastic bag, and throwing it in the household trash. Alternatively, many pharmacies offer medication take-back programs for safe disposal.

Importance of Checking Expiration Dates

Why is it crucial to check the expiration date of Excedrin Migraine? Expired medication may not only be less effective but could also be potentially harmful. The chemical composition of the drug can change over time, leading to unexpected side effects or reduced efficacy.

How often should you check the expiration date? It’s a good practice to check the expiration date each time you use the medication. If you find expired Excedrin Migraine in your medicine cabinet, dispose of it properly and replace it with a new package if needed.

Educating Others About Safe Excedrin Migraine Use

Promoting safe use of Excedrin Migraine extends beyond personal use to educating friends, family, and community members. Why is this important? Proper education can prevent misuse, reduce the risk of side effects, and ensure that those suffering from migraines get the most benefit from the medication.

What are some key points to include when educating others about Excedrin Migraine?

• The importance of following recommended dosages
• Potential risks of exceeding the recommended dose
• The need to consult a healthcare provider before long-term use
• Awareness of potential side effects and when to seek medical attention
• The importance of considering alternative and complementary migraine management strategies

How can this information be effectively communicated? Consider sharing reliable resources, such as FDA guidelines or information from reputable medical websites. Encourage open discussions about medication use and promote a culture of responsible self-medication.

Recognizing Signs of Medication Overuse

An important aspect of education is helping others recognize signs of medication overuse. What are some indicators that someone might be overusing Excedrin Migraine?

• Taking the medication more frequently than recommended
• Experiencing headaches that occur more often or become more severe
• Needing to take increasing amounts of the medication for relief
• Feeling anxious or restless when the medication isn’t available
• Experiencing withdrawal symptoms when trying to stop or reduce use

What should someone do if they suspect medication overuse? Encourage them to speak with a healthcare provider who can assess their situation and provide guidance on safely reducing medication use and exploring alternative treatments.

How Many Excedrin Migraine Can I Take? Exploring the Recommended Dosage

Introduction

Excedrin Migraine is an over-the-counter medication commonly used to relieve the symptoms of migraine headaches. It contains a combination of acetaminophen, aspirin, and caffeine, which all work together to reduce pain and inflammation, as well as to help improve blood flow to the brain. As with any medication, it’s important to understand the recommended dosage in order to ensure maximum benefit and safety.

Exploring the Recommended Dosage of Excedrin Migraine for Maximum Benefit

When it comes to taking Excedrin Migraine, it’s important to follow the recommended dosage for maximum benefit. The recommended dose for adults is two tablets every four hours, not to exceed 8 tablets in 24 hours. For children 12 years and older, the recommended dose is one tablet every four hours, not to exceed 4 tablets in 24 hours. It’s important to note that these dosages are only guidelines and should be adjusted according to your individual needs.

Benefits of Following the Recommended Dosage

By following the recommended dosage of Excedrin Migraine, you can get the most out of this medication. Taking too much or too little of the medication can lead to ineffective results, or even adverse effects. Additionally, taking too much of this medication can increase your risk of side effects, such as nausea, vomiting, stomach pain, and liver damage.

How Many Excedrin Migraine Should I Take for Headache Relief?

The amount of Excedrin Migraine you should take depends on several factors, including the type and severity of your headache. It’s important to understand the different types of headaches and their severity in order to determine the proper dosage for your individual needs.

Factors to Consider When Determining the Proper Dosage

Factors to Consider When Determining the Proper Dosage

When determining the proper dosage of Excedrin Migraine for headache relief, there are several factors to consider. Some of these include the type of headache (migraine, tension, cluster, etc.), the severity of the headache, any other medications you may be taking, and any underlying medical conditions you may have. It’s important to talk to your doctor before taking Excedrin Migraine to make sure it’s safe for you.

Understanding the Different Types of Headaches and Their Severity

Understanding the Different Types of Headaches and Their Severity

Headaches can range from mild to severe in intensity. The most common types of headaches are tension headaches, migraines, and cluster headaches. Tension headaches are usually caused by stress or muscle tension and can range from mild to moderate in intensity. Migraines are often accompanied by nausea, vomiting, and sensitivity to light and sound and can be extremely painful. Cluster headaches are intense headaches that occur in clusters and can last anywhere from 15 minutes to three hours.

Understanding the Benefits and Risks of Taking Excedrin Migraine

Understanding the Benefits and Risks of Taking Excedrin Migraine

Excedrin Migraine can be an effective treatment for headaches, but it’s important to understand the potential benefits and risks associated with taking it. The main benefit of taking Excedrin Migraine is that it can provide fast and effective relief from headaches. However, it can also cause side effects, such as nausea, vomiting, stomach pain, and liver damage. Additionally, it can interact with certain medications, so it’s important to talk to your doctor before taking it.

What to Know Before Taking Excedrin Migraine for Headaches

Before taking Excedrin Migraine for headaches, there are several precautionary measures you should take. First, it’s important to read the label carefully and follow the instructions for use. You should also talk to your doctor if you have any underlying medical conditions, such as high blood pressure, kidney disease, or liver disease. Additionally, you should avoid taking Excedrin Migraine if you are pregnant or breastfeeding.

When Is It Safe to Take More Than the Recommended Amount of Excedrin Migraine?

It’s important to always follow the recommended dosage of Excedrin Migraine for maximum benefit and safety. However, there may be times when it’s appropriate to increase the dosage. If you find that the recommended dosage isn’t providing enough relief, you should talk to your doctor before increasing the dosage. Your doctor can advise you on the best course of action.

How to Increase the Dosage Safely

How to Increase the Dosage Safely

If you and your doctor decide that it’s safe to increase the dosage of Excedrin Migraine, it’s important to do so gradually and cautiously. You should start by increasing the dosage by one tablet every four hours, not to exceed 8 tablets in 24 hours for adults, or 4 tablets in 24 hours for children 12 and older. It’s also important to keep track of how much you’re taking and not to exceed the maximum recommended dosage.

Tips for Managing Headaches Without Exceeding the Recommended Dose of Excedrin Migraine

In addition to taking Excedrin Migraine for headache relief, there are other non-drug treatment options that can be effective. These include getting plenty of rest, avoiding triggers such as bright lights or loud noises, drinking plenty of fluids, and practicing relaxation techniques. There are also natural remedies that can help relieve headache symptoms, such as peppermint oil, ginger, and magnesium.

Conclusion

Excedrin Migraine can be an effective treatment for headaches, but it’s important to understand the recommended dosage in order to get the most benefit and safety from this medication. It’s also important to understand the different types of headaches and their severity in order to determine the proper dosage for your individual needs. Additionally, there are other non-drug treatment options and natural remedies that can help manage headaches without exceeding the recommended dose of Excedrin Migraine.

Remember, it’s always best to talk to your doctor before taking any medication. They can help you determine the best course of action for your individual needs. By understanding the recommended dosage and potential risks of taking Excedrin Migraine, you can get the most out of this medication and safely manage your headaches.

(Note: Is this article not meeting your expectations? Do you have knowledge or insights to share? Unlock new opportunities and expand your reach by joining our authors team. Click Registration to join us and share your expertise with our readers.)

Can Stopping Excedrin Suddenly Cause A Severe Headache?

Excedrin is one of those trusted brands that has been around for decades. According to the current manufacturer (Novartis), Excedrin Extra Strength was the first “multi-ingredient headache treatment product on the market.” It was introduced in 1960. Could stopping Excedrin suddenly lead to caffeine withdrawal headaches? One reader shared just such a situation.

There are now four Excedrin products on the market, so we need to distinguish between them. It’s easy to get confused.

• Excedrin Extra Strength
• Excedrin PM Headache
• Excedrin Migraine
• Excedrin Tension Headache

We are totally fascinated by the marketing “genius” behind Excedrin products. A standard dose of Excedrin Extra Strength (2 tablets) contains 500 mg of acetaminophen, 500 mg of aspirin and 130 mg of caffeine. An 8 oz cup of coffee has 95 mg of caffeine (according to the US. Department of Agriculture).

You might imagine that Excedrin Migraine might have some other ingredients to distinguish itself from Excedrin Extra Strength. Nope! It has the identical ingredients: acetaminophen, aspirin and caffeine in the same exact dose. The dosage instructions do vary, however. The makers of Excedrin Migraine warn people “do not take more than 2 caplets in 24 hours unless directed by a doctor.” That is one fourth the maximum dose of Excedrin Extra Strength. We wonder how many migraine sufferers read and understand that instruction.

What is the Excedrin Dosage Recommendation?

The directions on the label of Extra Strength Excedrin say:

“adults and children 12 years and over: take 2 caplets every 6 hours; not more than 8 caplets in 24 hours. ”

Someone who takes the maximum dose would be getting 2,000 mg of acetaminophen, 2,000 mg of aspirin and 520 mg of caffeine. That would be the equivalent of about 5 cups of coffee in a day. Here is a question we received from a person who discovered the caffeine in Excedrin posed a problem when stopping the drug:

Q. Excedrin contains caffeine. Discontinuing Excedrin gave me a horrible caffeine-withdrawal headache. I had to cut down on the Excedrin dose gradually to be able to stop.

A. Rebound headaches can occur when people overuse their pain relievers. Experts suggest that if someone is relying on an analgesic more than 12 days a month, that is a red flag for problems. Cutting back, however, can be challenging and will likely require supervision by a headache specialist.

Caffeine can boost the pain-relieving power of aspirin or acetaminophen (Cochrane Database of Systematic Reviews, Dec. 11, 2014).  Stopping caffeine suddenly, however, can also lead to a rebound headache. An article in the journal Drug and Alcohol Dependence (Aug 1, 2012) points out that:

“Habitual caffeine consumers who abstain from caffeine experience withdrawal symptoms such as headache, fatigue, difficulty concentrating, mood disturbances, and flu-alike symptoms…

“Caffeine is the most widely used mood altering drug in the world. In the United States, 87% of children and adults regularly consume caffeine, with adult caffeine consumers ingesting approximately 280 mg per day on average…

“Caffeine withdrawal symptoms typically emerge after 12-24 h of caffeine abstinence, peak in the first day or two, and last from 2 to 9 days. Caffeine withdrawal can impair normal functioning (e.g., incapacitating headache, missing work) and it has been suggested that fatigue and performance decrements resulting from acute caffeine abstinence may have important implications for safety (e.g. , sleepiness while driving) and academic achievement.”

Stopping Excedrin Suddenly: Rebound Headaches?

Many people swear by Extra Strength Excedrin. When it became unavailable a few years ago because of quality issues, some people became quite desperate. The cost went up dramatically on the web. According to ABC news, the price jumped substantially with people paying “ridiculous prices on the black market.”

A headache sufferer who takes the maximum daily dose for several weeks might well experience a painful caffeine withdrawal headache after stopping Excedrin Extra Strength suddenly. You can appreciate the temptation to restart the medication to end the headache or other caffeine withdrawal symptoms such as fatigue and difficulty concentrating. Because caffeine withdrawal headaches can last for several days, this seems to us like a potential vicious cycle.

We Love Coffee:

Please do not get us wrong. We are coffee lovers. That little caffeine jolt after breakfast gets me going. But I try to keep my intake under 3 cups a day. What worries us about a headache remedy that contains caffeine is that some people may end up like the person who wrote to us. After stopping Excedrin, they might experience a caffeine-withdrawal headache.

Another Excedrin Product: Excedrin Tension Headache:

Excedrin Tension Headache is the newest pain reliever in the Excedrin lineup. It was introduced in 2003. Each caplet contains 500 mg of acetaminophen and 65 mg of caffeine. The recommended dose is:

“adults and children 12 years and over: take 2 caplets every 6 hours; not more than 6 caplets in 24 hours.”

That means someone who takes the maximum dose could be getting 3,000 mg of acetaminophen daily along with 390 mg of caffeine or about the equivalent of about 4 cups of coffee. We leave it to you to ponder the wisdom of that much caffeine on a regular basis for someone suffering tension headaches.

Learning More About Headaches:

If you would like to learn more about the dos and don’t of headache treatment we highly recommend a recent one-hour interview (Show # 1055) we did with Jennifer S. Kriegler, MD, titled “What are the Best Treatments for Headaches?”

Dr. Kriegler is director of the Headache Medicine Fellowship at the Cleveland Clinic. She is part of the Center for Neurological Restoration and the Headache Section of the Neurological Institute in the Department of Neurology of the Cleveland Clinic. The MP3 download is free, but only for another week.

Share your own thoughts about headache remedies in the comment section below.

Excedrin for migraine and pain of various origins

Contents

• 1 Analgesic effect
• 2 When and how to take Excedrin
• 3 Limitations when using Excedrin
• 4 Undesirable effects of the drug 90 006

Headache, arthralgia, myalgia interferes with daily activities deeds, disrupts sleep. Particularly painful is the pain caused by a migraine attack. Excedrin is included in one of the groups of drugs that can save a person from suffering from migraines.

Analgesic effect

Excedrin is one of the modern combined drugs for the relief of pain of various origins. What makes the pills have their positive effect on migraine and other diseases accompanied by pain and inflammation?

Excedrin contains three components: acetylsalicylic acid, paracetamol, caffeine. Such ingredients are found in a number of drugs. Despite this, Excedrin is preferred by a large number of people suffering from headache and toothache, myalgia, arthralgia and migraine. This is due to a well-chosen dose of active ingredients, their high speed of achieving the effect.

Acetylsalicylic acid included in the preparation at a dose of 250 mg improves the rheological properties of blood, prevents thrombosis. This improves microcirculation in the focus of inflammation. In addition, acetylsalicylic acid reduces inflammation, temperature and has an analgesic effect. 5-15 minutes after application, this component begins to act.

Paracetamol at a dose of 250 mg, which is part of the drug, helps to reduce the sensation of pain, has an antipyretic effect. The anti-inflammatory effect of paracetamol is practically not manifested. This component of Excedrin comes from the gastrointestinal tract into the systemic circulation half an hour after application.

Another component of Excedrin – caffeine in a dose of 65 mg relieves spasm of cerebral vessels and skeletal muscles, excitatory effect on the respiratory center. Thanks to caffeine, the drug improves mental and physical performance, does not cause drowsiness. Caffeine in a small dose does not have a tonic effect on the central nervous system and normalizes the natural vascular tone of the brain.

After application, Excedrin begins to act after 15-30 minutes, and after 45 minutes a noticeable effect is observed. This circumstance allows you to quickly get rid of the pain caused by migraine, arthritis, osteochondrosis, myalgia. The drug has its effect for 4 hours.

When and how to take Excedrin

Excedrin can be used successfully against mild to moderate pain. Basically, the drug is used to eliminate headache, toothache, neuralgia, myalgia, arthralgia and migraine. The medicine helps to cope with pain during menstruation, and is also used against the temperature that occurs against the background of certain infectious diseases.

Excedrin tablets, like other NSAIDs, have been used with some success in the treatment of migraine. However, the drug in some situations may be ineffective. This is due to the mechanism of migraine development and the time during which the drug was used.

According to one theory, migraine pain occurs due to the release of significant amounts of serotonin and vasoconstriction of the brain. When increasing pain bothers a person for several hours, it is more appropriate to use drugs from the triptan group. The mechanism of their action allows you to block the effect of serotonin on the vessels.

The drug must be taken orally after meals with half a glass of liquid. At the same time, the drug dissolves faster and is absorbed into the blood. Usually take 1 tablet every 4 hours. When it is necessary to take a medicine against a migraine attack, then two tablets are used at once. It is advisable to take the drug against migraine immediately, as soon as a person begins to feel an increase in pain.

Doubling the dose of the drug during an increase in a migraine attack contributes to the rapid development of the effect. However, you should not take the drug more than two tablets for migraine. Even if pain relief is not observed, it is not advisable to reapply the remedy. This can only aggravate the patient’s condition.

Restrictions when using Excedrin

The doses of the active components of Excedrin are selected in such a way as to minimize the negative effect of the active substances on the body. Despite this, side effects may occur. There are also contraindications when using Excedrin.

It should also be known that Excedrin, despite its relative safety, is not recommended to be taken more than 5 days in a row. If the drug is used against migraine, but the headache recurs, then it is not safe to use the medicine for more than three days in a row.

Excedrin should not be used in the presence of individual intolerance (allergy) to any of the substances that make up the drug. Tablets are not used for erosions on the walls of the gastrointestinal tract. It is not recommended to use the drug for bronchial asthma, since the drug contains non-steroidal anti-inflammatory drugs (paracetamol and acetylsalicylic acid).

Due to the fact that Excedrin tablets contain acetylsalicylic acid, the drug should not be used in conditions where blood clotting is impaired or surgical interventions are performed. With hemophilia, bleeding, hemorrhagic diathesis, the drug is not used.

Do not use Excedrin in women during pregnancy and lactation and in children under 15 years of age. Severe renal failure, glaucoma, coronary heart disease are also classified as conditions where the drug is not allowed to be used against pain.

Undesirable effects of the drug

The manifestation of undesirable side effects of Excedrin is associated with the drugs that make up its composition. If the drug is taken rarely, not exceeding the prescribed doses, negative effects usually do not appear.

Excedrin tablets may cause the following adverse effects when used:

• pain in the stomach;
• nausea or vomiting;
• allergy;
• bronchospasm;
• increased heart rate;
• increased blood pressure.

When tablets are used frequently, a negative effect on the kidneys, liver, deterioration of vision and hearing, the appearance of tinnitus, a tendency to bleeding is not excluded. The dosage should be carefully selected, as this may aggravate the patient’s condition.

If new symptoms appear during the use of the drug, the pain does not go away, and the general condition worsens, you should immediately seek help from a medical institution. Such a condition may indicate individual intolerance to the drug, its incorrect use or overdose.

You should know that the independent use of Excedrin in migraine is possible with full confidence in the diagnosis. Long-term regular use of the drug is unacceptable. It is necessary to periodically conduct a medical examination and apply means that prevent migraine attacks.

Related Articles Recommended:

Migraine Treatment: Prescription or Over the Counter | #06/15

Migraine is a widespread neurological disease with a complex pathophysiological mechanism that manifests itself as recurrent attacks of throbbing unilateral headache that can be severe and accompanied by associated symptoms such as nausea, photophobia and phonophobia. In a third of patients, the development of headache is preceded by transient neurological symptoms, which are most often visual, but may also affect other senses, as well as speech (migraine with aura [1]). Migraine is extremely common and is a very “expensive” disease. Thus, in the European population, it occurs in 17% of women and 8% of men [2], while the cost of migraine in Europe reaches 18 billion dollars a year [3]. At the same time, according to the World Health Organization (WHO), migraine is one of the twenty diseases that most often lead to disability [4].

For decades, the majority of headache patients have used over-the-counter analgesics, including acetaminophen (paracetamol), acetylsalicylic acid, other non-steroidal anti-inflammatory drugs (NSAIDs), and fixed combinations such as acetylsalicylic acid (ASA) + acetaminophen (AAF) + caffeine (K) [5]. It is known that more than 90% of patients who used over-the-counter combination drugs used them specifically for the treatment of headache [6]. In all the years that prescription and over-the-counter drugs have been used to treat migraines, there have been no studies that directly compare the two drug categories. Perhaps this was due to the fact that prescription drugs are a priori considered to be more effective [7]. Recently, however, more and more data have appeared, both confirming the effectiveness of over-the-counter drugs in the treatment of migraine attacks, and substantiating their use in terms of the pathogenesis of the disease.

The role of inflammation in the pathogenesis of migraine headache

It is believed that the development of migraine headache is associated with activation and sensitization (decrease in the excitability threshold) of the trigeminocervical system [8–11]. Due to the fact that her participation makes it possible to justify the appointment of a number of drugs used in the treatment of an attack, it seems interesting to make a small digression and dwell on it in a little more detail.

According to modern concepts, the development of migraine headache is associated with the activation and sensitization of afferent sensory fibers of the trigeminal nerve that innervate head tissues, including the meninges and their large blood vessels [9-eleven]. To date, there is no clear idea of ​​what exactly is the source of nociceptive impulses. These can be soft or hard membranes of the brain, as well as periarterial sensory fibers. It cannot be ruled out that each of these components contributes to the formation of the pain syndrome [10].

Based on a large amount of indirect evidence obtained both in preclinical and clinical studies, sterile inflammation of the meninges is considered as a key mechanism that may underlie the long-term activation and sensitization of perivascular meningeal afferent fibers during a migraine attack [10, 12, 13]. Such indirect data are an increase in the concentration of inflammatory mediators in the venous blood of the cranial veins during a migraine attack, as well as the effectiveness of non-steroidal anti-inflammatory drugs in the treatment of migraine attacks in most patients [12, 13]. In animal studies, activation of meningeal nociceptors in vivo leads to the release of vasoactive pro-inflammatory peptides such as calcitonin-binding peptide (CGBP) and substance P from peripheral nerve endings. These peptides induce vasodilation of meningeal blood vessels (predominantly due to CGSP), outflow of plasma from vessels, and local activation of dural mast cells (DMCs) with subsequent release of cytokines and other inflammatory mediators. In fact, we are talking about the development of neurogenic inflammation in the DM [11–13]. Degranulation of DM mast cells can lead to prolonged activation and sensitization of DM nociceptors (data obtained on rats), as well as cephalic tactile hypersensitivity [14]. Chemical inflammation of the dura mater in awake animals leads to the development of cutaneous allodynia in the facial area and in the area of ​​the hind legs [15], while the chronology of the development of these symptoms is similar to that in patients with migraine [16]. In addition, the pharmacology of allodynia induced by an “inflammatory cocktail” (an acidic mixture of potassium, prostaglandins, serotonin, bradykinin, and histamine that stimulates and sensitizes pain receptors, causing hyperalgesia) in animals allows for parallels with the clinical pharmacology of migraine pain [15] . The introduction of glycerol trinitrate, which can provoke a delayed migraine attack in patients (but not in healthy people!) that is almost indistinguishable from a spontaneous attack, causes the development of delayed inflammation in the dura mater of the rat [17].

However, the endogenous processes that cause the development of meningeal inflammation and peripheral sensitization during a spontaneous migraine attack remain unclear. Many researchers believe that neurogenic inflammation is the very endogenous inflammatory process that maintains the activation and causes sensitization of meningeal nociceptors during a migraine attack. The hypothesis of neurogenic inflammation is also supported by the fact that headache-inducing substances, such as ethanol and umbellulone (a volatile substance found in California laurel), activate peptidergic meningeal trigeminal afferent fibers (using various receptors: TRPV1 and TRPA1), which leads to the release of CGSP and the development of a neurogenic inflammatory response in the dura mater of experimental animals [18, 19].

An interesting fact: it is known that in a significant number of patients with migraine, an increase in headache occurs under the influence of light (photophobia). Relatively recently, the neuronal mechanism of this phenomenon was studied [20]. Neurons of the posterior thalamus innervating the DM receive monosynaptic projections from retinal ganglion cells (mainly internal photosensitive cells not involved in imaging), while light increases the activity of neurons innervating the DM. The hypothesis that a non-imaging pathway from the retina is involved in the development of photophobia is also supported by the fact that headache aggravation by light persists in blinded migraine patients who perceive light despite severe degeneration of rod photoreceptors and cones [20].

Thus, the modern theory of the development of a migraine attack suggests that the effectiveness of NSAIDs in such patients is associated with their effect on one of the key links in the pathogenetic process leading to the development of headache, namely, a sterile inflammatory process in the meninges of the brain.

“OTC” seizure therapy

Currently, a large number of large randomized placebo-controlled trials have been published on the treatment of migraine attacks. In most of these studies, the following criteria were used as criteria for successful treatment of a migraine attack [21]:

1) relief of pain after 2 hours;
2) decrease in intensity of headache from severe or moderate to mild or no headache after 2 hours;
3) the effectiveness of therapy is maintained in two cases out of three;
4) no headache recurrence and no need to take the drug within 24 hours of successful treatment.

Analgesics

Analgesics are the drugs of first choice for the treatment of mild to moderate migraine. Efficacy in the treatment of migraine has been confirmed in at least one placebo-controlled study for the following drugs: acetylsalicylic acid up to 1000 mg, ibuprofen 200-800 mg, diclofenac 50-100 mg, phenazone 100 mg, metamizole 1000 mg, tolfenamic acid 200 mg and paracetamol 1000 mg. Selective cyclooxygenase-2 (COX-2) inhibitors have also been studied in patients with migraine and have been shown to be effective. Analgesics with proven efficacy are presented in Table. 1. In order to avoid the development of abuse headache, simple analgesics should not be taken more than 15 days per month, and combined analgesics should not be taken more than 10 days per month [22].

What is a “recommendation level”? How is it evaluated? What does “A” mean? The concept itself came to us from evidence-based medicine and is derived from the level of evidence, which, in turn, is nothing more than a hierarchy of probably the best evidence indicating the effectiveness and safety of a particular drug (treatment method, medical device, etc.). . P.). Its meaning is to make it as easy as possible for the doctor (researcher, patient) to search for the probably best evidence of the effectiveness of the ongoing or planned therapy. At the same time, you need to be aware that levels of evidence are in no way a substitute for systematic reviews, do not judge the quality of the available evidence, do not constitute a recommendation, and do not say anything about whether you phrase the question correctly. For example, if a patient is diagnosed with influenza instead of meningitis, finding the best cure for influenza is unlikely to produce clinical results.

In table. 2 presents the levels of evidence for assessing the effectiveness of therapy, prevention, etiology, harm to health.

The relationship between levels of evidence and levels of recommendations is shown in Table. 3.

Combined preparations

In 1993, the US Food and Drug Administration (FDA) recommended that caffeine (when added to an ASA + AAF combination) be classified as a Category 1 analgesic adjuvant, with “recognized efficacy and safety”. » [23]. The presence of caffeine makes it possible to shift the dose/response curve to the left, increasing the analgesic effect by 40% [23, 24]. The synergistic effect of ASA, AAF and caffeine, leading to the suppression of prostaglandin E2 synthesis, may partially explain this phenomenon. Caffeine itself may have analgesic effects in certain types of human pain [25], but overall evidence from clinical trials is lacking.

In 1998, a combination of 250mg ASA, 250mg AAF, and 65mg caffeine became the first over-the-counter drug to receive FDA approval for the treatment of migraine, and later, in 1999, it was approved for the treatment of more than just migraine but also accompanying symptoms [7]. A similar combination has been approved in Europe and recommended by the European Federation of Neurological Societies (EFNS) as a first-line treatment for mild to moderate migraine (Table 1).

Data obtained in clinical studies indicate the safety and efficacy of fixed combinations of analgesics with the following dosages of active ingredients: ASA 250-265 mg, AAF 200-265 mg and caffeine 50-65 mg in one tablet. The optimal ratio of active ingredients of 1.0:0.8:0.2 (ASA, AAF and caffeine, respectively) was found in the course of pharmacological and clinical studies to find the optimal dose [23], while the minimum recommended dose of caffeine is 50 mg per tablet. . In patients with migraine with or without aura, the fixed combination is more effective than placebo not only in reducing the intensity of headache, but also in reducing the severity of nausea, photo- and phonophobia [26].

A comparative study of the fixed combination (ASA 250 mg + AAF 250 mg + caffeine 65 mg) and ibuprofen in the treatment of migraine showed that the effectiveness of both drugs exceeded that in the placebo group, while the triple combination was significantly more effective than ibuprofen [7]. The superiority of the fixed combination over ibuprofen was confirmed both statistically and clinically (reduction in pain intensity, earlier onset of a significant reduction in pain, as well as the frequency of patients with complete absence of pain and a headache response to the drug), where the most significant for patient performance indicators [27, 28]. In addition, in the fixed combination group, emergency drugs were used significantly less frequently, and the percentage of patients with complete relief of headache was higher than in the ibuprofen group [7].

Against the background of the prevailing opinion that prescription drugs are always the most effective, the data obtained in a comparative study of a fixed combination (ASA 250 mg + AAF 250 mg + caffeine 65 mg) with sumatriptan at a dose of 50 mg are interesting. Here, the effectiveness of the combination turned out to be higher in terms of the overall effectiveness of headache, relief of concomitant symptoms, the frequency of use of emergency drugs, and the overall assessment of the effectiveness of the drug [7].

In addition to the advantages associated with the effectiveness of the drug, the fixed combination has a number of other advantages compared to sumatriptan, in particular, it does not have cardiovascular contraindications that limit the use of triptans [29, 30].

The results of the study suggest that patients with migraine can use the triple combination at the first sign of an impending attack, while prescription drugs can be deferred for cases of refractory to OTC therapy, since most patients try OTC drugs before visiting the doctor. The assumption that prescription drugs are, by definition, superior to over-the-counter drugs can be challenged.

Conclusion

Thus, the data available to date confirm that over-the-counter drugs, in particular NSAIDs and their combinations, can be considered as effective pathogenetic agents for the treatment of mild to moderate migraine. That is how they are recommended by the European Federation of Neurological Societies and the US Headache Consortium.

Special mention deserves a fixed combination of ASA, AAF and caffeine in doses of 250, 250 and 65 mg, respectively. In Russia, this combination is available under the name Excedrin®. The advantages of the drug include compliance with the composition of European and American recommendations, effectiveness against both headache and concomitant symptoms of migraine (nausea, photo- and phonophobia) [26], as well as a favorable tolerability profile of the drug. A significant decrease in migraine headache is observed within 30 minutes after taking the drug. Data from clinical studies confirm that Excedrin® is an adequate and rational choice for the treatment of mild to moderate migraine headache, its effectiveness exceeds that of NSAID monotherapy [31], and in some cases is not inferior to triptans [7].

Literature

1. Lipton R. B., Bigal M. E., Steiner T. J., Silberstein S. D., Olesen J. Classification of primary headaches // Neurology. 2004. 63: 427–435.
2. Stovner L. J., Hagen K. Prevalence, burden, and cost of headache disorders // Curr. Opin. Neurol. 2006. 19: 281–285.
3. Olesen J., Gustavsson A., Svensson M., Wittchen H. U., Jonsson B. The economic cost of brain disorders in Europe // Eur. J. Neurol. 2012.19: 155–162.
4. Leonardi M., Steiner T. J., Scher A. T., Lipton R. B. The global burden of migraine: measuring disability in headache disorders with WHO’s Classification of Functioning, Disability and Health (ICF) // J. Headache Pain. 2005.6:429–440.
5. Lipton R. B., Newman L. C., Solomon S. Over-the-counter medication and treatment of migraine // Headache. 1994; 34:547–548.
6. Aicher B., Kraupp O. Effectiveness of fixed analgesic combinations exemplified by Thomapyrin® // Wien Klin Wochenschr. 1996; 108:219–233.
7. Goldstein J. et al. Acetaminophen, Aspirin, and Caffeine versus Sumatriptan Succinate in early treatment of migraine: results from the ASSET trial // Headache. 2005; 45:973–982.
8. Moskowitz M. A. The neurobiology of vascular head pain. Ann. Neurol. 1984.16:157–168.
9. Pietrobon D., Striessnig J. Neurobiology of migraine. Nat. Rev. neurosci. 2003. 4: 386–398.
10. Olesen J., Burstein R., Ashina M., Tfelt-Hansen P. Origin of pain in migraine: evidence for peripheral sensitization // Lancet Neurol. 2009.8:679–690.
11. Levy D. Migraine pain and nociceptor activation – where do we stand? // header. 2010. 50: 909–916.
12. Waeber C., Moskowitz M. A. Migraine as an inflammatory disorder // Neurology. 2005. 64: S9–15.
13. Levy D. Migraine pain, meningeal inflammation, and mast cells // Curr. Pain Headache Rep. 2009. 13:237–240.
14. Levy D. Endogenous mechanisms underlying the activation and sensitization of meningeal nociceptors: the role of immuno-vascular interactions and cortical spreading depression. Curr. Pain Headache Rep. 2012. 16: 270–277.
15. Edelmayer R. M., Vanderah T. W., Majuta L., Zhang E. T., Fioravanti B. et al. Medullary pain facilitating neurons mediate allodynia in headache-related pain // Ann. Neurol. 2009. 65: 184–193.
16. Burstein R., Cutrer M. F., Yarnitsky D. The development of cutaneous allodynia during a migraine attack: clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine // Brain. 2000. 123 (Pt. 8): 1703–1709.
17. Reuter U., Bolay H., Jansen-Olesen I., Chiarugi A., Sanchez del Rio M. et al. Delayed inflammation in rat meninges: implications for migraine pathophysiology // Brain. 2001. 124: 2490–2502.
18. Nicoletti P., Trevisani M., Manconi M., Gatti R., De Siena G. et al. Ethanol causes neurogenic vasodilation by TRPV1 activation and CGRP release in the trigeminovascular system of the guinea pig // Cephalalgia. 2008.28:9–17.
19. Nassini R., Materazzi S., Vriens J., Prenen J., Benemei S. et al. The ‘headache tree’ via umbellulone and TRPA1 activates the trigeminovascular system // Brain. 2012. 135: 376–390.
20. Noseda R., Kainz V., Jakubowski M., Gooley J. J., Saper C. B. et al. A neural mechanism for exacerbation of headache by light // Nat. neurosci. 2010. 13: 239–245.
21. Tfelt-Hansen P., Block G., DahloEf C. et al. Guidelines for controlled trials of drugs in migraine: second edition // Cephalalgia. 2000; 20:765–786.
22. Evers S., Afra J., Frese A. et al. EFNS guideline on the drug treatment of migraine — revised report of an EFNS task force // European Journal of Neurology. 2009, 16:968–981.
23. Hersh E. V., Moore P. A., Ross G. L. Over-the-counter analgesics and antipyretics: a critical assessment // Clin Ther. 2000; 22:500–548.
24. Laska E. M., Sunshine A., Mueller F., Elvers W. B., Siegel C., Rubin A. Caffeine as an analgesic adjuvant // JAMA. 1984; 251: 1711–1718.
25. Camann W. R., Murray R. S., Mushlin P. S., Lambert D. H. Effects of oral caffeine on postdural puncture headache. A double-blind, placebo-controlled trial // Anesth Analg. 1990; 70:181–184.
26. Lipton R. B., Stewart W. F., Ryan R. E., Saper J., Silberstein S., Sheftell F. Efficacy and safety of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain: three double-blind randomized, placebo controlled trials // Arch Neurol. 1998; 55:210–217.
27. Silberstein S. D. Migraine symptoms: Results of a survey of self-reported migraineurs // Headache. 1995; 35:387–396.