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Fioricet For Migraines: A Non-Evidence-Based Intervention

Fioricet is a brand name medication comprised of the following ingredients: butalbital (50 mg), acetaminophen (300 mg), and caffeine (40 mg).  The combination of a barbiturate (butalbital), a nonsteroidal anti-inflammatory drug (acetaminophen), and central nervous system stimulant (caffeine) – seem to act synergistically to alleviate various types of headaches.  Medically, Fioricet is approved by the FDA for the treatment of tension headaches, muscle contraction headaches, and post-dural puncture headaches.

In other words, those with various types of chronic headaches seem to derive significant benefit from Fioricet.  Interestingly, despite attaining FDA approval for the treatment of tension, muscle contraction, and post-dural puncture headaches, Fioricet was never approved for the treatment of migraines.  Comparatively, migraines differ from traditional headaches in that they are moderate to severe sensations of localized head pain accompanied by sensory sensitivity and/or nausea.

There remains a paucity of clinical evidence to suggest that Fioricet effectively treats migraines.  However, some individuals with migraines have pursued every clinically recommended treatment only to derive unsatisfactory symptomatic relief.  Among those with refractory migraine diagnoses, medical professionals may recommend trying Fioricet as an off-label treatment (based on the fact that it’s capable of treating other types of headaches).

How Fioricet May Treat Migraines (Mechanisms)

While certainly not everyone taking Fioricet will find it helpful for the management of migraines, a subset of users report significant benefit.  An analysis of anecdotal accounts reveals that many non-responders to traditional migraine treatments find Fioricet to be a drug that actually works.  If you’re taking Fioricet for migraines and/or have considered inquiring about it as an intervention, you may want to learn how it works.  Each component of Fioricet has a distinct mechanism of action, but when combined, a synergistic effect for migraine relief may result.

Butalbital (50 mg): Arguably the most potent component of Fioricet is butalbital, a barbiturate.  It functions principally by mimicking the inhibitory effects of the neurotransmitter GABA (gamma-aminobutyric-acid).  When ingested, butalbital binds to the GABAA receptors within the chloride receptor ionopore complex, a site distinct from that of benzodiazepines.  Binding to chloride receptor ionopore complex sites results in prolongation of chloride channel opening, allowing a greater quantity of chloride ions to enter the neuron.

Enhanced movement of chloride ions within the neuron induces a state of hyperpolarization (negative charge internally compared to externally), thereby making it less receptive to excitatory postsynaptic potentials.  Reduced receptivity to excitatory stimulation facilitates a CNS depressant effect characterized by relaxation, sedation, and/or drowsiness.  This CNS depressant effect alone may be associated with some degree of migraine reduction – especially if the migraines were fueled by vasoconstriction.

A study by Bigal et al. (2013) entitled “Occipital Levels of GABA are Related to Severe Headaches in Migraine” mentioned the roles GABAergic processes may play in the pathogenesis of migraines.  Authors of this study noted that GABAergic processes were subject to significant variation among those with severe headache attacks compared to others.  They believe that GABA can effectively suppress headache attacks and that low GABA could be implicated among those with migraines.

What’s more, GABA is understood to affect trigeminovascular nociceptive neurotransmission within the trigeminocervical complex.  Not only may the butalbital increase GABAergic transmission to prevent the occurrence of migraines, it may lessen the severity of already-occurring migraines.  The combination of butalbital’s ability to modulate nociception, vasodilation, and excitatory amino acids (L-glutamate and L-aspartate) likely contribute to its therapeutic efficacy for cases of migraines.

  • Source: https://pubchem.ncbi.nlm.nih.gov/compound/butalbital
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18505983
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11606331

Acetaminophen (300 mg): This is a common over-the-counter analgesic that is administered for the treatment of moderate pain and fever.  It elicits an analgesic effect and is generally prescribed as an opioid adjunct to treat post-surgical pain.  Its mechanism of action isn’t fully elucidated, but it is thought to function as a COX-2 inhibitor, which essentially reduces circulation of proinflammatory cytokines (e.g. IL-1B and IL-6).

A reduction of proinflammatory cytokines may decrease neuroinflammation (or inflammation of the brain) and facilitate analgesic effects.  Since neuroinflammation may cause migraine headaches (as a result of proinflammatory cytokines), administration of acetaminophen may provide direct benefit.  What’s more, acetaminophen metabolites are capable of acting upon TRPA-1 receptors, which modulates signal transduction from within the posterior grey column of the spinal cord.

Modulation of signal transduction within the spinal cord may also facilitate analgesic effects that could help a migraine sufferer to cope with his/her pain.  Acetaminophen also metabolizes to AM404 which functions as an anandamide reuptake inhibitor and modulates activation of the TRPV1 receptor.  Action upon the TRPV1 receptor may alter release of CGRP (Calcitonin Gene-Related Peptide) and alter vascular tone, thereby attenuating severity of migraines.

Additionally, the AM404 metabolite acts as a sodium-channel inhibitor.  Inhibition of sodium-channels have been shown to reduce pain, and may also contribute to the antimigraine properties of acetaminophen.  Though acetaminophen alone may benefit those with migraines, when combined with caffeine, it effectively reduces migraines in approximately 40% of sufferers.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11112243
  • Source: https://www.ncbi.nlm.nih.gov/pubmed/15987694
  • Source: https://www.ncbi.nlm.nih.gov/pubmed/17884974
  • Source: https://www.ncbi.nlm.nih.gov/pubmed/22109525

Caffeine (40 mg): Caffeine is regarded as a necessary constituent of Fioricet due to the fact that it constricts cerebral blood vessels and counteracts the sedative effect induced by butalbital.  Additionally, studies have shown that acetaminophen used in combination with caffeine are an effective first-line therapy for the treatment of migraines.  There may be some sort of synergistic mechanism associated with the administration of caffeine plus acetaminophen for migraines.

Some studies have shown that caffeine is more effective as a placebo (and equally effective as acetaminophen) for the attenuation of tension headaches.  When used at low doses and/or on an infrequent basis, caffeine can alleviate headaches.  However, with chronic long-term administration, caffeine is associated with tolerance onset, leading users to consume abnormally high dosages.

These high daily caffeine dosages can induce such significant vasoconstriction, that caffeine consumption may be directly responsible for causing migraines.  What’s more, if a user attempts to discontinue his/her coffee habit, caffeine withdrawal symptoms will likely occur – one of which could be migraines.  At the small dosage of just 40 mg included in this formulation, caffeine’s vasoconstriction properties are offset by the other constituents (butalbital and acetaminophen).

Caffeine acts as an adenosine receptor antagonist, thereby preventing the binding of adenosine at receptor sites; this bolsters alertness.  Studies have shown that when injected, adenosine can directly cause migraines.  Perhaps by inhibiting adenosine’s binding to receptor sites, caffeine elicits some sort of antimigraine effect.  Moreover, caffeine affects the neurotransmission of catecholamines (norepinephrine, epinephrine, dopamine) – each of which (or the combination of which) may be implicated in headaches.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20164566
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/12633594
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/7705215

Old Fioricet vs. New Fioricet Formulation

It is important to highlight the fact that the original version of Fioricet had undergone a minor formulation change since its inception.  The initial Fioricet was manufactured in the form of a tablet and contained 325 mg of acetaminophen.  This original format was considered a normal prescription-only pharmaceutical drug.

Recently, the formulation of Fioricet has shifted from tablet to capsules and the acetaminophen content has been reduced to 300 mg (for safety purposes).  While many argue that Fioricet should be a controlled-substance throughout the United States, it is only considered a Schedule III substance in four states: Georgia, Maryland, New Mexico, and Utah.  To add to the confusion, a spinoff of Fioricet, known as “Fiorinal” is a Schedule III substances throughout the United States.

The difference between Fiorinal and Fioricet is extremely subtle in that rather than containing acetaminophen, Fiorinal contains aspirin.  Patients are commonly prescribed Fioricet over Fiorinal, making it easier to attain their prescription without hang-ups over the Schedule III status of Fiorinal.  Moreover, some formulations of Fiorinal contain codeine – which increases its abuse potential.

Benefits of Fioricet for Migraines (Possibilities)

There are relatively few benefits associated with the usage of Fioricet for migraines.  Some studies indicate that upwards of 80% of Fioricet users derive benefit from its administration.  Additionally, it may be an effective intervention for those with treatment-resistant cases of migraines who don’t respond well to other prescriptions.

  • Comorbidities: Since the butalbital within Fioricet acts on the GABAergic system, it may be effective for the management of acute pain, panic disorder and/or insomnia. Taking Fioricet induces CNS depression and may cause users to feel less anxious and drowsy.  Though tolerance onset can occur quickly, when used selectively on an as-needed basis, it may not only help migraines, but non-indicated comorbidities.
  • Effective: There is some Level C (low-level) evidence to suggest that Fioricet may reduce symptoms among those with migraines. As a result of this evidence, its efficacy is difficult to entirely dismiss among all migraine suffers.  Some users have testified that Fioricet is more effective for their particular migraines than every other option they’ve tried.
  • Other headaches: We know that Fioricet has been FDA approved for the treatment of tension headaches. It has undergone randomized, double-blinded trials and was found more effective than a placebo control for management of certain headaches.  It is possible that someone with migraines may also suffer from comorbid tension headaches and/or may be misdiagnosed with migraines when they really have tension headaches.  For these individuals, Fioricet may be a useful medication.
  • Treatment-resistant cases: Migraines are known to significantly impair a person’s functionality and quality of life. Those with treatment-resistant migraines may be unable to function at work, school, and/or socially without some sort of pharmacological intervention.  Assuming all a person doesn’t respond to conventional therapies, Fioricet may provide be useful.

Drawbacks of Fioricet for Migraines (Possibilities)

There are a host of drawbacks associated with using Fioricet for migraines.  Most obvious, the evidence to support its usage for migraines is nonexistent.  Additionally, frequent users will become tolerant to its effects over time and/or dependent, resulting in a worsening of headaches and an array of withdrawal symptoms upon discontinuation.

  • Abuse potential: Some individuals may intentionally seek out Fioricet with the intent to attain some sort of physical and psychological “high.” Taking Fioricet at high doses facilitates CNS depressant effects via GABAergic modulation.  It is difficult for doctors to determine who is likely to abuse Fioricet and those who are unlikely to abuse it.  That said, even those who may not have considered abusing it prior to taking their first dose, may end up abusing it at some point in the future.  After all, barbiturates are regarded as some of the most addictive drugs compared to all pharmaceuticals.
  • Birth defects: A study published in 2014 discovered that butalbital-containing products may cause birth defects. Mothers that used butalbital during pregnancy were more likely to give birth to children with congenital heart defects, yielding lifelong health complications.  Specific birth defects associated with butalbital included: tetralogy of fallot, pulmonary valve stenosis, and secundum-type atrial septal defect. (Source: http://www.ncbi.nlm.nih.gov/pubmed/24001268).
  • Dosages: Patients taking low dosages of Fioricet on an intermittent basis may be safe, but high dosages may be problematic. High dosages are associated with a psychological relaxant-induced intoxication similar to that provided by alcohol.  If a high dosage is deliberately and/or unknowingly taken, the ensuing health complications may be significant and, in rare cases, fatal.
  • Dependency: Those who use Fioricet frequently tend to become tolerant to its effects quickly. The GABAergic stimulation provided by butalbital within Fioricet will eventually cease to be significant, that is, unless dosage is increased.  Since dosage cannot be increased (due to an array of risks), the patient is essentially “stuck” on his/her current dosage in fear of facing discontinuation symptoms.  Some individuals may become reliant on Fioricet for general functioning.
  • Ineffective: Not only do many Fioricet users find it completely ineffective, there is absolutely zero scientific basis to support the usage of Fioricet for migraine management.  The FDA has not approved it as an antimigraine for a reason – there’s no evidence suggesting that it provides statistically significant benefit compared to a placebo.  The lack of evidence to support its usage should be considered a noteworthy drawback.
  • Interactions: Fioricet already contains 3 substances (acetaminophen, butalbital, caffeine) – each of which can interact with other agents. The presence of butalbital alone may induce respiratory depression at high doses, especially if combined with another CNS depressant.  Those using Fioricet will need to beware of potential pharmacodynamic and/or pharmacokinetic interactions with other medications and supplements.
  • Long-term outcomes: We can bet on the fact that Fioricet will not maintain therapeutic value over a long-term when administered frequently. It may maintain its therapeutic value if administered sparingly on an infrequent, as-needed basis.  In addition to having a questionable long-term value as a therapy, it may lead to undesirable long-term effects.  There’s evidence to suggest that benzodiazepines are linked to dementia, and since butalbital acts similarly, it may also increase risk of neurodegeneration.
  • Rebound headaches: Multiple publications document the onset of rebound migraines during treatment and/or upon Fioricet discontinuation. These rebound headaches can occur as a result of medication overuse, abuse, or as a result of discontinuation.  All patients should be warned of this possibility prior to initiation of treatment with Fioricet.
  • Side effects: Fioricet users cannot expect to operate a motor vehicle nor operate heavy machinery after ingestion of this drug. The butalbital content yields neurophysiological effects similar to alcohol, facilitating equal amounts of impairment.  Although there is caffeine to help offset some of the CNS depression, users would be putting themselves (and others) at serious risk if they chose to drive and/or work with heavy machinery during treatment.  Examples of common unwanted side effects include: dizziness, drowsiness, lightheadedness, memory deficits, etc.
  • Tolerance: Those familiar with barbiturates understand that they are associated with rapid tolerance onset. Though Fioricet is not only a “barbiturate” it contains butalbital which can lead to both physical and psychological tolerance.  This tolerance is likely to also reduce Fioricet’s efficacy as an antimigraine.
  • Toxicity: There are toxicity concerns associated with Fioricet in that it may cause liver damage in some users. Additionally, potentially fatal overdose may occur as a result of CNS depression associated with abuse and/or high-dose usage.  When an overdose occurs, both acetaminophen and butalbital toxicity warrant treatment.
  • Withdrawal symptoms: Among those who consistently administer Fioricet for any reasonable duration of time, withdrawal symptoms will occur upon discontinuation. While withdrawal symptoms may not be as significant among low-dose/infrequent users, they will occur among those who attempt to discontinue treatment.  Ironically, a symptom of discontinuation is an increase in the occurrence and/or severity of migraines.  Studies show that patients may experience seizures during withdrawal if they quit “cold turkey” rather than taper.  (Source: http://www.ncbi.nlm.nih.gov/pubmed/15262744).

Fioricet For Migraines: Review of Literature (Butalbital-APAP-Caffeine)

Included below is a review of studies investigating the efficacy, safety, and/or feasibility of Fioricet administration for migraine headaches.  Most evidence indicates that the usage of butalbital-containing agents for the treatment of migraine headaches is unsubstantiated by science.  Perhaps most striking is the willingness of medical professionals to prescribe Fioricet as an off-label treatment without evidence to support its therapeutic value for migraines.

2015: The acute treatment of migraine in adults: The American headache society evidence assessment of migraine pharmacotherapies.

A report published in 2015 by Marmura et al. discussed pharmacological treatments for migraines.  Authors of this report analyzed various therapies and sought to determine whether their usage for migraine headaches was justified based on available scientific evidence published between 1998 and 2013.  They categorized evidence to support these therapies into either: Level A evidence (at least 2+ Class I studies) and Level B evidence (1 Class I or 2 Class II studies).

Medications fitting criteria for Level A evidence included: Triptans (Almotriptan, Eletriptan, Frovatriptan, Naratriptan, Rizatriptan, Sumatriptan), Zolmitriptan, and dihydroergotamine.  In other words, these interventions are all considered first-line, efficacious interventions for the treatment of migraines.  Other medications that were considered Level A options included: various NSAIDs (aspirin, diclofenac, ibuprofen, naproxen), opioids (butorphanol nasal), sumatriptan/naproxen, and acetaminophen/aspirin/caffeine combinations.

Only after all Level A options have been pursued by migraine sufferers should Level B options be considered.  Examples of medications that met criteria to be considered “Level B” agents or are hypothesized to be Level B included: antiemetics (chlorpromazine, droperidol, metoclopramide, and prochlorperazine, etc.), ergotamine, dihydroergotamine (variations), ketoprofen, ketorolac, magnesium (intravenous), isometheptine compounds, codeine/acetaminophen, tramadol/acetaminophen.  There was no Level A nor Level B evidence to support the usage of Fioricet or products containing butalbital for the treatment of migraines.

Researchers note that Level C agents could be considered: butalbital (and butalbital-containing agents) corticosteroids, lidocaine (nasal), meperidine, phenazone, and tramadol (intravenous).  Due to the fact that there are a multitude of viable Level A and Level B evidence-supported treatment options for migraine headaches, Level C agents such as Fioricet (and butalbital-containing products) cannot be recommended.  Level C evidence is considered poor quality, and for this reason, Fioricet should not be considered an evidenced-based treatment for migraines.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25600718

2012: Efficacy, end points and eventualities: sumatriptan/naproxen versus butalbital/paracetamol/caffeine in the treatment of migraine.

A report by Fox (2012) addressed the fact that migraine headaches is a problematic, widespread, chronic condition.  Fox wrote a follow-up response addressing the results from the Derosier et al. (2012) study noting the superiority of Sumatriptan/Naproxen compared to Fioricet (butalbital-containing agents).  In this report, Fox acknowledges the results suggesting that Sumatriptan/Naproxen may be superior as an intervention for migraines compared to Fioricet.

However, he is quoted as calling the primary endpoint of the study a “technical failure” for one notable reason – the pleiomorphic underpinnings of migraines.  In other words, not all migraines may appear to have the same neurophysiological biomarkers and/or causes.  For this reason, it is argued that the more treatment options available to patients, the more likely they are to eventually find something that provides migraine relief.

Fox recommends not dismissing the efficacy of barbiturate-based interventions (e.g. Fioricet) based on this study alone.  That said, it is understood that barbiturate-based agents (such as those with butalbital) are associated with risks.  Nonetheless, more research is warranted to distinguish the neurophysiological footprints of migraines associated with Fioricet responders compared to those who derive no benefit.

Personally, I’m not sure if I totally agree with Fox’s argument.  While deliberate elimination of barbiturate-based interventions from a migraine treatment arsenal is unjustified, liberal usage of such agents is equally unjustified.  Only a small subset of non-responders to safer, more universally effective options should be considered for treatment with evidence-unsupported options such as Fioricet.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23121272

2012: Sumatriptan-naproxen and butalbital: a double-blind, placebo-controlled crossover study.

Researchers Derosier et al. (2012) compared the therapeutic efficacy of Sumatriptan/Naproxen (85mg/500mg) with Fioricet (50 mg butalbital, 325 mg acetaminophen, 40 mg caffeine) for the treatment of moderate-to-severe migraines.  It was mentioned that butalbital-containing agents are associated with unwanted adverse reactions and may actually increase the chronicity of migraines when administered over an extended duration.  Nonetheless, butalbital-containing agents are commonly prescribed by clinicians for the management of migraines.

A study was organized and recruited 442 participants that had been treated previously with at least 1 butalbital-containing medication.  All participants treated 3 moderate-to-severe migraines using each of the following interventions: Sumatriptan/Naproxen, Fioricet, and a placebo.  The order in which participants received these agents was randomized and the study was considered double-blinded.

Of the 442 participants, it is worth noting some statistics such as: 88% were female, all were adults (average age of 43), and 78% reported that migraines “severely” impaired their quality of life.  Interestingly, prior to the study, 88% of participants were already using butalbital and 82% were satisfied with the results they were getting from butalbital.  Results indicated that the Sumatriptan/Naproxen combination provided more significant pain relief, migraine relief, and total symptomatic relief for 48 hours after administration – compared to Fioricet.

There were no significant differences in reporting of adverse reactions between the three interventions.  Researchers concluded that while most of the participants in this study were considered butalbital responders (as evidenced by the 88% statistic of using Fioricet prior to the study), they appeared to derive greater benefit from the Sumatriptan/Naproxen (by comparison).  Although Fioricet may treat migraines in some individuals, there are likely more effective agents such as Sumatriptan/Naproxen.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22103635

2011: Symptomatic treatment of migraine: when to use NSAIDs, triptans, or opiates.

Authors Taylor and Kaniecki (2011) write up an opinion piece on when to use NSAIDs, triptans, and opioids for the treatment of migraine headaches.  They discuss the fact that migraines are considered a biological disorder of the brain with attacks that can span between 4 and 72 hours, causing severe debilitation for patients.  Though the principal component of a migraine diagnosis is a severe, localized headache (or head pain) – other symptoms may occur including: nausea, sensory hypersensitivity, and vomiting.

Individuals susceptible to migraines typically notice that symptoms worsen with physical activity and/or environmental stimulation.  Taylor and Kaniecki mention that when considering migraine treatments, it is necessary for medical professionals to understand interindividual, as well as intraindividual variability among patients in regards to frequency, intensity, and duration of attacks.  In other words, not all patients will necessarily respond to the same treatments, and certain treatments may be better depending on the specific severity of a migraine that a patient experiences.

In cases of mild-to-moderate migraines, authors advise administration of NSAIDs.  In the event that a migraine is severe or unresponsive to NSAIDs, interventions such as Triptans and Dihydroergotamine are recommended.  Authors recommend that patients administer acute agents at the earliest warning signs of a migraine – as this may inhibit its onset and/or blunt its intensity.

Those experiencing frequent headaches (10+ days per month) are recommended to minimize acute interventions for only severe episodes to avoid medication overuse.  Additionally, all patients with severe migraines are recommended to be equipped with some sort of back-up therapy.  However, authors explicitly state that compounds containing butalbital (e.g. Fioricet) and opioids should NOT be used due to the fact that they may worsen migraine symptoms over time.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21125432

2010: Didactic Migraine Education in US Doctor of Pharmacy Programs

An investigation by Wenzel et al. (2010) assessed migraine education among doctor of pharmacy programs in the United States.  The specific aim of this study was to determine whether the education received at such programs was aligned with the evidence-based migraine treatment recommendations provided by the Headache Consortium.  To determine whether the education received by doctor of pharmacy programs was evidence-based, a survey was sent to 90 PharmD programs in the U.S.

Of the 90 programs that received the survey, a total of 77 responded and only 69 programs provided sufficient data to be utilized for this investigation.  Researchers noted that 55% of programs had taught the guidelines developed by the Headache Consortium.  Additionally, 49% discussed non-prescription vs. prescription drugs, 45% supported butalbital-based agents as a viable migraine intervention, and just 20% provided education regarding debilitation associated with migraines.

It was concluded that roughly half of all PharmD education incorporates treatment advice in alignment with recommendations provided by the U.S. Headache Consortium.  This suggests that education of recommended migraine treatments may be suboptimal at certain programs.  Researchers note that it is important for all PharmD programs to distinguish evidence-based interventions from non-evidence-based – and understand the risks associated with butalbital-containing agents.

This report is helpful because it highlights the subtle differences in migraine management approaches among PharmD programs.  Just under half of all programs support butalbital-containing agents, whereas the other half do NOT support the usage of such compounds.  Evidence is strong to recommend against the usage of butalbital-containing agents, and for this reason, educational curriculum of various programs may necessitate updates and/or revisions.

  • Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829152/

2008: The Pharmacological Management Of Migraine, Part 1

An extensive report written by George DeMaagd (2008) documented pharmacological strategies for the management of migraines.  In a subsection of the report, he discussed barbiturate analgesics, particularly butalbital-containing agents in migraine management.  Specifically, he noted that butalbital is an intermediate-acting barbiturate that has been utilized for years as an antimigraine agent.

DeMaagd notes that despite long-term historical administration of butalbital-containing agents (e.g. Fioricet) as medicinal interventions for migraines, there is no evidence to support their clinical utility.  What’s more, it appears as though many professionals fail to consider the adverse effects such as cognitive impairment and confusion, as well as the possibility of dependency and abuse (associated with a worsening of headaches and a host of other general deleterious effects).  For this reason, he recommends that patients being treated with barbiturate-containing agents be reevaluated and prescribed an alternative therapy.

The totality of risks (abuse, addiction, CNS depression, dependency, etc.) associated with agents such as butalbital for the treatment of migraines is staggering.  When considering these risks, as well as the fact that evidence does not support the efficacy of butalbital-containing products – one may wonder why they are utilized at all.  Only in cases of partial and/or non-responders to the assortment of FDA approved antimigraine agents may barbiturate analgesics warrant consideration as an intervention.

  • Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2740949/

2005: Eletriptan treatment of migraine in patients switching from barbiturate-containing analgesics: results from a multiple-attack study.

Researchers Martin et al. (2005) sought to determine the efficacy and tolerability of the drug Eletriptan among patients who had previously been using Fioricet or Fiorinal (barbiturate-containing agents).  A total of 160 participants were recruited for their study, all of which met diagnostic criteria for migraines and derived insufficient relief from butalbital agents for an entire year.  Eletriptan was administered at 40 mg for a duration of 3 months to treat migraine attacks.

To track efficacy and tolerability to Eletriptan, researchers assessed headache response, pain-free rates, and functional impairment at baseline.  They compared baseline assessments with assessments administered 2 hours post-Eletriptan dose.  Results indicated that around 71% of those treated with Eletriptan responded sufficiently to the treatment, and reported improvements in overall functionality.

What’s more, the Eletriptan administration was not associated with onset of tolerance nor adverse effects.  Researchers concluded that among individuals who respond poorly to butalbital-containing agents (e.g. Fioricet), Eletriptan appears effective.  Eletriptan is currently supported with Level A evidence as a migraine treatment and should be prescribed prior to Fioricet (and barbiturate-containing products) in all circumstances.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/16109055

2004: Transformed migraine and medication overuse in a tertiary headache centre–clinical characteristics and treatment outcomes.

A study was conducted by Bigal et al. (2004) to determine whether overuse of medication may contribute to chronic daily headache (CDH) syndrome and/or worsening of migraines.  Literature indicates that many headache sufferers overuse their medication.  Overuse could be considered administering a greater dosage than necessary for symptomatic alleviation or utilizing medication more often than is clinically recommended.

The impetus of this study was to elucidate patterns of medicinal overuse among those consulting a headache center for migraines compared to those who do not overuse medication.  A total of 456 patients that had been diagnosed with transformed migraine (TM).  Medication overuse was regarded as any of the following: analgesic usage exceeding 1000 mg over 5 days per week; combination analgesic usage of 3 tablets per day more than 3 days per week; opioids at 1 tablet per day for over 2 days per week; ergotamine tartrate at 1 mg (oral) or 0.5 mg (as needed) for more than 2 days per week; and triptans administered at over 1 tablet per day exceeding 5 days per week.

The 138 patients who were overusing (Group 2) medication were compared to 318 patients of similar age, sex, characteristics, etc. that had detoxified and were no longer overusing (Group 1).  After a full year, comparisons included: number of days with headaches per month; headache intensity; headache duration; headache score (frequency plus intensity).  Of the 138 overusers (Group 2), most had overused more than one type of agent for their migraines.

In this group, number of tablets taken per day ranged from 1 to 30, with an average of 5.2.  Authors of this study document the most overused agents among migraine sufferers include: butalbital combination products (48%), acetaminophen (46.2%), opioids (33.3%), aspirin (32%), ergotamine (11.8%), sumatriptan (10.7%), etc.  Perhaps most significant is the fact that non-overusers (Group 1) experienced a significant decrease in headache frequency by 73.7% compared to just 17.2% in overusers (Group 2).

Head pain duration was also decreased by 61.2% in Group 1 (non-overusers) compared to just 14.8% in Group 2 (overusers).  In addition, headache scores after a full year were 18.8 for Group 1 (non-overusers) and 54 for Group 2 (overusers).  This suggests that strict adherence to clinically recommended treatment guidelines yields the best long-term results for the treatment of migraines.

Patients who recovered from previous overuse experienced better clinical outcomes than those who overused.  This suggests that overuse may exacerbate migraines over a long-term and/or that strict adherence to administration guidelines provides the most sustainable benefit to migraine suffers.  Since agents like Fioricet (and other butalbital-containing agents) are most likely to be overused, and poorer functional outcomes are associated with overuse, they should be reserved as a last-line option.

The problem with Fioricet is not only its questionable efficacy, but that it can induce tolerance quickly as a result of the butalbital component.  Over time, this tolerance becomes problematic in that patients may continuously upping their dosage, perhaps because they are no longer getting headache relief (as a result of tolerance).  Upon trying to detoxify from such an agent, headaches may temporarily worsen – possibly trapping them in a cycle of overuse.

It’s easy to see how someone could get caught up in a vicious-circle of Fioricet administration for migraines, ultimately impairing their long-term outcomes.  Detoxification from such agents, as well as transition to an agent with lesser likelihood of overuse (e.g. Triptans) should be considered.  Medical professionals should underscore the importance of adherence to recommended dosage/administration guidelines of antimigraine agents – as this will improve long-term treatment outcomes.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15154858

2002: Do butalbital-containing products have a role in the management of migraine?

In 2002, Wenzel and Sarvis evaluated the usage of butalbital-containing agents for the management of migraines.  They utilized a systematic search via the Medline database from 1996 to 2001 to assess evidence to support the efficacy of butalbital-containing products.  They also reviewed the U.S. Headache Consortium’s guidelines for migraine treatment.

The review of evidence indicated that over 28 million individuals suffer from migraines, but management and diagnostic guidelines remain inadequate.  Of those that are diagnosed, up to 36% may be prescribed products containing butalbital.  Despite the fact that up to 1 in 3 patients receive butalbital-containing products for migraines, there was only one published controlled trial of such agents for this indication.

In this published controlled trial, butalbital-containing products was found to be inferior to butorphanol-containing (opioidergic) products.  Perhaps most appalling is the fact that there are many adverse consequences associated with butalbital-based interventions for migraines including: insufficient migraine relief, drug-induced headaches, and withdrawal symptoms.  In conclusion, despite frequent dispensing of butalbital-containing agents to migraine sufferers, there is zero literature to support their usage for migraines and therefore, they cannot be recommended.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/12173787

2001: Butalbital in the treatment of headache: history, pharmacology, and efficacy.

A study by Silberstein and McCrory published in 2001 analyzed the usage of butalbital for headaches throughout history.  Authors noted that compounds containing butalbital plus aspirin/acetaminophen and caffeine are often used for headache management.  In placebo-controlled trials, these agents containing butalbital are considered effective for the treatment of tension headaches.

It was highlighted that butalbital is a barbiturate, and as a result, has a tendency to provoke intoxication.  This intoxication is followed by a hangover and is associated with onset of tolerance, dependency, as well as toxicity.  The intoxicant effect associated with butalbital is considered “indistinguishable” when compared to that which occurs following alcohol intake.

Alarmingly, high doses of butalbital may lead to extended discontinuation effects or a post-acute withdrawal syndrome (PAWS).  Researchers highlight the fact that butalbital-containing agents are often overused and overuse can exacerbate headache, plus withdrawal symptoms can occur.  For this reason, they note that usage of products such as Fioricet warrant significant caution and professional oversight.  Moreover, it is recommended to only use butalbital-based agents when other safer options are ineffective.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11903523

Limitations associated with research of Fioricet for Migraines

There are some limitations associated with the research of Fioricet for migraines.  It is because of these limitations that approximately half of medical professionals will consider this as a feasible off-label treatment, while others will regard it as a clinically ineffective intervention.  The agent hasn’t been subject to robustly designed studies for the treatment of migraines.  Dismissal of its efficacy as an intervention for migraines may be premature, especially among non-responders to first-line interventions.  Future research should attempt to address some of these limitations.

  • Efficacy: Most research indicates that the efficacy of Fioricet is likely ineffective for the treatment of migraines. Unfortunately, whether the agent is actually ineffective may be subject to debate on the fact that it is effective for various types of headaches.  Additionally, it hasn’t been extensively assessed in robustly designed trials.  It may necessitate a large-scale, favorably-designed study to understand whether it holds any therapeutic value as an antimigraine.
  • Long-term outcomes: The long-term treatment outcomes associated with administration of Fioricet are unclear. Some speculate that Fioricet may be safe when used sparingly and/or infrequently over long-term.  Others highlight the fact that Fioricet is associated with abuse and tolerance onset, and as a result, its efficacy may dwindle with repeated administration.
  • Migraine subtypes: The pathoetiological underpinnings of migraine headaches may be subject to significant interindividual variation among suffers. It could be hypothesized that Fioricet may be useful for specific neurophysiological migraine footprints and completely useless for others.  Researchers may want to differentiate those who are likely to respond to Fioricet from those who are unlikely to respond.
  • Safety: There remain plenty of safer, more proven options on the market compared to Fioricet. While it is not classified as a “Schedule III” controlled-substance in all of the U.S., four states make it tougher for patients to attain Fioricet prescriptions.  Clearly it can impair motor skills which increases odds of a motor vehicle accident among those who pop a Fioricet before driving.  The barbiturate constituent (butalbital) is easily abused and withdrawal symptoms may be dangerous.
  • Study designs: To determine whether Fioricet is effective for the treatment of migraines, future studies should be placebo-controlled, double-blinded, and randomized with large sample sizes. The currently published evidence lacks the robust designs and large samples.  In the liberal trial designs that have tested Fioricet, it has shown no significant efficacy over a placebo for migraines.
  • Refractory migraines: A subset of individuals with refractory and/or unremitting migraines may report significant benefit from Fioricet. Since Fioricet is effective for other types of headaches, it may at least warrant consideration for seemingly unmanageable, refractory migraine cases.  Researchers may wish to investigate its efficacy strictly among those who are unresponsive for first-line and second-line options.

Based on the evidence, should Fioricet be used for migraines?

No. From a clinical perspective, there’s not strong enough evidence to support the usage of Fioricet for migraines.  That said, there is weak evidence to suggest that a subset of individuals derive antimigraine benefit from the drug when administered at a low dose, on an as-needed basis.  Since Fioricet is approved to treat tension, post-dural, and muscle contraction headaches – one could speculate that it may provide some benefit to those with uncommon forms of migraines.

It should also be considered that a subset of responders to Fioricet claiming to derive antimigraine benefit from its administration, may not actually have migraines at all.  There are likely symptomatic similarities between various types of headaches and migraines, blurring the diagnostic lines for patients and practitioners.  Someone with a severe tension headache may convey that he/she has a migraine, when in reality, he/she has tension headaches; taking Fioricet may prove extremely helpful for these individuals.

There are numerous drawbacks associated with using Fioricet for the management of migraines, and even headaches.  Those taking the drug will experience CNS depression as a result of the butalbital contents, thereby impairing their ability to operate a motor vehicle and/or heavy machinery.  Someone reliant on motor vehicle transportation and/or working as a machinist may be unfit for Fioricet usage; the barbiturate increases likelihood of accidents and injuries.

Most problematic is the fact that over a long-term, frequent usage of Fioricet is detrimental to general health.  Not only may migraines and/or headaches worsen with overuse, but users may become tolerant, addicted, and/or encounter potentially fatal contraindications associated with mixing Fioricet and another substance.  Additionally, those hoping to discontinue Fioricet will need to do so with extreme caution – as withdrawal symptoms (e.g. seizures) can be dangerous.

Among a small percentage of patients that fail to derive benefit from every other logical migraine intervention, Fioricet may be therapeutic if used cautiously and infrequently.  The bottom line is that there are a multitude of superior options to Fioricet for migraine management.  Unless someone has already employed all other first-line and second-line agents only to attain no symptomatic relief, Fioricet is not a smart treatment.

Have you tried Fioricet for migraines?

If you’ve tried Fioricet for the treatment of migraines, feel free to share a comment regarding your experience.  Prior to taking Fioricet, had you tested any other medications for your migraines?  If so, share how many medications you tried, the specific ones you tested, and whether they provided any symptomatic relief.

To help others get a better understanding of your situation, include some additional details in your comment such as: the dosage of Fioricet you take, how frequently you use it, and whether you take any other agents (supplements or medications) along with it.  While taking Fioricet, did you notice any unwanted side effects?  For those that have experience with long-term Fioricet usage, did you build up a tolerance to its effects?

Realize that most medical professionals will not prescribe Fioricet for migraines, but the ones that do prescribe it, may do so on the basis that it is FDA approved for tension headaches.  The literature indicates that individuals with legitimate migraine diagnoses are likely to derive more significant therapeutic benefit from other agents with FDA approval compared to Fioricet.  Nevertheless, anecdotes of those reporting subjective antimigraine relief from Fioricet will continue to circulate throughout the internet.

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{ 2 comments… add one }
  • N. Bullard March 10, 2016, 8:31 pm

    Butalbytal (Generic): Fioricet is a brand name medication comprised of the following ingredients: butalbital (50 mg), acetaminophen (300 mg), and caffeine (40 mg) most assuredly DOES work and extremely well. The key to it’s effectiveness in my experience has been, “The pill MUST be taken “IMMEDIATELY” at the first sign of an approaching Migraine.

    And I do mean IMMEDIATELY! When this is done, my Migraines never get the chance to get started. I carry these pills with me at all times as a Migraine can strike anywhere. I strongly advise anyone having difficulty finding an effective treatment, to discuss Fioricet/ Butalbytal with your physician. I refer to the exact combination posted above: butalbital (50 mg), acetaminophen (300 mg), and caffeine (40 mg).

    “Based on the evidence, should Fioricet be used for migraines?” Based upon my personal experience “YOU BET YOUR LIFE IT SHOULD BE USED FOR MIGRAINES.” This appraisal of the medication can only have been put forth by a competitor!

  • Wondering May 13, 2016, 5:59 am

    I have suffered from migraines, extending into severe atypical (classic, hemiplegic) migraines for most of my life, exacerbated after childbirth at the age of 25. I am now in my sixties. I have been prescribed Fioricet since the age of 29. I have tried other medications, to no avail. After the hemiplegia was taken into account, physicians decided that I shouldn’t be taking Triptans, as they could cause stroke (though I had tried them a few times, beforehand).

    The FDA, along with others, do not take atypical migraines into account. Triptans are also dangerous. NSAIDS can cause ulcers. Actually, all drugs have side effects. I ingest a small amount of Fioricet, daily. Yes, I am dependent — so what. If there is a war on and I cannot obtain my drugs, I will die, but I may have died, anyway.

    I do not think that I act drunk, any more than say, someone may have his/her affect modified with the use of an antidepressant, or other drug. I never got high on a Fioricet; it only dampened down my headache. Fioricet DEFINITELY helps migraines! So do opiates — used sparingly. The short time I injected Triptans (injectable, when they first came out), they didn’t work any better than Fioricet, and had other side effects.

    I would rather a small amount of Fioricet in my bloodstream, than the jolt of a Triptan drug… God only knows which is better for one’s vascular system. If Fioricet were to be taken off the market, I would definitely die. The easiest way for the Government to create drug addicts, is to overly regulate or discontinue such a medication (and btw, I have tried medical detoxes four times); the author of this article is wrong in his/her conclusion, but correct in noting that Fioricet is almost impossible to detox from…

    It would help if insurance companies would extend detox stays, but that is yet another issue). However, my point is that Fioricet works very well for many migraineurs, and is crucial to some. Therefore, it should not be discontinued.

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