Botox (onabotulinumtoxinA) is a purified toxin derived from fermentation of the anaerobic bacterium Clostridium botulinum type A. Most people are familiar with the cosmetic application of Botox whereby it is injected into facial muscles with the intent of reducing wrinkles, enhancing skin smoothness, and improving facial aesthetics.
However, in addition to its cosmetic use, Botox is frequently recommended for the management of various medical conditions, including migraine headache. In fact, as of 2010, Botox has been approved by the FDA as a prophylactic (preventative) treatment for chronic migraine.
This FDA approval was based upon evidence from large-scale randomized controlled trials in which Botox was discovered to be safe, well-tolerated, and effective (relative to a placebo) in migraine patients. Because Botox is medically-endorsed for the treatment of chronic migraine, anyone with a history of migraine may want to consider Botox as an adjunct or alternative to antimigraine medication.
Botox for Migraines: According to research, is It Effective?
Yes. Nearly all large-scale, randomized controlled trials indicate that Botox is an effective treatment for chronic migraine in adults – hence its approval by the United States FDA in 2010. The Guideline Development Subcommittee of the American Academy of Neurology reports that there’s Level A evidence to support the clinical use of Botox as a migraine preventative.
Strongest evidence to support the safety, tolerability, and effectiveness of Botox as a migraine preventative is derived from the PREEMPT (Phase 3 Research Evaluating Migraine Prophylactic Therapy) clinical trial. The PREEMPT clinical trial included 1384 adults with chronic migraine who participated in a 24-week double-blind, randomized controlled trial in which either Botox OR placebo injections were administered twice.
After the initial 24-week randomized controlled trial, PREEMPT implemented an open-label phase in which 1236 patients (i.e. all patients who completed the first RCT phase) received 3 Botox treatments (one every three months) over a 32-week duration. An analysis by Aurora et al. (2018) indicated that recipients of Botox exhibited significant reductions in the frequency of headache days compared persons who received a placebo.
Furthermore, recipients of Botox exhibited significant reductions in: frequency of migraine days, number of moderate/severe headache days, and total hours of headache. Considering these findings, it appears as though long-term treatment with Botox (over 56 weeks) is safe, effective, and well-tolerated among adults with chronic migraine.
Additionally, when compared to migraine prophylactic medications, Botox exhibits equal efficacy, significantly fewer side effects, and lower rates of discontinuation (due to unwanted side effects). Blumenfeld et al. (2008) reported that Botox: was equally as effective as Depakote (a migraine prophylactic medication); exhibited a trend for greater reduction of headache severity (versus Depakote), and had lower rates of discontinuation due to side effects (3.3%) compared to Depakote (27.6%).
A study by Mathew and Jaffri (2009) reported that Botox was as effective as Topamax (100-200 mg/day) in preventing migraine and was associated with fewer adverse effects (2.7% Botox vs. 24.1% Topamax). Other randomized controlled trials and clinical observational studies support the usefulness of Botox as a migraine prophylactic.
What’s more, Botox appears effective for refractory chronic migraine (in which 3+ conventional migraine therapies are ineffective), pediatric chronic migraine, and common migraine comorbidities such as: anxiety, cervical dystonia, depression, and myofascial pain. A significant percentage of persons who pursue Botox for migraine derive substantial long-term therapeutic benefit and exhibit improvements in health-related quality of life.
How Botox (onabotulinumtoxinA) works for migraine headaches (Mechanisms of Action)
Although data clearly indicate that Botox is effective for the prevention of migraine headache, the mechanism(s) by which it works for migraine aren’t fully understood. Ramachandran and Yaksh (2014) outline several mechanisms by which botulinum toxins (BoNT) likely prevent migraine headaches [in patients who respond to Botox therapy], including: muscle tone modulation; anti-inflammatory actions; antinociceptive actions; and neuronal modulation.
However, other researchers like Solomon (2011) believe that the efficacy of Botox in migraine is solely attributable to placebo effect. Included below is a summary of the possible mechanisms by which Botox injections may reduce the prevalence and/or magnitude of migraine attacks.
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Myorelaxation (Muscle Relaxation)
Another way in which Botox might treat migraines is via the induction of myorelaxation (muscle relaxation). It has been suggested that chronic or pathological muscle tension within the face and/or head might cause and/or trigger migraine headaches – at least for a subset of migraine patients.
After Botox injections, a myorelaxant effect occurs such that the chronic or pathological muscle tension is attenuated. Specifically, Botox is thought to block acetylcholine release from motor neurons which yields relaxation of overactive muscle fibers.
Relaxation of [previously-overactive] muscle fibers may reduce the secretion of inflammatory mediators that sensitize primary nociceptive neurons. Because muscle tension (within the face or head) might significantly decrease from Botox injections, this might prevent migraines or reduce the frequency of migraine attacks in certain persons.
Although this could be a mechanism by which Botox prevents migraines (in a subset of patients), researchers remain skeptical that Botox-induced myorelaxation is culpable for antimigraine effects. Skepticism of this action stems from the fact that: (1) Botox alleviates migraine in patients with cervical dystonia (a condition with heightened muscle tone); (2) no reduction in muscle tension have been observed in studies following Botox administration.
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Anti-inflammatory effect (Neuropeptide inhibition)
Another possible means by which Botox injections might treat migraine is via the generation of an anti-inflammatory effect. For general context, when stimulated locally, peripheral terminals of unmyelinated sensory afferents exhibit calcium-dependent vesicle-mediated release of neuropeptides such as: substance P (SP) and calcitonin gene-related peptide (CGRP).
Both substance P and CGRP can trigger downstream reactions such as: mast cell degranulation (cellular release of antimicrobial, cytotoxic, or other molecules from vesicles) and chemotaxis (cellular movement) of inflammatory cells. The combination of degranulation and chemotaxis can activate peripheral nerve terminals and facilitate neuropeptide release.
The release of neuropeptides in migraine patients may have unfavorable consequences, including: vasodilation and increased capillary permeability – each of which have been linked to migraine. Following the administration of Botox, the release of peptides from nerve terminals, and unfavorable consequences like vasodilation and capillary permeability, are blocked.
In fact, the localized blockade of neuropeptide release provided by Botox occurs within just hours of injection. Essentially, Botox may break a loop of chronic inflammation stemming from a combination of overactive muscle fibers, nociceptive neurons, peptide release, and peripheral/central sensitization – to prevent and/or reduce migraine attacks.
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Central afferent transport modulation
Research indicates that Botox might prevent migraine by modulating central afferent transport. Scientists have noted that the localized paralytic action of Botox is associated with the uptake of Botox in both motor neuron terminals and sensory afferents – especially C poly-modal peptidergic nociceptors – as is evidenced by alterations in antidromic vasodilation and neurogenic inflammation following injections.
Furthermore, it appears as though Botox is not only uptaken by sensory and motor terminals, but transported rapidly via axons to central terminals. This central terminal transport has been proven using radioactive tracers and observed via animal studies in which cleavage of SNARE protein in the dorsal root ganglion and motor neurons was observed after Botox injection.
The effect of Botox on central afferent transport is evidenced by: (1) inhibition of substance P release from ipsilateral primary C fibre afferents and inhibition of ipsilateral cFOS expression; (2) inhibition of substance P and cFOS activation in the dorsal horn; (3) and an antinociceptive response. Additionally, animal studies indicate that the central effects of Botox can be countered with axon transport blockers.
Findings to date indicate that peripheral Botox is uptaken in afferent axons and transported in an active form to the spinal root ganglion of axons innervating the injection site. Moreover, some speculate that from the spinal root ganglion, Botox is able to modulate inputs from intracranial meninges to prevent migraine – possibly by reducing substance P, cFOS, and CGRP release.
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Transsynaptic Movement
One way in which Botox has been hypothesized to prevent migraines involves transcytotic movement within neurons and glial cells. (For reference, transcytosis refers to a type of cellular transport in which macromolecules are transported across the inside of a cell).
Evidence suggests that Botox may undergo transsynaptic movement from the central afferent terminal to “second order neurons” (neurons which relay information from the CNS to the thalamus). The transsynaptic movement of Botox is also thought to reach meningeal afferents that are implicated in the release of proinflammatory neuropeptides.
Despite the fact that there are no strong data indicating that transsynaptic movement of Botox is responsible for its antimigraine effect, this is a hypothetical mechanism of action that warrants further investigation. Assuming Botox injections decrease SNARE-mediated actions, it’s possible that this could (presynaptically) alter inputs of meningeal afferents or excitation of second-order neurons – such that migraines become: less frequent and/or easier to tolerate.
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Placebo Effect (?)
Seymour Solomon (MD) makes a case that the primary means by which Botox prevents migraine is through a placebo effect. Solomon notes that the placebo effect has been shown to: (1) suppress activation within excitatory pain processing areas of the brain, and (2) activate cortico-brainstem pain inhibitory pathways.
In his paper, Solomon mentions that the most important determinants in generating a placebo effect include: (1) expectation (whether someone expects the intervention to be effective) and (2) conditioning (environmental content of the treatment). It is known that many trials have showcased the power of expectation in generating placebo analgesic effects and augmenting preexisting pain suppression.
According to Solomon, expectation that a treatment (like Botox) will work for migraine – ends up changing cortical activity: neuronal activity increases throughout inhibitory pathways of the prefrontal cortex and periaqueductal grey area. What’s more, some studies suggest that open/observable placebo administration is more effective than hidden administration.
When Botox is administered for chronic migraine, nearly every factor necessary for induction of a strong placebo effect is present:
- Botox is a needle-administering therapy: Needle-based therapies generate a stronger placebo response when compared to pills.
- Botox is novel and invasive: Novel and invasive therapies are generally associated with stronger placebo responses than standard and/or non-invasive therapies.
- Botox involves many injections: Multiple administrations of a placebo usually generates a stronger placebo response than a single administration.
- Patients observe Botox injections: The ability of patients to observe placebo administration is understood to generate a stronger placebo effect than when procedures are unobservable.
- Patients see rapid results: When Botox is administered, patients quickly observe that it reduces wrinkles – and expect that it’s also working rapidly for headache. (Solomon pointed out that in trials of Botox for migraine, patients could tell if they weren’t receiving Botox based on whether it reduced wrinkles; meaning a true placebo was not employed in clinical trials).
- Clinical trial participation: Patients being informed that they were participating in a “clinical trial” was suggested to strengthen any placebo effect resulting from Botox.
- Botox cost: The expense of Botox treatment (usually around $1000 per treatment) adds to the expectation that it should work for migraine.
- Authority presence: The authority of doctors and medical staff telling a patient that Botox may work – adds to preexisting expectation which could strengthen the placebo effect.
Considering the case presented by Solomon, it’s reasonable to surmise that the effectiveness of Botox in migraine prophylaxis (and other conditions) could be attributable to a strong placebo response. Nevertheless, even if Botox ends up generating a placebo response to prevent migraine – this placebo response appears therapeutically valuable.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/21631480
- Source: https://www.ncbi.nlm.nih.gov/pubmed/22082429
- Source: https://www.ncbi.nlm.nih.gov/pubmed/26193319
- Source: https://www.ncbi.nlm.nih.gov/pubmed/26170679
- Source: https://www.ncbi.nlm.nih.gov/pubmed/248193
Benefits of Using Botox for Migraines
Below is a list of benefits associated with using Botox as a migraine prophylactic. Some of the most significant benefits of using Botox to treat migraine include: its long-term therapeutic effect; its favorable side effect profile (especially compared to antimigraine medications); and the fact that it’s an evidence-based therapy (supported by high-quality, Level A evidence).
Adjunct intervention: One advantage of using Botox for the management of migraine is that it won’t require patients to discontinue preexisting migraine prophylactic medications and/or abortive agents (e.g. triptans). Because Botox injections don’t interact with antimigraine medications, patients can reap the simultaneous antimigraine effects of prophylactic medication plus Botox.
Moreover, it’s possible that in some cases, there may be synergistic benefit attained from the combination of Botox and a migraine prophylactic medication (e.g. topiramate). For patients who aren’t willing to discontinue preexisting migraine prophylactic medications – Botox is an adjunct worth trying.
All ages (?): Large-scale randomized controlled trials (e.g. PREEMPT) indicate that Botox is safe, tolerable, and effective for the treatment of chronic migraine in adults. That said, there’s preliminary evidence suggesting that Botox may also be safe, tolerable, and effective in pediatric (non-adult) populations with chronic migraine.
For example, a study by Chan et al. (2009) reported that 6 adolescents (ages 14 to 18) with chronic migraine who received Botox exhibited: improvements in headache symptoms; lower headache pain; and better quality of life – as a result of the therapy. An analysis by Kabbouche et al. (2012) encompassing 45 pediatrics with chronic migraine discovered that Botox treatment significantly reduced headache/migraine frequency.
Alternative to medications: It is understood that migraine prophylactic medications and abortive therapies (e.g. triptans) can cause unwanted side effects in many users. In addition to antimigraine medications causing unwanted side effects, some patients with chronic migraine derive insufficient benefit from the use of medications.
Furthermore, it is well-documented that patients with severe chronic migraine frequently overuse abortive therapies (e.g. triptans) which can have negative health consequences. Comparative research (Botox versus an antimigraine medication) indicates that Botox is equally as effective as migraine prophylactic medications (e.g. Depakote, Topamax, etc.) and causes significantly fewer side effects – making it a favorable (perhaps superior) alterative to medication.
Comorbid depression, anxiety, cervical dystonia: Another significant advantage associated with using Botox for the treatment of migraine is that it may effectively treat comorbid medical conditions. A few comorbid medical conditions that Botox may treat include: major depression, anxiety, and cervical dystonia. (Read more: “Botox for depression“).
If you have a comorbid condition (in addition to chronic migraine) for which Botox has been shown to treat – you may be able to effectively treat 2 conditions with one non-medication therapy. Research by Ranoux et al. (2017) documented that Botox significantly reduced myofascial and cervical pain in 63 patients and a study by Winner et al. (2012) noted that Botox reduced symptoms of cervical dystonia (in addition to reducing headache frequency).
Maasumi et al. (2015) reported that Botox treatment decreased symptoms of depression among persons with moderate-to-severe depression and migraine at baseline. Research by Boudreau et al. (2015) also suggested that Botox can treat chronic migraine while reducing symptoms of comorbid depression and anxiety.
Cosmetic enhancement: Though the purpose of using Botox in migraine is to reduce the frequency and severity of migraine attacks, an added benefit that many patients attain from this procedure is cosmetic enhancement. When injected into facial muscles, Botox blocks nerve signaling to these muscles such that they can no longer contract.
Because the facial muscles are unable to contract after Botox injections, the appearance of wrinkles becomes more relaxed, softer, and less pronounced. Most middle-aged and/or older adults with preexisting wrinkles in areas such as the forehead, near the eye, and mouth – will notice improved facial aesthetics after a Botox procedure.
Evidence-based: Botox is no longer considered some random experimental procedure for the treatment of migraine – it has been approved by the United States Food & Drug Administration (FDA) as a migraine prophylactic since 2010. According to the Guideline Development Subcommittee of the American Academy of Neurology, there’s “Level A” evidence to support the use of Botox for chronic migraine.
Level A evidence means that Botox is clinically effective and should be offered to patients with chronic migraine. Considering the strong evidence substantiating the effectiveness of Botox in the treatment of chronic migraine – it should have a good chance of eliciting a therapeutically-relevant migraine prophylactic effect in most patients.
Long-term effect: Another appealing aspect of using Botox to treat migraines is that a single set of injections generates a long-term therapeutic effect – usually lasting at least 3 months. Some research suggests that for certain migraine sufferers, the migraine prophylactic effect from Botox may extend beyond 3 months – usually for a maximum of 4 months.
Nonetheless, the long-term antimigraine effect from a single set of Botox injections is probably preferred by most patients with migraine over the short-term effect of most migraine prophylactic medications (which generally once or twice daily administration). Moreover, there’s evidence to suggest that the effect of Botox seems to improve over time – such that there’s a greater reduction in migraine frequency after 5 treatment sessions compared to 2.
Quality of life improvement: A major problem associated with untreated chronic migraine is that it significantly impairs health-related quality of life (HRQoL), or the combination of physical, mental, emotional, and social functioning. Numerous studies indicate that, in addition to effectively preventing migraine attacks, Botox enhances health-related quality of life in migraine sufferers.
A report by Escher et al. (2017) noted that there’s “Level B” evidence to support the idea that Botox improves health-related quality of life in persons with chronic migraine. Moreover, an analysis of the PREEMPT trial by Lipton et al. (2016), specifically assessing change in quality of life in patients with chronic migraine after Botox treatment, documented significant improvement in domains of health-related quality of life.
Rapid onset of action: Most studies suggest that Botox exhibits a rapid onset of therapeutic action in preventing migraine attacks. Some studies have reported significant reductions in migraine frequency and severity within the first month after a single Botox treatment – suggesting that it takes effect quickly.
If you receive Botox for migraine and respond favorably, the antimigraine effect should be noticeable soon after your injection. Certain Botox recipients report immediate benefit (right after the injection is administered), whereas others report benefit within several days of the injection.
Refractory & chronic migraine: Certain individuals with migraine are diagnosed as having refractory chronic migraine. Chronic migraine is defined as headache occurring 15+ days per month for over 3 months – with at least 8+ days per month of migraine.
Refractory chronic migraine indicates that a patient diagnosed with chronic migraine has failed at least 3 first-line migraine treatments. Studies by Ranoux et al. (2017), Oterino et al. (2011), and Conway et al. (2005) support the idea that Botox appears safe and effective for the management of refractory chronic migraine.
Tolerability: When compared to antimigraine medications, Botox is less likely to provoke severe and/or unwanted side effects and is better tolerated. Fewer patients using Botox end up discontinuing treatment due to adverse effects than patients using migraine prophylactic medications.
For example, one comparative study indicated that 27.6% of Depakote users discontinued treatment due to adverse effects – whereas only 3.3% of Botox users stopped receiving Botox injections due to adverse effects. Another comparative study noted adverse effects in 24.1% of Topamax users – and in just 2.7% of Botox users.
Moreover, research suggests that adverse effects resulting from Botox are generally transient (such that they spontaneously resolve within days or weeks of injections) and are of mild or moderate severity.
Drawbacks of Using Botox for Migraine
Despite the fact that there are significant benefits associated with using Botox for migraine, there are also a few drawbacks that warrant discussion. Several drawbacks associated with using Botox for migraine include: high cost per treatment; adverse long-term effects; and ineffectiveness for a subset of migraine sufferers.
High cost: Botox is certainly not a cheap intervention for the treatment of chronic migraine. Although some studies suggest that by reducing the frequency of disabling attacks, use of triptans, and migraine-related emergency room visits – Botox actually saves the patient money in the long-term, others remain skeptical.
The cost of Botox for migraine will vary depending on the clinic at which you receive injections, as well as your geographical location. Most sources online suggest that the cost of Botox for migraine costs over $500 per vial (100 U) and the typical migraine dose is 155 U.
Hypothetically, assuming you required 2 vials for a 200 U dose – this could cost between $1000 and $1500 per treatment. Because Botox will need to be administered once every 3 months, you may end up paying around $4000 per year in Botox treatments for migraine.
Compared to generic prophylactic medication and triptans (which shouldn’t cost more than a few hundred dollars per year) – you’ll probably end up spending significantly more money on Botox. Even if routine doctor visits for prescription refills are factored into the equation, the Botox will likely end up being more expensive.
Long-term effects: Botox is generally a very safe and useful procedure, even when administered regularly over a long-term. However, one report documented “local muscle atrophy” as an adverse reaction in a small percentage of migraine patients who had been receiving Botox treatment for over 5 years to control migraine symptoms.
Local muscle atrophy is not a surprising adverse reaction to Botox – most medical doctors are aware of this potential complication. Muscle atrophy occurs from prolonged Botox exposure due to the fact that Botox is preventing nerve signals from reaching facial muscles.
Lack of nerve signaling to these muscles inhibits contraction, and inhibition of contraction causes atrophy or wasting over time. That said, most medical professionals do not consider facial muscle atrophy from Botox to be a serious or clinically significant complication – when properly administered, muscles should still be able to slightly contract and maintain tone.
Not universally effective: Like all interventions for migraine, Botox is not effective in all chronic migraine patients. Certain individuals may pursue Botox treatment for chronic migraine (spending over $1000) and end up with zero change in the frequency and/or severity of migraine attacks.
Others may pursue Botox treatment for migraine and derive partial or insignificant benefit from its administration. Although Botox is effective for a majority of patients with chronic migraine, anyone pursuing this therapy should be informed of the possibility that it is not universally effective (such that it may not work in certain patients) and that its therapeutic effect may vary in magnitude among patients.
Possibly ineffective long-term: While research suggests that cumulative therapeutic benefit is attained for 5 Botox treatment sessions among patients with chronic migraine – some studies suggest that the efficacy of Botox diminishes after 1 year in a subset of patients who originally responded well to the therapy. In other words, there’s a chance that Botox might provide migraine relief for a lengthy duration (e.g. 1-2 years) followed by lack of effect thereafter.
Although the effect of Botox might fade over time such that it no longer reduces the frequency and/or severity of migraine headaches in a subset of persons who initially responded well to Botox, most evidence indicates that Botox gets more effective over time in migraine patients. Nevertheless, lack of reliable therapeutic effect beyond 1 or 2 years could be a relevant drawback in a small percentage of recipients.
Slow onset of action: While most individuals who receive Botox for migraine will respond quickly to its effect, others may not report any noticeable benefit until at least 1-month following injection. A study by Byun et al. (2017) documented that 10 patients with migraine who displayed “no response” to Botox at the first 4-week follow-up – ended up displaying significant improvements in migraine symptoms at the 3-month follow-up.
Considering this observation, it’s possible that some individuals may not respond to Botox for migraine until at least 1 month has passed after the injections. If you are a slow or delayed responder to Botox – you may question whether Botox really worked (because no effect was noticed in the first month) OR you may think that Botox didn’t work (even if it did) due to the delay in onset of therapeutic relief.
Botox for Migraines (The Research & Studies)
Included below are summaries of studies in which Botox was investigated as a migraine prophylactic. Understand that while there are limitations associated with several of the studies listed below (e.g. small sample size, confounds, duration, sample homogeneity, lack of controlling), there are also many well-designed studies with no significant limitations.
As you’ll read, nearly all studies and/or literature reviews support the idea that Botox is a safe, tolerable, and effective as a migraine prophylactic. There don’t appear to be any studies in which Botox was reported as ineffective, unsafe, and/or intolerable. Strongest evidence to substantiate the use of Botox as a migraine prophylactic is derived from the 56-week PREEMPT clinical trial.
2018: OnabotulinumtoxinA for treatment of chronic migraine: pooled analyses of the 56-week PREEMPT clinical program.
Aurora et al. conducted a study to determine the safety and efficacy of Botox as a migraine prophylactic. For their study, researchers pooled data from the 56-week PREEMPT (Phase 3 Research Evaluating Migraine Prophylaxis Therapy) – consisting of multiple 24-week double-blind, parallel-group, placebo-controlled studies – followed by a single 32-week open-label single-treatment trial.
A total of 1384 individuals with migraine participated in these trials and were assigned at random to receive Botox (155-195 U) or a placebo – every 12 weeks for 5 cycles. The primary endpoint for analysis was average change in the number of headache days from baseline.
Secondary endpoints included: number of patients with severe Headache Impact Test-6 scores; average changes in frequencies of migraine days (from baseline); number of days with moderate/severe headaches; number of migraine episodes; total hours of headache on headache days; and use of headache medication. Of the 1384 starting participants, 1236 completed the initial randomized controlled phase – and participated in the open-label phase.
Results indicated that recipients of Botox throughout the trial exhibited substantial reductions in the frequency of headache days (compared to a placebo) – throughout 56 weeks. Additionally, Botox recipients exhibited substantial improvements on secondary measures such as: frequencies of migraine days; number of moderate/severe headache days; and total hours of headache on headache days.
Based on these findings, researchers noted that treatment with 5 cycles of Botox appeared effective, safe, and well-tolerated among adults with chronic migraine. This analysis supports the use of Botox as a migraine prophylactic.
2017: Utilization and safety of onabotulinumtoxinA for the prophylactic treatment of chronic migraine from an observational study in Europe.
Matharu et al. sought to determine the usage rates and safety of Botox as a migraine prophylactic when administered in routine clinical settings. Researchers designed a prospective, observational, post-authorization study in which data were collected from 1160 adult patients (~84% female) with chronic migraine who received Botox treatment from 85 physicians (81% neurologists) at 58 practices throughout Europe.
It was noted that data were collected at the first study injection and every ~3 months thereafter for a total of up to 52 weeks (to determine utilization) and up to 64 weeks (to determine safety). Before Botox treatment, 85.8% of patients had chronic migraine/transformed migraine – and reported approximately 11.3 severe headache days per 28 days.
Over half of all participants in this study (50.6%) had previously used Botox for chronic migraine. Based upon observation of 4,017 treatment sessions – the number of Botox injection sites (~31) and dosages (~155 U) were consistent among study participants. The median time between Botox treatment sessions was 13.7 weeks.
Results indicated that 291 (25.1%) of the 1160 participants experienced at least one adverse effect – the most common being neck pain (4.4%). Patient satisfaction with Botox for migraine was high; 74.4% of patients were reportedly “satisfied” or “extremely satisfied” with the treatment. Researchers concluded that Botox appears to be safe and effective in real-world clinical settings among patients with migraine.
2017: Botulinum toxin in the management of chronic migraine: clinical evidence and experience.
Escher et al. reported that Botox was approved by the FDA in 2010 for the prevention of migraine – in patients diagnosed with chronic migraine. In the report by Escher et al., it was mentioned that, according to the Guideline Development Subcommittee of the American Academy of Neurology, there’s “Level A” evidence to support the use of Botox for chronic migraine.
For general reference, “Level A” evidence means that an intervention is clinically effective and should be offered to patients. In addition to “Level A” evidence in support of Botox for chronic migraine, there’s “Level B” evidence suggesting that Botox can improve health-related quality of life (HRQoL) in persons with chronic migraine. (Level B evidence means that an intervention is likely effective and warrants consideration).
Authors of this report concluded that Botox is well-tolerated and effective for migraine, plus might improve health-related quality of life in migraine patients. Although the long-term effectiveness and cost-effectiveness of Botox remain somewhat unclear – this report suggests that Botox is an excellent treatment option for migraine patients.
2017: Acupuncture and botulinum toxin A injection in the treatment of chronic migraine: A randomized controlled study.
Naderinabi et al. conducted a randomized controlled trial in which the efficacies of acupuncture, Botox, and antimigraine medication were compared for the treatment of chronic migraine. A total of 150 patients (48 males, 102 females) participated and completed the trial in which they were assigned at random to receive: (A) TCM acupuncture; (B) Botox; or (C) antimigraine medication (sodium valproate 500 mg/day) – for a 3-month period.
At baseline (pre-trial) and throughout the study, a physician (blinded to the treatments) documented the following: adverse reactions; pain severity; medication use; days per month of pain; number of days per month of medication use; and days in which headache impaired functioning. Severity of pain was based upon scores from a Visual Analogue Scale (VAS).
Of the 150 participants, pain severity was significantly reduced in all 3 groups – with greatest reduction observed among TCM acupuncture recipients. Although results of this study indicated that TCM acupuncture was the most effective intervention for migraine with the fewest side effects – results still suggest that Botox injections and antimigraine medication effectively treat migraine.
2017: Prolonged Effect of OnabotulinumtoxinA on Chronic Migraine in 87 Koreans.
Byun et al. wrote a letter to the editor of the “Journal of Clinical Neurology” discussing the prolonged therapeutic effect of Botox in 87 Koreans with chronic migraine. The authors stated that, despite its estimated ~3-month efficacy for migraine prophylaxis, it remained unclear as to whether a single Botox treatment could generate a longer-term prophylactic effect (over 3 months) in a subset of migraine patients.
Additionally, until this report, the effectiveness and adverse effects of Botox hadn’t been reported in Korean populations. Data were presented from a study in which 100 Korean adults received a single Botox treatment session for migraine prophylaxis.
All participants were instructed to return for follow-up appointments at 4 weeks; 3 months; 6 months; and 1 year – post-treatment. Researchers measured: headache severity at each of the aforementioned follow-up checkpoints and categorized patients into 3 groups: (1) good responses (with no migraine attacks after treatment); (2) moderate responses (with significant improvement); or (3) no response.
It was stated that 9 patients were lost at the first follow-up (4 weeks) and 4 patients received multiple Botox treatments, leaving 87 patients for analysis (74.7% female). Moreover, it was stated that 51 of the 87 had been using antimigraine medications before receiving Botox treatment.
At the first follow-up (4 weeks post-treatment), 11 patients (12.6%) exhibited “good responses,” 52 patients (59.8%) exhibited “moderate responses,” and 24 (27.6%) exhibited “no responses.” Fewer patients returned for the 6-month (60 patients) and 1-year (41 patients) follow-up appointments, however, 75% and 63.4% displayed continued migraine improvement (over a long-term).
Furthermore, 10 patients with “no response” at the initial 4-week follow-up displayed improvements at the 3-month follow-up. Adverse effects were reported in 8 (9.2%) participants including: skin rash, injection site pain, dizziness, and headache – all of which resolved spontaneously without treatment.
Based on results of the presented trial, authors suggest that the therapeutic benefit of Botox may extend beyond its pharmacological action of 3 months – possibly due to modulation of central nociception. According to this report, Botox appears safe, effective, and well-tolerated in Korean adults with chronic migraine.
2017: OnabotulinumtoxinA injections in chronic migraine, targeted to sites of pericranial myofascial pain: an observational, open label, real-life cohort study.
Ranoux et al. conducted an open-label, real-life study in which 63 patients with refractory chronic migraine were observed following the administration of Botox (70 U to 150 U per treatment). Patients were characterized as “responders” if they exhibited at least a 50% reduction in the number of headache days for a minimum of 2 consecutive treatment cycles.
Of the 63 patients observed, 41 (65.1%) were “responders.” In 70.7% of “responders” the number of headache days was reduced by 70% – indicative of a large effect size. Concurrent cervical pain and muscle tenderness, reported in 33 patients, had decreased by 50% in 31 (94%) following Botox treatment.
Furthermore, usage of triptans (abortive medications) decreased significantly (by ~81%) in “responders” and no serious adverse effects were observed. Researchers concluded that Botox appears safe and effective for the treatment of chronic migraine and myofascial comorbidities – yielding an average patient satisfaction rating of 8.5 out of 10.
2016: OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine over one year of treatment: Pooled results from the PREEMPT randomized clinical trial program.
Lipton et al. analyzed pooled results from PREEMPT (Phase 3 Research Evaluating Migraine Prophylaxis Therapy) to determine the effect of Botox upon quality of life of patients with chronic migraine. In the PREEMPT trial, 1236 patients with chronic migraine were randomly assigned to receive Botox or a placebo (2 treatment sessions) over an initial 24-week period.
After the initial 24-week randomized controlled phase, all participants received 3 Botox treatments over the span of 36 weeks; 1 treatment was administered every 12 weeks. To determine the effect of Botox on health-related quality of life, researchers analyzed relevant data from the Headache Impact Test (HIT-6) and the Migraine-Specific Quality of Life Questionnaire (MSQ).
Data indicated that Botox recipients in the initial 24-week phase exhibited substantial reductions in HIT-6 and MSQ scores – compared to placebo recipients. In the open-label phase, HIT-6 scores were substantially reduced at week 28, week 36, and week 48 – among participants who received Botox in both the initial 24-week phase.
All measures of MSQ domains revealed improvements in health-related quality of life among participants compared to baseline, however, only one quality of life domain (role restrictive) was significantly improved among participants who received Botox in both trial phases (compared to the other group). It was concluded that Botox appears to improve quality of life among patients with chronic migraine.
2015: Onabotulinum toxin A (Botox) for chronic migraine treatment: an Italian experience.
Grazzi and Usai conducted a study in which 75 patients suffering from chronic migraine (who had been overusing antimigraine medication) received Botox injections. The aim of this study was to verify the effectiveness of Botox as a prophylactic for chronic migraine.
Prior to receiving Botox injections, patients underwent a 5-day hospitalized withdrawal from antimigraine medications that they had been overusing. Thereafter, patients received Botox treatment (31 injections at 155 UI per treatment) once every 3 months for the span of 1 year.
A total of 46 patients completed 3 Botox treatment sessions, and of these patients, the average number of headache days per month significantly decreased through the first 3 Botox sessions. At baseline, average number of headache days per month was ~21.7 – whereas by the end of the third session, average number of headache days per month was ~8.7.
It was also noted that the use of antimigraine medication significantly decreased among the 46 patients who completed 3 sessions. Among 20 patients who completed the full 1-year study, significant reductions in migraine days per month were observed. Though this was a small-scale uncontrolled trial, it supports the evidence that Botox is a useful and well-tolerated migraine prophylactic with an extended duration of action.
2015: Long-term experience with onabotulinumtoxinA in the treatment of chronic migraine: What happens after one year?
Cernuda-Morollón et al. noted that clinical trials only examined the effect of Botox [in the treatment of chronic migraine] for up to 1 year. Due to the relatively limited duration of clinical trials, researchers endeavored to determine the effect of Botox beyond 1 year of treatment in patients with chronic migraine.
For their study, researchers recruited 132 chronic migraine patients (mostly female) for participation. Of the 132 participants, 108 (81.8%) exhibited therapeutic responses to Botox in the first year. To determine the effect of Botox beyond 1 year of treatment, the 108 patients who had received Botox for 1 year (4 total injections; one per quarter) had their fifth injections postponed.
Results indicated that 49 (45.4%) of participants experienced a worsening of migraine symptoms as a result of injection postponement. It was reported that injections were stopped in 14 participants due to lack of efficacy (9.3%) or due to attenuation of attacks (3.7%).
Additionally, it was suggested that after ~2 years of Botox treatment, usage of abortive medication use decreased by 53% and emergency medical visits decreased by 61%. Researchers conclude that long-term Botox administration is an effective migraine prophylactic in around 75% of chronic migraine patients.
After the first year, Botox is no longer effective in around 10% of patients. In 40% of patients in this study using Botox injections as a long-term migraine prophylactic, injections could be delayed up to 4 months after the first year. Results of this trial indicate that Botox is a safe and effective long-term migraine prophylactic for patients with chronic migraine.
2015: Effect of OnabotulinumtoxinA Injection on Depression in Chronic Migraine.
Maasumi et al. retrospectively assessed the effectiveness of Botox injections on depression in patients who received injections to treat chronic migraine. Symptoms of depression were determined based upon changes in scores on the following measures: Patient Health Questionnaire-9 (PHQ-9); European Quality of Life (QOL); Headache Impact Test-6 (HIT-6); and Pain Disability Index (PDI) – over 6-12 months (with a minimum of 2 Botox treatments).
A total of 429 patients (mostly Caucasian females) met inclusion criteria set by researchers and generated relevant data for the retrospective analysis. Results indicated that Botox treatment in migraine patients significantly: reduced depressive symptoms among patients with moderate-to-severe depression at baseline; decreased headache scores; and improved quality of life.
2015: Prophylactic onabotulinumtoxinA in patients with chronic migraine and comorbid depression: An open-label, multicenter, pilot study of efficacy, safety and effect on headache-related disability, depression, and anxiety.
Boudreau et al. organized an open-label trial to assess the effectiveness of Botox in patients with chronic migraine plus comorbid depression. A total of 32 participants participated in the full duration of the study and received Botox treatment (155 units) at baseline and again at Week 12 (after 3 months).
Results indicated that within 24 weeks, there were significant improvements (relative to baseline) in headache/migraine frequency and scores on the following tests: Headache Impact Test; Migraine Disability Assessment; Beck Depression Inventory; Patient Health Questionnaire; Generalized Anxiety Disorder Questionnaire. No major adverse reactions were noted among participants.
In the 30% of patients who experienced adverse reactions, most were considered mild or moderate. Researchers concluded that Botox is an effective prophylactic for migraine and appears to alleviate comorbid symptoms of depression and anxiety.
2014: OnabotulinumtoxinA for chronic migraine: efficacy, safety, and tolerability in patients who received all five treatment cycles in the PREEMPT clinical program.
Aurora et al. conducted a secondary analysis of PREEMPT clinical trials specifically focusing on patients who received all 5 Botox treatment cycles and completed the entire study. As was mentioned, the PREEMPT clinical trials involved a 24-week randomized controlled phase (participants receive either Botox OR placebo) followed by a 32-week open label phase (all participants receive Botox).
According to researchers, 1005 of 1384 participants received all 5 treatment cycles; 513 received Botox throughout the entire study – and 492 received placebo in the controlled phase followed by Botox for the remainder of the trial. Results indicated that significant improvements in migraine were observed among patients who received all 5 Botox treatment cycles – compared to those who only received 3 Botox treatment cycles (during the open-label phase).
Based on this finding, researchers suggested that the prophylactic of Botox for the treatment of migraine may increase or compound over a long-term (56 weeks). In other words, the maximal therapeutic effect of Botox in migraine prophylaxis may not be attained until at least 5 consecutive treatment sessions have been completed.
2012: OnabotulinumtoxinA in pediatric chronic daily headache.
Kabbouche et al. conducted a retrospective review evaluating the efficacy and tolerability of Botox in pediatrics diagnosed with chronic migraine. Data for this review was collected from a large pediatric headache center between 2004 and 2010 – encompassing 45 patients and 252 Botox injections.
Results of the retrospective analysis indicated that patients exhibited reductions in migraine disability scores following Botox injections, however, these reductions were not deemed statistically significant. Nevertheless, statistically significant reductions were reported for headache/migraine frequency such that the number of headache days per month significantly decreased after Botox injections – at follow-up assessments.
Researchers concluded that Botox treatment was of substantial therapeutic value among pediatric patients with chronic migraine. Although more research of Botox as a migraine prophylactic is warranted in pediatrics, preliminary evidence suggests that it’s safe and effective.
2012: Concurrent onabotulinumtoxinA treatment of cervical dystonia and concomitant migraine.
Winner et al. examined the effect of Botox on symptoms of cervical dystonia among 25 patients diagnosed with migraine and comorbid cervical dystonia. Researchers hypothesized that Botox may prove effective as a standalone treatment for each of these medical conditions (migraine and cervical dystonia).
The 25 patients received 2 Botox treatments (separated by 3 months) and symptoms of cervical dystonia and migraine were recorded over a 7.5-month duration. Results indicated that patients exhibited substantial reductions in symptoms of cervical dystonia, number of headache days, and migraine disability following Botox injections – compared to baseline.
Researchers concluded that treatment with Botox is effective and well-tolerated among patients with migraine and comorbid cervical dystonia. There were no major adverse effects associated with Botox treatment.
2011: Experience with onabotulinumtoxinA (BOTOX) in chronic refractory migraine: focus on severe attacks.
Oterino et al. reported upon clinical experience with the use of Botox among 35 patients with chronic refractory migraine. The 35 patients received Botox injections (up to 200 U doses) once every 3 months and maintained headache diaries.
Patients were asked about the effect of Botox on: incidence of severe migraine attacks; triptan use; and emergency visits (to treat disabling attacks). Among the 35 patients receiving Botox injections: the number of Botox treatments ranged from 2 to 15.
A total of 9 patients (26%) exhibited reductions in headache days by at least 50% (compared to baseline). Additionally, incidence of severe migraine attacks decreased to 46%, triptan use decreased by 50% (in the 29 triptan users) from ~22 pills per month to ~11, and emergency visits dropped from ~3 to ~0.4 per trimester – following Botox therapy.
Though data compiled for this report is derived from clinical practices rather than randomized controlled trials, it suggests that Botox is effective in treating patients with refractory chronic migraine. Because Botox reduced severe migraine attacks, triptan use, and emergency visits – authors suggest that it is a cost-effective intervention.
2010: OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program.
Dodick et al. analyzed results from the PREEMPT clinical trial in which 1384 adults with chronic migraine were randomly assigned to receive either Botox or a placebo (2 treatment sessions) for an initial 24-week randomized controlled phase – followed by a 32-week open-label phase in which all participants received 3 Botox treatments (3 months apart). The aim of this analysis was to reflect upon the safety, tolerability, and efficacy of Botox.
The analysis revealed significant reductions in number of headache days (primary endpoint) among Botox recipients (relative to baseline and the placebo group) at week 24 and all other checkpoints. Furthermore, the analysis indicated that Botox recipients exhibited significant improvements in most secondary endpoints relative to the placebo.
Though some adverse effects were reported, most were manageable and very few participants discontinued as a result of adverse effects (3.8%). It was concluded that Botox is an effective, tolerable, and safe prophylactic for adults with chronic migraine compared to a placebo.
2009: A double-blind comparison of onabotulinumtoxina (BOTOX) and topiramate (TOPAMAX) for the prophylactic treatment of chronic migraine: a pilot study.
Mathew and Jaffri conducted a trial comparing the effect of Botox with Topamax (topiramate) for the prophylaxis of migraine – in patients with chronic migraine. A total of 60 patients were recruited for participation and assigned to receive either: Botox plus an oral placebo OR Topamax (100-200 mg/day) with saline placebo injections – over a ~10.5-month duration.
Injections (Botox and saline) were administered once at baseline and again after 3 months. Follow-up assessments were conducted at Month 1, Month 3, Month 6, and Month 9 – throughout the trial and adverse reactions were recorded. Of the 60 participants, just 36 patients completed the Month 9 follow-up assessment: 19 received Botox and 17 received Topamax.
Results of the study indicated that both Botox and Topamax were effective as migraine prophylactics among patients with chronic migraine. Comparatively, Botox was better tolerated (with just 2.7% of Botox recipients experiencing adverse reactions – compared to 24.1% of Topamax recipients) and had lower rates of discontinuation.
2009: Botox treatment for migraine and chronic daily headache in adolescents.
Chan et al. evaluated the efficacy of Botox as a migraine/headache prophylactic among 12 adolescents (14-18 years of age) who had been diagnosed with chronic migraine or headache. Of the 12 adolescents, 6 patients received long-term therapy with Botox injections once every 3 months.
The duration of treatment among participants ranged from 3 to 29 months. The effectiveness of Botox was determined by using pain scales and a quality of life survey. Among the 6 patients receiving long-term therapy, all 6 (100%) exhibited: reductions in headache symptoms; reductions in pain (33%-75%) scores; and improved quality of life (33%-75%).
Furthermore, 2 of the 6 long-term patients experienced no headaches between injections, 4 patients had favorable results after one set of injections, and 2 patients had no improvement from the injections. Although some adverse effects were noted, researchers concluded that Botox may prove effective as a treatment for migraine and/or chronic headache in adolescents.
2008: Botulinum toxin type A and divalproex sodium for prophylactic treatment of episodic or chronic migraine.
Blumenfeld et al. conducted a randomized controlled trial to compare the efficacies of Botox and Depakote (divalproex sodium) for the prophylaxis of migraine. A total of 59 patients participated in the trial and were assigned to receive either: Botox (100 U) with a placebo (b.i.d.) OR Depakote (250 mg, b.i.d.) with placebo injections. Injections were administered at baseline, and again after 3 months.
Participants were assessed at Month 1, Month 3, Month 6, and Month 9. Results indicated that both Botox injections and Depakote significantly reduced migraine disability scores, number of headache days, and headache index scores. There was a trend of reduced headache severity observed among Botox recipients – compared to Depakote recipients, however, it was not statistically significant.
That said, a significantly greater number of Depakote recipients reported adverse effects (75.8%) compared to Botox recipients (50%); 27.6% of Depakote users discontinued due to adverse effects whereas only 3.3% of Botox users discontinued due to adverse effects. Researchers concluded that both Botox and Depakote are effective migraine prophylactics – and Botox is more tolerable.
2005: Botox therapy for refractory chronic migraine.
Conway et al. conducted an open-label trial to determine the effectiveness and safety of Botox as a migraine prophylactic in patients with refractory chronic migraine. A total of 56 patients with chronic migraine who failed to respond to 3 or more prophylactic medications were recruited for participation; 75% female, ~47.2 years old, 16% experienced headaches for 15+ days per month.
The 56 patients with chronic migraine received Botox treatment and were instructed to maintain headache diaries until a follow-up appointment 6 weeks later. Results indicated that 23 of 56 patients (~41%) reported headaches as being “much better” after the treatment – and an additional 12 patients [who didn’t meet outcome criterion] reported headaches as being “somewhat better” or “much better” after the treatment.
Among the 23 responders, the average number of debilitating headache days per month decreased from ~15 to ~2 – and abortive therapy days per month decreased from ~21 to ~4. It was noted that, of the 56 participants, 38 patients were using prophylactic medications at baseline and continued using these agents throughout the trial.
Nonetheless, response rates were the same among patients irrespective of prophylactic use. Although this was an uncontrolled, small-scale study – it supports the idea that Botox therapy is effective for the management of chronic migraine among refractory cases (that don’t respond to several pharmacological therapies).
2000: Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine Clinical Research Group.
Silberstein et al. organized a randomized, double-blind, vehicle-controlled trial in which the safety and effectiveness of Botox was evaluated in the prevention of migraine. A total of 123 individuals with a history of experiencing 2-8 migraine attacks (moderate-to-severe) per month were recruited for participation and assigned at random to receive: Botox (25 U or 75 U) or placebo injections.
Results indicated that, recipients of Botox (25 U and 75 U) exhibited significantly: fewer migraine attacks per month; reduced migraine severity; and decreased need for antimigraine medications – when compared to placebo recipients. It was concluded that Botox appears safe and effective for migraine. It reduced: migraine frequency, severity, need for abortive medication, and migraine-related vomiting.
2000: Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study.
Binder et al. conducted an open-label trial to determine whether Botox might prove useful in the treatment of migraine headache. A total of 77 individuals (mostly female) with migraine participated in the trial and received Botox injections at various sites throughout the head and neck regions.
Responses to Botox for migraine were classified as: (1) full remission; (2) partial remission; (3) no response. Of the 77 migraine patients: 51% reported “full remission” for ~4.1 months post-injection and 38% reported “partial remission” for ~2.7 months post-injection. It was concluded that Botox appears safe and effective as an acute and prophylactic in migraine.
Have you tried Botox for migraines?
If you’ve tried Botox injections in attempt to treat chronic migraine, feel free to share your experience in the comments section below. By sharing your experience, you may help someone else who’s thinking about trying Botox for migraines.
To help others get an accurate understanding of your situation, provide details such as: your specific diagnosis (e.g. chronic refractory migraine); your history of migraine prophylactic and/or abortive medication use; and comorbid medical conditions. After receiving Botox, did you notice a reduction in the frequency and/or severity of migraine attacks?
Assuming you benefitted from receiving Botox to prevent migraine, how significant was the benefit? (Leave a subjective numeric rating on a scale from “1” to “10” – with higher numbers indicating greater benefit). Also mention the amount of time it took for you to fully reap or notice the migraine prophylactic effect of Botox after the injections.
If you’ve been receiving Botox injections regularly for a long-term (several years), have you noticed any change in effect over time? (Such as the efficacy of Botox for migraine prevention increasing or decreasing). In your experience, how much do you typically pay for a Botox treatment?
Do you consider the cost of Botox to be a reasonable value relative to the benefit you attain? After receiving Botox injections to treat migraine, did you discontinue antimigraine medications (e.g. prophylactics, abortive therapies, etc.)? Overall, would you say that Botox has decreased your need for abortive therapies (e.g. triptans)?