Mini-CAT
Scenario
36 year old female with PMH of migraines presents with severe migraines for over 1 week. She states she’s been experiencing at least 1 migraine per day, each lasting 30-60 minutes. She’s been taking 800mg Ibuprofen, and tried hot and cold compresses, resting, drinking water, ear plugs, and an eye mask, all with no effect. She states she hasn’t been sleeping, and admits to decreased appetite, photophobia, nausea, and vomiting. In the past, her migraines were less severe and less frequent; however she’s never been able to adequately prevent them from coming on. She states she gets at least 5-10 migraines per month, and is usually able to treat them acutely with warm/cold compresses and rest.
Aside from treating her current migraines, she wants to know if there is any therapy she can use to prevent migraines and decrease the frequency of getting them. She also states she does not like taking medications so she is looking for an alternative therapy to pharmacotherapy.
Define your Search Question
For patients who suffer from frequent/recurrent migraines, are Botox injections a significantly effective method for preventing migraine headaches?
Identify the PICO Elements
P = Patients with frequent & recurrent migraines
I = Botox injections
C = No treatment, other treatment
O = prevention of migraines
Search Strategy:
PICO Search Terms
| P | I | C | O |
| Chronic migraines | Botulinum toxin | No treatment | Reduced frequency of migraines |
| migraines | botox | Other treatment | Reduction in number of migraines |
| Migraine headaches | Botox injections | No prophylaxis | Prevention of migraines |
| Recurrent migraines | Onabotulinum toxin A | No Botox | Migraine prophylaxis |
| Botulinum toxin A | Reduction of migraine recurrence |
Search Tools:
Databases & Searches Used:
- PubMed:
- “Efficacy of botox for migraine prophylaxis,” Publication Date within past 5 years, Medline Journals (114 results)
- “(botulinum toxin) AND (prevention of migraines),” Publication date within past 5 years, Medline Journals (272 results)
- “(onobotulinum toxin A) AND migraines, Publication Date within past 5 years, Medline Journals (1,030 results)
- (chronic migraines) AND botox, Publication Date within past 5 years, Medline Journals (220 results)
- Science Direct
- “(botulinum toxins) AND (migraine prevention),” 2016-2021 (259 results)
- “efficacy of botox for migraine prophylaxis,” 2016-2021 (148 results)
- “botox efficacy for migraines” 2016-2021 (133 results)
- Google Scholar
- “botox vs no botox for migraine prevention,” 2016-2021 (9,830 results)
- “(botulinum toxins) AND migraine prophylaxis,” 2016-2021 (11,000 results)
- “efficacy of botox in reducing migraine recurrence,” 2016-2021 (4,980 results)
How I narrowed my choices to the articles I selected:
I narrowed my search to include only articles within the past 5 years, to keep my article selection up to date with our current patient population. I also tried to include more of the reliable systematic reviews and meta-analyses, which produce high level evidence, and excluded many of the less reliable retrospective and prospective cohort studies since they produce evidence that is not as reliable. Additionally, for the articles I included which focused on Botox as an acute treatment for migraines, I made sure they also evaluated the prophylactic efficacy of the treatment in preventing migraines. Finally, since it was difficult to find reliable studies that evaluated the efficacy of Botox alone (when compared to a placebo group), I included studies that compared the efficacy of Botox to other well-established and effective prophylactic treatments for migraines, to further evaluate the effectiveness of Botox as a migraine prophylaxis as well.
Articles Chosen
| Article 1 |
| Citation: Herd, C. P., Tomlinson, C. L., Rick, C., Scotton, W. J., Edwards, J., Ives, N. J., Clarke, C. E., & Sinclair, A. J. (2019). Cochrane systematic review and meta-analysis of botulinum toxin for the prevention of migraine. BMJ open, 9(7), e027953. https://doi.org/10.1136/bmjopen-2018-027953 |
| Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661560/ |
| Abstract: “Objectives: To assess the effects of botulinum toxin for prevention of migraine in adults. Design: Systematic review and meta-analysis. Data sources: CENTRAL, MEDLINE, Embase and trial registries. Eligibility criteria: We included randomised controlled trials (RCTs) of botulinum toxin compared with placebo, active treatment or clinically relevant different dose for adults with chronic or episodic migraine, with or without the additional diagnosis of medication overuse headache. Data extraction and synthesis: Cochrane methods were used to review double-blind RCTs. Twelve week post-treatment time-point data was analysed. Results: Twenty-eight trials (n=4190) were included. Trial quality was mixed. Botulinum toxin treatment resulted in reduced frequency of −2.0 migraine days/month (95% CI −2.8 to −1.1, n=1384) in chronic migraineurs compared with placebo. An improvement was seen in migraine severity, measured on a numerical rating scale 0 to 10 with 10 being maximal pain, of −2.70 cm (95% CI −3.31 to −2.09, n=75) and −4.9 cm (95% CI −6.56 to −3.24, n=32) for chronic and episodic migraine respectively. Botulinum toxin had a relative risk of treatment related adverse events twice that of placebo, but a reduced risk compared with active comparators (relative risk 0.76, 95% CI 0.59 to 0.98) and a low withdrawal rate (3%). Although individual trials reported non-inferiority to oral treatments, insufficient data were available for meta-analysis of effectiveness outcomes. Conclusions: In chronic migraine, botulinum toxin reduces migraine frequency by 2 days/month and has a favourable safety profile. Inclusion of medication overuse headache does not preclude its effectiveness. Evidence to support or refute efficacy in episodic migraine was not identified.” |
| Why I chose this article: I chose this article because it used a systematic review and meta-analysis which are study types that produce high level, reliable evidence. Additionally, this study included 28 studies with a total of 4,190 participants, which is a large sample size. Plus, all of the studies included were randomized controlled trials, which are scientific studies that most reliably evaluate and compare the efficacies of treatments. Of those studies, 23 compared Botox to placebo injections, while 3 compared Botox to alternative prophylactic agents. The PICO question I asked evaluates the efficacy of Botox, and therefore RCTs that compared botox to no treatment at all (placebo groups) are the most applicable in formulating an answer to my PICO question. Therefore, the fact that the results of this current systematic review and meta-analysis were based most heavily on RCTs such as those, makes this study completely relevant and beneficial to my research. Finally, this article was published in 2019, within the past 3 years, making its results recent, relevant, and adequately up to date. |
| Article 2 |
| Citation: Affatato, O., Moulin, T. C., Pisanu, C., Babasieva, V. S., Russo, M., Aydinlar, E. I., Torelli, P., Chubarev, V. N., Tarasov, V. V., Schiöth, H. B., & Mwinyi, J. (2021). High efficacy of onabotulinumtoxinA treatment in patients with comorbid migraine and depression: a meta-analysis. Journal of translational medicine, 19(1), 133. https://doi.org/10.1186/s12967-021-02801-w |
| Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011097/ |
| Abstract: “Background: Migraine and depression are highly prevalent and partly overlapping disorders that cause strong limitations in daily life. Patients tend to respond poorly to the therapies available for these diseases. OnabotulinumtoxinA has been proven to be an effective treatment for both migraine and depression. While many studies have addressed the effect of onabotulinumtoxinA in migraine or depression separately, a growing body of evidence suggests beneficial effects also for patients comorbid with migraine and depression. The current meta-analysis systematically investigates to what extent onabotulinumtoxinA is efficient in migraineurs with depression. Methods: A systematic literature search was performed based on PubMed, Scopus and Web of Science from the earliest date till October 30th, 2020. Mean, standard deviation (SD) and sample size have been used to evaluate improvement in depressive symptoms and migraine using random-effects empirical Bayes model. Results: Our search retrieved 259 studies, eight of which met the inclusion criteria. OnabotulinumtoxinA injections administered to patients with both chronic migraine and major depressive disorder led to mean reduction of −8.94 points (CI [−10.04,−7.84], p<0.01) in the BDI scale, of −5.90 points (CI [−9.92,−1.88], p<0.01) in the BDI-II scale and of −6.19 points (CI [−9.52,−2.86], p<0.01) in the PHQ-9 scale, when evaluating depressive symptoms. In the case of the migraine-related symptoms, we found mean reductions of −4.10 (CI [−7.31,−0.89], p=0.01) points in the HIT6 scale, −32.05 (CI [−55.96,−8.14], p=0.01) in the MIDAS scale, −1.7 (CI [−3.27,−0.13], p=0.03) points in the VAS scale and of −6.27 (CI [−8.48,−4.07], p<0.01) migraine episodes per month. Comorbid patients showed slightly better improvements in BDI, HIT6 scores and migraine frequency compared to monomorbid patients. The latter group manifested better results in MIDAS and VAS scores. Conclusion: Treatment with onabotulinumtoxinA leads to a significant reduction of disease severity of both chronic migraine and major depressive disorder in patients comorbid with both diseases. Comparative analyses suggest an equivalent strong effect in monomorbid and comorbid patients, with beneficial effects specifically seen for certain migraine features.” |
| Why I chose this article: Although the population I am assessing in my PICO question involves patients who suffer from chronic and recurrent migraines, this article looks specifically at patients with chronic migraines who also suffer from depression. With that being said, this article is still a great study to evaluate the efficacy of Botox as a prophylactic treatment for migraines in patients with chronic/recurrent migraines, since the article explains that migraine disease and depression are highly prevalent and overlapping disorders. Therefore, acknowledging this fact and finding an effective therapy that prevents migraines in patients with comorbid depression is definitely appropriate and in fact necessary, since the majority of patients with chronic migraines (i.e. my PICO population) do suffer from comorbid depression. The article also used a meta-analysis, which is a type of study that produces high level evidence. It was also published recently in 2021, making the results of the study relevant to our current patient population. Finally, the article helped answer my research question by evaluating outcomes of Botox in migraine patients, specifically outcomes such as frequency and severity of migraines, as well as side effects of the medication, while also evaluating how the medication affects depressive symptoms as well. In doing so, the study not only helped answer my PICO question, but also helped provide well-rounded information that goes beyond the PICO question. |
| Article 3 |
| Citation: Bruloy, Eva M.D.; Sinna, Raphael Ph.D., M.D., M.B.A.; Grolleau, M.D., Jean-Louis; Bout-Roumazeilles, Apolline M.D.; Berard, Emilie M.D.; Chaput, Benoit M.D., Ph.D. (2019). Botulinum Toxin versus Placebo: A Meta-Analysis of Prophylactic Treatment for Migraine, Plastic and Reconstructive Surgery: January 2019 – Volume 143 – Issue 1 – p 239-250 doi: 10.1097/PRS.0000000000005111 |
| Link: https://journals.lww.com/plasreconsurg/Fulltext/2019/01000/Botulinum_Toxin_versus_Placebo__A_Meta_Analysis_of.46.aspx?casa_token=HvP8kips-NUAAAAA:YGfzW4JOhns_3TJAgS_mt3U1Ph7RCF0WOG3R4F-Mes7DbFJUf5BGN3e08SmsdKSymOHLnULgQd7bS7XuJHisTAte |
| Abstract: “Background: The purpose of this study was to assess the efficacy of botulinum toxin in reducing the frequency of migraine headaches. Methods: The MEDLINE, Embase, and Cochrane Library databases were searched to identify randomized, double-blind, placebo-controlled trials that compared patients receiving botulinum toxin versus placebo injections in the head and neck muscles, for the preventive treatment of migraine. The primary outcome was change in the number of headache episodes per month from baseline to 3 months. Results: There were 17 studies including a total of 3646 patients. Overall analysis reported a tendency in favor of botulinum toxin over placebo at 3 months, with a mean difference in the change of migraine frequency of −0.23 (95 percent CI, −0.47 to 0.02; p = 0.08). The reduction in frequency of chronic migraines was significant, with a mean differential change of −1.56 (95 percent CI, −3.05 to −0.07; p = 0.04). Analysis of chronic migraine frequency was also significant after 2 months. The findings also highlighted an improvement of the patient’s quality of life at 3 months in the botulinum toxin group (p < 0.00001). Further adverse events were traced in the botulinum toxin type A group with a statistically significant risk ratio of 1.32 (p = 0.002). Conclusions: This meta-analysis reveals that botulinum toxin type A injections are superior to placebo for chronic migraines after 3 months of therapy. For the first time, a real benefit in patient quality of life is demonstrated with only few and mild adverse events.” |
| Why I chose this article: I chose this article because is was a meta-analysis that included only RCTs that were double-blinded and placebo-controlled, making it a reliable study that produced high level evidence. It was also published recently in 2019, making the results current and relevant. The article also evaluated the efficacy of Botox, compared to placebo, in preventing migraines with the primary outcome being frequency of migraines (number of migraine episodes per month), which are the exact variables and outcomes being questioned in my PICO. Finally, I thought this article was especially beneficial to my research since it specifically evaluated the efficacy of Botox as a migraine prophylaxis within 3 months of initiating therapy, demonstrating its ability to significantly and rapidly prevent migraines, which is important for patients suffering from frequent migraines. Like the articles previously mentioned, this article further proved that although Botox is associated with the development of adverse events, those events are mild and transient, making the treatment relatively safe overall. Again, this is an important factor to consider when discussing treatment options with patients, which is one of the reasons this article provided great insight into the research topic. |
| Article 4 |
| Citation: Ryu, J. H., Shim, J. H., Yeom, J. H., Shin, W. J., Cho, S. Y., & Jeon, W. J. (2019). Ultrasound-guided greater occipital nerve block with botulinum toxin for patients with chronic headache in the occipital area: a randomized controlled trial. Korean journal of anesthesiology, 72(5), 479–485. https://doi.org/10.4097/kja.19145 |
| Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781206/ |
| Abstract: “Background: Ultrasound-guided greater occipital nerve (GON) block has been frequently used to treat various types of headaches, and botulinum toxin has recently begun to be used in patients with headache. Our study presents the long-term effect of botulinum toxin on GON block using ultrasound in patients with chronic headache in occipital area. Method: Patients with occipital headache were divided into two groups (bupivacaine: BUP group [n = 27], botulinum toxin: BTX group [n = 27]), and ultrasound-guided GON block was performed at the C2 level. GON was detected with ultrasound and distance from GON to midline, from the skin surface to GON, and size of GON were measured in both groups. Visual analogue scale (VAS) scores and Likert scale were assessed at pretreatment and at 1, 4, 8, and 24 weeks after treatment in both groups. Results: The distance from GON to midline was 18.9 ± 4.4 mm (right) and 17.3 ± 3.8 mm (left). The depth from the skin was 12.9 ± 1.5 mm (right) and 13.4 ± 1.6 mm (left). GON size was 3.1 mm on both sides. The VAS score and patient satisfaction score (Likert scale) in 4, 8, and 24 weeks after injection were superior for the BTX than the BUP group. Conclusions: Ultrasound-guided GON block using BTX is effective in reducing short-term and long-term pain in patients with chronic headache in the occipital area.” |
| Why I chose this article: I chose this article because it used a double-blinded randomized controlled trial, which is a type of study that produces high level evidence and reliably evaluates the efficacy of one treatment compared to a placebo (no treatment) or another alternative treatment. Although the Botox treatment in this study is different from that used in the other studies, since this study tested the efficacy of Botox as a nerve block (and not the traditional muscle paralytic) compared to other local anesthetics, it helped further proved the efficacy of Botox in treating and preventing migraines. This study provided greater insight when combined with the studies listed above, since it showed that Botox can be injected into muscle and also toward the greater occipital nerve to provide significant long term relief from migraines in patients who suffer from frequent migraines. Overall it helps answer my PICO, and also demonstrates the overall need for further studies to be done on the use of Botox as a nerve block. Finally, this article was published in 2019, making its results relevant and up to date. |
| Article 5 |
| Citation: Stark, C., Stark, R., Limberg, N., Rodrigues, J., Cordato, D., Schwartz, R., & Jukic, R. (2019). Real-world effectiveness of onabotulinumtoxinA treatment for the prevention of headaches in adults with chronic migraine in Australia: a retrospective study. The journal of headache and pain, 20(1), 81. https://doi.org/10.1186/s10194-019-1030-z |
| Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734349/ |
| Abstract: “Background: OnabotulinumtoxinA (BOTOX®, Allergan plc, Dublin, Ireland) is approved for the preventive treatment of headaches in adult patients with chronic migraine (CM) in Australia by the country’s reimbursement mechanism for medicines, the Pharmaceutical Benefits Scheme (PBS). To our knowledge, this study represents the first focused report evaluating real-world evidence of onabotulinumtoxinA treatment via the PBS in Australian clinics. Methods: This study reviewed the medical records of adults with inadequately controlled CM from 7 private neurology practices in Australia who, beginning in March 2014, received PBS-subsidized onabotulinumtoxinA per product labelling for the first time. The primary effectiveness measure was the percentage of patients achieving a response defined by 50% or greater reduction in headache days from baseline after 2 treatment cycles. Additional data were recorded in the case report form when available and included demographics, clinical characteristics, headache severity and frequency, Headache Impact Test (HIT-6) score, medication use, and days missed of work or study at baseline, after 2 treatment cycles, and at last follow-up. Differences in mean changes from baseline were evaluated with a 1-tailed t-test or Pearson’s chi-squared test (p < 0.05). Results: The study population included 211 patients with a mean (SD) of 25.2 (5.3) monthly headache days at baseline. In the primary outcome analysis, 74% of patients achieved a response, with a mean (SD) of 10.6 (7.9) headache days after 2 treatment cycles (p < 0.001). Secondary effectiveness outcomes included mean (SD) reductions in HIT-6 score of − 11.7 (9.8) and − 11.8 (12.2) after 2 treatment cycles (p < 0.001) and final follow-up (p < 0.001), respectively, and mean (SD) decreases in days per month of acute pain medication use of − 11.5 (7.6) after 2 treatment cycles (p < 0.001) and − 12.7 (8.1) at final follow-up (p < 0.001). Conclusion: This study provides additional clinical evidence for the consistent effectiveness of onabotulinumtoxinA for the treatment of CM in Australia. This effectiveness was made evident by reductions in migraine days, severe headache days, and HIT-6 scores from baseline.” |
| Why I chose this article: One of the reasons I chose this article is because it was published in 2019, making its results up to date and current. The article also evaluated the exact intervention being assessed in my PICO question (onabotulinum toxin A, which is botox), as well as a similar population (patients with chronic migraine) and the same outcomes (prevention of migraine/headache). Although the article used a retrospective cohort study, which provides lower level evidence compared to systematic reviews, meta-analyses, and even randomized controlled trials, the study used a real-world design to assess the overall effectiveness (including efficacy and tolerability) as opposed to just efficacy alone for botox injections in chronic migraine patients within the typical clinical setting. Additionally, the article explains it used a large and diverse sample with participants with high degrees of disease burden and unmet treatment need at baseline, as demonstrated by a median of 28 headache days per month with severe impact and inability to achieve adequate improvement with at least 3 prior medications. Finally, I chose this study because although my PICO question asks about the efficacy of botox for treating patients with frequent and/or recurrent migraines, and does not specifically ask about patients with chronic migraines (which is defined by a significantly greater frequency in migraines per month compared to recurrent migraines), one could infer that if a treatment is effective for preventing migraines in patients with more severe and more frequent migraines per month, then it should be highly effective in preventing migraines overall, especially in patients with less frequent (yet still recurrent) migraines. |
Summary of the Evidence:
| Author (Date) | Level of Evidence | Sample/Setting (# of subjects/ studies, cohort definition etc. ) | Outcome(s) studied | Key Findings | Limitations and Biases |
| Herd, C. P., Tomlinson, C. L., Rick, C., Scotton, W. J., Edwards, J., Ives, N. J., Clarke, C. E., & Sinclair, A. J. (2019). Cochrane systematic review and meta-analysis of botulinum toxin for the prevention of migraine. BMJ open, 9(7), e027953. | Systematic review & meta-analysis | The study conducted a systematic review and meta-analysis of articles that were published up until March 2019 that evaluated the effects of botulinum toxin (the class of medication that Botox belongs to) compared to a placebo and/or other alternative treatments for the prophylaxis of episodic and chronic migraine in adults. The study included 28 studies, most of which were randomized controlled trials that compared Botox to placebo injections, while some compared Botox to alternative well-established oral prophylactic agents. The total number of participants included were 4,190, and the treatment periods in these studies included up to 3 treatments (injections) with 12 weeks between each injection. | The primary outcome studied was frequency of migraine days per month. Other outcomes frequency of other headache days (including tension and cluster), frequency of migraine attacks, severity of migraine (i.e. impact of each migraine), duration of migraine, 50% responder rate, global impression scales, and quality of life measures following treatment. Additionally, the study assessed the safety profile of botulinum toxin injections, demonstrated by adverse effects reported, as well as withdrawal rate compared to other treatments. | The study found that overall Botox injections into the head and neck muscles significantly reduced the number of migraine days experienced per month. Specifically, the average frequency of migraine days in patients with chronic and episodic migraines (up to 20 migraines/month) was reduced significantly more by the Botox treatment than by the placebo. Additionally, the Botox group suffered from less headaches (including tension and cluster headaches) per month overall, compared to the placebo group. Furthermore the study found that Botox treatment does not only prevent migraines effectively, as demonstrated by significantly reducing the frequency of migraines following therapy, it also significantly reduced the impact of each migraine attack, demonstrated by a significant reduction in migraine severity reported among the Botox treatment group compared to the placebo group. It’s important to note that the results also showed that Botox has a good safety profile, however it also showed an increased risk of adverse effects associated with Botox compared to the placebo. With that being said, these events were transient and not serious. When comparing Botox to alternative well-established migraine prophylaxes, specifically topiramate and valproate sodium, the study found that Botox was equally as effective to those treatments in preventing migraines, and that the withdrawal rate from Botox was much lower than those other first line prophylaxes. In conclusion, the article found that Botox effectively reduces the duration and severity of migraines in patients suffering from chronic and recurrent episodic migraines. | Limitations of the study include that reporting of outcomes was generally poor, with only 6 of the 28 trials reporting data on the primary outcome as a usable format, with an additional 5 studies providing data for frequency of migraine attacks. Also, many of the included studies were small in size and failed to fully report their data, thereby impacting the quality ratings and content of the meta-analyses. Finally, neither the efficacy nor safety data were available for long-term treatment with Botox, and the longest treatment period in any of the studies included was 3 treatments with 12 weeks between, so the implications of Botox injections over a period of longer than 9 months is unknown. |
| Affatato, O., Moulin, T. C., Pisanu, C., Babasieva, V. S., Russo, M., Aydinlar, E. I., Torelli, P., Chubarev, V. N., Tarasov, V. V., Schiöth, H. B., & Mwinyi, J. (2021). High efficacy of onabotulinumtoxinA treatment in patients with comorbid migraine and depression: a meta-analysis. Journal of translational medicine, 19(1), 133. | Systematic Review & Meta-Analysis | The systematic review included a search of prospective and retrospective studies that assessed the efficacy of onabotulinum toxin A (Botox) in treating/preventing migraines patients over 18 years old suffering from chronic migraine, as defined by the International Headache Society criteria and HIT6, MIDAS, and VAS scales. The studies also assessed the efficacy of Botox for treating chronic migraines and depression in patients with comorbid Major Depressive Disorder, as defined by any established criteria (e.g. PHQ-9 & BDI scales). Ultimately, 8 studies were selected for the meta-analysis with a total of 1,492 patients. | The purpose of the article was to assess whether Botox could treat migraine and depression symptoms in patients with comorbid migraines and depression. For depression outcomes, the study assessed the change/improvement in depressive symptoms and quality of life following treatment, as measured through the PHQ-9, BDI and BDI-II scales. The study evaluated migraine outcomes such as migraine severity, impact, and frequency via the MIDAS, HIT6 and VAS scales. Finally, other outcomes included reported side effects of Botox. | The article begins by explaining that there is a strong and significant overlap between migraine disorders and depression, such that most patients with chronic migraines suffer from comorbid depression. Additionally, the article explains that suffering from one of these disorders significantly increases the risk of developing the other. Therefore, in evaluating the efficacy of a prophylactic treatment for migraines, it’s important to evaluate its efficacy in patients with comorbid migraine and depression. The article specifically wanted to assess the efficacy of onabotulinum toxin A for treating both migraines (reducing the frequency and severity of them) and depression in patients with comorbid chronic migraine and major depressive disorder. The meta-analysis found that treatment with onobotulinum toxin A significantly improved both migraine and depressive symptoms in comorbid patients. For depression outcomes, the study showed a significant decrease in depression symptoms and improvement in quality of life following onobotulinum toxin A treatment. For migraine treatment, onobotulinum toxin A significantly improved the severity/impact of migraines, and significantly reduced the frequency of migraines. Additionally, the studies with larger sample sizes showed that the efficacy of Botox in treating and preventing migraines was greater for patients with comorbid disorders compared to those with chronic migraine only. This suggests that there’s a better outcome regarding migraine frequency in comorbid patients compared to patients with migraine alone, which indicates that Botox has great efficacy in migraine patients with depressive symptoms. Similar to the previous article, this article also noted an increase in side effects associated with the Botox therapy. Specifically, patients in the Botox treatment group had higher rates of reported neck pain, eyelid ptosis, musculoskeletal stiffness, injection site pain, and headache. However, these side effects were again found to be mild and transient. | One limitation was that the variety of the scales used to assess the impact and severity of migraine and depression led to the need for performing statistical analyses on smaller subgroups. Dividing the overall large sample sixe into subgroups weakened the statistical power of the study, and the heterogeneity in the scales makes the results less reliable. Additionally, some issues with Botox therapy overall could be related to poor compliance and a high number of patients giving up on continuing treatment, making it more difficult to perform further studies and slowing down the progress of future research. |
| Bruloy, Eva M.D.; Sinna, Raphael Ph.D., M.D., M.B.A.; Grolleau, M.D., Jean-Louis; Bout-Roumazeilles, Apolline M.D.; Berard, Emilie M.D.; Chaput, Benoit M.D., Ph.D. Botulinum Toxin versus Placebo: A Meta-Analysis of Prophylactic Treatment for Migraine, Plastic and Reconstructive Surgery: January 2019 – Volume 143 – Issue 1 – p 239-250 | Meta-Analysis | This article used a meta-analysis of randomized, double-blinded, and placebo-controlled trials that compared migraine patients who received botulinum toxin (Botox injections) versus placebo injections into head and neck muscles as preventative treatment for migraine. The criteria for chronic and episodic migraine, for which participants of the included studies were selected, was defined by the International Headache Society. The studies involved in this meta-analysis only evaluated Botox as a prophylactic therapy, as acute migraines were treated with abortive medications such as NSAIDs, triptans, and acetaminophen. The meta-analysis searched articles from various databases (e.g. Medline, Embase, Cochrane) up until 2016, with participants suffering from chronic and episodic (frequent but not chronic) migraine. Ultimately 17 RCTs with a total of 3,646 patients (57% had episodic migraine, and 45% had chronic migraine) were used in this meta-analysis. | The primary outcome studied was the change in number of migraine episodes per month from the starting point until 3 months following the initiation of therapy. Secondary outcomes studied included frequency of migraines at month 2, quality of life at month 3, and reported adverse events. | The meta-analysis showed a reduction in frequency of episodic and chronic migraines at month 3 in patients who received Botox injections compared to those who received the placebos. Botox was also shown to be more effective than placebo at month 2, as demonstrated by a significant reduction in migraine frequency following treatment. There was also a significant improvement in patients’ quality of life at month 3 in the Botulinum Toxin Type A group compared to the Placebo group; however more adverse events were reported in the treatment group than in the placebo group.Again, no severe side effects were reported, and any side effects were mild in severity, transient and resolved without sequelae. Overall, the meta-analysis showed that botulinum toxin type A (Botox) is superior to a placebo for chronic and episodic migraine at 2 and 3 months after initiating therapy, indicating it is an effective and rapid prophylactic treatment for migraines. | A limitation of the study is that the study did not include controlled trials that examined other prophylactic oral medications in the meta-analysis. Other studies have compared Botox injections to various prophylactic oral medications (e.g. topiramate, amitriptyline, valproate, methylprednisolone), however it’s important to note that these studies do not demonstrate any superiority of other treatments over Botox. |
| Ryu, J. H., Shim, J. H., Yeom, J. H., Shin, W. J., Cho, S. Y., & Jeon, W. J. (2019). Ultrasound-guided greater occipital nerve block with botulinum toxin for patients with chronic headache in the occipital area: a randomized controlled trial. Korean journal of anesthesiology, 72(5), 479–485. | Randomized-Controlled Trial | The study was a double-blinded, randomized controlled trial, done to evaluate the efficacy of botulinum toxin when used as a greater occipital nerve block, compared to local anesthetics, for the management of chronic migraine. The study used 54 patients ages 18-85 years old who suffered from migraine, tension-type, cluster, and daily persistent headaches specifically in the occipital area. The treatment (Botulinum Toxin) group received ultrasound-guided greater occipital nerve (GON) block with botulinum toxin type A (Botox). The control (Bupivacaine) group was given ultrasound-guided occipital nerve block with a local anesthetic, Levobuviciane/Dexamethasone. GON blockades were formed with patients in the prone position, with an ultrasound probe placed over C2 along the obliquus capitis inferior muscle in the posterior neck (inferior to the occipital bone of the head), since the obliquus capitis inferior muscle has been proven to be a reliable and consistent landmark for the GON. A needle was then inserted until the tip reached the GON, and patients with headaches on both sides were injected on both sides during the same day with the same drug. | The VAS and Likert scales were used to measure migraine severity and patient satisfaction before and after injection at 1 week, 4 weeks, 8 weeks, and 24 weeks after treatment. Other outcomes studied included reported adverse effects and complications. | The article explains that blocking a specific sensory nerve has been shown to be a useful method for managing frequent headaches to prevent migraines and other headache attacks from coming on. Although intramuscular Botox injections have already been studied for the prophylactic treatment of chronic migraines, the use of Botox as a nerve block for the treatment of migraines has not yet been adequately been evaluated. The current study found that ultrasound-guided GON block with Botox was an effective and relatively safe treatment method, and that patient satisfaction and the treatment effect of Botox were higher than local anesthetics during long-term follow-up. This study combined with those of the previous articles demonstrate that Botox is effective in treating and preventing migraines both when it is injected into head and neck muscles as a muscle relaxant/paralytic, and also when it is injected toward the greater occipital nerve and used as a nerve block. | One major limitation of the study includes the high dropout rate at 6 month. Since 6 patients dropped out after 24 weeks in the Botox group, and 16 in the control group, and the VAS score was evaluated after 24 weeks in only 11 patients in the control group, the VAS score at 24 weeks after treatment in the control group was relatively low. |
| Stark, C., Stark, R., Limberg, N., Rodrigues, J., Cordato, D., Schwartz, R., & Jukic, R. (2019). Real-world effectiveness of onabotulinumtoxinA treatment for the prevention of headaches in adults with chronic migraine in Australia: a retrospective study. The journal of headache and pain, 20(1), 81. | Retrospective Cohort Study | The purpose of this study was to be the first study to evaluate the real-world effectiveness of government-subsidized botox treatment in Australian clinics. The study used a multicentre retrospective review adults with chronic migraine who were treated with botox for headache prophylaxis to assess real-world treatment outcomes, to evaluate the efficacy and tolerability of Botox in the general patient population. This included a review and analysis of medical records from 7 private practices in Australia between April 2016 and January 2017, with at least 2 treatment cycles required for the data to be included. The patients were all 18 years and older, under the care of a neurologist, and had experiences an average of 15 or more headaches per month, with at least 8 migraine days over a period of 6 months or longer. Of the 236 medical records reviewed, 211 patients were included, with an average HIT-6 (migraine scale) score of 68.2, which is above the threshold score of 60 considered indicative of severe impact migraines. | The main outcome studied was the proportion of patients with a 50% or greater reduction in monthly headache days from baseline after 2 botox treatment cycles. Other outcomes were mean changes from baseline in number and severity of headache days, number of migraine days, oral preventative and acute treatment use, HIT-6 scores, missed work or study days, and medication use. | The data overall showed a reduction in headache frequency at 2 treatment cycles and beyond. The results also showed a reduction in severity of headaches, monthly migraine days, HIT-6 scores, missed days of work/study, and use of acute pain medications including opioids. Thus, the results support the clinical benefits botox in patients with chronic migraines under real-world conditions. These findings are in agreement with previously published efficacy results and several observational studies that documented the efficacy and tolerability of botox for the treatment of chronic migraines (especially in those whom previous prophylaxes proved inadequate) across Europe and North America. | Limitations of the study include its retrospective design with a lack of control group for comparison. Also, variability across treatment sites with respect to patient selection and data collection is likely to be higher for retrospective compared to prospective trials. With that being said, the real-world design of the study and its large diverse sample makes this study significant. |
Conclusion(s):
Herd et al concluded that Botox injections into head and neck muscle significantly reduced the number of migraine days per month (frequency of migraines), as well as overall headache days per month (frequency of cluster and tension headaches) when compared to the placebo. Botox also reduced the impact/severity of each migraine attack. Although patients who received Botox experienced more side effects than the Placebo group, the side effects were all transient and minor, and the article concludes that Botox does in fact have a good safety profile making it both effective and safe to use for migraines. Finally, when comparing Botox to other well-established alternative treatments (e.g. topiramate, valproate sodium), Botox was shown to be equally effective in preventing migraines, and was associated with a lower withdrawal rate than other first-line prophylaxes. Overall, the article concludes that Botox is a relatively safe treatment that effectively reduces the frequency, duration, and severity of migraines in patients with chronic, recurrent, and episodic migraines.
Affatato et al found that Botox significantly improved both migraine and depression symptoms in patients with comorbid chronic migraines and major depressive disorder. Regarding the treatment of depression, patients who received Botox injections showed a significant decrease in depression symptoms and improvement in quality of life. Regarding the treatment and prevention of migraines, Botox significantly reduced the severity/impact and frequency of migraines. Of the studies included in this meta-analysis, those with larger sample sizes also showed that the efficacy of Botox for migraine treatment and prevention was greater for patients with comorbid chronic migraine and depression compared to those with chronic migraine alone. Finally, in terms of safety profile, this study showed similar results to those of the previous study described above, in that the Botox treatment group was associated with a higher rate of reported side effects compared to the control group; however, again these side effects were all mild and transient. The overall conclusion is that Botox is relatively safe, and significantly prevents and treats episodes of depression and migraines in patients with comorbid chronic migraine and major depressive disorder. This efficacy of Botox was also shown to be greater in the comorbid population compared to patients with chronic migraine alone, who also showed significant improvement in their migraine disorder with Botox injections.
Bruloy et al concluded that patients with episodic and chronic migraines who received Botox injections had a significant reduction in frequency of migraines at 2 and 3 months into treatment. Patients who received Botox also demonstrated a significant improvement in quality of life at 3 months, when compared to the placebo group. However, the Botox treatment group was also associated with more adverse event that, again, were transient and not severe. Therefore, the study concluded that Botox is a significantly effective and fast-acting prophylactic method for treating chronic and episodic migraines, with a relatively safe profile.
Ryu et al found that ultrasound-guided greater occipital nerve blocks with Botox (a different type of Botox injection that does not involve conventional injection into head/neck muscles) was relatively effective and safe for preventing migraines in patients who suffer from chronic migraine. Additionally, patient satisfaction and treatment effect of Botox was significantly greater than that of local anesthetics at long-term follow ups.
Stark et al concluded that in the Australian patients with chronic migraines studied, all of whom did not receive adequate results with at least 3 previous migraine prophylaxes, Botox significantly reduced frequency of migraines, frequency of severe headaches, HIT-6 scores, and missed work or study compared to patients’ baselines. Nearly 75% of patients demonstrated a reduction in monthly headache days by at least 50% in the first 6 months, and the benefits of Botox treatment had sustained up to the patients’ final follow-up visit with a trend toward further improvement after the first 2 treatment cycles. Overall, the results of this study add to the worldwide body of clinical evidence in support of using Botox for chronic migraine prevention. Additionally, this real-world study approach shows that Botox continues to show effectiveness in migraine patients whom previous preventative treatments were inadequate.
My overall conclusion is that in terms of efficacy, the studies prove that Botox is significantly effective in preventing migraines/headaches in patients who suffer from chronic, recurrent, and episodic migraines. Additionally, it not only has been shown to reduce the frequency of migraine attacks (days) per month, it has also been shown to reduce the impact, severity, and duration of each migraine following treatment. The findings also show that Botox was equally as effective to alternative first-line migraine prophylaxes, and was even shown to be effective in patients who had failed other previous therapies. Furthermore, these results were consistent in patients with comorbid chronic migraine and major depressive disorder, such that Botox was shown to be effective in treating and preventing migraines as well as depression in this population of patients. In fact, the results show that the efficacy of Botox for migraines was even greater in this patient population. Finally, not only was Botox effective when administered conventionally as an intramuscular injection, it was also highly effective and relatively safe when used as a greater occipital nerve block as well.
Clinical Bottom Line:
The bottom line is that the use of Botox injections has been shown to be an effective and relatively safe method for preventing migraines in patients who suffer from frequent, recurrent, episodic, and chronic migraines. In addition, the studies above showed that not only is Botox a significantly effective prophylactic therapy for migraines, as indicated by its ability to effectively reduce the frequency of migraine attacks, but it is also highly effective in reducing the severity and impact of each migraine episode. Furthermore, one study even showed that it significantly improved patients’ quality of life overall, which is an important aspect to consider when discussing this treatment option with patients. It should also be noted that all studies demonstrated that Botox was associated with a higher risk for side effects and adverse events, which is definitely important to consider. However, all studies agreed that these effects and events were mild and transient, and that Botox was still considered to have a good safety profile overall.
It’s also important to note that the results of the second article found that not only is Botox an effective migraine prophylaxis in patients with frequent/chronic migraines overall, but that it is specifically effective and beneficial in patients with comorbid migraine and depression disorders. Patients with both these comorbidities, which are highly overlapping disorders such that majority of patients with chronic and episodic migraines also suffer from comorbid depression, reported a significant reduction in frequency and severity of migraines as well as a reduction in depression symptoms following treatment with Botox injections. Finally, the fourth study showed that not only is Botox effective when used in the conventional way (i.e. injected into head and neck muscles as muscle paralytic), but it is also effective when injected toward the greater occipital nerve in the back of the head as a nerve block. Thus, overall, Botox has been shown to be a safe and effective prophylactic treatment for migraines when injected into muscle and also as a nerve block.
Weight of the Evidence
1 Herd, C. P., Tomlinson, C. L., Rick, C., Scotton, W. J., Edwards, J., Ives, N. J., Clarke, C. E., & Sinclair, A. J. (2019). I weighed this study the strongest for multiple reasons. First, this is a systematic review and meta-analysis, which are studies with high level evidence. It was also published recently within the past 5 years, in 2019, and included a search of studies up until 2019. Additionally, it included a total of 28 studies (n = 4,190), which is a large sample size, and all of which were randomized controlled trials, which have a much higher level of evidence than cohort studies, case control studies, or observational studies. This study not only included the largest number of RCTs, but also all of the results were based solely off those RCTs, and were not influenced by other less reliable study designs. In terms of answering my PICO, which asks about the efficacy of Botox for preventing migraines in patients who suffer from frequent migraines, RCTs are effective in doing so since they are the relatively more reliable for evaluating the efficacy of a treatment method. Finally, most of the RCTs included compared Botox injections to placebo injections, while a few of the studies compared Botox to alternative first-line oral prophylaxes. This enables the researchers to conclude whether or not Botox is a significantly effective migraine treatment/prophylaxis, and to evaluate how the efficacy of Botox compared to that of other established treatments.
2 Bruloy, Eva M.D.; Sinna, Raphael Ph.D., M.D., M.B.A.; Grolleau, M.D., Jean-Louis; Bout-Roumazeilles, Apolline M.D.; Berard, Emilie M.D.; Chaput, Benoit M.D., Ph.D. (2019). I weighed this article second, because although it included 17 studies (n = 3,646) in its meta-analysis which is slightly less than of the study listed above, this study also performed a meta-analysis of only randomized controlled trials, all of which were double-blinded and placebo-controlled. As mentioned, meta-analyses produce the highest level evidence, and specifically meta-analyses of RCTs are the most reliable since RCTs are the best scientific studies for evaluating the efficacies of treatments. The study was also published in 2019, which makes its findings recent and relatively up to date. Finally, the study evaluated the efficacy of Botox in preventing migraines within 3 months of treatments, and therefore the population, intervention, and outcomes studied were consistent with those in my PICO question, while also demonstrating the ability of the Botox to produce significant results in a short period of time.
3 Affatato, O., Moulin, T. C., Pisanu, C., Babasieva, V. S., Russo, M., Aydinlar, E. I., Torelli, P., Chubarev, V. N., Tarasov, V. V., Schiöth, H. B., & Mwinyi, J. (2021). I weighed this study next because it was published very recently in 2021 and used a systematic review and meta-analysis, which produce the highest level evidence. On the other hand, the study analyzed prevovious prospective and retrospective studies to assess the efficacy of Botox for migraine prevention, which produce lower level evidence compared to randomized controlled trials. Additionally, the population of patients in my PICO question is patients who suffer from frequent migraines, however the primary population assessed in this study was patients with comorbid migraine disorder and major depressive disorder. Although the findings add to my overall discussion, they are less significant to my PICO than those produced by studies that directly assessed the exact same population and variables asked in my research question. Finally, the study analyzed 8 previous studies (n = 1,492), which is a smaller sample size than that of the studies listed above.
4 Ryu, J. H., Shim, J. H., Yeom, J. H., Shin, W. J., Cho, S. Y., & Jeon, W. J. (2019). I weighted this study next because it was a double-blinded randomized controlled trial, which is more reliable and a better study design overall compared to a cohort study (such as the retrospective study conducted by Stark et al). However, being a randomized controlled trial, this study design typically produces lower level evidence compared to meta-analyses and systematic reviews, such as the articles weighted above. Additionally, although this study provides more insight into the overall discussion on Botox as migraine prophylaxis, it assesses a different type of Botox from the conventional Onabotulinumtoxin A injections into head and neck muscles. This study sought to evaluate the efficacy of Botox injections for migraine treatment and prophylaxis when used as a greater occipital nerve block, essentially as a local anesthetic. The results of the study prove that Botox is effective as both an intramuscular injection and a GON block for migraine treatment and prevention, which is still helpful in answering my PICO question in that the question asks about Botox injections in general with no specific emphasis on conventional (intramuscular) Botox injections. Thus, while this article is still helpful in answering my research question, it used a randomized controlled trial and unconventional methods, and therefore was weighted fourth out of the 5 studies I used.
5 Stark, C., Stark, R., Limberg, N., Rodrigues, J., Cordato, D., Schwartz, R., & Jukic, R. (2019). I weighed this study last because the study type was a retrospective cohort study, which produces lower level evidence compared to systematic reviews, meta-analyses, and randomized controlled trials. The cohort also lacked a control group, which again makes it less reliable than the other studies I selected. Additionally, the cohort was from Australia, and although the article concluded that the results were consistent with and relevant to European and North American populations/data as well, the sample for this study did not include participants from the United States. With that being said, I still selected this study for my research because it used a real-world design and evaluated the efficacy of Botox in patients with migraines, which is what my own PICO question sought to do.
Magnitude of Effects:
1 Herd, C. P., Tomlinson, C. L., Rick, C., Scotton, W. J., Edwards, J., Ives, N. J., Clarke, C. E., & Sinclair, A. J. (2019): Of the 28 RCTs (N = 4,190) included in this systematic review and meta-analysis, 23 trials (n = 3,912) compared Botox to placebo injections, while 3 compared Botox to alternative established oral prophylactic drugs. The meta-analysis of the primary outcome (number of migraines per month) for the trials showed a significant reduction of 2 days of migraine per month (95% CI -2.8 to -1.1) in favor of Botox. The Migraine Severity score improved significantly overall by -3.3cm (91% CI -4.2 to -2.4). For the trials that compared Botox to alternatives, the results showed no significant difference in change scores for migraine frequency between the two groups (p=0.80, 2 trials, n=101).
2 Bruloy, Eva M.D.; Sinna, Raphael Ph.D., M.D., M.B.A.; Grolleau, M.D., Jean-Louis; Bout-Roumazeilles, Apolline M.D.; Berard, Emilie M.D.; Chaput, Benoit M.D., Ph.D. (2019): In this meta-analysis, 17 studies (n = 3,646) were analyzed an found that the patients who received Botox injections had significantly less frequent episodic and chronic migraines compared to patients in the Placebo group at month 3, with a mean difference of change in migraine frequency of -0.23 (95% CI, -0.47 to 0.02; p=0.08). Botox also significantly reduced migraine frequency at month 2 with a mean difference in rates of migraines of -0.21 (95% CI, -0.47 to 0.06; p=0.13). There was also significant improvement in patients’ quality of life at month 3 in the Botox group, with a mean difference of scores of -0.43 (95% CI, -0.59 to -0.27; p<0.00001). Regarding safety outcomes, more adverse events were reported in the Botox group than in the Placebo group, with a statistically significant risk ratio of 1.32 (95% CI, 1.11 to 1.57; p=0.002). No severe side effects were reported and any side effects were mild, transient, and resolved without sequelae.
3 Affatato, O., Moulin, T. C., Pisanu, C., Babasieva, V. S., Russo, M., Aydinlar, E. I., Torelli, P., Chubarev, V. N., Tarasov, V. V., Schiöth, H. B., & Mwinyi, J. (2021): This meta-analysis included 8 studies, that consisted of patients with comorbid chronic migraine and major depressive disorder. The studies showed a significant decrease in depression symptoms, indicated by a mean reduction of -8.94 points in the BDI scale (CI -10.04 to -7.84, p<0.01), -5.90 points in the BDI-II scale (CI -9.92 to -1.88, p<0.01), and -6.19 points in the PHQ-9 scale (CI -9.52 to -2.86, p<0.01). There was also a significant decrease in migraine-related symptoms with a mean reduction of -4.10 points in the HIT-6 scale (CI -7.31 to -0.89, p=0.01), -32.05 points in the MIDAS scale (CI -55.96 to -8.14, p=0.01), -1.7 points in the VAS scale (CI -3.27 to -0.13, p=0.03), and -6.27 change in number of migraine episodes per month (CI -8.48 to -4.07, p<0.01). Comorbid patients showed better improvements in BDI, HIT6 and migraine frequency compared to patients with chronic migraine alone.
4 Ryu, J. H., Shim, J. H., Yeom, J. H., Shin, W. J., Cho, S. Y., & Jeon, W. J. (2019): There were no statistical differences in VAS scores before injection at 1 week after treatment between the Botox group (66.8 +/- 3.1 and 24.9 +/- 3.9) and Bupivacaine group (63.0 +/- 2.8 and 27.5 +/- 4.5). VAS scores at 4, 8, and 24 weeks after treatment were significantly lower in the Botox group (13.9 +/- 3.3, 9.3 +/- 2.6, & 12.3 +/- 3.8) compared to the Bupivacaine group (27.2 +/- 4.1, 31.0 +/- 4.2, & 34.8 +/0 5.8). All P<0.05. There was no statistical difference in Likert scale at 1 week after treatment between both groups, yet Likert scales at 4, 8, and 24 weeks were significantly lower after treatment in the Botox group (1.6 +/- 0.2, 1.4 +/- 0.1, & 1.5 +/- 0.2 respectively) compared to the Bupivacaine group (2.4 +/- 0.2, 2.8 +/- 0.2, & 3.1 +/- 0.3), with all P<0.05.
5 Stark, C., Stark, R., Limberg, N., Rodrigues, J., Cordato, D., Schwartz, R., & Jukic, R. (2019). The study used 211 patients with an average of 25.2 monthly headache days at baseline. The primary outcome showed 74% of patients achieved a significant response following Botox, with a mean of 10.6 headache days after 2 treatment cycles (p<0.001). There were also significant reductions in HIT-6 scores of -11.7 and -11.8 after 2 treatment cycles (p<0.001) and final follow-up (p<0.001), respectively, and mean decreases in days per month of acute pain medication use of -11.5 after 2 treatment cycles (p<0.001) and -12.7 at final follow-up (p<0.001).
Clinical Significance:
Overall, the articles agree that Botox was shown to significantly improve migraine symptoms and reduce the frequency of migraines, indicating that it is a significantly effective treatment and prophylaxis for patients with chronic, recurrent, and frequent episodic migraines. Herd et al’s study, which was weighed the heaviest, showed that Botox significantly reduced the frequency and severity of migraine episodes following treatment. However, the efficacy of Botox was not superior or significantly different from that of alternative oral first-line migraine prophylaxes (e.g. topiramate). The article by Bruloy et al further proved that Botox reduced the frequency of migraines, while also improving patients’ overall quality of life. Affatato et al found that in patients with with chronic migraine disorder and major depressive disorder, Botox significantly reduced migraine severity and frequency, while also reducing depression symptoms and improving overall quality of life. Although migraine symptoms and frequency following Botox treatment were also reduced in patients with chronic migraine alone, the magnitude these effects were greater in patients with comorbid chronic migraine and depression. Ryu et al proved that in addition to conventional intramuscular Botox injections, Botox injections that are used as greater occipital nerve blocks also significantly reduced the frequency and symptoms of migraines. Finally, Stark et al showed that Botox was an effective prophylactic for migraines in a real-world study design after 2 treatment cycles, further demonstrating the rapid effects of Botox in managing migraines. The articles also showed that while Botox was associated with more adverse events than placebos, the effects were all mild and transient. Overall, the articles prove that Botox is an effective and relatively fast acting prophylaxis and overall treatment for migraines with a good safety profile. It is even effective when used as a GON block, and it is even more effective when used in patients with comorbid chronic migraine and depression.
Other Considerations:
Since one article showed Botox to be an effective migraine treatment/prophylaxis when used as a GON block, I believe more studies should be done to compare the efficacy of Botox when used as a GON block to that of Botox when used as an intramuscular injection into head and neck muscles. Although both treatments were shown to be effective in reducing migraine symptoms and frequency, determining which treatment is most effective, as well as which treatment is safer, could help guide providers who administer Botox for migraines in the future. Additionally, future research should be done to evaluate the relationship between migraines and major depressive disorder, since if there is a correlational or causative relationship, then perhaps other migraine treatments can be used to treat depression, or depression treatments could be used to treat migraines.
