Complementary and Integrative Health Treatments for Migraine

Background: Migraine is a chronic disabling neurologic condition that can be treated with a combination of both pharmacologic and complementary and integrative health options.Evidence acquisition: With the growing interest in the US population in the use of nonpharmacologic treatments, we reviewed the evidence for supplements and behavioral interventions used for migraine prevention.Results: Supplements reviewed included vitamins, minerals, and certain herbal preparations. Behavioral interventions reviewed included cognitive behavioral therapy, biofeedback, relaxation, the third-wave therapies, acupuncture, hypnosis, and aerobic exercise. Conclusions: This article should provide an appreciation for the wide range of nonpharmacologic therapies that might be offered to patients in place of or in addition to migraine-preventive medications.

Disease of the Year: Migraine Section Editors: Kathleen B. Digre, MD Deborah I. Friedman, MD, MPH Complementary and Integrative Health Treatments for Migraine Palak S. Patel, MD, Mia T. Minen, MD, MPH Background: Migraine is a chronic disabling neurologic condition that can be treated with a combination of both pharmacologic and complementary and integrative health options. Evidence Acquisition: With the growing interest in the US population in the use of nonpharmacologic treatments, we reviewed the evidence for supplements and behavioral interventions used for migraine prevention. Results: Supplements reviewed included vitamins, minerals, and certain herbal preparations. Behavioral interventions reviewed included cognitive behavioral therapy, biofeedback, relaxation, the third-wave therapies, acupuncture, hypnosis, and aerobic exercise. Conclusions: This article should provide an appreciation for the wide range of nonpharmacologic therapies that might be offered to patients in place of or in addition to migrainepreventive medications. Journal of Neuro-Ophthalmology 2019;39:360-369 doi: 10.1097/WNO.0000000000000841 © 2019 by North American Neuro-Ophthalmology Society M igraine affects over 36 million Americans and is the second-most disabling condition worldwide in disability-adjusted life years (1,2). With the increasing interest in complementary and alternative medicine (CAM) (at least one-third of Americans use complementary treatments (3)), it should be of no surprise that people with migraine also try these treatments to treat migraine. Research has shown that up to 50% of those with severe headaches/ migraine use CAM and integrative medicine treatment options (4). However, CAM treatments are costly. In the United States in 1 year alone, .$30 billion was spent out of pocket on visits to CAM practitioners and on CAM Departments of Neurology (PSP, MTM) and Population Health (MTM), NYU Langone Health, New York, New York. M. T. Minen has funding from NCCIH K 23 AT009706-01. The author reports no conflicts of interest. Address correspondence to Mia T. Minen, MD, MPH, Department of Neurology, NYU Langone Health, 222 East, 41st Street, 9th Floor, New York, NY 10017; E-mail: [e-mail] 360 purchases (4-6). About one-third ($11.9 billion) was spent on visits to practitioners (6). Nearly 85% of providers report that they lack the knowledge to properly inform their patients about CAM treatments (7). Thus, we seek to review which CAM treatments are evidence-based and might be helpful to people with migraine. CAM therapies consist of supplements and behavioral interventions. In this article, we will focus on the more commonly studied CAM treatments. Of note, evidence-based guidelines from the American Academy of Neurology (AAN) and American Headache Society (AHS) on NSAIDs and other complementary treatments for episodic migraine prevention in adults were published in 2012 (8). However, they were retired (9), and new guidelines are in development. Neuro-ophthalmologists should be aware of the literature on complementary and integrative treatments for migraine, given the high prevalence of migraine and the fact that many patients present with eye complaints that are really part of migraine. For example, people with migraine may think that they have a visual acuity issue because of blurred vision, but really, they are experiencing photophobia, they may have visual disturbances meeting criteria for aura, they may complain of eye sensitivity which can be allodynia or eye pain from the pain of migraine itself. When patients present with these symptoms, and a diagnosis of migraine is made, many patients also want treatment for their migraine. SUPPLEMENTS Supplements include vitamins, minerals, and certain herbal preparations. Their use among people with migraine is on the rise despite lack of adequate FDA regulation regarding their safety and efficacy in humans' studies (9-13). Also, despite touted as safe, there is a lack of data regarding their safety in pregnancy and lactation (14). Magnesium Magnesium use has been studied for both the management and prevention of acute migraine attacks. Magnesium is the Patel and Minen: J Neuro-Ophthalmol 2019; 39: 360-369 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Disease of the Year: Migraine second-most common intracellular cation in the body. It plays a salient role in glucose metabolism, nucleic acid synthesis, muscle activity, and cell membrane stabilization. About 67% of magnesium in human bodies is stored in bones and the rest intracellularly (15). Only 1%-2% is available extracellularly; thus, measured serum levels are a poor indicator of true total body stores. Low magnesium levels in the serum and low intracellular concentrations in various cells and the brain have been linked to migraine both ictally and interictally (16-21). It is postulated that people with migraine secrete excessive amounts of magnesium due to stress leading to hypomagnesemia which in turn potentiates cortically spreading depression and neurotransmitter release including substance P, platelet aggregation, and vasoconstriction (22). A recent meta-analysis of 5 double-blind, placebocontrolled randomized trials showed a reduction in the number of migraine attacks by 22%-43% with oral magnesium treatment (23). The study by Piekart et al (24) (included in the above meta-analysis) provides the best evidence regarding the efficacy of oral magnesium. In this study, trimagnesium dicitrate 600 mg, administered to 81 subjects with migraine over a period of 12 weeks, was compared with the placebo. People with migraine treated with magnesium had a 41.6% reduction in the number of attacks compared with 15% in the placebo group. Based on this, the AAN-AHS gave oral magnesium a level of evidence B for the prevention of episodic migraine (8). In practice, it is recommended to take 400 mg of magnesium oxide or chelated magnesium (e.g., magnesium gluconate, glycinate, or aspartate) daily with food (25). Stomach ache, nausea, and diarrhea are possible adverse effects that may occur with the use because of poor absorption, but if tolerated, it should be used at least for a month before benefits are observed. If no benefits are noticed after 1 month and it is well tolerated, the dose can be raised to 400 mg 2 or 3 times a day. By contrast, IV magnesium is commonly used in combination with other agents for the treatment of acute migraine in the emergency department. Administration of 1 g of IV magnesium provided relief of .50% in pain intensity in about half of the patients who had low serum ionized magnesium levels in one study (18). However, a metaanalysis of 5 randomized controlled trials showed no benefit of IV magnesium in the acute treatment of migraine in comparison with other drugs including the placebo (26). Thus, there is a lack of sufficient evidence to recommend the use of IV magnesium alone in migraine attacks as noted in the AHS Emergency Department Management of Migraine Guidelines (27). It is important to note that magnesium should be avoided in renal failure. It is secreted in urine, and in renal failure, it can cause risk of toxicity (arrhythmias, hypotension, confusion, coma, and death). Patel and Minen: J Neuro-Ophthalmol 2019; 39: 360-369 Riboflavin Riboflavin or vitamin B2 is an important cofactor for enzymes involved in energy production in mitochondria through the Kreb's cycle and electron transport chain. It is one of safest and least expensive migraine prophylactic treatments (28). The basis for use of riboflavin comes from the theory of mitochondrial dysfunction in the brain leading to reduced energy production and an imbalance in cortical excitability (29) In support of this theory, a pharmacogenetic study showed an effective clinical response in patients with migraine who were non-H mitochondrial DNA haplotypes (30). A recent metaanalysis of 11 clinical trials in adults and children showed mixed results regarding the efficacy of riboflavin in migraine prevention (31,32), and Schoenen et al conducted a Class 1 randomized trial comparing riboflavin 400 mg with the placebo in 55 patients with migraine. There was a significant reduction in the attack frequency and days with migraine after 3 months as compared to the placebo. The retired AAN/AHS guidelines give the level of evidence B to riboflavin use in the prevention of migraine. The recommended regimen is 400 mg daily of riboflavin orally for at least 3 months to notice any effect. Side effects are minimal and include diarrhea, polyuria, and yellowish discoloration of urine. Co-enzyme Q 10 (Co-Q10) Co-enzyme Q 10 is a cofactor in the mitochondrial electron transport chain. Its action, as an antioxidant and antiinflammatory by reducing production of H2O2 and matrix metalloproteinases, is believed to be the likely antimigraine mechanism. The first randomized controlled trial of CoQ10 was conducted in 42 patients. A Co-Q10 dose of 100 mg 3 times a day was administered in the active treatment group. A response rate (.50% reduction in attack frequency) of 48% was observed in the active group vs 14% in the placebo group, and there were no significant side effects reported (33). In another study with a larger study population of 1,550 patients, about 33% of the subjects were found to have low Co-enzyme Q10 levels. This subgroup was administered Co-Q10 1-3 mg/kg per day with improvement in levels at follow-up and a reduction in attack frequency and headache disability (34). More recently, Co-Q10 at doses of 100-150 mg per day in combination with magnesium, riboflavin, and feverfew was quite effective in reducing intensity and days with headache compared with the placebo (35,36). In the United States, Co-Q10 is available over the counter and is well tolerated. The old AAN/AHS guidelines consider Co-Q10 as possibly effective (level of evidence C) in migraine prevention. The recommended dose per guidelines is 1-3 mg/kg/d (37). Butterbur Butterbur, also known as Petasites hybridus, is a perennial shrub that contains chemotypes "petasins," which are believed to have anti-inflammatory properties (38). It is 361 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Disease of the Year: Migraine an herbal product available in over-the-counter preparations for use in migraine and allergic rhinitis. The leaves, rhizomes, and roots of the plant are used to make solid extracts that are commercially marketed for migraine prophylaxis. Recent research has shown that the butterbur constituent isopetasin is a transient receptor potential ankyrin-1 tropic agent that stimulates the channel causing desensitization of peptidergic trigeminal nerve terminals. This, in turn, was found to attenuate the terminals' abilities to release calcitonin gene‐related peptide and to signal pain (39). Several Class I studies have reported effectiveness of butterbur in decreasing headache attack frequency. Of these, the most cited one is by Lipton et al (40), where 100 and 150 mg twice daily of butterbur was compared with the placebo in a 16-week trial after a 4week baseline period in 233 subjects with migraine. Subjects who took the 150 mg dose of butterbur showed a significantly higher response rate at 4 months and a greater reduction (by 45%) in attack frequency from baseline compared with the 100-mg dose (32%) and the placebo (28%). A previous study (41) showing an increased responder rate with 100 mg of butterbur compared with the placebo in 120 subjects was reanalyzed by Diener et al (42) in light of several drawbacks in the original protocol and analysis. Compared with a baseline 4-week period, patients in the butterbur group showed a decrease in mean attack frequency with a high responder rate (45% vs 15%) compared with the placebo. A similar trend was observed in randomized trials in the pediatric population (43,44). Based on available evidence, the retired AAN/AHS guidelines gave butterbur use a Level A indication as an effective therapy for migraine prevention. More recently, however, its use has been surrounded in controversy due to several reports from various countries of liver toxicity ranging from reversible hepatitis to fulminant liver failure requiring liver transplants (37,45). It is believed that liver injury occurs with a higher and long-term use of butterbur and is secondary to the pyrrolidine alkaloids found in the extracts (37,46). The original formulation of butterbur, Petadolex (which was studied in various trials), was marketed by a German company, Weber & Weber, using a methylene chloride solvent extraction process that removed these alkaloids. However, this method of removal was changed in 1988 leading to revocation of the production license by the German regulatory agencies in 2009 (13). Subsequently, several countries including the European Union rescinded the registration of commercially available butterbur in light of safety concerns due to alkaloid impurities (13,37). In the United States, recent testing of commercially available butterbur supplements demonstrated that 7 dietary supplements had pyrrolizidine alkaloids, which are considered to be toxic to the liver (47). Owing to the absence of FDA regulation and in the light of these recent findings, the AAN/AHS retired its recommendation regarding the use of butterbur in migraine prevention (9). Thus, the authors of this article would not recommend prescribing butterbur at this time. 362 Melatonin Melatonin, an endogenous hormone secreted by the pineal gland, plays an important role in the regulation of circadian rhythm. It is used for various clinical conditions but recently proposed for migraine prevention because of its anti-inflammatory effects against calcitonin gene-related peptide and other proinflammatory mediators in vitro, proregulatory effect in the circadian rhythm, and low melatonin levels in serum and urine due to hypothalamic dysfunction in patients with migraine (48-52) The first open-label study of melatonin 3 mg in 32 patients with migraine showed a 78% responder rate with reduction in overall frequency, intensity, duration of headache days at 1 and 3 months as compared to baseline (53). Subsequently, 3 randomized controlled trials have been performed for migraine with 2 studies showing negative results (54,55) and 1 study with positive results (56). In the latter one, melatonin was found to be more tolerable than amitriptyline. Its tolerability was similar to that of the placebo. A recent systemic review was unable to pool the data on the melatonin studies due to significant methodological differences, small sample sizes, and some uncertainties regarding randomization. The authors concluded that the quality of evidence for outcomes was very low and is not currently sufficient to support use of melatonin in clinical practice (57). BEHAVIORAL INTERVENTIONS With the realization that migraine is a chronic disabling neurologic condition that is often comorbid with various psychiatric conditions such as depression and anxiety and triggered by stress, several behavioral treatments were extended in the management of migraine with the primary aim of prevention. Most of the interventions described below have been extensively studied in clinical trials and often used an adjunct to with pharmacotherapy. However, studies have also shown that they are effective even without preventive medications/supplements (58,59). Based on the research data, the AAN in 2000 endorsed relaxation training (RT), thermal biofeedback combined with RT, electromyography (EMG) biofeedback, and cognitive behavioral therapy as Grade A level evidence for migraine prevention and its use with preventive drug therapy as Grade B (AAN 2000) (60). These treatments are cost-effective and have minimal risk of adverse effects in comparison with the drug therapy (61). They are suitable for patients who are drug-resistant, at high risk of adverse effects such as children, and have preference for nondrug treatment or contraindications as in pregnancy. In practice, these treatments are under-utilized because of a shortage of qualified therapists and limited insurance coverage (62-64). Table 1 lists some sample resources physicians might provide to their patients. Patel and Minen: J Neuro-Ophthalmol 2019; 39: 360-369 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Disease of the Year: Migraine TABLE 1. Complementary integrative health migraine resources Headache toolbox (patient handout) on evidence-based integrative health treatments: https://onlinelibrary-wiley-com. ezproxy.med.nyu.edu/doi/full/10.1111/head.13555 Free relaxation audios on websites like DawnBuse.com Additional reading material: https://americanmigrainefoundation.org/resource-library/?search=mindfulness Cognitive Behavioral Therapy Cognitive behavioral therapy (CBT) is a psychotherapeutic approach, originally developed by Aaron Beck for the treatment of various mental health disorders. It is based on the premise that our thoughts influence how we feel and behave (65). CBT targets the dysfunctional thoughts (e.g., "My headache will never get better," "I will never be able to perform," and "My wife will leave me") by challenging them or using certain behavioral techniques (e.g., problem-solving skills and relaxation) leading to positive behavior and improved function that in turn will reduce the intensity of the negative thoughts and eventually replace them with positive ones (25). CBT increases self-efficacy and thus functional outcomes in patients with migraine, thereby reducing stress, anxiety, depression, and improving quality of life (61). In a recent systematic review of studies, CBT showed a reduction in headache intensity in the range of 16.2%-71.9%, reduction of medication intake by 20%- 25%, as well as a reduced depression, anxiety, and pain catastrophizing while improving pain acceptance and coping (66). CBT programs often incorporates components of biofeedback and relaxation and can also be combined with pharmacological treatment, in which case it is found to be superior to monotherapies (59,67). Well-designed clinical trials in both pediatrics (58) and in adults (59) showed that CBT optimized with abortive migraine medication works effectively. This is important because medications for preventing migraine, especially in pediatrics, may not always be ideal. In a well-designed trial comparing amitriptyline, topiramate, and placebo, there were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent migraine in the various arms at 24 weeks. However, the amitriptyline and topiramate groups had higher rates of adverse events (68). Thus, in the case of pediatric migraine, behavioral therapy such as CBT is considered first-line. Biofeedback Biofeedback is a behavioral technique wherein information learned about involuntary body functions as measured by external devices is manipulated to achieve desired physiological response (69). The goal is to have patients learn to develop awareness and control of various physiological parameters such as heart rate, breathing, and muscle tension through relaxation techniques. Once learned, these behavioral methods can be used in disease conditions even without the requirement of sensors or external devices. In migraine management, biofeedback enables patients to Patel and Minen: J Neuro-Ophthalmol 2019; 39: 360-369 become aware of the physiological changes during RT and improvement in disability and function (61). Biofeedback can be applied through various modalities such as blood volume pulse (BVP) feedback, thermal biofeedback, and EMG feedback, and the response is presented either in the form of audio or visual images (70). In neurofeedback, patients observe real-time displays of electroencephalogram waves and learn to change them to achieve a calmer state. In various meta-analyses, biofeedback produced medium effect sizes in headache parameters and associated psychological symptoms (61,71). BVP feedback, which can also be administered during acute attacks, produced stronger effects than thermal and EMG feedback in these studies. The level of evidence for neurofeedback in migraine is lacking due to absence of rigorous studies (72). Relaxation RT, often, used in combination with CBT, works by decreasing sympathetic activation and central pain processing (61,70). Various forms of relaxation techniques are used in migraine prevention, for example, autogenic training, progressive muscle RT (PMRT), diaphragmatic breathing, guided imagery, meditation, and hypnosis. PMRT is one of the popular methods, which incorporates alternative activation and relaxation of decreasing number of muscles during progressive sessions. Patients learn to differentiate the contrasting sensations and use these exercises during periods of stress. These techniques can be self-taught through print, audio, or online (e.g., Apps or YouTube) materials. Relaxation techniques should be practiced regularly to be effective. In a meta-analysis of clinical trials of migraine prevention, RT produced medium-size effects and is compared with that produced by CBT and biofeedback (73). Third-Wave Therapies Meditation is a form of mental technique aimed at improving attentional capacity, self-awareness, and emotional regulation. Based on how the attention is focused, 2 types of meditational styles are identified in scientific research: concentrative type and mindfulness type (MM) (74). Concentrative style involves focused attention on a given object such as an image or a mantra (also known as transcendental meditation), whereas mindfulness meditation is characterized by nonjudgmental moment-tomoment awareness of one's internal and external stimuli including thoughts and feelings (74). These practices are well tolerated and suitable for pregnant women, adolescents, and other patients who may have contraindication to 363 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Disease of the Year: Migraine medications and are limited by medication side effects or medication overuse issues (66). Mindfulness-based stress reduction (MBSR), mindfulness-based cognitive therapy (MBCT), and acceptance and commitment therapy (ACT) are 3 major MMs-based interventions well studied in mental and physical disorders. MBSR is a secular intervention developed from Buddhist philosophy by Kabat-Zinn which is found to be effective in management of chronic pain related to several medical conditions (75). Standard MBSR is conducted in 8-weekly 2-hour group sessions with a concluding day "mindfulness retreat" of about 6-hour duration (76). Wells et al conducted one of the first randomized controlled trials of MBSR in 25 people with episodic migraine. Patients were assigned to either usual care (pharmacological prophylaxis) or usual care combined with MSBR (77). One month after MSBR, the MBSR group had reduced headache duration and disability and improved self-efficacy. There have been at least 2 subsequent MBSR studies to date examining patients with migraine or tension-type headache (78,79). The first study consisted of 37 adult participants with 15 or more headache days who were randomized to MBSR and usual medication treatment. The MBSR group showed less pain intensity and improved quality of life as compared with usual treatment (78). The second was an online MBSR program compared with usual medical treatment in patients with migraine or tension type headache (79). The MBSR group did not have improvements in sensory pain sensation but did have improvements in the emotional dimension of pain, disability, mindfulness, and distress. Both of these studies had small sample sizes. Despite small sample sizes of studies, a recent meta-analysis showed improvement in headache intensity with MSBR (80). Spiritual meditation, a form of transcendental meditation, showed improvement in headache frequency, intensity, and anxiety in several randomized trials (81-83). Mindfulness-based cognitive therapy (MBCT) is another integrative approach that was originally developed for the prevention of depression relapse (84). Day et al (85) conducted a pilot study that showed that MBCT was feasible and acceptable to headache patients and was effective in improving self-efficacy and pain acceptance but did not significantly change daily headache outcomes. Seng et al have subsequently conducted a randomized controlled trial in a larger group of migraine patients. In this study, MBCT effectively reduced perceived headache-related disability and day-level migraine-related disability (86). ACT (pronounced as "act") is another mindfulnessbased approach shown to be effective in the treatment of mental health disorders and chronic pain (87,88). Based on this success, its use has been extended in treatment of headaches. Developed by Steven C. Hayes, it integrates both cognitive and behavioral therapy to improve the psychological inflexibility caused by avoidance behavior and cognitive fusion that supports these behaviors. Major processes 364 involved in ACT include noticing and acceptance of unwanted private events such as pain without considering them as barriers to action, while observing these in self-ascontext and acting in direction of personally valued goals to improving overall functioning (89). Three randomized controlled trials of ACT in people with migraine have shown ACT as effective in improving symptoms of depression, anxiety, disability, general function, and affective dimensions of pain compared with wait-list or usual care (89-91). Hypnosis Hypnosis is a state of consciousness wherein there is a heightened focus with reduced peripheral awareness and an enhanced capacity to respond to suggestion. The use of hypnosis for therapeutic purposes is referred to as hypnotherapy. Hypnosis has been used since the 18th century for the treatment of pain (92), and efficacy for therapeutic purposes was established by recommendations from The National Institute of Health Technology Assessment Panel (93,94) and the American Psychological Association (95,96). Beginning in the 1970s, several studies showed the effectiveness of hypnotherapy in migraine (97,98). A recent systematic review identified 8 randomized controlled trials of hypnosis in primary headaches including migraine, which showed a positive effect on reduction of headache activity, medication usage, and quality of life in adults without any adverse effects (99). It is an alternative form of therapy that can be used for patients who have poorly responded to pharmacotherapy or have contraindications to it. Hypnosis has most frequently been used in conjunction with visual imagery and relaxation techniques and can be also be self-administered after training with other means such as audiotapes (99). Yoga Yoga is a form of mind-body intervention targeting different physical and mental health conditions. The conceptual framework of Yoga is derived from Indian philosophy and involves a combination of specific physical postures (termed "asanas" of Hatha Yoga), breathing techniques (pranayama), and meditations (100). There are different schools of Yoga based on the priority of the spiritual or physical practices. The usual duration of a session is between 1 and 2 hours. It is a secular form of intervention aimed at increasing physical flexibility, coordination, strength, and achieving mental calmness and awareness (101). Yoga has been studied in a number of pain-related conditions (102), and a recent meta-analysis showed an overall positive effect on pain disorders including headache (101). John et al conducted a randomized trial to assess the effect of Yoga in 65 patients with migraine. Patients were randomized to Yoga intervention or self-care. After 3 months of intervention, the Yoga group showed statistically significant reductions in frequency, intensity, duration of attacks, overall intensity, and anxiety/depression scores compared with the self-care group (103). In another study, Patel and Minen: J Neuro-Ophthalmol 2019; 39: 360-369 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Disease of the Year: Migraine in addition to improvements in headache intensity and frequency, Yoga had added benefits in modulating autonomic function by increasing vagal tone in combination with conventional therapy vs conventional therapy alone (104). It is theorized that Yoga also helps relieve stress (believed to be one of the triggers of migraine) by decreasing sympathetic activity through inhibitory effects on angiotensin II and NO (104). A recent study also showed that Yoga in combination with Ayurveda (Indian traditional medicine system) showed w.75% reduction in the number of participants with severe headache, nausea, vomiting, analgesic requirement, duration of headache, and number of headaches in the past 3 months as compared to symptomatic treatment with NSAIDs (105). Advantages of Yoga therapy are its cost-effectiveness, added effects on flexibility, stress/depression/anxiety, and quality of life without many side effects. However, most of these studies were conducted in India (limiting generalizability), had small sample sizes, were short-term in duration (up to 3 months), and were variable in the types of Yoga practices. Acupuncture Acupuncture is an ancient Chinese therapy based on the theory of disease causation secondary to energy imbalance in the body. Acupuncture involves inserting needles at acupoints (specific points along the energy meridians) in the body leading to the release of the obstructed energy (referred to as "Qi" in Chinese), thus bringing the body in balance and curing the disease (106). Despite recent debates about the validity and placebo effects of acupuncture (107,108), several studies argue that it may have a scientific basis in the treatment of migraine (109-114). A meta-analysis of 22 trials that included 4,985 patients showed that acupuncture lead to a 50% reduction in headache frequency in 41% of the patients compared with the no acupuncture group, 50% compared with the sham acupuncture group, and 57% compared with prophylactic medication therapy, suggesting that acupuncture is slightly more effective than sham and as effective as medication prophylaxis. Subsequent trials showed a similar trend toward the effectiveness of acupuncture in migraine prevention although the quality of evidence is low (115,116). Like Yoga, there are different styles of acupuncture. Acupuncture generally requires a minimum of 6-8 sessions to see a decrease in symptoms. Adverse effects range from serious such as pneumothorax, infection, bleeding, bruising, nerve injury to minimal such as a change or increase in pain intensity or failure of therapy. It is contraindicated where there is skin and soft tissue infection. It can be recommended for patients who have failed other forms of pharmacological therapy. Aerobic Exercise Exercise is often recommended in prophylaxis of migraine attacks (117). The effect of aerobic exercise may be mediated by a decrease in the neurovascular inflammation and Patel and Minen: J Neuro-Ophthalmol 2019; 39: 360-369 improvement in self-efficacy for migraine management after the achievement of aerobic fitness (118). In a recent systematic review of studies, aerobic exercise was associated with an improvement in headache parameters when used as an adjunct to other behavioral therapies (119). To be effective, an endurance exercise program (e.g., cycling, jogging, or rowing) of at least 30-60 minutes 3 times a week for 8 weeks is recommended from various studies (119,120). This regimen is also associated with a low likelihood to trigger migraine attacks that can occur in patients with migraine (121). Despite certain studies showing the benefits of aerobic exercise (122-125), the overall data are still insufficient to recommended aerobic exercise as a single therapy for migraine prevention because of methodological limitations (117). Education Finally, education regarding key lifestyle factors is also very helpful and important in reducing migraine. A simple session could consist of educating patients about the importance of the following a) limiting pain medication to no more than 2-3 days per week because frequent medication use can actually worsen headache; b) taking the medication right away at the start of the headache can lead to a shortened time to pain relief and less medication in the long run; c) sleep hygiene (maintaining the same bedtime and time of awakening during the week and during the weekend; and d) exercise because aerobic exercise has been effective in reducing migraine (62). CONCLUSION In conclusion, there are a multitude of nonpharmacologic treatment options for migraine, ranging from supplements to many types of behavioral interventions. Traditionally, they were called complementary and alternative treatments. Now, they are better known as complementary and integrative health treatments. They can be beneficial to patients alone and in conjunction with medications. 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