Event 3: Multimodal Treatment Plans

Medication overuse headache (MOH) occurs in genetically susceptible individuals after they have self-treated with acute analgesics for their worsening headaches. The treatment approach to every patient with headache should be multimodal. The goal is to identify and decrease the modifiable risk factors and enable the patient to return to their baseline or improved headache frequency. When patients have unaddressed medication overuse (any analgesic medication use more than 1-2 days per week, for any type of pain), we find that preventive measures are not nearly as effective as they would be without that use. Discontinuing or reducing exposure to the acute medications is an essential starting point for the healing journey but may not be enough to restore them to episodic headache.

Melissa On Multimodal Treatment Approach

The following recommendations will facilitate the recovery for Melissa, and many patients like her suffering from MOH.  Clinical studies show response rates of up to 85% in patients being treated for MOH with a preventive medication. The success rate is lower at the 5-year interval, closer to 50%.21 These poorer long term results may be related to the lack of multimodal treatment and education to develop good patient compliance and sustained recovery from headaches, often without long term or routine frequency of follow up.7

Step One: Reduction or Discontinuation of Acute Medications

Approach to reduce acute medication exposure: Abrupt Withdrawal versus Slow Taper of Medications in MOH

There are two options when trying to decide how to discontinue the offending medication, abrupt withdrawal or slow taper. Currently there is limited research to support a specific method. If opioids are the offending medication, titrate first the long acting, then the short acting medication over time.7 The Center for Disease Control has a pocket guide to taper opioids. If butalbital is the overused medication, avoid abrupt withdrawal due to the risk of seizures.7 These patients can be transitioned to phenobarbital and then weaned over several days. The goal is to match recommendations with patient preferences. The Mayo Clinic is currently conducting a study titled the Medication Overuse Treatment Strategy Trial to evaluate the treatment options for MOH.40 It is estimated to be completed in year 2021.32 Additional information can be found at https://www.motstrial.org/.

Encourage the patient to keep a headache diary to identify adherence and treatment outcomes. Consultation with a mental health provider can be helpful in teaching techniques to deal with anticipatory anxiety during either discontinuation process.

Educate patients that during the withdrawal processes from the offending medication, headaches may get worse before getting better. Patients with severe comorbid or medical, psychiatric illnesses, or those on prescribed daily opioids or barbiturates may require pain consultation and management. Pain specialists may use long-term medication assisted treatment for detoxification. 

Option 1: Abrupt Withdrawal

Some patients may choose to either immediately stop or quickly withdraw the offending acute treatments. If choosing to do so, the provider can offer bridge therapy options to ease the difficulty of this process. 
Bridge Therapy Options (to be prescribed alone or in combination):

  • Corticosteroids for 10-21 days if safe and tolerated. Example: Prednisone 20 mg daily x 10-14 days, then reduce to 10 mg x 10-14 days, then stop. Often short 5 day or 10 day courses may not be enough time to reset the system and headache may recur. 
  • Preventive medication therapy: Beta blocker such as propranolol 20 mg daily gradually increasing up to three times a day; anti-epileptic such as Topiramate 12.5-25 mg daily, slowly increasing up to 50 mg twice a day if tolerated; tricyclic antidepressant or serotonin norepinephrine reuptake inhibitor at lowest doses available. 
  • Preventive and/or acute neuromodulation devices: Cefaly device (supraorbital transcutaneous stimulator 20-60-minute daily treatment), GammaCore device (vagal nerve stimulator 2-minute bilateral treatment), Spring TMS (transmagnetic stimulator handheld device).

Option 2: Slow Taper

Other patients may be hesitant to set aside acute treatments altogether right away. For these patients, it is important to reinforce the message not to treat low level headaches and to limit acute treatments to only 1-2 days per week. Reinforcing the message also that preventive therapy is essential, as any acute treatment will not work as well for chronic headache as it once did for episodic headache. The same bridge therapies may be used in the slow taper option; however, expectations should be set to see slower improvement. 

Step Two: Employ Multimodal Approach

Considering how complex headache pathophysiology and all the potential modifying risk factors present for developing chronic migraine, it is not a stretch to recommend a well-rounded treatment approach that addresses all aspects of a patient’s life. Recommendations for a comprehensive treatment plan may include neuromodulation, supplements, nutrition changes, exercise, stress management, sleep management in addition to preventive medications and other bridge therapy options.


Neuromodulation entails the use of an abortive and/or preventive device for headache treatment. There are three primary neuromodulation devices now FDA approved for migraine headache:

  • Supraorbital transcutaneous stimulator device (only available from Cefaly): works by providing neuromodulation to the trigeminal nerve in 20-60 minute daily sessions. Data are available since 2008, with two sham controlled randomized control studies demonstrating safety and effectiveness of the device.33,34
  • Vagal nerve stimulator device (only available from GammaCore): works by providing neuromodulation to the vagal nerve in 2 minute sessions, if needed, several times per day. Data available since 2018, with one published sham controlled randomized controlled trials demonstrating efficacy and safety of this device for acute migraine treatment with potential for preventive treatment for migraine.35
  • Transcranial magnetic stimulation (only available from eNeura): works by providing a single magnetic impulse that disrupts the migraine process acutely and can also be used as prevention. There are data from double blinded sham controlled randomized control trials showing safety and effectiveness for the acute treatment of migraine with aura.36

Sleep Modulation

Nonrestorative sleep is frequently a problem for patients with MOH.37 
Recently, prolonged wakefulness has been linked to the inhibition of the glymphatic system, a network of paravascular tunnels that filter out cortical interstitial solutes and metabolites from the parenchyma.38 The glymphatic system most efficiently clears solutes during sleep. A lack of sleep causes the solutes and metabolites to accumulate in the brain.38 This can be one explanation for why we find that poor sleep frequently precedes headache and why falling asleep can abort headache.39 Two treatment strategies to help regulate disordered sleeping patterns are cognitive behavioral therapy for insomnia (CBTI) and melatonin supplementation.


The American College of Physicians recommends CBTI as the first line treatment for chronic insomnia.40 CBTI focuses on identifying the underlying causes of insomnia instead of relieving symptoms. It helps one develop healthy sleep habits and avoid behaviors that inhibit sleep. Common CBTI techniques include: stimulus control therapy, sleep restriction, sleep hygiene, sleep environment improvement, relaxation training, remaining passively awake and biofeedback. Randomized-controlled trials have shown significant improvement in insomnia symptoms. Some have even seen greater than a 50% improvement in sleep symptoms.41 The U.S Department of Veteran Affairs has created a great smart phone app called “CBT-i Coach”. Please click on the following link for additional information on how the app works: https://mobile.va.gov/app/cbt-i-coach.

For more information on CBT-I techniques: https://www.mayoclinic.org/diseases-conditions/insomnia/in-depth/insomnia-treatment/art-20046677


Chelated Magnesium (Citrate, taurate, glycinate, etc.)

The recommended dose is around 400-600 mg daily in divided doses depending on tolerability. It is recommended to start slowly, as magnesium can also lead to increased bowel movements or diarrhea. This supplement can be very helpful in preventing headache and migraine aura, calming nerves, muscles and even mood.42

A double-blind controlled study showed reduction in the number of days with headache in women with menstrual migraines as well as improvement in premenstrual syndrome symptoms.43 The American Academy of Neurology and American Headache Society rate magnesium treatment for migraine as level B.

Riboflavin (B2)

The recommended dose is 400 mg daily. It is theorized that Vitamin B2 improves energy metabolism which may help reduce the mitochondrial dysfunction seen in some migraine patients. There are mixed data on efficacy of B2 for migraine prevention, and currently the American Academy of Neurology recommends this treatment as probably effective.42

Melatonin Supplementation

The recommended dose, depending on patient tolerability, may range from 1-10mg 30 minutes prior to bedtime. Melatonin synchronizes the circadian rhythm and improves sleep onset, duration and quality. Melatonin was also seen to reduce migraine equally as effectively as a tricyclic antidepressant due to the anti-inflammatory nature of the supplement as well as improvement in sleep.44

Boswellia (Indian frankincense)

The recommended dose is 800 mg three times per day. Boswellia is made from the sap of the Indian Frankincense tree which possesses anti-inflammatory and analgesic properties. These properties are created by the pentacyclic triterpene acids within the extract. These acids interfere with the body’s natural inflammatory response by inhibiting cytokines and leukocyte activity. The researchers of one cohort study published in 2013 found improvement in headache for patients treated with Boswellia for chronic cluster headache.45

Feverfew (Tanacetum parthenium)

The recommended dose is 1-3 cups per day. Feverfew is a plant that can be ingested raw, as a tincture or as a tea. The parthenolide chemical found within this plant holds anti-inflammatory properties which can inhibit prostaglandin synthesis and phospholipase A. Data from two randomized controlled trials showed statistical reduction in headache frequency as compared to a placebo group.46,47 Feverfew may potentially cause interactions with medications that are metabolized through the CYP450 enzyme, such as warfarin. It can also cause increased risk of mouth ulcerations or gum bleeding if chewed. Feverfew is not regulated in the United States but is endorsed by the American Headache Society as a preventive and acute treatment for migraine.42

SAMe (S-adenosyl-L-methionine)

The suggested dose is 200 mg a day. SAMe is found naturally in the body and is an important cofactor needed for production of serotonin. Other modalities aimed at increasing production of or availability of serotonin are helpful in migraine prevention, however it should be stated that there are currently no randomized-controlled trials available to support its use in headache treatment.48

Early Morning Light

Early morning light increases natural serotonin and melatonin. Some patients may find it difficult to get outside for early morning light, and could instead consider a light therapy box with a light intensity of 10,000 LUX. Evidence supports the use of a light box 30-120 minutes each day for increased production of serotonin.49


Research has demonstrated that chronic inflammation may be the link connecting a stressful life and disease.50 An anti-inflammatory diet supports healthy lifestyle and may be additionally helpful for weight loss or weight maintenance.

It is important not to skip meals or consume meals high in simple carbohydrates. Both hypoglycemia and marked elevation in blood sugar can trigger headaches.52 The microbiome also plays a role in pain and headache and dietary modifications may also work through this mechanism, but this is not well understood.


Gentle exercises, combining both muscle building and aerobics exercise are recommended to decrease and prevent headache. In a study with almost 47,000 participants, low level of physical activity was associated with a higher prevalence of migraine and headache.53 A follow-up study compared aerobic exercise (40 minutes 3 times a week), Topiramate and relaxation training and found exercise to be as effective as medication or relaxation training in the prevention of migraine.54


There is extensive literature indicating patients who experience pain and maintain a sense of control of their symptoms have lower levels of anxiety, depression and disability.55 Techniques to help facilitate this process include: biofeedback, hypnosis, Cognitive Behavioral Therapy (CBT), Acceptance and Commitment Therapy (ACT), and increasing the amount of fun time spent with friends and family.


Biofeedback has been shown to produce long-term benefit for headache treatment. Biofeedback and relaxation training has been shown to yield a 45%-60% reduction in headache frequency and severity.56 This is equivalent to the reduction seen with many headache medications. Biofeedback uses an instrument that monitors a bodily response as the person tries to modify that response, such as muscle tension, heart rate or skin temperature. The ability to observe instant and continuous feedback on these involuntary processes allows the patient to learn how to modify their body’s reaction to stress. Success requires daily practice. Benefits have been shown to last up to 5 years.56

For information on programs and national certification for biofeedback therapy for medical providers, you can access the website of the Biofeedback Certification International Alliance: http://www.bcia.org/i4a/pages/index.cfm?pageid=1

Melissa on Biofeedback

Side Note

For a video describing one type of biofeedback technology termed, “Heart Rate Variability", check out:


(Please note: this is an external video link, and not 508 compliant.)

Test Your Knowledge

What resources can you offer patients immediately to access biofeedback? (There may be more than one correct answer.)

Correct. Rationale: As stated in the previous section all the answers are examples of resources that that can be provided to the patient at the time of the visit.
Correct. Rationale: As stated in the previous section all the answers are examples of resources that that can be provided to the patient at the time of the visit.
Correct. Rationale: As stated in the previous section all the answers are examples of resources that that can be provided to the patient at the time of the visit.

Clinical Pearl

It is important to spend time addressing realistic expectations. It can take 3 months or more to start seeing positive effects of interventions.  These interventions then must be maintained consistently for 6-12 months to see dependable ongoing results.

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