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Chronic Migraine : Pharmacologic Management

Chronic migraine management depends on a multimodal approach, including pharmacotherapy, physical therapy, behavioral therapy, and other strategies, with the primary focus on preventive therapy, including avoidance of migraine triggers. Identification and treatment of comorbid conditions is an essential element of chronic migraine management. Use of acute headache medications should be kept to a minimum to avoid occurrence of medication overuse headache. While complete elimination of migraine attacks may not be achievable, the goal of prophylactic treatment is reducing both the frequency and/or severity of migraine attacks.[1]

Pharmacologic Prophylaxis

Generally, the same prophylactic pharmacotherapies that are used in the treatment of episodic migraine are also used to prevent chronic migraine. First-line treatments include drugs from the following classes: antidepressants, antiepileptics, and antihypertensives (beta-blockers).[1] Since diagnostic criteria for chronic migraine have only recently been defined, only a small number of placebo-controlled clinical trials using standardized inclusion criteria have been conducted. Therefore, the evidence-base for making treatment recommendations is small.[2] Table 1 shows prophylactic drug treatments that have been evaluated in clinical trials of chronic migraine patients. Effective prophylactic pharmacotherapy (defined as decreasing migraine frequency ≥50%) should be continued for 3 to 6 months before discontinuation.[1, 3-5]


Table 1. Prophylactic agents evaluated in chronic migraine


Initial Dose

Typical Total Daily Dose

Common Side Effects

Serious Side Effects

Topiramate (mg)



ParesthesiasFatigueWeight loss Acute angle closureGlaucomaMetabolic acidosisHyperthermia
Gabapentin (mg)



Levetiracetam (mg)



Divalproex sodium (mg)



Weight gainTremorNauseaAlopecia PancreatitisLiver failureThrombocytopenia
Fluoxetine (mg)



InsomniaAstheniaTremor Prolonged QT interval
Amitriptyline (mg)



SedationWeight gainConstipation Cardiac dysrhythmias
Propranolol (mg)



DepressionFatigue Bradyarrhythmia
Atenolol (mg)



DepressionFatigue Bradyarrhythmia
Memantine (mg)



Botulinum Toxin Type A (IU)



Neck painMuscular weakness
Tizanidine (mg)



SomnolenceDry mouthAsthenia Hepatitis
Adapted from Garza I, Schwedt TJ. Semin Neurol. 2010;30:154-66 and Mathew PG, Garza I. Semin Neurol. 2011;31:5-17, with data from Diener HC, Holle D, Dodick D. Curr Pain Headache Rep. 2011;15:64-9 and Diener H, et al. Cephalalgia. 2010;30:804-814.


Selection of Pharmacotherapy

Individual patient factors often determine the selection of a specific prophylactic drug to treat chronic migraine. These factors include the presence of comorbidities and symptoms, such as psychiatric disorders, medical disorders, fatigue, sleep disorders, other pain disorders, and gastrointestinal complaints. For example, antidepressant medications may be chosen for the patients who is depressed or have a history of depression, while antihypertensives may be well suited for hypertensive patients. With certain agents, typical dosing used for migraine may not be sufficient for the comorbid disorder and may have to be adjusted.[1]

Nonpharmacologic Therapy

Nonpharmacologic treatments, including biofeedback, relaxation therapy, cognitive-behavioral therapy, and physical therapy may be effective as part of a multimodal treatment strategies as an adjunct to pharmacotherapy for chronic migraine. Cognitive-behavioral therapy has been associated with short-term and long-term reductions in migraine burden.[6] Biofeedback has been shown to be effective in reducing markers of physiologic stress, including nitric oxide, in migraine patients.[7] Research has demonstrated that aerobic activity results in significant improvements in migriane symptoms.[8]

Written by: Jonathan Simmons, PhD | Last reviewed: March 2012.
1. Garza, I. and T.J. Schwedt, Diagnosis and management of chronic daily headache. Semin Neurol, 2010. 30(2): p. 154-66. 2. Vargas, B.B. and D.W. Dodick, The face of chronic migraine: epidemiology, demographics, and treatment strategies. Neurol Clin, 2009. 27(2): p. 467-79. 3. Diener, H., et al., OnabotulinumtoxinA for treatment of chronic migraine: Results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia, 2010. 30(7): p. 804-814. 4. Diener, H.C., D. Holle, and D. Dodick, Treatment of chronic migraine. Curr Pain Headache Rep, 2011. 15(1): p. 64-9. 5. Mathew, P.G. and I. Garza, Headache. Semin Neurol, 2011. 31(1): p. 5-17. 6. Martin, P.R., M.R. Forsyth, and J. Reece, Cognitive-behavioral therapy versus temporal pulse amplitude biofeedback training for recurrent headache. Behav Ther, 2007. 38(4): p. 350-63. 7. Ciancarelli, I., et al., Relationship between biofeedback and oxidative stress in patients with chronic migraine. Cephalalgia, 2007. 27(10): p. 1136-41. 8. Lockett, D.M. and J.F. Campbell, The effects of aerobic exercise on migraine. Headache, 1992. 32(1): p. 50-4.