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Early Intervention in a Case of Migraine With Depression


The patient presented with left-sided, throbbing headaches that had gradually increased in severity and frequency. These headaches, which occurred once or twice a month, were associated with photophobia, phonophobia, and nausea, and usually lasted 8 to 12 hours. The headaches affected the patient's job performance and attendance, and she complained of fatigue, lack of sleep, and difficulty in concentrating.


The patient-a 25-year-old white woman employed as a fourth-grade teacher-presented with left-sided, throbbing headaches that had gradually increased in severity and frequency.

Her headaches began at age 13 with menarche. These headaches, which occurred once or twice a month, were associated with photophobia, phonophobia, and nausea, and usually lasted 8 to 12 hours. They gradually progressed in severity (from mild/moderate to moderate/severe) and frequency (to 2 or 3 per week). The headaches affected the patient's job performance and attendance, and she complained of fatigue, lack of sleep, and difficulty in concentrating. She also reported increasing stress in her home life: after her husband lost his job a year earlier, she had been the sole support of her family, including her 2 young children.

The patient had been taking aspirin/butalbital/caffeine tablets for her headaches. She increased the dosage to obtain pain relief, but nausea and/or heartburn developed as a result. She occasionally resorted to the emergency department, where she received meperidine. She had previously treated her headaches with acetaminophen/aspirin/ caffeine tablets and, before that, with ibuprofen and acetaminophen.

This patient was 5 ft 5 ½ in tall and weighed 125 lb. Results of the neurologic examination were normal. Her heart rate was 78 beats per minute and regular, and her blood pressure was 110/74 mm Hg. Her chest was clear, and she appeared well nourished and otherwise healthy. However, she exhibited signs of depression.

Laboratory test results (including complete blood cell count, blood chemistry, and levels of thyroid-stimulating hormone) were normal, as was an MRI scan of the brain. The patient's Beck depression scale indicated moderate depression.

The diagnosis was migraine headaches, depression, and overuse of caffeine-containing analgesics.

She was counseled to discontinue caffeine-containing medications, to eliminate caffeinated foods and drinks from her diet, to establish consistent daily sleeping and eating patterns, and to increase her daily physical activity. To help wean her from caffeine-containing analgesics and foods, and to assuage potential withdrawal symptoms, bridge therapy with tapering doses of a corticosteroid was started. For pain relief, the patient also took 500 mg of naproxen twice daily for 1 month. Amitriptyline, 10 mg/d, and sertraline, 50 mg/d, were prescribed for her depression. For acute-migraine treatment, almotriptan, 12.5 mg, was to be taken at the first sign of a headache; the dose could be repeated once in 2 hours if the headache did not resolve, for up to 4 doses per week.

The Dialogue:

Primary care doctor: What are the common migraine triggers?

Headache specialist: Certain foods (Table), alcohol, stress, and menstruation are among the most common triggers.1,2 A comprehensive treatment plan should include the identification of triggers to prevent attacks.

This patient reported overuse of caffeine, lack ofsleep, and stress-all of which could trigger her migraines.Lifestyle changes and medication were thereforenecessary to control her migraines. Although it isimportant to identify migraine triggers in individual patients,a long list of items to avoid can be burdensome.Therefore, I generally counsel my migraine patients toeliminate caffeine, chocolate, monosodium glutamate,artificial sweeteners, and alcohol; to maintain regularsleeping and eating habits; and to exercise regularly.

Primary care doctor: How can comorbid conditions affect migraine?

Headache specialist: Affective disorders, such as depression, are common in migraineurs. Both clinic-based and epidemiologic studies support an association between migraine and major depression. Epidemiologic studies also support an increased prevalence of bipolar disorder, panic disorder, and some anxiety disorders in migraineurs. Other comorbid conditions frequently found in migraineurs include epilepsy, stroke, rheumatologic disorders, and essential tremor.3 Some comorbid conditions may limit treatment options. Other comorbidities may provide unique therapeutic situations in that some drug classes may be effective for both conditions. For example, certain antiepileptic agents can prevent both migraine and seizures.

In this patient's case, antidepressant therapy mayhave helped relieve her depressive symptoms as well asher migraines.4 Antidepressants offered an appropriatesubstitute for her original analgesics, which were ultimatelydiscontinued.

In short: for a migraineur with a comorbid condition,maximal therapeutic effect depends on treatmentof the comorbidity.

Primary care doctor: What are the goals of therapy for acute migraine?

Headache specialist: There are several facets5:

  • Treat attacks rapidly and consistently.

  • Prevent headache recurrence.

  • Restore the patient's ability to function.

  • Minimize use of backup medication.

  • Promote the patient's involvement in care, and optimize the tolerability of treatment.

Primary care doctor: How is migraine management stratified to achieve these goals?

Headache specialist: Therapy is stratified according to the degree of pain intensity and associated disability. This patient had recurrent moderate to severe migraines that adversely affected her ability to function. The severity of symptoms and her high level of disability indicated the need for acute migraine-specific therapy. A triptan was the logical choice. These agents have been shown to reduce or eliminate headache pain, prevent headache recurrence, and improve functioning.6

Primary care doctor: Why was this patient advised to medicate at the first sign of headache?

Headache specialist:

Our understanding of migraine pathophysiology supports early intervention. Migraine is progressive: it begins with the sensitization of the intracranial blood vessels and meninges. In susceptible patients, these impulses of pain-if uncontrolled or untreated-act on the trigeminal nucleus caudalis, which further activates the peripheral system. If these impulses are allowed to progress to the second- and third-order neurons, then cutaneous allodynia and central sensitization exacerbate the inflammatory process.


Activation of these second-order neurons in the thalamus and third-order neurons in the cortex results in hypersensitivity and throbbing pain. Early intervention when the pain is still mild (ie, during the first hour of a migraine attack before central sensitization occurs) may constitute a window of therapeutic opportunity for such medications as the triptans.

This patient had been waiting for her pain to becomemoderately intense before taking almotriptan.This diminished the efficacy of the medication.

Primary care doctor: Are there any clinical trial data to support the early use of triptans?

Headache specialist: Yes. There are good and plentiful data demonstrating that all triptans-when used as an early intervention in migraine attacks-will abort headaches more quickly and result in a greater pain-free response than they will if headache treatment is delayed.6,9-12 Several studies indicate that early intervention:

  • Interrupts progression from intracranial vessel sensitization to central sensitization.

  • Results in an increased 2-hour pain-free rate.

  • Reduces the need for rescue medication.

  • Reduces the rate of headache recurrence.

  • Increases patient relief.

Because of these findings, the use of triptans during the mild phase of migraine attack is gaining support.9,12-14


At 1 month, the patient had stopped using caffeine-containing medications and had eliminated caffeine from her diet. Both the frequency and severity of her headaches had decreased, and her sleep patterns had improved. To combat depression, the dosage of sertraline was increased to 100 mg/d.

At 2 months, headache frequency was significantly reduced, but the patient continued to experience 2 to 5 episodes per month. Most of these resolved with a single dose of almotriptan, although an additional dose was occasionally necessary. The patient's depressive symptoms diminished, and she had more energy and a greater ability to cope with activities of daily living.

At 3 months, headache frequency had dropped to 1 to 3 times per month and symptoms resolved with a single dose of almotriptan. The patient reported that she was no longer missing work and was able to enjoy her home life again.

Table - Foods that can trigger migraines




Dodick DW. Acute and prophylactic management of migraine.

Clin Cornerstone.



National Headache Foundation. Diet and headache. Available at:

www. headaches.org/consumer/topicsheets/diet_headache.html

. Accessed February 21, 2006.


Shechter AL, Lipton RB, Silberstein SD. Migraine comorbidity. In: Silberstein SD, Lipton RB, Dalessio DJ, eds.

Wolff's Headache and Other Head Pain.

New York: Oxford University Press; 2001:108-118.


Punay NC, Couch JR. Antidepressants in the treatment of migraine headache.

Curr Pain Headache Rep.



Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.




Ferrari MD, Goadsby PJ, Roon KI, Lipton RB. Triptans (serotonin 5-HT1B/D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials.




Burstein R, Cutrer MF, Yarnitsky D. The development of cutaneous allodynia during a migraine attack: clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine.


2000;123(pt 8):1703-1709.


Burstein R, Jakubowski M. Analgesic triptan action in an animal model of in-tracranial pain: a race against the development of central sensitization.

Ann Neurol.



Cady RK, Sheftell F, Lipton RB, et al. Effect of early intervention with sumatriptan on migraine pain: retrospective analyses of data from three clinical trials.

Clin Ther.



Pascual J, Cabarrocas X. Within-patient early versus delayed treatment of migraine attacks with almotriptan: the sooner the better.




Mathew NT. Early intervention with almotriptan improves sustained pain-free response in acute migraine.




Hu XH, Raskin NH, Cowan R, et al; United States Migraine Study Protocol (USMSP) Group. Treatment of migraine with rizatriptan: when to take the medication.




Schoenen J. When should triptans be taken during a migraine attack?

CNS Drugs.



Pascual J. Clinical benefits of early triptan therapy for migraine.


2002;42(suppl 1):S10-S17.

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