Depression Can Be Migraine’s Tipping Point

Depression in patients with episodic migraine is an independent risk factor for transformation of their headache pattern into far more burdensome chronic migraine, according to data from the landmark American Migraine Prevalence and Prevention study.

“The study indicates that we need to look for depression in patients with episodic migraine or chronic migraine. We need to take it seriously and address this issue with patients – make the referral to a psychiatrist or treat them yourself if you’re comfortable with that. And the depression should be addressed as a problem separate from the headaches,” Dr. Sait Ashina said at the European Headache and Migraine Trust International Congress.

Dr. Sait Ashina

AMPP study participants who had episodic migraine and depression were 1.65-fold more likely to progress to chronic migraine within the next year than were nondepressed participants who had episodic migraine, in an analysis extensively adjusted for potential confounding variables, reported Dr. Ashina of Albert Einstein School of Medicine, New York.

Moreover, a dose-response relationship was evident between depression severity and risk of progression from episodic to chronic migraine. That is, the nearly 1,400 AMPP participants with episodic migraine and moderate depression as defined by a Patient Health Questionnaire–9 (PHQ-9) score of 10-14 out of a maximum possible 27 had an adjusted 1.77-fold greater risk of converting to chronic migraine within the next year than did the 10,898 episodic migraine sufferers with no or mild depression, while the 656 with moderately severe depression as evidenced by a PHQ-9 score of 15-19 had a 2.35-fold increased risk, and the 420 individuals with a PHQ-9 score of 20-27 were at 2.53-fold increased risk.

The AMPP study is an ongoing longitudinal, population-based study in which 24,000 adults with severe headache were surveyed annually during 2004-2009. Dr. Ashina’s analysis involved nearly 13,500 participants who met criteria for episodic migraine in the 2005 or 2006 surveys. Transformation from episodic to chronic migraine within the next year occurred in 2.4% of the 2005 cohort and 2.2% of the 2006 group. Episodic migraine was defined in standard fashion as migraine headaches occurring on not more than 14 days per month averaged over the past 3 months, while chronic migraine entailed headaches on an average of 15 or more days per month.

The depression/migraine chronification analysis was adjusted for cutaneous allodynia, physician diagnosis of an anxiety disorder, headache pain intensity, headache frequency, migraine symptom score, use of antidepressant medications, headache-driven medication overuse, age, sex, body mass index, income, and health insurance status. The two strongest predictors of migraine chronification in the multivariate analysis proved to be depression and medication overuse involving triptans and/or opioids.

Dr. Ashina said that prior studies have established that depression and migraine are cotravelers, and that the relationship is bidirectional: That is, migraine is a risk factor for new-onset depression, and depression is a risk factor for new-onset migraine.

For example, one classic study conducted by some of the coinvestigators in Dr. Ashina’s current AMPP analysis showed a 2-year incidence of new-onset migraine of 9.3% in patients with major depression, compared with 2.9% in controls without major depression (odds ratio, 3.4). There also was a 2-year incidence of new-onset depression of 10.5% in migraineurs, compared with 2% in controls without migraine or other severe headache, for an odds ratio of 5.8 (Neurology 2003;60:1,308-12).

And in a combined analysis of two other studies, the prevalence of depression as defined using the PHQ-9 was 9.2% in the general population, 17.2% in persons with episodic migraine, and 30.2% in those with chronic migraine.

However, the relationship between depression and transformation of episodic to chronic migraine hasn’t previously been carefully looked at, which was the impetus for the AMPP analysis, he explained.

Back transitions from chronic to episodic migraine are known to be common, occurring in roughly one-quarter of patients with chronic migraine per year. Whether effective treatment of depression in chronic migraine patients promotes back transition to episodic migraine, or for that matter, whether antidepressant therapy in patients with episodic migraine reduces the risk of transformation to chronic migraine, are unanswered questions – and priorities for further research, in Dr. Ashina’s view.

At the international congress, Dr. Ashina received the prestigious Enrico Greppi Award from the Italian Society for the Study of Headaches for his research.

The AMPP study is funded by a grant from Ortho-McNeil Neurologics. Dr. Ashina’s analysis received supplemental funding in the form of a research grant from Allergan. He reported having served as a consultant to NeurogesX and Depomed.

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