Triptans and Serotonergic Medications in Migraine Patients: Should We Worry?
Abstract & Commentary
By Dara Jamieson, MD, Associate Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Jamieson reports she is a retained consultant for Boehringer Ingelheim, Merck, and Ortho-McNeil, and is on the speaker's bureau for Boehringer Ingelheim and Merck.
Synopsis: Concern about serotonin syndrome should not prevent migraineurs who have mood disorders from being treated judiciously with the combination of triptans and serotonergic medications.
Sources: Bigal M, et al. Rates and predictors of starting a triptan: Results from the American Migraine Prevalence and Prevention Study. Headache 2010;June 1. (Epub ahead of print). Beghi E, et al. Headache, anxiety and depressive disorders: The HADAS study. J Headache Pain 2010;11:141–150. Evans R, et al. The FDA Alert on Serotonin Syndrome with Use of Triptans Combined with Selective Serotonin Reuptake Inhibitors or Selective Serotonin-Norepinephrine Reuptake Inhibitors: American Headache Society Position Paper. Headache 2010;50:1089-1099.
Despite its high prevalence and significant disability, migraine is underdiagnosed and undertreated. When migraine headaches are not effectively prevented or treated, patients suffer and become frustrated, often abandoning medical consultation. In the absence of effective treatment, patients may resort to excessive use of over-the-counter medication, with risk of developing medication overuse headache. Triptans, 5HT1B,1D agonists, are first-line acute treatment for migraine headaches with attack-related disability. Although diagnostic rates for migraine have increased over the past five years, the proportion of migraine sufferers using triptans has remained essentially stable. While some migraine patients may have contraindications to the use of triptans and others may be able to treat headaches with occasional use of over-the-counter medications, the majority of patients with disabling migraine headaches should be treated with these migraine-specific pain medications. Bigal and Beghi and their colleagues, in their research papers, address the issues of use of triptans and the prevalence of mood disorders in migraineurs as a background to evaluating the concerns about treatment with the combination of triptans and antidepressant medication, as addressed in the American Headache Society (AHS) position paper.
Data from the American Migraine Prevalence and Prevention Study, a longitudinal study conducted in a representative sample of headache sufferers in the U.S. population, was used to assess the rate of new triptan prescriptions among persons with migraine and the predictors of initiating therapy. Only 4.9% of episodic migraineurs not using triptans in 2005 who continued to have migraine and provided treatment data in 2006 (n = 6865) used triptans in 2006. In multivariate analyses, younger age, higher income, having insurance, using preventive medications, greater headache-related disability, and cutaneous allodynia were independent predictors of starting a triptan. Gender, race, education, and depression were not predictive of initiation of triptan use. This low rate of initiation of triptan use in a population-based sample of migraine sufferers seems to indicate that patients are not being offered appropriate acute medication to treat their migraine headaches.
Headaches, especially migraine headaches, and mood disorders have been linked epidemiologically and may also share pathophysiologic mechanisms. The HADAS study assessed the prevalence and characteristics of anxiety and depression in patients with migraine without aura and tension-type headache, in isolation and in combination. Psychiatric comorbidity was tested through structured interviews and the Mini International Neuropsychiatry Interview (MINI) in 158 adults with migraine without aura and in 216 adults with tension-type headache or migraine plus tension-type headache. Psychiatric disorders were found in 10.9% of patients with migraine, 12.8% of patients with tension-type headache, and 21.4% of patients with migraine plus tension-type headache. Depression was found in 3.6% of patients with migraine, 8.5% of patients with tension-type headache, and 10.7% of patients with migraine plus tension-type headache. The corresponding values for anxiety were 6.5%, 6.4%, and 14.6%. Using MINI results, a depressive episode was recorded in 59.9% of patients with migraine without aura, 67.0% of patients with tension-type headache, and 69.6% of patients with migraine plus tension-type headache. The study also found a correlation between migraine and panic disorder and between migraine plus tension-type headache and obsessive-compulsive disorders.
If triptans should be used more often in patients with migraines who also warrant treatment for mood disorders, are there concerns? In 2006, a U.S. Food and Drug Administration alert warned about the potential life-threatening risk of serotonin syndrome when triptans are used in combination with selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs). However, this recommendation was based on a limited number of anecdotal clinical reports. The AHS Position Paper reviewed the available evidence of the potential risk of combining triptans with other serotonergic agents, using established criteria for diagnosing serotonin syndrome (e.g., Sternbach Criteria and Hunter Serotonin Toxicity Criteria). Of 29 reports of serotonin syndrome reported in association with concomitant SSRI or SNRI and triptan use, 10 may have met the Sternbach Criteria and none met the Hunter Criteria. The conclusion of the review was that insufficient data are available to determine the risk of serotonin syndrome with the addition of a triptan to SSRIs / SNRIs or with triptan monotherapy. The currently available evidence does not support limiting the use of triptans with SSRIs or SNRIs, or the use of triptan monotherapy, due to concern about serotonin syndrome. However, given the seriousness of serotonin syndrome, caution in prescribing is appropriate and monitoring for evidence of serotonin toxicity is warranted.
Commentary
Patients with chronic headaches, including migraines, have a significantly increased risk of suffering from mood disorders and may need long-term treatment with SSRIs / SNRIs. Triptans are appropriate to abort migraine headaches in these patients on SSRIs / SNRIs; however, use of these medications in combination should be monitored. Concern about serotonin syndrome with the combination of triptans and SSRIs / SNRIs is based on rare, anecdotal reports of presumed symptomatic interaction between the medications. Some other medications used to treat mood and migraine (e.g., tricylic antidepressants, opioids, antiemetics) may also have serotonergic properties that need to be considered when used in addition to SSRIs / SNRIs and triptans. While multiple serotonergic medications may be appropriate when treating migraineurs with mood disorders, patients on two or more daily serotonergic medications should be cautioned to use triptans for acute treatment sparingly.
Concern about serotonin syndrome should not prevent migraineurs who have mood disorders from being treated judiciously with the combination of triptans and serotonergic medications.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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