Lex Denysenko, MD.
Assistant Professor of Psychiatry, Thomas Jefferson University Hospitals; Director, Behavioral Headache Medicine, Jefferson Headache Center.
Dr. Denysenko has no financial relationships with companies related to this material.
TCPR: What do psychiatrists need to know about migraine?
Dr. Denysenko: Migraines are more common in psychiatric patients, and some of our medications can serve a dual purpose there, like valproate (Depakote), amitriptyline, and topiramate.
TCPR: Let’s start with the antidepressants. How do they affect migraine?
Dr. Denysenko: The tricyclics have the strongest effect, reducing both the frequency and intensity of migraine. The best evidence is for amitriptyline, and then its metabolite nortriptyline. After that there are the SNRIs, which prevent migraine in the higher dose range (Molyneux PD, Evid Based Med 2011;16(3):75–76) (Editor’s note: See table “Antimigraine Medications With Psychiatric Benefits”). Looking at it the other way, some migraine therapies can help depression. We’ve seen that with onabotulinum toxin (Botox), which is FDA approved for migraine prevention (Arnone D et al, J Psychopharmacol 2021;35(8):910–918).
TCPR: Do all antidepressants improve migraines?
Dr. Denysenko: No. The SSRIs, bupropion, and mirtazapine don’t help with migraine, but they do have some evidence for tension-type headache, which is the most common type of primary headache.
TCPR: How are tension headaches different from migraines?
Dr. Denysenko: Tension-type headaches cause a steady ache, like a band squeezing the head, and affect both sides of the head. Migraine headaches have a pulsating quality and usually affect one side of the head. Migraines are also more severe and more episodic, coming on in bouts that last from several hours to several days. Nausea and vomiting are often part of the picture with migraines, and patients will tell you that they get worse with light (photophobia), noise (phonophobia), smell (osmophobia), and physical activity.
TCPR: Are migraines preceded by auras?
Dr. Denysenko: Only about 30% of migraine patients have auras. These are sensory symptoms that come on before the headache. Usually they are visual, like flashes of light, shimmering blocks, or blind spots. Separate from the auras, some patients have depressed mood, euphoria, restlessness, talkativeness, food cravings, or yawning in the hours before a migraine attack.
TCPR: Can psychiatric medications make migraines worse?
Dr. Denysenko: Trazodone produces a metabolite that can cause migraine-like headaches, m-chlorophenylpiperazine (mCPP), particularly in patients who already have a migraine disorder. We also see this with antidepressants that are similar to trazodone—nefazodone and vilazodone—so I try to avoid all the “azodones” in migraine.
TCPR: What about general headache as a side effect?
Dr. Denysenko: Most antidepressants list headache as a side effect. But among the second-generation antidepressants, only bupropion and escitalopram have a higher risk (Telang S et al, J Affect Disord 2018;236:60–68).
TCPR: Can patients take a triptan for migraines while on a serotonergic antidepressant?
Dr. Denysenko: Yes. There is an older FDA warning about serotonin syndrome with that combination, but it has not stood the test of time. The two medications are agonists at different receptors, and several large studies have found no increase in serotonin syndrome when they are combined (Orlova Y et al, JAMA Neurol 2018;75(5):566–572).
TCPR: How do mood stabilizers affect migraine?
Dr. Denysenko: This is an important area because migraine is more common in bipolar disorder. One in three people with bipolar have migraine, so bipolar disorder is never too far from my mind when I see a patient with migraines and mood problems. Among the mood stabilizers, only one is FDA approved for both bipolar disorder and migraine prevention—valproic acid (Depakote)—but it’s usually not my first choice for migraine.
TCPR: Why is that?
Dr. Denysenko: While it is effective, it is often poorly tolerated, so I’m unlikely to use valproic acid unless the patient also has bipolar disorder. Topiramate is FDA approved for migraine prevention and is better tolerated overall, particularly the extended-release version, but topiramate doesn’t help in bipolar disorder. It’s better tolerated than valproic acid, although cognitive side effects and—rarely—depression and suicidality can happen with topiramate. Lamotrigine has some promising reports, but it did not work in two controlled trials, one that compared it to placebo and another to topiramate (Gupta P et al, Headache 2007;47(3):402–412; Steiner TJ et al, Cephalalgia 1997;17(2):109–112).
TCPR: What about antipsychotics?
Dr. Denysenko: These can be helpful for acute migraines. Patients with migraine have dopamine hypersensitivity, and we often use promethazine or prochlorperazine, but sometimes we advance to chlorpromazine, haloperidol, or droperidol for acute migraine.
TCPR: Can you speak about lithium?
Dr. Denysenko: Lithium doesn’t have a role in migraines, but we sometimes use it to treat refractory chronic cluster headache.
TCPR: Are other psychiatric disorders more common in migraine as well?
Dr. Denysenko: Outside of mood disorders, migraine is more common in anxiety disorders, and this manifests in several ways. There is the anxiety of living with pain, and anticipatory anxiety because the patient never knows when the next migraine attack is going to come. But anxiety can also be a symptom of migraine itself. Some people have more anxiety in the prodrome leading up to a migraine attack, or in the residual phase after the attack. Other psychiatric disorders, including PTSD, ADHD, substance use disorder, and personality disorders, are more common in migraine. One treatment we use for social anxiety, the beta blocker propranolol, can also help as a migraine preventive.
TCPR: Do all patients need a migraine preventive, or can some get by on rescue medications?
Dr. Denysenko: Patients who have only one or two migraine attacks per month can successfully treat them with an abortive medication. But when they have more than four migraines a month, or the attacks are especially debilitating, or the abortive medications don’t work well—that’s when we recommend preventives. Any way you can minimize the use of abortive medications is generally a good idea, because the patient can develop medication overuse headache.
TCPR: What is overuse headache?
Dr. Denysenko: When abortive treatments are used too often, it sensitizes the pain receptors, causing rebound headaches that overlap with the regular headache disorder. Patients with this problem usually find that the abortive medication still appears to work, but it’s no longer bringing their headache down to zero, and they develop a chronic, baseline headache on top of the migraine attacks. And this isn’t limited to migraine—this can also happen with tension-type headache and other headache disorders as well. Medication overuse headache can occur with triptans, opiate agonists (including tramadol), NSAIDs, and combination analgesics that contain butalbital or caffeine.
TCPR: How excessive does the use have to be?
Dr. Denysenko: You don’t have to reach medication doses that your average layperson might think would be excessive. Just 10 pills a month for a few months or a few years could cause medication overuse headache.
TCPR: Is the goal to reduce the frequency of migraines or eliminate them altogether?
Dr. Denysenko: Much like in psychiatry, we aim for functioning. So, a reasonable goal could be to resume activities and hold a job and enjoy life without too much interference from the migraine. This is a very disabling illness, but it is also a hidden illness, which means that patients suffer a lot of stigma around it, much like people with psychiatric disorders do. People tell them, “It’s just a headache. You can handle this.” I have seen mental health practitioner colleagues dismiss them as hysterical somatizers or personality disordered, or even ask me why I would ever want to work with such “difficult patients.” This all just perpetuates the sigma and reduces access to care.
TCPR: Do migraines improve when psychiatric illness is treated?
Dr. Denysenko: Yes, and the other way around. There are many reasons behind this “bidirectional” effect. Stress leads to inflammation, inflammation leads to pain, depression can cause increased sensitivity to pain, and patients with depression are more likely to have difficulty sticking with their headache treatment plans. This shouldn’t be interpreted to mean that migraines are psychological. Those kinds of explanations are very off-putting to patients.
TCPR: On the other hand, is psychotherapy helpful?
Dr. Denysenko: Absolutely. Psychotherapy often helps, either by reducing the direct symptoms of migraine or by helping the patient manage their lives better in the face of those symptoms. Biofeedback, relaxation therapy, and cognitive behavioral therapy have good evidence to prevent migraines (Nestoriuc Y and Martin A, Pain 2007;128(1–2):111–127), and there is also support for newer psychotherapies like mindfulness and acceptance and commitment therapy (ACT).
TCPR: What’s new in migraine treatment?
Dr. Denysenko: Migraine treatment has undergone quite a revolution in the last couple of years. On the abortive side, we have lasmiditan (Reyvow). Like the triptans, it is a serotonin receptor agonist, but it works on a different receptor (5-HT1F), which means it lacks the vasoconstrictive side effects of triptans. Calcitonin gene-related peptide (CGRP) receptor blockers, collectively known as “gepants” (ubrogepant, rimegepant, atogepant) are another novel acute treatment that is generally well tolerated. There are portable devices that treat migraine, like Cefaly, Relivion, and Nerivio. There is also a portable TMS device (SAVI Dual), delivering a single pulse to the occipital lobe, that has recently come to market. For patients with significant anxiety and migraine, I like to consider Gammacore, which is a vagal nerve stimulation device applied to the neck. Gammacore has also recently obtained FDA breakthrough designation for PTSD (Schoenen J and Ambrosini A, Prog Brain Res2020;255:249–274).
TCPR: What else is new in this area?
Dr. Denysenko: In 2018 a monoclonal antibody, erenumab (Aimovig), was approved for migraine prevention. Several others have followed, including fremanezumab (Ajovy), galcanezumab (Emgality), and eptinezumab (Vyepti). These interact with either the CGRP receptor or the CGRP inflammatory protein directly involved in migraine attacks, and they have been game changers for many people with migraine. The CGRP protein may be of additional interest for psychiatry, especially in view of the inflammatory hypothesis for major depression.
TCPR: One last question—how does one become a headache psychiatrist?
Dr. Denysenko: The question I have is: Why aren’t there more? A background in consultation-liaison psychiatry, or working closely with a headache medicine provider, is a good starting point. The United Council for Neurologic Subspecialties offers a certification exam in headache medicine, which is open for psychiatrists to take.
TCPR: Thank you for your time, Dr. Denysenko.
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