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Chronic Migraine: Case History, Part 2 Lawrence Robbins,M.D. and Delia Snediker* Our patient Heather initially came in at age 24, and we chronicled her history and early treatment(PPM,Oct.,2008). In summary, Heather has moderate daily headache(CDH), with migraine 6 times per month. She also suffers from anxiety and depression(the mild end of the bipolar spectrum). Heather has irritable bowel syndrome(IBS…primarily diarrhea), plus neck pain. She was prescribed topiramate as a preventive, plus abortively the following: sumatriptan, naproxen, ondansentron(for nausea), and occasional hydrocodone. Heather reports that the topiramate helped her headaches, but possibly exacerbated her depression, and caused mild memory disturbances. 50mg of topiramate is the most she can tolerate, as she experiences memory disturbances on a higher dose. Sumatriptan is only mildly helpful, but otc naproxen is useful, and ondansentron relieves her nausea. She exercises 20 minutes daily, sees a therapist, and is learning biofeedback. We added quetiapine, slowly increasing to 50mg at nite, and substituted rizatriptan for sumatriptan. Quetiapine helps her moods, but she cannot tolerate more than 25mg qHS. Rizatriptan was not all that helpful, and during our last visit we prescribed zolmitriptan nasal spray. Heather returns 6 months later at age 25. Her menstrual migraines are severe, but zolmitriptan nasal spray helps(with naproxen), at least most of the time. Heather cycles in and out of depression, alternating with hypomania. She is chronically somewhat irritable and angry, which interferes with relationships. Heather has had a rough go of it lately. She has a deadbeat boyfriend, Eric, who somehow neglected to inform her of his wife and 2 kids, and Heather deals with an alcoholic, abusive mom(Sandy). Heather does not ruminate about suicide, but occasionally wishes she were dead. She has no active suicidal plans. Heather loves her job, finds solace in the salon, but has been bickering with Alan, a new stylist. Alan has been stealing some clients. So, along with headaches and neck pain, Heather is angry and depressed. She finds herself looking at every young, married woman with envy. Her 2 sisters are fairly supportive. WHAT TREATMENT OPTIONS WOULD YOU CONSIDER? Of course, we have a long talk with Heather about psychotherapy. She is reluctant to go, due to money, time, and stigma. We push Heather, suggesting a “sliding scale” therapist or a publicly funded therapy organization. We try to “de-stigmatize” going to therapy. I often say.”if it was up to me, everybody in our country would see a therapist.” I have found that it may take many years of pushing and suggesting to get reluctant patients into therapy. Heather’s headaches are somewhat controlled on 50mg of topiramate and 25 of quetiapine, with abortives: zolmitriptan nasal spray, naproxen, ondansentron(for nausea), and occasional hydrocodone. Her moods are more of an issue at this point. We should search for medication options that may help Heather’s(mild) bipolar moods, and also the headaches as well. Possibilities include: lamotrigine, oxcarbazepine, sodium valproate, another atypical(such as aripiprazole), or lithium. Ideally, we would like to avoid antidepressants, although some with bipolar tolerate antidepressants, if they are on an adequate mood stabilizer. Lamotrigine would be the first choice, with minimal side effects(rarely does lamotrigine cause tiredness or weight gain). Oxcarbazepine is a mild(and often overlooked) mood stabilizer; while related to carbamazepine, oxcarbazepine has markedly fewer adverse effects. Sodium valproate may help moods, plus Heather’s headaches. However, valproate does tend to cause weight gain and fatigue, and greatly increases risks with pregnancy. Heather is on quetiapine, but another atypical could help, such as aripiprazole, which does not tend to cause the weight gain and fatigue that quetiapine may produce. Lithium in low doses is often very effective. Lithium is probably underutilized in the “mild” bipolar population. However, with lithium, particularly in higher doses, weight gain, fatigue, and hypothyroidism somewhat limit use. We decide to proceed with lamotrigine, slowly increasing to 100mg daily. The risk with lamotrigine is Stevens- Johnson Syndrome(SJS), along with TEN(toxic epidermal necrolysis). These serious systemic and skin reactions are only observed in approximately 1 in 2,500 patients on lamotrigine. A “regular” drug rash is often seen(in at least 10% of patients). With any rash, I stop the lamotrigine(or any drug new to the patient). Stevens-Johnson is an immunologically based, severe form of erythema multiforme. SJS and TEN are probably manifestations(SJS at the milder end of the spectrum, TEN more severe) of the same disease process. SJS usually involves the mucous membranes and skin. With SJS, the male-to-female ratio is 2:1, with a genetic predisposition. Infectious SJS begins with nonspecific URI symptoms, with a sudden onset of skin lesions. Drug causes are varied, from oxicam nsaids to sulfa to anticonvulsants. The more severe TEN implies more skin area involvement than is seen with SJS. TEN carries a mortality of 30 to 50%(SJS=1 to 5%). We give Heather 25mg. of lamotrigine, to increase after 10 days to 50mg. Some patients do well on low doses(25mg.), while others require 300 or 400mg. per day. Heather calls 3 weeks later, and has not had a rash, but has had no improvement in moods. We increase the lamotrigine to 75mg. for 10 days, then 100mg. per day. She is, of course, instructed to discontinue lamotrigine with any rash. Six weeks later, Heather comes in and states that her mood is significantly improved; she is less irritated and depressed, and her mind racing is less. She has been working out her work differences with Alan. The economy and decreased business helps fuel her depression. Mind racing can be from several conditions, particularly anxiety vs. mania(or hypomania). It is important to inquire as to the “quality” of the rumination and racing. If it is constant worry, anxiety is the likely cause. With hypomania, it may simply be random thoughts racing thru the brain, not necessarily connected to worry or anxiety. Heather’s headaches are more severe on the lamotrigine. She is now on 50mg. of topiramate(as a headache preventive), 25mg of quetiapine(for moods, sleep, headache), and 100mg of lamotrigine(for moods, but lamotrigine may alleviate headaches in some patients). It is possible that the lamotrigine has exacerbated Heather’s headaches. This is a common situation with comorbid conditions, where we are juggling various meds. A drug may help one condition, while worsening another. At this point, Heather’s moods are better on lamotrigine, but headaches are more severe. WHAT MEDICATIONS CHANGES WOULD YOU CONSIDER? We could add meds for Heather’s headaches, or decrease the lamotrigine. I usually choose to decrease medication that is causing significant side effects, rather than add more medication. There are exceptions to this, as(for instance) when a patient finally finds a drug that is the only one that has ever been helpful. With Heather, we choose to back off of the dose of lamotrigine, from 100mg to 75mg. per day. This may help her headache situation; if not, we may need to decrease further. However, lamotrigine has been very helpful for Heather’s moods, and we will try to work with the drug. At this point, Heather is 26y.o., and on: lamotrigine(75mg), topiramate(50mg),and quetiapine(25mg). Due to side effects, she cannot tolerate more of any of these. Her moods and irritability improved on lamotrigine, but headaches are not well controlled. Botulinum toxin type A injections are now given to Heather, 16 units in each temple and frontal(48 units total; this is a low dose). Botulinum toxin has a 55 to 65% chance of producing reasonable improvement for 2 to 3 months. Some patients require 100 to 200 units. Repeated injections over time(every 3 months for 1 year) may have a beneficial, cumulative effect. Botulinum toxin probably works via anti-inflammatory(at the neuronal level) mechanisms. Botulinum may be an effective inhibitor of the inflammatory compound, CGRP, which is crucial in the propogation of chronic migraine pain. Heather is now seeing a psychotherapist to deal with many issues. She has stopped seeing her terrible boyfriend, and is learning to set limits with her difficult, alcoholic mom. Heather is doing yoga, and she exercises. She is much more positive about her future. Massage has not been very helpful. She tried acupuncture, which can be beneficial, but her results were short-lived. We will consider food sensitivity testing due to her migraines and IBS. For 3 months post-botulinum injections, Heather’s headaches are 40% improved. We re-do the low dose(48units) botulinum injections, which help her for 2.5 months. Her moods are improved, and we leave the meds alone. One year later, at age 27, Heather’s headaches increase, basically with a daily moderate migraine. Her moods remain stable on lamotrigine and quetiapine. We increase the topiramate, but 50mg is the maximum she can tolerate. We are not sure if the topiramate is still helpful. This is commonly seen with preventive meds, as they may lose effectiveness over time. The only way to evaluate if the med is still somewhat effective is to decrease or discontinue it. Many patients can only tolerate 25 or 50mg. of topiramate. She cannot afford botulinum toxin A injections, as her hair salon has closed. Heather is also experiencing widespread pain in many muscle groups, with tenderness. She saw a rheumatologist and was diagnosed as having fibromyalgia. She now has 3 commonly linked “central sensitization” syndromes: migraine, IBS, and fibromyalgia. The headaches and fibromyalgia pain greatly affects her QOL. Outside of meds, we encourage Heather to continue with exercise, yoga, and to take her vitamin D(which may help, among other conditions, depression and headaches). She tried acupuncture, but the relief was only 2 days. AT THIS POINT, WHAT WOULD SOME OF THE MEDICATION OPTIONS BE? Various medication choices include: 1. adding a muscle relaxant, 2. opioids(not a great choice, at her young age(27)), 3. short course of low-dose steroid, which could exacerbate her bipolar, and will only help for a brief period, and 4. add an antidepressant used for pain(tricyclics, duloxetene, etc.(she is on mood stabilizers, and may be able to tolerate low doses of an antidepressant without becoming hypomanic). Heather has cycled back into a depression, primarily due to losing the salon job. She is lonely and under financial stress. We encourage Heather to get back into psychotherapy, but she is reluctant to do so. Therapy is crucial for many reasons, and in Heather’s situation, she has somewhat recreated her childhood(abuse) by being with an abusive man. Unfortunately, recreating childhood pathology as an adult is all too common. With the depression, Heather is no longer working out, and she overeats. She is back together with Eric, her lying, abusive boyfriend. Unfortunately, it is all too common for women to go back to the abusive relationship. Of course, childhood pathological relationships(Heather has a very difficult mother) often are played out, and repeated, in adulthood(which makes the case for psychotherapy). Unfortunately, the reality is that most people with difficult childhoods do not receive the long-term therapy that is necessary to work thru the issues. Because of the chronic pain(fibromyalgia, headache) and depression, we add a low dose(30mg.) of duloxetine. Heather finds it is too stimulating, and while not hypomanic, she cannot sleep. We add a low dose(10mg.) of nortriptyline at nite. Nortiptyline is a (milder) metabolite of amitriptyline, with less sedation and anticholinergic side effects. The tricyclics such as these may be helpful for sleep, headache, fibromyalgia, and IBS with diarrhea. Heather has all of these conditions. In an effort to minimize meds, we attempt to find drugs that treat several comorbidities concurrently. Heather tolerates the nortiptyline well, with minimal sedation and dry mouth. Due to her bipolar, we may not be able to raise the dose of nortriptyline past 25 mg. Six months later, at age 28 Heather is improved, as far as moods and headache. She is working at a new salon, has left Eric(her terrible boyfriend), and is in group therapy. She exercises and continues to practice yoga. Despite her past abuse, Heather has shown some resilience. Resilience is a fascinating concept. There is a major genetic component to resilience: the length of the serotonin transporter gene. It is predictable, in the face of childhood abuse(physical,sexual,emotional), how one will function into adulthood, by examining the shape of the serotonin gene. Two long arms to the gene are good, two short arms usually leads to a dysfunctional adult(with severe Axis I and Axis II pathology). Nature and nurture comes into play: if a person has two short arms(bad), but a very good, non-abusive childhood, they usually will be ok. If one has two long arms to the gene(good), even in the face of abuse, they usually are fairly functional and do well as adults. There have been prospective monkey studies, where they took 2 groups:very young monkeys with the short arms, and those with long arms to the gene. They then gave those monkeys an “abusive” childhood, being raised not by mom, but by the other adolescent monkeys. Those monkeys with the long arms to the gene did fairly well, and functioned as monkeys should. Those with short arms were dysfunctional, sitting in the corner, asocial, biting, etc. In our case history here, Heather had significant abuse as a child, but is not a personality disorder, and has shown resilience and insight; she probably has two long arms to the gene. Unfortunately, abuse as a child influences the developing neurotransmitter pathways, and often results in Axis I and Axis II pathology, as well as in chronic pain. We will re-visit Heather at age 30 in a later article. She is on a common mix of mood stabilizers, antidepressants, and abortive meds. Botulinum toxin has been helpful. While her history and medications are somewhat complex, I believe that her situation is commonly encountered in practice. GENERIC AND BRAND NAMES (meds cited in this article) GENERIC Aripiprazole Abilify botulinum toxin type A carbamazepine Tegretol duloxetine Cymbalta hydrocodone Vicodin, lamotrigine Lamictal nortriptyline Pamelor naproxen Naprosyn ondansentron Zofran oxcarbazepine Trileptal quetiapine Seroquel rizatriptan sumatriptan Imitrex topiramate Topamax zolmitriptan * Delia Snediker is a medical assistant in Northbrook, Ill.


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