Recent studies have found that there is a possible link between migraines and mental illnesses like bipolar disorder, depression and other mental health conditions. Why does this occur and what do you need to know about it?

Join in as experts discuss theories on the source of the connection between migraines and mental illnesses and ways to approach each type of condition. From anxiety and phobias to depression and bipolar disorder, our experts explain what may be happening in the brain to cause symptoms of both conditions and why some people are more at risk.

As always, our expert guests answer questions from the audience.

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Now here’s your host, Rick Turner.

Rick Turner:

Studies show a significant association between migraine and mental illnesses such as depression and bipolar disorder. How are these conditions linked? Does one cause the other? And are people who get migraines at higher risk for mental illness? Hello and welcome to our program, Migraines and Mental Illness: What’s the Connection? I’m Rick Turner.

Joining us on the program today is Dr. Roger S. McIntyre. Dr. McIntyre is an associate professor of psychiatry and pharmacology at the University of Toronto and head of the Mood Disorders Psychopharmacology Unit at the University Health Network in Toronto, Canada.

Welcome to the program, Dr. McIntyre.

Dr. Roger S. McIntyre:

Thanks so much for having me, Rick. I really appreciate it.

Rick:

It’s our pleasure.

So the medical community is becoming more and more aware that there is a significant connection between migraine headaches and certain types of mental illnesses. Dr. McIntyre, which mental illnesses are being linked to migraine?

Dr. McIntyre:

The mental illnesses linked to migraine, at least the ones that are most strongly associated are major depressive disorder and bipolar disorder, and these are the two so-called mood disorders that are very common in the general population. In addition to mood disorders, major depression and bipolar disorder, there are also links between migraine headaches and anxiety conditions as well as so-called personality disorders.

Rick:

Is this fairly new that we are finding this out?

Dr. McIntyre:

I think what’s new is the level of refinement regarding our understanding between mood disorders and migraine. In fact, going back many centuries, the association between migraine and headache syndromes as well as melancholia and psychiatric disorders have been described. And for those of your listening audience who have an interest in some very old writings, it goes back to antiquity. But in point of fact, this information has really become more of the conversation in medicine just during the last decade given some of the observed associations in more contemporary work.

Rick:

So this might be a bit redundant for some of our listeners, but let’s do a little basic review here of a migraine headache, Dr. McIntyre. What is a migraine? What are its symptoms?

Dr. McIntyre:

It’s important to start off with what migraine is not. Migraine is not simply a tension headache or a headache because of stopping a medication or because of changes in lifestyle. Migraine is a well-characterized headache syndrome. Typically it can be unilateral, sometimes bilateral, and it’s often accompanied by a host of other very disturbing changes such as sensitivity to light and to sound. If you will, people’s acoustics are turned up for these types of things, and it’s a type of headache syndrome that’s indeed recurrent. We have learned over the years that migraine headache certainly affects women, but it affects men as well, and it’s a very common syndrome, one of the more common headache syndromes that are encountered by headache specialists but also by primary care providers.

Rick:

We also hear a lot about the presence of aura with migraines.

Dr. McIntyre:

Yes. It’s absolutely one of the cardinal features that’s been classically described, which is like a warning that’s it’s coming on, so to speak. In many cases people may not have aura, but certainly aura is very classic.

Rick:

In terms of diagnosis then, Dr. McIntyre, is it just a matter of taking a personal history, or are there some more definitive tests that can nail down a diagnosis of migraine?

Dr. McIntyre:

Certainly there is no CT scan, X-ray or any kind of blood tests that would indicate you have migraine or not. That being said, the diagnosis of migraine is still very much a clinical diagnosis based on features of the headache syndrome and sitting down in an unhurried way with a clinician who is familiar with the criteria for migraine that are articulated in what’s known as International Headache Society Criteria, and other criteria that have been put forth to give us an organizational road map to define this condition. But it is a clinical diagnosis. In some cases, blood tests are carried out more or less to rule out other causes, not actually to rule in the possibility of migraine.

Rick:

Is another one of the key criteria for diagnosing a migraine the extent to which it disrupts your life?

Dr. McIntyre:

For sure. I think that by definition people who have these conditions are not only suffering greatly, but they have tremendous impacts on their quality of life and functioning. And for those who suffer from migraine, all you need to do is mention migraine to them, and you can see them sort of wince [over] the pain that’s accompanied and the effect it has on them.

Rick:

Then in terms of treatments, what is available today, what is in that array of treatments, and how effective are they?

Dr. McIntyre:

Treatments can be broadly broken into two categories: There is acute treatment, which is intended to abort or to eliminate the migraine that’s active today, and there are so-called prophylactic agents that are available which are to prevent the migraine from returning.

There is a variety of agents that are very familiar, ranging from mild over-the-counter to prescription analgesic-type compounds for acute relief. Prescription agents, however, have become more advanced in the last ten, 20 years and include such agents as the triptans, which are very familiar. And there are other agents that are used in more extreme situations in psychiatry, using some of the psychiatric medications that have been used historically for that such as some of the anti-psychotic agents which are used off label for their pain and analgesic properties.

In addition to that, the prophylactic therapies are often considered; there is a variety out there. One class that comes to mind is, for example, the anti-convulsant agents which are shown to be very effective in delaying or stalling the return of migraine in people who suffer.

Rick:

In terms of side effects that people should be aware of, that’s a wide range of drugs you just described – what are some of the key things people should know about?

Dr. McIntyre:

I think the key things that people often need to know about – particularly as it relates to our topic here today, that is, this overlap with mood disorders more specifically – is the issue around central nervous system side effects. Anti-convulsant agents often have central nervous system side effects such as headache or sedation or somnolence. Other side effects that relate to these compounds relate to the monoamines that they target, like serotonin. Whenever you target a monoamine like serotonin, you are looking at [central nervous system] side effects, but also gastrointestinal side effects can be a problem in terms of nausea and so on. But all in all, I think that the tolerability of these agents is certainly considerably improved in the last five to ten years now with some of the newer agents.

Rick:

Beyond that array of drugs, are there any alternative treatments that you might recommend to people living with migraines?

Dr. McIntyre:

There is a host of experimental ideas around migraine. Certainly in our experience in our program, we have had a lot of focus on this. I think the best treatment has been preventative – primary prevention interventions have really been taking off: avoiding some of the irritants to this in terms of smoking, some of the aspects around exercise. Some foods sometimes can trigger, so avoidance of triggers [can help].

I think through bolstering or enhancing some of the protective factors that some people have noticed, that really has really been an area that has been acceptable to patients, and it’s an intervention at least in our patient population that has tremendous relevance, given the fact that we are not only trying to prevent migraines from returning, but also one of the greater irritants, and that’s mood disorders.

Rick:

We always get questions from listeners about things like diet, stress management, yoga, that sort of thing. Have any of those been shown effective in treating or helping migraine?

Dr. McIntyre:

There is, I would just say, disparity in the quality of how these studies are conducted looking at these interventions. Nevertheless, I think there is certainly compelling literature that stress management techniques do in fact hold promise to reduce the probability of recurrence of these syndromes, and I think that’s been something that is generally well-known. There is sort of a general wisdom about that.

There is, in fact, less evidence for some of the other sundry items that you mentioned. This is very similar to depression where there seems to be a lot of interest in alternative therapies, in which there are certainly reports that there are beneficial effects. There is even, in many cases, a plausibility that they may be effective, but we don’t have the robust data set that I think we are looking for to make a clear recommendation to patients that they should consider one of these [alternative therapies]. So I think that really staying with what’s been proven, what’s been FDA-approved along with effective stress management seems to be the appropriate chronic disease management techniques here.

Rick:

You mentioned that a key is avoiding triggers if they can be identified. If someone has a pretty good idea of what their triggers are and they really work hard at avoiding them, how much success can they have in just avoiding migraine altogether?

Dr. McIntyre:

The complete avoidance of all episodes I think is obviously wished for. I think it still remains out of reach for many individuals. I do think – and this is mostly anecdotal, but it is supported by in fact some clinical data – that these techniques do make a difference in terms of reducing the overall frequency, the duration, the severity of episodes people have. So we think about migraines in many ways like a chronic disease wherein what we are tying to do is reduce the overall illness burden. Yes, we would like to completely eradicate it, that’s our dream. But if we can reduce the illness burden, it makes a heck of a difference not only for quality of life, but also, as the comment you made earlier, it does make a difference in terms of functional outcome.

Rick:

So the theme of this program is the link between migraine and certain types of mental illness. And you gave us a 101, if you will, on migraine. Can you do the same for us now for depression?

Dr. McIntyre:

Major depressive disorder is a common mental disorder in the general population. It is estimated to affect between ten and 20 percent of the general population at some time in their lives. We know that it affects women more than men, and like migraine, like diabetes, hypertension, we now think of this as a chronic disease. And across America, major depression is not only common, it’s one of the most common reasons people are not working optimally. They are not employed. They are often receiving disability benefits. It’s an extremely costly disorder.

Major depressive disorder is to be distinguished from bipolar disorder – and I should probably be using the plural, bipolar disorders and major depressive disorders because in fact these are really heterogeneous syndromes. And bipolar disorder shares in common with major depressive disorder recurrent periods of depression, but in addition, individuals who have bipolar disorders also have episodes of what we call mania. Mania is a very distinct disturbance in which someone is often very anxious, often very irritable, agitated, very angry. Along with that, they have an oversupply of energy, but they just can’t seem to use it wisely most of the time.

I think many of your listeners might think of mania the way Hollywood portrays it, insofar as patients will have grandiose beliefs, and they will be very energetic and very productive. Indeed, that is the case for a subpopulation of people who have bipolar. That’s the classical description of mania. But most clinicians know that that’s not commonly encountered relative to the more dysphoric or irritable or agitated experiences patients have which we call a sort of mixed stage, which is this very difficult admixture of mania and depression. So bipolar are recurrent periods of mania and depression, while major depression is recurring episodes of depression.

Across the United States, bipolar disorder is now thought to affect between three and five percent of the population, so quick mathematics between major depression and bipolar disorders tells us that about one in four, one in five to one in four people may have one of these conditions at some time or another. It’s a very, very common disease.

Rick:

That’s a lot. Now, in terms of correlation between those two, depression and bipolar disorders, and migraine, how strong of a link is there?

Dr. McIntyre:

The link is extremely strong and as I said, it’s been described for centuries. But more sophisticated description along with the help of our statistician – in research you’re only as good as your statistician these days – and our statisticians have been able to tell us that the odds ratio, the link between these two separate constructs, these two separate phenotypes, is very strong. Let me just give you some numbers if I can.

It is estimated that in individuals who have major depressive disorders, as many as 20 to 40 percent of them may in fact also have migraine at some time in their lives. That is a big range, and of course the range comes from the fact that there is disparity in the methodology and disparity in the way migraine has been defined and mood disorder has been defined and also disparity in some of the composition of samples that have been evaluated, but taken together, you are looking at about 20 to 40 percent. Where things become even more interesting is if we look at the rates of bipolar disorder, it’s seemingly higher, ranging from 20 up to as high as 60 to 70 percent.

And that is interesting to us for a number of reasons. First, it’s important to be aware of that overlap when it comes to detecting this condition and screening for mood disorders in migraine populations and vice versa. But in addition, from a research perspective it raises a really interesting series of questions around why that’s the case. So the estimates are certainly significant. And those estimates are in clinical populations, people who are seeking healthcare. But when we go to the general population and look at epidemiological samples, we also see this overlap. So it’s not just simply a byproduct of patients who are utilizing healthcare. It seems to be a real association, if we can say it that way, that has also been observed in a non healthcare-seeking population. That’s people in the general population.

Rick:

Interesting. And of course that will affect how the issues are treated as well, right? We are going to get to that in just a little bit, but in terms of treating both of those at the same time. And then you also mentioned that there is a connection between migraine and personality disorders. Describe those for us and how strong that link is.

Dr. McIntyre:

About personality disorder – I think there has been a lot of misunderstanding, and there has been a lot of myth and distortion around that, and in many ways propitious timing because this week we hear that NFL All Star player Herschel Walker has been in the media talking about his characterological disturbances, more specifically dissociative identity disorder, which the press has been referring to as multiple personality disorder. So these things become very confusing. Let me just be very clear with this.

First of all, personality disorder in psychiatry simply refers to a pattern, an enduring pattern wherein the individual has – dating back to their teenage years right through their adult years – a pattern of unstable, insecure relationships, and that’s a very broad definition. There is a much more refined definition to it, but I think it’s an important central point in the definition. People who have these types of relationships, they usually have multiple partners. They often don’t form stable relationships. They often have brief, short-term, stormy relationships, and – just like we said earlier with depression and bipolar – there are many different types of personality disorder. But what they all share in common is interpersonal problems, and it causes them tremendous problems in their personal life and work life.

There are many types of personality disorder, and some are more common than others. Some of these conditions, one comes to mind called borderline personality disorder, which is a severe personality disturbance in which people have terrible instability of their mood, instability of their behavior, their interpersonal relationships, their sense of identity. These folks are reported to have fairly high rates of migraines. Now, one of the challenges that we have, quite frankly, when it comes to parsing out these associations between personality disorder and migraine is that personality disorder is really not only a disturbance itself. People often have depression, a lot of these folks have bipolar, some of these folks have substance abuse problems and other factors that confound the association.

So the link between personality disorder and migraine is less clear in terms of more sophisticated statistics and science than it would be for mood disorders, but historically, dating back centuries, there was so-called a migraine personality, which was more folksy and colorful in its description, but it’s still not clear what that really means with modern science and statistics.

Rick:

Fascinating.

Dr. McIntyre, let’s talk about the connection now between depression and migraine and what’s going on in the body. How good an idea do we have what’s happening physiologically or chemically or electronically in the brain or in the body of anyone who is living with both of these conditions?

Dr. McIntyre:

It’s a fascinating question, and I think it starts with, first of all, what’s our understanding of the pathophysiology of depression and mood disorders in general? And then, what’s the understanding regarding the pathophysiology of migraine, and where are the points of commonality between these two?

When we think about mood disorders – and I am going to lump major depression and bipolar disorder together just for the purpose of convenience here – when we are looking at the pathophysiology of these conditions, we have moved a long way away from the notion that these are just simply a serotonin imbalance or a chemical imbalance. Although that’s still an important paradigm, it’s not really a fully explanatory paradigm. What we now know is that, in depression, there are abnormalities in the function of a variety of brain structures in regions of brain that are important for emotion and for thinking. In other words, we think of depression and bipolar as a brain circuit disorder, and these brain circuits communicate through chemistries like serotonin and other chemicals.

Now, that’s not the only theory. There are other aspects that relate to energy supply to the brain, and of course energy supply implicates issues of cortex and subcortex excitation as well as a vascular availability and so on. Now, when we think about migraine, interestingly migraine was stigmatized for years and thought to be psychodynamic in its origins for many, many years.

It’s now, in fact, believed that there are issues around electrophysiological abnormalities. There may be vascular abnormalities and maybe some regional abnormalities in the brain, the cerebellum or other hypothalamic structures and so on that are involved. So when you actually begin to parse out some of these things – like the electrophysiology, the neurochemistry, the neuroanatomy – that we think are conspiring to create the syndrome migraine, it overlaps considerably what we think is conspiring to create mood syndromes. So taken together, one of the ways to illuminate one’s understanding of a syndrome of interest is to carefully explore another syndrome that co-occurs, co-segregates or differentially affects that group.

And then looking through the back door, if you will, at trying to find out what’s going on here. So when we think about the substrate of mood and the substrate of migraine disorders, what we are finding is that there are these points of commonality which we think is providing at least a rationale for why we are seeing them so commonly together in the clinics.

Rick:

And yet not everyone with depression gets migraines, right? And not everybody with migraine is depressed.

Dr. McIntyre:

That’s right. And that’s a really key point, because earlier we talked about major depressive disorders and bipolar disorders, and I think migraine is also a pluralistic society. There is more than one type of migraine. And what that tells us is that not only do we have heterogeneity in how these syndromes present, but we also have heterogeneity in how they are probably caused and how they are mediated. So, although there are points along this matrix that subserve these conditions that are similar, there are also probably points that are dissimilar and very distinct. So this is why we are not seeing a hundred percent concordance between the two conditions. We are seeing high rates, but not a hundred percent. There are areas that are, in fact, distinct.

Rick:

Right. But given the commonalities you described that are going on in the body, do you ask the “chicken and egg” question? Can a migraine bring on a depression, or can depression actually cause you to have a migraine?

Dr. McIntyre:

It’s a great question, and it’s a question many patients wonder.

It’s a really important question. And one of the other points I haven’t mentioned so far is that if in fact you have depression with migraine, it’s a classic example of one plus one equals three, wherein things are really bad for you in terms of the functional consequences and your overall level of impairment. So people are concerned for this.

The way I think about this is thinking about, for example, diabetes. People who have diabetes have increases in sugar, glucose, and they also have abnormalities in their lipids, their triglycerides or cholesterol. And there is in fact a relationship between disturbances in sugar and disturbances in cholesterol, although they are distinct pathways.

And the way I would think about it is somebody who has the conspiracy of genetics and environment – a propensity to depression and a propensity to migraines. They have this substrate in their central nervous system, and it’s unlikely the case that depression causes migraine or migraine causes depression and more likely the case this person has that vulnerability to begin with. And for reasons that are unknown, depression might appear first or migraine or vice versa, and the activation of one phenotype may herald the onset of the other, but it’s not really causing it. It’s more two syndromes superimposed on a common scaffolding, if you will.

Rick:

They are just coinciding.

Dr. McIntyre:

Yeah. Yeah.

Rick:

And you also mentioned there is an even stronger relationship between migraine and bipolar. Do we see more of an overlap in what’s going on physiologically with bipolar and migraine?

Dr. McIntyre:

There are implications of that. The cardinal feature of all mood disorders is that they are recurrent conditions, but when we think about mood disorders, depression and bipolar, the bipolar disorder is a highly recurrent condition. It’s a cyclicity disorder, as we say. It cycles. And when we think about bipolar, it cycles around day-night schedules, in women around their menstrual cycle. And it cycles around seasons. There is something about bipolar that seems to be entrained to circadian rhythms and to general biological rhythms. And of course this is a classic feature of migraine. And people have thought, “Well, maybe the hypothalamus, which is really the pacemaker of our brain, it’s the rhythm center of the brain that’s playing such a key role here. That’s quite possible. But there are many aspects around bipolar disorder, at least phenotypically that look more like migraine than maybe depression does. Depression, yes, it’s recurrent, but it’s not as cycling as is bipolar, and what’s interesting is that – and we’ll get into this maybe – some of the treatments that we prescribe for bipolar often overlap with migraines.

Rick:

We will get into that in just a moment here. But again, can you also say with bipolar and migraine that one does not cause the other per se?

Dr. McIntyre:

Yeah. I think that’s probably the fair way to say it. I don’t think we can say that one is causing [the other]. I think that there are in fact two phenotypes that are sharing a scaffolding in common, although there is probably unique – keeping with that metaphor – unique bars and beams and two-by-fours for each one of them, but there is in fact an overlap. And I think the way to think about it is that for reasons unknown, one might appear before the other, and certainly the appearance of one seems to hasten the onset of the other.

Rick:

And you said earlier that up to 60 percent of people with bipolar have migraines. Is that right?

Dr. McIntyre:

Yes. That seems to be a number many groups have reported in clinical samples. Again there is a variation in the rates, sometimes even a little higher than 60 percent. But almost half of people, if not more than half, have migraines. And one of the comments I had earlier is that bipolar disorder is, again, a pluralistic group. It’s [a spectrum of] many different types. There are severe forms of bipolar – what we call bipolar I disorder, which is severe mania and depression, and then there is what we call bipolar II disorder, which is a much milder expression in many ways of bipolar, where people have depression still, but their times of agitation or elevation are much briefer in amount and duration and severity. And these individuals with the milder expressions of bipolar, which very much occurs more often in women, seems to be the ones who are really tightly associated with migraines, the so-called soft bipolar spectrum of conditions.

Rick:

We focused so far on the connection between migraine and three types of mental illness, depression, bipolar and personality disorder. Are there any other common mental illnesses that have been linked with migraine?

Dr. McIntyre:

There certainly have been historical associations between migraine and anxiety conditions. Experience however has been that the anxiety conditions probably have a closer association with so-called tension headaches. So when we think about other mental disorders, what comes to mind are substance abuse disorders. There have been associations with headache for many years with substance abuse disorders, but I think that differential diagnosis for behavioral reasons is much easier to identify. But the classic association, where the most compelling literature lies is this link between major depression and bipolar disorder.

Rick:

So then, Dr. McIntyre, given the prevalence of this connection between migraine and a couple of really common mental illnesses, how common in your experience is it for someone who suffers from migraine to go undiagnosed with that mental illness?

Dr. McIntyre:

It would be the rule rather than the exception, Rick. And it really is unfortunate. I do think however that many practitioners are aware of the relationship between migraine and depression. I think that the association with bipolar is certainly less well established, at least in their minds.

So I think that if you were to look at groups of people who have depression with migraine, the majority of them would probably not be detected, so they would not be receiving guideline concordant care. But that somewhat dire comment would be even worse for bipolar populations because I think many clinicians still have a notion of bipolar disorder that it’s a rare disorder or relatively rare, and it’s a disorder which is characterized by this grandiosity and euphoria, which in fact it is, but it’s more than that. I think that the phenotypic variance of bipolar disorder have been less well communicated through teaching programs, residencies, med schools and so on. And as such, I don’t think that there is the type of awareness of that association of bipolar and migraines. So very often it is missed.

Rick:

And if it is missed, what are the consequences? What are the risks?

Dr. McIntyre:

Well, you are talking about two very dangerous medical syndromes. Major depression and bipolar disorder are both very, very dangerous conditions. Not any type of alarmist way, but I mean that in the sense that these are conditions that are associated with premature mortality. You have a condition like bipolar, for example, [if] not treated, you are going to lose between 20 and 30 years of life. And this is from a variety of causes. People think about suicide and unnatural causes, but the most common cause of death in these patients is actually due to cardiovascular disease, which is very high due to the chronic activation of stress systems in their bodies and a variety of other behavioral and economic reasons.

But the key point here is that leaving someone with untreated depression and bipolar disorder is a morbid situation for the individual and will only compound if not synergize the functional impairment that accompanies the migraine.

Rick:

So then let’s go to the next step, Dr. McIntyre, and talk about some of the treatments you have alluded to. If someone is diagnosed with depression or bipolar disorder and migraine, what are the treatment options?

Dr. McIntyre:

I think the key thing is that we all like to bandy about evidence-based medicine, and I think that there are reasons why evidence-based medicine and algorithmic care is preferred. It’s part of a larger chronic disease management, and so-called decision support is what we would encourage. That being said, I can tell you that there are really no randomized controlled trials that have been conducted with placebo and adequate power and sufficient design evaluating people who have both bipolar and migraine. So it’s an unfortunate reality of our evidentiary base.

Rick:

So you have been flying a bit by the seat of your pants here.

Dr. McIntyre:

Absolutely. And that’s what medicine is about, and that is what it will always be about insofar as it’s the art and science of this practice.

I think that the guiding principles are to adhere to chronic disease management tactics, and for each respective syndrome, adherence to guideline concordant care is encouraged. There are in fact some important caveats and issues. First of all is that we do know, on a positive note, many agents for major depression and bipolar, such as anti-depressant therapies and anti-convulsant treatment as well as lithium, are not only beneficial for major depression and bipolar respectively, but are also very helpful for migraine headaches. So that’s a positive.

So you could in fact have the proverbial “kill two birds with one stone” phenomenon. Which of course, if we could have simplicity in a patient’s pharmacotherapy, that’s desired. There are in fact some important hazards or concerns, and that is that there is always the risk of drug-drug interactions which can occur pharmacokinetically or pharmacodynamically. And one of the better known ones – we spoke earlier about one of the treatment options for migraine, at least acutely – is the use of triptans.

Triptans are serotonin-based anti-migraine therapies, and many of the anti-depressants that we use are also serotonin-based. Of course, everyone knows Prozac or fluoxetine.

[There are] many, many other types of drugs. And when you in fact co-prescribe a triptan with an SSRI (selective serotonin reuptake inhibitor), which we do, you need to do it carefully and with education of your patient because sometimes what you can do is you can overstimulate the serotonin system, and that has unpleasant side effects. In some cases it can be quite dangerous and result in what’s called a serotonin syndrome. [Serotonin syndrome occurs when the body’s serotonin levels are too high; symptoms may include mental status changes, difficulty with muscle control, heavy sweating, nausea.] Now, that is more than a theoretical risk. It’s a real risk, but we can do it, and we do it in carefully selected patients. It’s something that we need to be very cautious about. And there are certainly other types of interactions. That’s one that I think is a very practical one that many primary care providers find themselves faced with.

Rick:

Now, in terms of bipolar itself, is there anything specific that can be used to treat both bipolar and migraine?

Dr. McIntyre:

We certainly have a long history of using lithium. It’s an old medicine. We have had it since 1817, and it’s been used in bipolar for a long, long time. It’s well known that it has a positive affect, a salutary effect for migraine as well as bipolar disorder. Lithium is not as popular today as it was years ago. Anti-convulsants are something a lot more popular nowadays in treating bipolar than lithium. And some of these agents are approved, and some of these agents are not approved for bipolar. For example, we use divalproex (Depakote) a fair bit in managing bipolar, particularly mania, and it has evidence of some efficacy in migraine.

I think one of the agents that we often use in treating bipolar comorbidity is a drug topiramate (Topamax) or gabapentin (Neurontin). These compounds are not FDA-approved for bipolar but are approved for other conditions that differentially affect bipolar. In the case of topiramate, migraine – which it has indications for – we also use topiramate or Topamax for weight loss in addition to psychosocial strategies. And also, in the case of gabapentin or Neurontin, this is also an agent that we use in treating anxiety comorbidity in bipolar disorder. It’s an agent that also has evidence of efficacy in terms of migraine.

That’s not an exhaustive list, but certainly several anti-convulsants that we are using either on-label or off-label in bipolar, we also use to target migraines. And as a clinician, I can tell you that we have been very pleased with using these agents for both targets, bipolar and migraine.

Rick:

You mentioned the risk of using some serotonin medications, things that are affected by triptans and that sort of thing. Can there be treatments for migraine that cause or exacerbate someone’s mental illness? And on the other hand, can there be treatments for mental illness that cause or exacerbate migraines?

Dr. McIntyre:

Absolutely. The first part, the treatments for migraine that can potentially intensify or engender psychopathological symptoms like depression or bipolar disorder, the answer is yes. And, for example, when one thinks about the use of triptans, there has been in some cases scenarios in which they have destabilized people who have bipolar disorder. I don’t want to imply that this is a common issue or it’s an epidemic issue or anything like that, but these are always concerns.

When we think about patients who are taking bipolar agents, the anecdotal experience has not in fact [shown] an intensification of migraines, but what is the case in some scenarios is that anti-depressant medication for some reason may actually bring on migraines. Most of the time it doesn’t. In fact most of the time it actually treats migraines, but in some cases it can actually bring them on.

And I will tell you where one of these situations actually happens is when patients discontinue their bipolar medication or when they discontinue their anti-depressant medication, for reasons that we just don’t know we have certainly seen in some cases almost an irritating effect where it can actually bring on a migraine, and there may be aspects related to sleep deprivation or something. For example, many people who stop anti-depressants abruptly will have problems sleeping for a few days, and that may bring on the migraine perhaps.

I mean, this is speculation, but it’s something anecdotally that we have seen. So “do no harm” of course is our guiding principle, and there have been reports that both anti-bipolar therapies and anti-depressants could worsen migraine and vice versa, but it’s not common. We don’t see that very often. And more often than not, you see what you desire. You see a beneficial effect of the anti-mood agent on migraine severity and recurrence.

Rick:

How about psychotherapy, [which is] often used to treat people suffering from depression or bipolar disorder, can that help a migraine at all?

Dr. McIntyre:

Going back to what we said earlier, when we think about cognitive behavioral therapy as one so-called manual-based depression-specific psychotherapy, cognitive behavioral therapy is very effective in treating depression, particularly mild to moderate depression, recurrent or maybe even chronic depressions. And there is plenty of evidence now that it not only reduces the depressive symptoms’ burden but also benefits people in other aspects in terms of quality of life, functional outcomes, interpersonal matters, vocational matters and stress management.

I think these outcomes, vis-à-vis for example better stress management, bode well for other stress-related disorders such as migraine. So I think that individuals who have migraine as well as mood disorders, it’s been my clinical experience that once you have a medical condition like migraine in addition to the mood disorder, that adding the cognitive behavioral therapy often provides the patient really a better outcome in the long term. The obvious question is what is the active ingredient of cognitive therapy? Still it’s a great question. There is no immediate answer. I think what we have is we have left the old, anachronistic way of thinking that talking to someone is just simply just talking. Talking to someone also has biological effects on the brain, and so it’s quite possible that through an effective, skilled, cognitive therapy you may be seeing a direct effect on brain physiology, brain chemistry, or indirectly through some other mediating or moderating variable.

Rick:

Then beyond psychotherapy, if someone wants to try an alternative, natural approach to treating both, be it stress reduction, be it Chinese herbs, is this something they should do on their own, or do they need to go through their doctor for this?

Dr. McIntyre:

I think it’s something people should do very cautiously. I think that for a variety of reasons, many patients have gravitated through push or pull towards some of these so-called alternative treatment interventions. I have many patients who come to my office and say, “Dr. McIntyre, I would like to try such and such. It must work because it’s natural.” I have to remind them that tobacco is also natural, and it’s the number one killer of many people due to lung disease and so on. So natural does not mean it’s healthful.

I think that what we need to remind ourselves is that many of these interventions have not been tested. The notion that they are without side effects or safety concerns is categorically false and wrong. There are very serious safety concerns with some of these interventions. And when it comes to recommending treatment, I think [those] treatments need to be concordant with what the evidence shows. And I think it remains an open question whether some of these herbs or naturopathic therapies or Chinese medicines [really work], and so on. It’s an open question.

I always tell my students, lithium – which is an incredibly unique and wonderful drug for patients who do well with it – back in the 1800s it was used as table salt, and if you would have told someone in the 1800s that this table salt that I am sprinkling on my food could be a wonderful treatment for someone with a chronic, severe mental illness like bipolar, you probably would have been laughed at.

So, we have to keep an open mind on these things. At the same time, an open mind doesn’t mean an uncritical mind, and I think an uncritical mind is a dangerous mind. We need to be very open, yet critical and provide our patients the best proven therapies. And I think a lot of these interventions just haven’t really passed that grade yet.

Rick:

Thanks a lot, Dr. McIntyre. We have some questions coming in, so let’s get to them. The first one is from Averill Park, New York, and June writes, “Is there also a link between migraines and the possibility of having a stroke?”

A question we get quite often, Dr. McIntyre. What’s your reaction to that?

Dr. McIntyre:

Certainly that’s an issue that’s been talked about for many, many years, and I think that the best evidence right now indicates that that possibility still exists. As people have tried to parse out what is the mechanism here, I think that there is still a lot that we don’t know as to what actually may be related to that.

Vasospasm is one of the theories that was propounded for many, many years. It’s not the only theory, but certainly one theory. And certainly the clustering of vascular risk factors has been noted in this patient population for a while. In addition we think about reproductive hormonal events as also being contributory. But I think that that association certainly remains, and it certainly remains a concern in the healthcare community for older people, particularly those who have vascular risk factors.

Rick:

Is there anything anyone who has migraine should do prophylactically to prevent a stroke?

Dr. McIntyre:

Well, I think that it’s important to highlight that a stroke is probably more likely to occur in individuals who have other risk factors. So when we are planning a treatment, a schedule for somebody, we identify what those factors are, and as part of the chronic disease management, we initiate some type of intervention.

For example, people who have obesity or diabetes, who are habitually inactive, things like that, or in addition to migraine have hypertension, I think that the effective treatment of these other factors on their own has been shown to be beneficial for long-term outcome. And those benefits would likely translate ultimately with migraines. So what we need to do is identify – if you have got migraine, you have got migraine, and you need to effectively control it. But in addition, if you have other factors, they also need to be dealt with.

I think this question is really important because when we think about depression and bipolar disorder, I mentioned earlier in the program that the most common cause of premature mortality is cardiovascular disease. People who have these mood disorders are at very high risk for vascular disorders including cerebrovascular disease, and so it’s important if you have depression or bipolar as part of migraine that you have that depression and bipolar treated so that you are at least a lower risk of some of these physical health consequences like stroke and so on.

Rick:

The next question comes from Joy in Kansas. This is one we didn’t touch on, “Does having OCD, obsessive compulsive disorder, have anything to do with migraines?”

Dr. McIntyre:

I think it’s still an open question. It’s a fascinating one. I don’t think we have that answer at this point in time. There are reasons why that’s a viable and a very plausible hypothesis, and I think that anxiety for years, decades has been linked to migraines. But I mentioned earlier in the program that certainly the link to tension headaches is well established. I think for anxiety disorders in general, more specifically OCD, obsessive compulsive disorder, and migraine, it remains an open question.

Rick:

Katie in Dallas, Texas writes, “If migraines and mental illness have some sort of connection, my question is about triggers. We are well informed about all the many possible triggers for migraines. Are there triggers for panic attacks, as an example, or for phobic behavior?

Dr. McIntyre:

It’s a great question, and the answer is yes. By definition panic attacks, at lease as part of panic disorder, are uncued. They come out of the blue. That being said, many people notice that panic attacks are situationally bound. They occur in certain environments, for example, approaching a subway station or walking into an open plaza or approaching some other street corner that maybe a traumatic event occurred or something like that. So certainly we do know that there are psychosocial stressors or psychosocial elements that have been associated with triggering panic attacks as part of panic disorder.

But keep in mind, panic attack is not a psychiatric diagnosis. Panic attack is like having a rash or a fever. It’s a constellation of features that tells us that something is not right, but it doesn’t tell us a diagnosis, and panic attacks can be seen in many different psychiatric and medical conditions. So there are triggers to panic attacks, indeed, and many of these have been identified and reported on, and often they relate to aspects related to anxiety and triggering anxiety, like being in an anxious environment.

Rick:

Lisa in Plymouth, Massachusetts writes – and this goes to the issue of an accurate diagnosis – she says, “I am a migraine sufferer and have depression. How do I know if I suffer from bipolar disease as well?”

Dr. McIntyre:

Great question. I think that I would encourage the listener to speak to the healthcare provider and assure that there has been a systematic screening for bipolar disorder. And it’s now recommended, the product insert for all anti-depressants in the U.S. PDR (Physician’s Desk Reference) based on the FDA recommendations encourages all practitioners before they prescribe an anti-depressant to rule out bipolar disorder.

And so how the person would know? They should speak to their healthcare provider, and that person would be well skilled and trained on some of the key questions to rule that condition out or rule it in.

Rick:

Gina in Vancouver, Washington writes, “I am on state disability due to my bipolar disorder and some other health problems. Due to my situation, only certain bipolar meds are covered. I have had severe migraines for years. They get so bad that someone else has to take care of my son. What specific medications should I talk to my doctor about for treating both, bipolar and my migraines?”

Dr. McIntyre:

I think that it’s an unfortunate reality check that we have just heard in that question – we don’t have all agents available all the time. This issue as well as co-pays and so on, makes it difficult for someone to access treatment. The short answer would be Depakote, or divalproex, is one agent that comes to mind that we treat both conditions with. I would also extend that though – I mentioned during the program earlier that Topamax and Neurontin, those are drugs that are not FDA-approved for bipolar disorder, but have approval in efficacy in treating migraines, and so those are two agents that have shown to be beneficial for some aspects of bipolar but are not approved for bipolar, and something that could be discussed with their provider.

Rick:

I know you are in Canada, but generally speaking, are the treatments you described earlier to cover both migraine and bipolar or migraine and depression, are they generally covered by private insurance in the United States?

Dr. McIntyre:

Yeah, they are. I mean, there is a general coverage, but I think there are a number of different fine-print aspects here. Many of the agents we have spoken to during this program are covered, but recognize whether you are public or whether you are in the private system, which system you have is these tremendous variations. I have had the privilege of being in 48 of the 50 United States, and I have been struck by the tremendous variations between states in terms of coverage, so I think it is going to come down to each person’s provider.

Rick:

Right. We have an e-mail from Pennsylvania, “Could mental illness be caused by the migraines because of damage done to the brain by the headaches?”

So, is there damage being caused physically to the brain because of the migraine?

Dr. McIntyre:

Extremely interesting notion that that person raises, and I think it’s an open question. What we can say is that we know that when someone is in a state of migraine, there is an activation of a variety of physiological systems that could disrupt bipolar disorder or depression. Rick and I spoke earlier about points of commonality in the pathophysiology here. And so if you can imagine, depression, bipolar and migraine being linked together through different scaffolding, and once you pull or you compromise one aspect of the scaffolding, the whole system is affected. Metaphorically, that is the way I would see it, and it’s quite possible that the activation of both of these systems could in fact be particularly toxic for optimal brain structure and function. So in theory, it’s quite possible, but I think it still remains an open question in reality.

Rick:

Yes. Sherry in Pennsylvania writes, “I have suffered with migraines all my life. I am now struggling to live with fibromyalgia as well. My doctor has told me that every person he has seen with fibromyalgia also has migraines. Why is this? And is it being looked into?”

Dr. McIntyre:

Again, I think fibromyalgia is a very complicated syndrome, and we know relatively little about its pathophysiology. But we have learned something, and that is that the underlying biology in fibromyalgia again overlaps with mood disorders and overlaps with migraines in terms of some of the alterations that we talked about earlier.

I think that if we were to take people with fibromyalgia and take people who have that syndrome, almost all of which have some type of lifetime psychiatric condition like depression or anxiety, and you were to take away the depression from fibromyalgia, the association to the migraine would be probably less pronounced. In other words, what I am getting at here, if you can imagine the Venn diagram, the overlapping circles with fibromyalgia, mood disorders and migraine, again another example of a phenotype that’s probably boring some of the underlying scaffolding that depression and migraine share.

Rick:

And another question regarding this connection, from Dottie in Owingsville, Kentucky. She says, “I have migraines, depression, anxiety, bipolar, restless legs, insomnia and irritable bowel. Do you think they are all connected?”

Dr. McIntyre:

Well, I know this: It’s a very complex presentation. It’s a very unfortunate and complex scenario. Here’s the way I look at it: If someone has the flu, they feel nauseated, they lose their appetite, they feel achy, they can’t sleep, they are often coughing, they are just generally feeling a malaise. What we can agree upon is that the virus or the bacteria is the cause, and it presents in multiple different ways. And when someone has that list that you have described, which is very unfortunate, or another related list, we would like to say that there is just one single cause. That may be a bit overly simplistic, but I think it’s fair to say that probably what we are seeing here are many different expressions of a condition that probably has a lot more in common underneath the surface than we originally thought.

Rick:

We have a quick question from Stevensville, Michigan, “My daughter is 10, has been having migraines for the past year. She has a very hectic school, social, and athletic schedule. She has been through all the neurological tests. Brain images are normal. Could this busy schedule be the cause?”

Dr. McIntyre:

I think a busy schedule is generally a healthy phenomenon, but a busy schedule that is met with anxiety and resistance is stressful. Though busy in itself is not good or bad – I lean more toward it’s good – it’s busy when it collides with coping strategies, that’s where you have problems. I think one needs to look at how is this person coping? How is this person managing? It’s good to be busy, but if it’s outstripping her capabilities, then the stress related to that may in fact be toxic in terms of migraine.

Rick:

And with that we are just about out of time. But before we go in the final 90 seconds we have here, I would like to get some final thoughts from our guest, Dr. Roger McIntyre. What would you like to leave our listeners with today, doctor?

Dr. McIntyre:

I think there are three messages I would like to leave today, Rick, if I can. First of all, I would like to leave a message that we now know that major depression and bipolar disorder affect people with migraine more often than we previously thought.

The second point I wanted to mention is that we now know that if you have a depression and bipolar, it can worsen migraine, and migraine in depression and bipolar can make that condition worse, so there is sort of a [symbiotic] phenomenon.

And really the third, which is more of a prescription here is that for people who have migraine and have problems related to their mood, I would strongly encourage them to ask their healthcare provider to carefully screen them for bipolar disorder and assure that they don’t or they do have that condition, and if they do, let’s get it properly treated.

Rick:

Thank very much for joining us, Dr. McIntyre.

Dr. McIntyre:

Thanks very much for having me, Rick. I appreciate it.

Rick:

Thank you in the audience for being there. From Health Talk, I am Rick Turner.