OCD Awareness Week

It’s OCD Awareness Week!

This week, organized by the International OCD Foundation, its local chapters, and other organizations, is a great way to enhance public understanding of OCD and related conditions, and for OCD suffers and their families to reach out and get information, help, and support.  There are events on-line and around the country.  There’s a lot of information on the IOCDF website.

At 1 o’clock today, I’ll be doing a live chat with the IOCDF’s Jeff Szymanski about treatment – whether therapy or medications, or both, are right in a particular situation, and what the various options are.  You can get to this live chat at 1PM EDT by going to http://iocdf.org/ocdchat/.  I think our discussion will be archived there, too.

Then, tomorrow, the Connecticut chapter of the IOCDF will be hosting an educational and support event for patients and their families.  This event, Living with OCD, will begin at 9 AM with a presentation by myself and my colleague Michael Bloch about the manifestations of OCD and how to treat it with medications and other brain-based treatments.  Next, Amy Cawman, an experienced therapist and a member of the CT OCD Scientific and Clinical Advisory Board, will present on Cognitive Behavioral Therapy and Exposure with Response Prevention: what does it look like, and why does it work?  In the afternoon there will be a group of breakout sessions for patients and families, focusing on a variety of important topics relating to the treatment and experience of OCD.

I hope that you can make it to of these events, or to an OCD Awareness Week event near you!

 

What does an OCD brain look like?

Recently, several people with OCD have written to me to ask: “Should I get a brain scan?”   It’s not an uncommon question.  Is my brain normal?  Would a brain scan help with my diagnosis?  With my treatment?

OCD was one of the first psychiatric disorders in brain scans showed evidence of abnormal brain activity in specific regions.  The earliest work was from UCLA in the 1980s, by Baxter and colleagues.  They used PET imaging to measure brain activity (actually brain metabolism and blood flow, but those are thought to correlate pretty closely with activity).  These PET scans produce images of the brain, like this (From Baxter et al, 1987):

The top row of brains here is from an individual without any diagnosis; the bottom row is from a patient with OCD.  The images are reconstructed horizontal slices through the brain; the front of the brain is at the top, as if the person was lying on his or her back.  The colors correspond to brain activity (if we allow a few technical assumptions that need not trouble us here).  The warmer colors – reds and yellows – correspond to brain regions with higher activity; the cooler ones – blues and greens – are brain areas with less activity.  (This is at rest – these folks aren’t doing anything while their brains are imaged; they’re just lying there in the PET scanner.)  By comparing the images in the top row with those in the bottom, you can see at a glance that, while the overall patterns are quite similar, a few brain regions markedly more active in the OCD brain.  The two most prominent are the orbitofrontal cortex (OFC), at the front of the brain just above the eyeballs, and the caudate nucleus, a component of the basal ganglia deep within the brain.  Remember those terms – we’re going to come back to them.

These structures – the OFC and other parts of the cortex, and the caudate and other parts of the basal ganglia, connect together in a series of parallel loops, like this:

(From Pittenger et al, 2011; hat tip to Ben Kelmendi for making a great figure a few years back.)

The details here aren’t that important for our discussion; but you can see how the cortex (at the top) projects to the striatum (the caudate and related structures), down to the thalamus, and back again to the cortex.  It’s like a positive feedback loop.  And, somehow, this loop is in overdrive in OCD. At least, that’s how it looks from the neuroimaging data.

A few decades of subsequent work have refined but largely supported this picture.  Additional areas of hyperactivity have been identified, such as the anterior cingulate cortex (ACC), the anterior thalamus, and, in some studies, the insula.  Increased activity in these regions has been found to worsen when symptoms are provoked by, for example, showing patients images that trigger their symptoms.  Similar patterns have been shown using other brain imaging techniques, such as functional magnetic resonance imaging (fMRI).  Hyperactivity in these regions correlates with symptom severity, predicts treatment response, and normalizes with successful medication therapy or psychotherapy.  Very recently, new ways of using fMRI to measure how different parts of the brain are functionally connected to one another have revealed patterns of abnormality in the OCD brain that center on – you guessed it – the OFC and the basal ganglia.  (My own group has recently done a study on fMRI measures of functional connectivity in the brain in OCD that I’m rather proud of; but we’ll save that for another day.)

It’s a little more complicated than that, of course.  In the brain, it’s a safe bet that things are always more complicated than you think!  There are other brain regions involved, too; and the precise pattern of brain activity may be different depending on what type of OCD symptoms an individual person has.  Still, the overall picture is clear: there are functional abnormalities in the brains of people with OCD, within the cortex-basal ganglia circuitry, and they almost certainly contribute to symptoms.

Which brings us back to the original, clinical, question: is there any utility in a brain scan for a person with OCD?  Will it help clarify diagnosis?  Will it help us choose the best treatment?

I dream of the day when I can say ‘yes’ to those questions.  It’s a Holy Grail of psychiatry research – to be able to run a brain scan (or any other quantitative, objective test – genetics; blood testing; EEG; whatever) and have it tell us what’s going to work for an individual patient.  But today?  Not so much.

The problem is, even when we are pretty sure there are differences between brain activity in folks with OCD and those without, on average, that doesn’t necessarily help us make predictions about a given individual.  It’s kind of like the relationship of height to sex.  On average, men are taller than women.  But if I just tell you someone’s height, you’re not going to be very accurate in guessing their sex.  And if I tell you whether someone is male or female, you’re not going to be able to guess their height with any great precision.  There is an indubitable relationship between height and sex, on average, but it doesn’t do you a whole lot of good in an individual case.

Similarly, we’re pretty sure that there are relationships between abnormal activity in the OFC, basal ganglia, and other brain structure and the symptoms of OCD, but this doesn’t do us much good in an individual case.  It’s an important scientific insight, but it’s not a diagnostic test.  The fact is, the vast majority of the time, a brain scan in someone with OCD looks completely normal.

What about outlier cases?  If I tell you that someone is 6 foot 8, you’re going to have a pretty good guess as to their sex.  (You might be wrong, of course; but your guess would be reasonable.)  Is there a parallel to this in the brains of individuals with OCD?  Is there any particular brain abnormality that might, in an extreme case, provide us with some guidance?  Unfortunately, the answer is still ‘no’.  We just don’t know enough yet.  If the only thing we know about someone is that their OFC is thin or has a particularly high level of activity, I suppose that might increase the odds that they have OCD.  But we know that with much more confidence through a much lower-tech approach: talking to them.  And, at least today, that is a far more sure guide to a diagnosis than any brain scan.

It’s a frustrating answer: no, getting a brain scan won’t help us diagnose you, and it won’t help us choose the best treatment.  Some day, I hope!  But not today.

Therapy or meds?

The first-line treatments for OCD are specific forms of cognitive behavioral therapy and a particular class of antidepressants, the selective serotonin reuptake inhibitors (or SSRIs).  As a practitioner, I am equally comfortable with recommending either (or both) in particular cases.  But the choice between them is a complex one.

Some practitioners, and many patients and families, end up having very strong feelings on this issue.

For some, thinking of OCD as a brain illness and not ‘all in my head’  implies that it should be treated with a medication.  Accepting that a treatment based just on talking and behavioral exercises could be effective can seem to undercut the reality or the seriousness of the illness, which to some may make it seem more like a moral failing or a form of weakness, rather than a disease.  I have talked to many patients who express this view in one way or another and are not willing to countenance psychotherapy for their symptoms.

Needless to say, I disagree with this perspective.  There is absolutely no contradiction between OCD (or any other mental disorder) having biological roots, with clear heritability and demonstrable correlates in the brain, and the fact cognitive-behavioral treatments can be highly efficacious.  We know that experience has measurable effects on brain structure and function.  Effective CBT can lead to normalization of perturbed brain circuits in patients with depression or OCD.  And so being wedded to a biological model of disease in no way argues against CBT as a primary therapeutic modality.

Others are dead set against medication.  This may be grounded in concern about side effects or a general aversion to drugs.  Some patients I have spoken to are wedded to the idea that they should be able to overcome their symptoms through effort and that relying on medication as a ‘crutch’ is in some way a sign of weakness.  Others have a more general sense that medications are ‘unnatural’.  In some cases such a concern may synergize with their OCD symptoms, with medication being seen as an intolerable form of contamination.  Such concerns are understandable, and can be very powerful.  My own view, however, is that anything that helps reduce symptoms and alleviate suffering can be a good thing.  Medication can help patients with OCD, and in a great many cases, both anecdotally and in studies, the benefits very clearly outweigh any side effects.

Which works better?  This is a more complicated question than you might think.  It has been most directly asked by a group of studies from Edna Foa and colleagues at the University of Pennsylvania (and collaborators other sites) directly comparing  intensive, expert CBT and standardized pharmacotherapy, in both adults and children.  In adults, the results are quite clear: medication is of benefit, but patients receiving twice-weekly, expert CBT do better.  However, this superiority of CBT is not so clear in children.  Furthermore, the comparisons done in the most rigorous studies do not necessarily reflect typical circumstances in the real world.  Typically psychotherapy in these studies is done by experts, under highly controlled conditions, at moderate to high intensity – ideal circumstances that are rarely attainable in clinical practice.  Psychotherapy outcomes can be quite variable, even between expert sites.  Pharmacotherapy in these studies, on the other hand, is  pretty rigid, with single agents and limited options for clinicians to change medications, optimize treatment, or attempt pharmacological augmentation.  Thus, while it is reasonably clear that optimal psychotherapy is superior to rigid pharmacotherapy, it is not clear how this comparison plays out in clinical practice more generally.

Things are also somewhat murky regarding combination treatment.  In the large trial of adults from the Penn group, combining medication with CBT provided no additional benefit; in the study in children, on the other hand, combination therapy was clearly superior.  Again, this is with fairly inflexible pharmacotherapy and optimal psychotherapy, so it’s possible that the real-world benefits of medications are understated by these studies.

One issue on which there is substantial agreement in the literature (and in my clinical experience) is on the benefit of adding CBT when medications alone aren’t doing the job.  Again, the best studies come from the Penn group (and their collaborators at Duke, Columbia, and elsewhere).  Both in adults and in children, when pharmacotherapy has led to only modest improvements (or none at all), the addition of expert CBT is of clear benefit.

My view is that, in the real world, looking across these and other studies and combining them with my own clinical experience and with that of colleagues, expert CBT and competently managed pharmacotherapy are about equally effective.  Both can be of substantial benefit to 50-60% of patients, and of some moderate help to more than that.  About 25-30% of patients don’t receive much benefit from either.

This brings us back to where I started – with the reality that the choice of CBT or medication, or their combination, is a highly individualized one.  Patient preference plays a huge role; there’s no point in pushing someone towards a treatment that they don’t believe in.  Medication side effects can prevent individual patients from ever having a good trial of an SSRI (or other meds).  An inability or unwillingness to tolerate the symptom provocation and anxiety that necessarily accompany CBT may limit an individual’s ability to benefit from it, even under otherwise ideal circumstances.  Speaking of ideal circumstances (and the lack thereof), the limited availability of skilled CBT therapists can be a huge factor.  The fact is, medication is easier to administer with fidelity (it’s not that hard for a doctor to write a prescription, or for a patient to take a pill as directed) than therapy, which needs to be done properly by a well-trained practitioner to be maximally effective.  Past history can be a valuable guide – certainly, if a patient has had a good experience with CBT in the past, I’m inclined to refer them back to it, and if they’ve had a good response and few side effects with a particular medication, then that’s a good place to start.

The last thing I want to comment on in this post is the problem of not knowing when to stop when a treatment isn’t helping.

Most CBT treatment trials last from 8-16 weeks.  It’s clear that, in some cases, there is ongoing benefit for longer than this – there’s nothing magic about an 8, 12, or 16-week trial; these are just the somewhat arbitrary durations that have been picked for studies.  But at some point, response plateaus.  Ideally this is after substantial improvement; but sometimes it becomes clear that a patient just isn’t getting better.  Continuing therapy beyond this point has drawbacks – it may be inconvenient, consume patient and health-care resources, expose the patient to ongoing exposure-induced anxiety without benefit.  A much bigger problem is the foregone opportunity to consider something new – a switch of therapist or technique; addition of medication; referral to an intensive program.

(I don’t mean to disparage the utility of ongoing supportive therapy in sick patients; this can be really valuable and help them manage their symptoms and their lives in important ways.  I’m speaking here about treatment aimed at symptom reduction.)

The risk of continuing a futile treatment is greater with medications, because of the possibility of ongoing or cumulative side effects.  It can be much easier, for a psychiatrist, to start a medication than to stop one.  Stopping medications in sick patients can be a very anxiety-provoking thing to do – what if the meds are in fact helping, and I destabilize someone by stopping them?  It’s easier to add something new.  Sometimes this can help; there is clear evidence that adding additional medications on top of standard SSRI pharmacotherapy can help some patients, and the identification of additional strategies for such pharmacological ‘augmentation therapy’ is a very active area of research.  But all too often medication piles on top of medication, with new ones being added, or doses raised, to manage crises or side effects.  This can lead to astonishing cocktails and to side effects that are every bit as bad as the original symptoms.  Medications can help, but they can also harm, and they need to be managed with care.  It is hard, for both psychiatrists and patients, to admit that the available options just aren’t working.  All too often, however, this is a fact that we must acknowledge.

We are fortunate to have treatments for OCD that often work.  That wasn’t true 30 years ago.  But choosing among them in individual cases is often more art than science, requiring the integration of factors more complex and personal than can be captured in any formal study.  I dream of the day that I can use some objective test – a brain scan, a blood test, whatever – to identify the treatment that will work best for a new patient sitting in front of me, without guesswork or trial-and-error.  That day may come; it’s a focus of research in my Clinic, and at other centers.

For now, the best my patients and I can do is to work together to figure out which of the alternatives is the best fit for them. We know that many will improve, but some will not.  It’s frustrating.  But it’s a start.

Coming out of the shadows

I’ve been taking care of individuals with OCD, teaching students and residents about it, and doing research into its manifestations and causes for a while now.  And it continues to amaze me how little this disorder is understood, even by many professionals.

OCD isn’t rare.  Measurements of its prevalence – that is, the number of people who have it at any particular time – vary from study to study.  The recent numbers in which I have the most confidence come from a 2012 study by Richard Kessler and colleagues, drawing on data from the monumental National Comorbidity Survey, which evaluated a representative slice of the US population at multiple sites across the country.  They found 1.2% of the population to have OCD in any given year.  Over the course of a lifetime, that number rises to 2.7%.  That’s one person in 40 — which means almost 8 million people in this country and, assuming that these numbers generalize internationally, something like 176 million people worldwide.  That’s an enormous slice of humanity.

Any such calculations mask a great deal of complexity, obviously.  Symptoms of OCD are much more common in the population; they’ve been reported in 13% of the population in a survey across European countries published in 2010, 21% in a 2013 study of individuals in Switzerland, and 28% in the United States in the National Comorbidity Survey.  The variation between these numbers probably relates more to the way such symptoms are measured than to actual differences between the populations; regardless, it is clear that there are a lot of people out there who have potentially significant obsessive-compulsive symptoms that are not of sufficient severity to merit a formal diagnosis of OCD.  The measured rate of OCD, therefore, will depend on how this severity threshold is set, and how it is measured.  Some individuals with moderate obsessive-compulsive symptoms are going to get a diagnosis at some times but not at others, as the severity of their condition fluctuates.

In any case, OCD is not rare.  It is more common than schizophrenia or bipolar 1 disorder, which each occur in about 1% of the population. Furthermore – as most people reading this blog surely know – it is often very disabling.  In the original 1995 edition of the World Health Organization’s Global Burden of Disease study it was projected to be one of the top 20 sources of disability, worldwide.  (It has fallen off this top-20 list in more recent versions of this survey, due to changes in some underlying assumptions and in methodology – in the most recent version OCD is lumped in with ‘anxiety disorders’ and its morbidity is not separately calculated.)  In the National Comorbidity Survey, 60% of people with moderate OCD and 80% of those with severe OCD experienced severe role impairment in home management, work, relationships, and/or social life.

Given this prevalence and this level of morbidity, the surprising thing is that OCD is not better recognized than it is.  There are a number of reasons for this.  Perhaps chief among them is the fact that many individuals with OCD can, and do, hide their symptoms, even from those closest to them.  It is difficult to hide mania, psychosis, or crushing depression from those around you; in contrast, in all but the most severe cases many people can hide their specific obsessions (if not their anxiety) and their time-consuming compulsions from others and perform them in private, in surreptitious ways, or entirely internally.

A primary motivation for this, in many cases, is the fear of ‘looking crazy’.  Most people with OCD know very well how excessive or irrational their obsessions are, and how they might look to others.  I call this the ‘curse of insight’.  As one patient once told me, years ago: “I feel crazy in a way that crazy people don’t.”  I find this a very striking comment.  If I had thoughts in my head, every hour of every day, that I knew would look ‘crazy’ to many people if I gave voice to them, I would do everything in my power to hide them, too.  Wouldn’t you?

The fact that OCD symptoms are often hidden, at least in proportion to how common and severe they are, is not without consequences, however.  It was recently noted that a typical person may spend 17 years between first symptoms and getting appropriate treatment.  Hopefully that number would be lower now than it was back in 2004, when Michael Jenike made the observation, but it is appalling.  When people are doing everything they can to hide their symptoms, they are less likely to seek help.  And when they do seek help, it’s all too often a matter of luck whether the person they consult with is knowledgeable in the diagnosis and treatment of OCD.

This last fact is particularly troubling to me, as it represents a failure of our training system.  Shouldn’t anyone who is trained and credentialed as a psychiatrist or a therapist know the signs and symptoms of a major mental health condition, and be qualified to diagnose and treat it (or at least make a referral for appropriate treatment)?  But the fact that they’re often not is a direct consequence of the tendency of OCD to remain hidden.  Psychiatric or psychological training is only as good as the knowledge base of the people providing it, and the experience gained during training is constrained by the patients that students or postdocs come into contact with.  If OCD patients are not seeking treatment in proportion to the prevalence and severity of their symptoms, it is no wonder that many trainees complete a residency or training program without having seen one.  Furthermore, many training programs are associated with hospitals, and OCD patients are not hospitalized in general hospitals, at least for their OCD, nearly as often as those with schizophrenia, bipolar disorder, PTSD, depression or any of a dozen other major mental illnesses.

There’s another pernicious consequence to the way that OCD tends to remain in the shadows.  It receives far less attention from the major funders of research – the National Institutes of Health and the pharmaceutical industry – than other conditions of comparable severity.  A quick search of the abstracts of NIH grants in the ‘ProjectReporter‘ database reveals 134 grants containing ‘obsessive compulsive’ in their Abstracts; for schizophrenia, there are 1,227.  Prior to Roche pharmaceuticals’ ongoing ‘Skylyte‘ trial of the new glycine reuptake inhibitor bitopertin,* the pharmaceutical industry has not pursued a new drug for OCD since the 1987 trial of fluvoxamine.  (There have been several trials looking at already-approved drugs, with OCD as a secondary indication, but this represents both less risk for Pharma and less benefit for patients, since those drugs are available to be prescribed ‘off-label’ in any case.)

Fortunately, this situation is gradually changing.  There are speciality OCD programs at more and more major training centers, which ensures that OCD will not be ignored.  And as the disorder is better understood in the population at large, more and more patients are seeking appropriately qualified help.  The efforts of patient advocacy groups, especially the International OCD Foundation, has played a major role here, as has the sympathetic portrayal of individuals with OCD in television shows such as ‘Monk’ and the recent spate of reality-style shows depicting OCD treatment (even if they are sometimes sensationalized).

And as OCD comes further and further out of the shadows, training will improve, and funding for research and education will grow.  I was, honestly, surprised that there are 134 grants on OCD at the NIH; I’m sure that number would have been much lower five years ago.  The decision of a major pharmaceutical player to invest in a study of a new medication for OCD is a very promising sign.  Philanthropic activity in this area, which will permit growth of grant programs such as that of the IOCDF, is growing.

So I’m hopeful.  Patients will always do better when they are willing to seek appropriate help and share their experience, and when their caregivers recognize their condition immediately.  Treatment, either psychotherapeutic or pharmacological is always better when the provider knows what they’re doing.  Understanding and treatment will always advance more quickly when it is funded appropriately.  And all of these things seem to be moving in the right direction.  Let’s keep it up.

* Disclosure: my own Clinic is one of the sites for this study.

The Yale OCD Research Clinic Director’s Blog

Obsessive-compulsive disorder is a remarkable condition.  It affects around 2.5% of the population – one person in 40 – and yet is often hidden from view.  Some symptoms can seem, to people without the disorder, like everyday thoughts or behaviors that are simply carried to an extreme.  Others are so far removed from most people’s experience as to be quite alien.  This disconnect can be isolating and often leads sufferers to hide their symptoms – sometimes very effectively indeed.

I have directed the Yale OCD Research Clinic since 2007.  This Clinic was started in the 1980s by Wayne Goodman, Dennis Charney, and their colleagues, and it has been a major site for research into OCD and related disorders ever since.  Our current work, which is one of the things I hope to talk about here, encompasses everything from brain imaging to genetics, and from the development of new pharmacological and non-pharmacological treatments to trying to better understand patients’ experiences, in all their dizzying variety.

This Blog will be an opportunity for me, and perhaps other members of the Clinic, to write about all aspects of OCD, and related issues of brain biology, clinical experience, and society.  I hope that it will be of interest to professional colleagues, other researchers, patients and their families, and anyone else interested in OCD, and related conditions like Tourette syndrome, trichotillomania, and hoarding.

I hope that some of the observations I record here are of interest.  I hope even more that the research that I will write about, in this Clinic and by colleagues around the world, leads to a deepened understanding of these conditions and to new ways of treating them – in time, perhaps even preventing them.  Much suffering would thereby be alleviated.