Showing posts with label GAD-7. Show all posts
Showing posts with label GAD-7. Show all posts

Sunday, November 22, 2015

NEJM Review of Generalized Anxiety Disorder




















There was a review of Generalized Anxiety Disorder (GAD) in this week's New England Journal of Medicine by Stein and Sareen (1).  I just did a bit of a critical review of the concept here and thought I would look at what these authors had to say.  

They start the review with a clinical vignette of a 46 year old married woman with insomnia, headaches, back pain, and excessive worry about a number of daily stressors.  She is also drinking alcohol on a daily basis to "self-medicate".  She is described as a person who comes in frequently for appointments.  After reviewing the phenomenology,  comorbidity, and differential diagnosis - the authors come back to this case and apply what is in the review.

Their review of the diagnosis does highlight a few things that are problematic about the diagnosis.  The key diagnostic feature is chronic excessive worry.  The worry has to be there for at least 6 months.  In their review of other psychiatric causes of anxiety they omit diagnoses that can cause short term worry or anxiety - the adjustment disorders.  They point out that GAD is more common in primary care clinics where it usually presents with a chief compliant of somatic problems rather than excessive worry.  They discuss major depression as a common co-occuring condition and suggest that anhedonia may be a distinguishing symptom for depression.  They also describe anxious depression as episodic depression superimposed on chronic anxiety.  There is no mention of the low diagnostic reliability of the disorder and why that might occur.  I think that any psychiatrist who sees GAD over time experiences the same problem that occurred in the DSM-5 field trials, the diagnosis can seem to change between visits from GAD to major depression, even in the absence of any new stressful life events.  Critics of psychiatry frequently cite this as a problem with DSM-5.  I think that DSM-5 does a good job with the symptom descriptors, but we don't know why this change occurs and I have not heard anyone talk about it like it is a real phenomenon.

Alcohol use is described as a common co-morbidity with 35% of people with GAD "self-medicating."  I put that term in quotes because it suggests that alcohol can actually be used for the purpose of medication.  What really occurs is that over time the person becomes more anxious and sleep deprived because of the negative effects of alcohol on sleep, baseline anxiety, and baseline mood.  Practically everyone I talk with who has an alcohol use disorder can recognize this pattern and modify any remarks about self-medication to "feel better for a few hours" or "knock myself out and forget about my problems".  There is also the issue of alcohol use being the cause of an anxiety disorder rather than temporary relief.  While I am on the topic of substance use and GAD, at one point the authors make the statement: "Data are also lacking on the use, usefulness, and safety of medicinal marijuana for generalized anxiety disorder" (p. 2066).  Many if not most anxious people are averse to the use of marijuana for anxiety.  Initial use of marijuana typically causes a drop in blood pressure with a compensatory tachycardia.  Tachycardia especially if there is a noticeable accentuation of heart beats is not tolerated well by patients with anxiety.  Many have had panic attacks.  Others have cardiac awareness and are sensitive to any changes in heart rate or intensity.  Many people tell me they thought that marijuana was effective for anxiety, but over time it seemed to make them more and more anxious, they developed panic attacks, and they had to stop using it.  These features combined with a tendency of patients to stop talking to their primary care physicians about substance use are good reasons to heavily educate them about these problems at the earliest possible time.

The authors take a risk factor analysis approach to looking at historical features that can also be associated with the diagnosis.  They point out that they are nonspecific and amy be associated with other psychiatric diagnoses.  I would encourage a more developmental approach, looking back at the first recollection of anxiety - usually at some point in childhood and how that developed in the childhood environment.  It is fairly common for the patient to describe one or both parents being anxious and how that was transmitted to them  eg. ) "I started to worry about the same things my  mother worried about" or "I started to worry about my mother because she was worried all of the time - I worried that something was going to happen to her."  Those learning patterns associated with adult anxiety are fairly common and may explain the low heritability (15-20%) of the disorder.  The authors do discuss one feature that is important in this context and that is intolerance of uncertainty.  Clinically that translates to excessive and at times catastrophic worry about uncertain situations.  They are unsure about the biological or experiential origins of the symptom.  I think the important part is that with a careful enough history and sometimes collateral information the learning aspects of this bias can be examined and it can be unlearned in therapy.

The authors advocate for a stepped approach to treatment and I certainly agree.  This approach would include an initial medical assessment to look for common medical conditions that can cause anxiety followed by education about anxiety and lifestyle changes to address sleep, exercise, caffeine intake and alcohol use with monitoring response to those interventions.  Those first two phases could be accomplished at the initial visit.  If those initial interventions don't help moving on to "low intensity psychological interventions" like self-help books, computer-assisted psychotherapy, and support groups.  The next step up is more intensive psychological interventions like individualized cognitive behavioral therapy (CBT) or pharmacological management based on the patient's preference.  The highest level of care would include pharmacotherapy and more intensive CBT alone or in combination with other therapies (psychodynamic or acceptance and commitment therapy (ACT)).  The practical issue with this 4 step algorithmic approach to care is that it is generally not available in primary care settings.  In many of those settings, the patient is screened with the Generalized Anxiety Disorder 7-item questionnaire (GAD-7) and the patient is treated with a medication.  This is viewed as "cost-effective" care by managed care systems because an inexpensive prescription and a 20 minute appointment with a physician is apparently much more "cost effective" to the organization than maintaining computerized psychotherapy or educational and monitoring systems.  There is also the largely undetermined effect of the patient taking a completely passive role in their care.  There is a significant difference between a patient who is actively engaged in lifestyle changes and self education and one who expects a complete cure from a pill.  The actively participating patient has better outcomes.   

The authors include a table of 16 medications used to treat GAD.  They point out that the effects of medication are modest at best and no single medication has better efficacy.  They discuss vilazodone as a promising medication in clinical trials and do not include it in the list.  My current prescribing information says that it is FDA approved only for major depression, but only 4 of the 16 drugs on the list are approved for GAD: paroxetine, venlafaxine XR, duloxetine, and buspirone.   The authors comment on the practice of using hydroxyzine for GAD and suggest not to use it.  I am in complete agreement with that recommendation and think that any anti-anxiety effect comes from the non-specific sedating effect of antihistamines.  The side effect profile is also not very favorable.  They point out the benzodiazepine paradox with GAD - they are recommended for short term (3-6 month) use but the condition is chronic.  There is even more subtlety there.  Some early studies of GAD treated with antidepressants suggests that patients needed to take the medication only 30% of the time over ten years of treatment.  I don't think you will see a similar study with benzodiazepines and I think it has to do with the behavioral pharmacology of the drug.  The single-most important issue when it comes to benzodiazepines is the informed consent and letting the patient know that they are taking a potentially addictive drug.  

The  authors are silent about the fact that GAD may be the most heterogenous of all of the DSM-5 categories.  In October and November of this year, I went to three excellent conferences.  One of the central themes was phenotypic diversity in DSM-5 categories and what it implies for biology and genetics.  GAD seems to offer some of the best clinical features for distinguishing intermediate phenotypes and I outline a few in my previous post.  There are problems with a diagnostic category that says "excessive worry" is a discriminating feature and ignores real physiological markers like persistent tachycardia, hypertension, body mass index, and hyperarousal at the time of sleep.   This also points out how basic science can drive clinical diagnoses in psychiatry and hopefully at some point in the near future we will see this kind of research.
    
I think that we have gotten as much as we can out of the GAD diagnosis at this point and it is time to break it down into what can be more reliably observed. 


George Dawson, MD, DFAPA


References:

1: Stein MB, Sareen J. Generalized Anxiety Disorder. N Engl J Med. 2015 Nov 19;373(21):2059-68. doi: 10.1056/NEJMcp1502514. PubMed PMID: 26580998.

Friday, July 11, 2014

"Good News - Your Care Today Was Free"

"The bad news - we don't know how to make this diagnosis".



I woke up on Monday morning with a 2 inch diameter bright red rash on the inside of my right ankle.  It was mildly pruritic (itchy).  I could not recall any exposure to insects or trauma of any kind and it did not appear to be infected, so I applied some topical corticosteroid cream and went to work.  That night at home the rash seemed very mildly improved but it still itched.  I decided to get some medical input at that point.  The usual choices in my area are the Emergency Department or Urgent Care, but recently my health plan started to offer online consultation through a combination of limited diagnoses and procedures,  an algorithmic set of questions, the ability to upload images, and consultation with a nurse practitioner.  I looked at the list of conditions they were set up to diagnose and treat, noted that "rash" was one of them and logged on.

Health care IT is still in its infancy so nobody should be surprised that it took me much longer than expected to log in to the appropriate interface.  At first the program suggested I could just use my existing login and that would also integrate previous test results and conditions into the current evaluation.  After needing to call them I established a separate login and password for this episode.  Rather than the expected details up front, the program started to ask me all of the usual questions about the rash.  There were 28 screens in all, including some that forced an answer.  That question was "What do you think is causing the rash?".  Possible answers were: insect bite, infection, allergy exposure, poison ivy, etc.  There was nothing on that list that seemed likely.  That was after all the reason I was calling in.  I could not proceed past that point without giving an answer so I clicked "insect bite".  After completing 28 screens there was a text field and I entered: "Even though I answered "insect bite" on question #8, I only did that because I could not proceed if I did not provide an answer."

Next came the expected demographic data.  I live in a town that the U.S. Postal Service never gets right.  If I list a Zip Code the wrong town name pops up.  This software was no exception.  It took me extra time to enter and reenter data that was already there somewhere in my healthcare company's database.  The final screen was the billing and financial data including credit card information.  More data that my healthcare company has know for the last five years.  At this point I am about 20 minutes into the process and it is time to upload the photos.  I had 4 photos of the ankle and the program accepted 3 of them.  Sign off occurred at the 25-30 minutes mark.  As I waited for the return e-mail or call,  I marvelled at how health care companies have transferred all of this clerical work to physicians over the last 20 years and now they are transferring it to the patient.  I just did the work of the intake person and financial person in any clinic or hospital.

In 20 minutes I got a call from the nurse practitioner.  She said that although it was clear that I had a rash, it was not a rash they could diagnose in the system.  I told her that I was applying a potent corticosteroid and she said to just keep doing that but to go into a primary care clinic and get it checked out by my primary care physician.  Within 2 minutes, I got an e-mail from them:


Dear George,

Thanks again for taking the time to talk with us on the phone. Your health and safety is our top priority. Based on the information you shared with us, we think that an in-person visit is the best way to handle this specific condition. And, please know that you will not be charged for your visit today.

We're sorry we couldn't help you this time, but please keep us in mind the next time you're feeling ill. Thanks for choosing us.



Good to know I guess, but no diagnosis or specific treatment plan.  I continued the corticosteroid and the next night after work I stopped into an urgent care clinic after work.  I saw a family medicine physician who inspected and palpated the rash, took my pulses and determined that they were good in the area, and asked me clusters of questions that were clearly designed to rule in/out various pathological processes.  His conclusion:  "Well it's not an infection and its not due to trauma, but it clearly is an inflammatory process like atopic dermatitis.  So at this point I would keep applying the corticosteroid."  He asked me for questions.  My mind was preoccupied with tales of devastating spider bites lately so I blurted out:  "This does not in any way look like a brown recluse spider bite does it?"  He laughed and said: "Absolutely not."

So what have I learned from all of this and how do those lessons apply to psychiatry?  First off, it appears that human diagnosticians are safe for now.  Keep in mind that the system is set up to diagnose and treat a restricted list of conditions that are considered to be the least complicated in medicine.  Second,  the human diagnostician's superior capabilities depend on pattern matching and that in turn depends on experience.  It reminded me of a course I taught for 15 years on how to avoid diagnostic errors and pattern matching was a big part of that.  The two examples were rashes and diabetic retinopathy.  Dermatologists were much faster and much more accurate in classifying rashes from pictures than family physicians.  Ophthalmologists are much more accurate using indirect ophthalmoscopy than family physicians using direct ophthalmoscopy in diagnosing diabetic proliferative retinopathy.  In fact, the family physicians were slightly better than chance.

The lessons for psychiatry are two fold.  Remember the idea of a restricted list of conditions that are not considered complex?  It turns out that depression and anxiety are on that list.  Even though there is no call center where you can call and complete the paperwork like I did,  it would probably not be much of a stretch to say that many if not most primary care clinic diagnoses of depression and anxiety are keyed to some rating scale.  Like the studies of Dermatologists and Ophthalmologists, there are no expert pattern matchers looking at the patient.  That can result in a diagnosis that is essentially dialed in.

The second aspect here is the design of the algorithm and its implications.  My rash algorithm had a forced choice paradigm.  I could not proceed to the end unless I picked an answer that was clearly wrong.  That is the way it was set up.  That is the problem with so-called "measurement based" care.  There is the appearance of a quantitative result.  The Joint Commission called the 10-point pain scale "quantitative" in the year 2000 with their pain treatment initiative in the year 2000.  I have spent a good deal of my adult life talking with patients about their moods, sleep and appetite patterns, and other symptoms.  The most important part of my job is coming up with a plausible scenario for their current distress.  I can say without a doubt that over half of the people I see cannot describe discrete episodes of mania or depression.  The usual description of depression I get is that it is life long with no remissions.  Certain personality characteristics predict descriptions of symptom severity in the initial interview.  Some people completely minimize symptoms and other people will flat out tell me that they do not want to discuss their inner thoughts even if they are experiencing thoughts that may place them in danger.  Map those response patterns onto a psychiatrist and hopefully that will result in a diagnostic formulation and a plan to deal with the nuances.  Map those response patterns onto a PHQ-9 and suddenly you have a number that somebody believes has meaning.   Looking only at Question 9:

"Thoughts that you would be better off dead or of hurting yourself in some way."  

Suddenly people are alarmed with the person with a personality disorder and chronic suicidal thinking or chronic obsessions involving suicidal thinking endorses "nearly every day" as their response.  We are falsely reassured when the patient who has a significant personality change and depression endorses "not at all".  We have forced them to make a choice and they have, rather than using all of the information necessary to make an evaluation.

As a discipline - we should be moving in the direction of using all of the relevant information in clinical situations and not less.  My rash today is an example of what can happen in an organ governed by much less genetic, metabolic and signalling information than the human brain.  Even in that situation a diagnosis with no clear etiology or diagnostic features can present itself.

Forcing choices reduces the information flow rather than facilitating it.  If primary care physicians find this checklist approach to diagnosing anxiety and depression useful I would see no problem with that, but it might be useful to look at the medications being used based on the PHQ-9 and the kind of impact this approach is having on medication utilization.  It also might be useful to have a seminar or two on the problem of over prescribing medications.  The correlation between overprescribing opioids and the use of a "quantitative" scale to measure everyone's pain is undeniable.

The question that applies in all of these circumstances is whether a number on a subjective rating scale is ever enough of a reason to prescribe a medication.

You already know what I have to say about that.

George Dawson, MD, DFAPA