NEJM Review of Generalized Anxiety Disorder

There was a re-survey of Generalized Anxiety Disorder (GAD) in this week’s New England Journal of Medicine ~ means of Stein and Sareen (1).  I virtuous did a bit of a exact review of the concept here and contemplation I would look at what these authors had to recite.  

They start the review with a clinical vignette of a 46 year primitive married woman with insomnia, headaches, back rack, and excessive worry about a reckon of daily stressors.  She is in addition drinking alcohol on a daily groundwork to “self-medicate”.  She is described of the same kind with a person who comes in commonly for appointments.  After reviewing the phenomenology,  comorbidity, and discriminating diagnosis – the authors come back to this plight and apply what is in the inspect.

Their review of the diagnosis does highlight a not many things that are problematic about the diagnosis.  The explanation diagnostic feature is chronic excessive worry.  The worry has to subsist there for at least 6 months.  In their re-survey of other psychiatric causes of disquiet they omit diagnoses that can undertaking short term worry or anxiety – the pacification disorders.  They point out that GAD is again common in primary care clinics in which place it usually presents with a leading compliant of somatic problems rather than exuberant worry.  They discuss major stagnation as a common co-occuring condition and suggest that anhedonia may subsist a distinguishing symptom for depression.  They in like manner describe anxious depression as episodic indentation superimposed on chronic anxiety.  There is nay mention of the low diagnostic trustworthiness of the disorder and why that puissance occur.  I think that a single one psychiatrist who sees anxious over time experiences the corresponding; of like kind problem that occurred in the DSM-5 region trials, the diagnosis can seem to modify between visits from GAD to major depression, even in the absence of ~ one new stressful life events.  Critics of psychiatry many times cite this as a problem by DSM-5.  I think that DSM-5 does a competent job with the symptom descriptors, further we don’t know why this make some ~ in. occurs and I have not heard anyone chat about it like it is a certain phenomenon.

Alcohol use is described being of the kind which a common co-morbidity with 35% of the million with GAD “self-medicating.”  I utter that term in quotes because it suggests that pure spirit can actually be used for the purpose of medication.  What in fact occurs is that over time the somebody becomes more anxious and sleep deprived as of the negative effects of alcohol on sleep, baseline anxiety, and baseline frame of mind.  Practically everyone I talk with who has an alcohol use riotousness can recognize this pattern and alter any remarks about self-medication to “experience better for a few hours” or “box myself out and forget about my problems”.  There is moreover the issue of alcohol use actuality the cause of an anxiety put out of place rather than temporary relief.  While I am up~ the body the topic of substance use and GAD, at individual point the authors make the specification: “Data are also lacking on the practice, usefulness, and safety of medicinal marijuana on this account that generalized anxiety disorder” (p. 2066).  Many allowing that not most anxious people are adverse to the use of marijuana in opposition to anxiety.  Initial use of marijuana typically causes a pendant in blood pressure with a compensatory tachycardia.  Tachycardia especially allowing that there is a noticeable accentuation of courage beats is not tolerated well by patients with anxiety.  Many bear had panic attacks.  Others possess cardiac awareness and are sensitive to in ~ degree changes in heart rate or energy.  Many people tell me they consideration that marijuana was effective for worry, but over time it seemed to flow them more and more anxious, they developed panic attacks, and they had to forbear using it.  These features combined by a tendency of patients to blockade talking to their primary care physicians are best fruits reasons to heavily educate them nearly these problems at the earliest feasible time.

The authors take a hazard factor analysis approach to looking at historical features that have power to also be associated with the diagnosis.  They naze out that they are nonspecific and amy have ~ing associated with other psychiatric diagnoses.  I would help a more developmental approach, looking back at the primitive recollection of anxiety – usually at more point in childhood and how that developed int he childhood environment.  It is fairly ~-place for the patient to describe some or both parents being anxious and in what condition that was transmitted to them  eg. ) “I started to worry hind part before the same things my  spring worried about” or “I started to worry here and there my mother because she was worried total of the time – I worried that matter was going to happen to her.”  Those erudition patterns associated with adult anxiety are fairly inferior and may explain the low heritability (15-20%) of the disease.  The authors do discuss unit feature that is important in this context and that is intolerance of uncertainty.  Clinically that translates to immoderate and at times catastrophic worry in regard to uncertain situations.  They are unsure near the biological or experiential origins of the indication.  I think the important office is that with a careful sufficiency history and sometimes collateral information the erudition aspects of this bias can have existence examined and it can be illiterate in therapy.

The authors advocate because of a stepped approach to treatment and I certainly agree.  This push forward would include an initial medical tax to look for common medical stipulations that can cause anxiety followed ~ the agency of education about anxiety and lifestyle changes to indite sleep, exercise, caffeine intake and highly rectified spirit use with monitoring response to those interventions.  Those primary two phases could be accomplished at the in the first stages visit.  If those initial interventions slip on’t help moving on to “moo intensity psychological interventions” like self-help books, computer-assisted psychotherapy, and suffer groups.  The next step up is again intensive psychological interventions like individualized cognitive behavioral therapy (CBT) or pharmacological care based on the patient’s predilection.  The highest level of care would take in pharmacotherapy and more intensive CBT alone or in connection with other therapies (psychodynamic or pleasure and commitment therapy (ACT)).  The practical issue with this 4 step algorithmic approximate to care is that it is usually not available in primary care settings.  In numerous of those settings, the patient is screened with the Generalized Anxiety Disorder 7-in like manner questionnaire (GAD-7) and the resigned is treated with a medication.  This is viewed for example “cost-effective” care by managed care systems for the reason that an inexpensive prescription and a 20 circumstantial appointment with a physician is manifestly much more “cost effective” to the forming than maintaining computerized psychotherapy or educational and monitoring systems.  There is too the largely undetermined effect of the assiduous taking a completely passive role in their care.  There is a betokening difference between a patient who is actively engaged in lifestyle changes and self education and one who expects a consummate cure from a pill.  The actively participating quiet has better outcomes.   

The authors comprehend a table of 16 medications used to behave toward GAD.  They point out that the effects of medication are modest at most excellent and no single medication has more valuable efficacy.  They discuss vilazodone since a promising medication in clinical trials and be enough not include it in the selvage.  My current prescribing information says that it is FDA approved singly for major depression, but only 4 of the 16 drugs put ~ the list are approved for GAD: paroxetine, venlafaxine XR, duloxetine, and buspirone.   The authors make notes on the practice of using hydroxyzine because of GAD and suggest not to conversion to an act it.  I am in perfect agreement with that recommendation and meditate that any anti-anxiety effect comes from the non-limited sedating effect of antihistamines.  The border effect profile is also not real favorable.  They point out the benzodiazepine seeming contradiction with GAD – they are recommended towards short term (3-6 month) practice but the condition is chronic.  There is calm more subtlety there.  Some at the opening of day studies of GAD treated with antidepressants suggests that patients needed to take the medication only 30% of the time over ten years of handling.  I don’t think you have a mind see a similar study with benzodiazepines and I exercise the mind it has to do with the behavioral pharmacology of the unsalable article.  The single-most important issue while it comes to benzodiazepines is the informed approval and letting the patient know that they are agitation a potentially addictive drug.  

The  authors are quiescent about the fact that GAD may exist the most heterogenous of all of the DSM-5 categories.  In October and November of this year, I went to three of the first water conferences.  One of the central themes was phenotypic difference in DSM-5 categories and which it implies for biology and genetics.  GAD seems to essay some of the best clinical features instead of distinguishing intermediate phenotypes and I outlines a few in my previous post.  There should have existence obvious problems with a diagnostic universal aspect that says “excessive worry” is a discriminating turn of expression and ignores real physiological markers like steady tachycardia, hypertension, body mass index, and hyperarousal at the time of sleep.   This also points out in what condition basic science can drive clinical diagnoses in psychiatry and hopefully at some point in the near future we direct see this kind of research.


I cogitate that we have gotten as abundant as we can out of the GAD diagnosis at this mark and it is time to lessen the force of it down into what can have existence more reliably observed. 

George Dawson, MD, DFAPA


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.

On enlargement a cardiovascular doctor said of this endocrinology would receive another 60 walls of practice.

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