I was in internal medicine and psychiatry combined residency, and I was the primary care physician for part of my residency. And I recall how difficult it was to find time to address depression and anxiety. When you have a relatively short follow-up visit, and you're expected to handle diabetes, heart failure, and hypertension, you realize how difficult it can be to address anxiety and depression, which, of course, are very important as well.
WHEN TO DIAGNOSE SOMEONE WITH GENERALIZED ANXIETY DISORDER?
So the first question that I've challenged my colleagues in behavioral health to think of is how often does a given patient in primary care have generalized anxiety disorder as their only psychiatric diagnosis?
Probably not very often, as comorbidity is the rule. That's one of the takeaway points that I'd like to convey. Generalized anxiety disorder really does not exist by itself. It often exists with depression, substance abuse, and other anxiety disorders.
And I think that's where a lot of the challenge is. We know that when you have a generalized anxiety disorder and a comorbid condition like major depression, they're both hard to treat.
DO I HAVE ANXIETY OR GENERALIZED ANXIETY DISORDER?
The other important aspect is defining anxiety. So anxiety is a normal adaptive response. We all have it. We all do it. But when does it cross the line and become pathological? When does it become excessive? And when does that meet the criteria for a disorder?
One way to think about it is “worry” is normal, but excessive worry or dysregulation of worry, where the person can't control it, or it affects their function or causes avoidance of important things in their life, crosses the line to a disorder.
The focus of the worry is really no different than all of us. We all worry about school, work, finances, but in GAD patients, the worry is excessive, and they just can't control it. Anxiety just can be hard to ask about. I ask patients about anxiety, and maybe I shouldn't lead with that term, but they sometimes freeze, and they don't know how to respond. They're not sure how to define anxiety.
Anxiety may not present with the patient saying anxiety or, “I'm worried,” as it so often presents with the other aspect of the diagnosis, the somatic or the physical: headaches, muscle aches, tiredness, inability to sleep, etc.
These are extremely common presentations. And a lot of times, the patients may present with that and not with actual worry. That can make the challenge of diagnosis more tricky.
WHY IS ANXIETY HARD TO DIAGNOSE?
It can also delay the diagnosis and delay the time until the patient gets those evidence-based treatments. There's also a system-level talent, just like I talked about. I had a 30-minute visit. We were already over. I didn't have the time, or necessarily the tools, in the clinic to help the patient with their anxiety.
It is a common diagnosis. And again, here's that comorbidity again, not comorbidity just with mental illness, but comorbidity with physical medical conditions. So we know that the more medical problems you have, the more likely you're going to have generalized anxiety disorder.
And we know that chronic disease risk factors like smoking, alcohol use, and a sedentary lifestyle are also higher rates in patients with anxiety disorders.
HOW TO EXPLAIN ANXIETY TO MY PATIENTS?
Break the anxiety down into two parts. The psychological part is the worry and the somatic symptoms, including physical tension, fatigue, sleep disturbance, muscle aches or tension, and sometimes autonomic hyperactivity, sweating, tremors, and GI disturbance.
The rates and the prevalence of GAD can vary. It is somewhat hard to study at times. Sometimes generalized anxiety disorder is looped in with other anxiety diagnoses that can make studying it challenging. But a lot of surveys of primary care populations show the prevalence in primary care can be 8%.
WHEN DOES GENERALIZED ANXIETY DISORDER APPEAR?
Like a lot of other mental health diagnoses, it's at a young age. It’s young adulthood, but it does have a wide range. Childhood-onset is quite possible and common. And so you have to look for school-age children with somatic symptoms, school refusal, those types of things.
There might be a second peak of GAD in older adulthood related to increasing medical problems. The risk factors for GAD may not be particularly helpful clinically. There's a lot of overlap with mood disorders. But as you'd expect, adverse events can trigger GAD – being isolated, widowed, divorced, separated, having a family history, having other psychiatric diagnoses, etc. It usually occurs in a female to male ratio of two to one.
The cause is interesting. It's not something fully understood. Like many things multifactorial, there are going to be genetic elements. There's a strong association in terms of heritability with major depressive disorder and the personality trait, neuroticism, from a biological or neuropsychiatric standpoint.
There have been some functional MRI studies, and although this area is a little complicated, I’d like to really simplify it: I like to think about the emotional part of the brain, the limbic area, the amygdala, and then maybe the frontal prefrontal part. And it can be thought of as perhaps an over-activation of the limbic area. And the connection with the frontal lobe, which is supposed to modulate that and dampen anxiety, is aberrant if the connections aren't that well-formed.
So you can see how you have an overactive part, and the part that is supposed to regulate is not quite in sync. There is a psychological construct that's very common in patients with GAD called intolerance of uncertainty. So they have a really difficult time tolerating uncertain situations, and that's an extremely common finding.
WHAT TO WATCH FOR WHEN SCREENING FOR GAD?
A common clinical screening tool is a GAD-7. It's a validated screening tool for GAD in the primary care setting that asks about the symptoms in the past two weeks, so we use this in our practice. I do find it very useful. So we have anxious patients whose anxiety may be due to something else, or they may be self-medicating.
So I asked not just about prescribed medications that are on their medication list, but alcohol and tobacco use. I ask about caffeine use, and it may seem simple, but a lot of times, patients are using excessive caffeine and sometimes that doesn't explain the anxiety disorder entirely. Reducing caffeine gradually can really help anxiety and sometimes insomnia.
Of course, illegal drugs are part of the routine screening questions. I've also broadened, at times, to include other ways patients may get medications. I've had cases where patients get medications through the mail from a different country, but it's a controlled substance, and they were trying to self-medicate an undiagnosed symptom of anxiety.
Or are they using a family member's medications? The medical evaluation is in your wheelhouse. This is the bread and butter of primary care, working up fatigue, and other somatic symptoms. There is no standard evaluation. It depends on the presentation of the patient.
A lot of times, if there's anxiety, you wouldn't want to rule out hypothyroidism since that could present as anxiety, of course, as a treatable medical condition. If there's something atypical about the presentation, you'd also probably broaden your medical workup. So if the age of onset didn't quite fit – in there was a patient in their 70s, and they were just suddenly anxious – you'd think about medical causes, or if there's cognitive or personality changes that don't quite fit.
Not all anxiety is generalized anxiety. I think, sometimes, we can get into the habit of doing that and not looking a little further to see what is the exact diagnosis. Is it more panic? Is it more PTSD? Is it a medical cause?
So many times, patients come in with a stigma or a family member telling them, just don't worry so much. I think helping the patient with validation can be helpful. Anxiety can be a terrible experience, and they may not know what to call it or what it is. And I've noticed that explaining to the patient that you recognize it's an awful experience, and it's a serious condition but treatable, can go a long way.
THE DSM-5 DEFINITION OF GENERALIZED ANXIETY DISORDER
Anxiety is excessive. It's difficult to control. There are somatic elements: being restless, keyed up, fatigue easily, concentration difficulty, irritability, muscle tension, sleep disturbance. One distinguishing thing is in children: only one of those items is required.
And of course, it's not by something else – a psychiatric diagnosis, a medication, or substance – and it causes distress or impairment in their life. Why should we think about this? And what should we be worried about? Well, GAD adversely affects school, work, life, and health.
And these patients have higher health care costs, higher prescription rates, and perhaps the greatest burden is between the ages of 15 and 34, obviously a very important time in one's life.
Effects on health have also been studied. Quality of life is impaired. Suicide risk has been looked at again, but it’s difficult to distinguish because anxiety is comorbid with depression. When you look at that GAD diagnosis, there are also some studies looking at GAD in middle-aged women and looking at the risk for cardiovascular outcomes.
And there is some thought that GAD, even by itself, maybe should be considered a cardiovascular disease risk factor for a middle-aged woman, even when they controlled for the standard risk factors and for metabolic syndrome.
DOES GENERALIZED ANXIETY GET BETTER? DOES IT GO AWAY?
I think of GAD as a chronic illness, but it does wax and wane. So it could be there for a period of weeks or months because it was exacerbated, and it may also go away for a while. But it's generally a chronic condition, meaning the rates of complete and sustained remission for the patients with GAD is rather low.
There is some thought that, as patients get older, those meeting criteria of the GAD diagnosis may go down. But the other interesting thing is that the criteria for a somatic anxiety disorder may go up, as you would expect: predictors of poor prognosis, medical problems, personality disorder, co-occurrence, current conditions, and long duration before treatment.
HOW CAN I TREAT FOR GAD?
So much in the same way you would approach an initial case of hypertension or dyslipidemia, you're going to focus on education and lifestyle modifications for generalized anxiety disorder.
You're going to talk about education. You're going to talk about exercise, good sleep habits, minimizing alcohol and caffeine. And have the patient do their own learning. But the most evidence-based approach for psychotherapy for GAD is Cognitive Behavioral Therapy (CBT).
COGNITIVE BEHAVIORAL THERAPY
The definition I like best of CBT is from colleague Dr. Sawchuk, and he phrased it so:
“CBT is a practical skill-building approach that emphasizes self-efficacy and self-management of symptoms while working toward defined and measurable treatment goals.”
You actually want to expose the patient to what makes them anxious and what they don’t like. But in the long term, it is helpful. And then the concept of response prevention, reframing their thoughts that have gone awry.
A standard therapy session is 12 to 16 sessions, one hour, and probably about once per week. Now, patients don't always follow that exactly, and that's OK, but that's the standard CBT approach. There have been modifications, for example, using CBT integrated into the primary care practice, going shorter than an hour, less than 12 sessions have been shown to be effective for anxiety and depression as well.
Group therapy is another option. Now, a lot of times, anxious patients don't like group therapy, so this can present a challenge. But sometimes, the group therapy experience can be beneficial because patients can learn from each other, and they have the peer support component. Delivering therapy in novel ways because patients are often so busy, using computer models and outreach telephone methods to rural areas, have also been studied.
How do we know if our patient is using evidence-based treatment or not? Well, there are some questions you can ask. A primary care doctor could ask, what skills are you working on in treatment? What are your treatment goals? How are you and the therapist monitoring your progress toward goals? And does your therapist give you homework between sessions, and is your treatment time limited?
MEDICATIONS FOR GAD
Now let's say a 28-year-old patient comes in extremely frustrated. They have been prescribed, let's say, four antidepressant trials for generalized anxiety disorder. The patient says I'm not depressed. I'm anxious.
Four trials of medications and the patient say nothing helps. In fact, these medications make me feel worse. They cause me to have more anxiety, more insomnia, and I feel emotionally blunted.
Well, I think one way to approach it is, again, education. Antidepressant is in some ways a misnomer: SSRIs and SNRIs are first-line treatments for generalized anxiety disorder. But because the patient understands they are antidepressants, they may be confused and believe their anxiety is not being treated.
So I think educating on that point is very important. There are several other things we have to tell the patient with antidepressants. #1, They don't work right away. #2, Your anxiety will not be relieved in the first few days. It may take several weeks. And #3, And it may take more than one antidepressant trial.
When I think about dactyl medications for GAD, in some ways, it’s is similar to depression. But I think about three general categories because there are so many medications. The first category is the first line with the most evidence, SSRIs and SNRIs. I think primary care providers are usually comfortable with some of these because they will be used for depression as well.
EFFECTIVE AND PROVEN MEDICATIONS FOR GAD
If there is anxiety, even generalized anxiety, and most definitely if there are panic attacks or panic disorder, you generally want to start with half of the usual starting dose of the SSRI or SNRI. I usually do that for about a week to make sure the patient tolerates it before increasing it to the standard starting dose.
For example, if I was starting, certainly I might start 25 milligrams per day for a week and, if they're tolerating it, then I would do 50 milligrams per day. SSRIs and SNRIs for GAD, again, are the first line.
They may work better for reducing that cognitive worry, more so than the somatic symptoms. And I think that's where we face a lot of challenges. Patients want relief from that physical tension, the upset stomach, the concentration. Sometimes, insomnia and SSRIs may not do that or may take too long.
Here's another important point: there's really no evidence that anyone’s SSRI or SNRI is better than the others approved or commonly used. So, much like depression, you're going to go by patient experience, the medication at hand, and their comorbid conditions. If they do not have a good response, and it's been eight weeks or so, it is reasonable to consider augmentation.
Suppose there's some response or no response: we need a different strategy. Therapeutic dosing is usually about the same for general anxiety and major depression. But like depression, a partial response is the norm. And it's common to have to go through two or three or more medication trials until you get some response.
WHAT MEDICATIONS SHOULD BE AVOIDED WITH GAD?
Well, that's tricky because it's so often comorbid with other conditions. But if you're really treating just GAD, bupropion is not indicated for any anxiety disorder and may make it worse.
There's also a handful of "newer antidepressants" that have come to the market, say, over the past ten years or so. None of these have really proven to be more effective for depression or anxiety than the other antidepressants. So sometimes, we don't use these because there are greater costs to the patient.
Many of the "newer antidepressants" also were approved for major depression and not generalized anxiety, so that's a problem as well. There may be one exception: vilazodone, for example, based on the mechanism where some people liken it to an SSRI and buspirone.
Tricyclics, overall, would have a limited role in treating GAD by itself. Of course, they have a known role in treating depression. Imipramine is not FDA-approved but has undergone some controlled studies for GAD.
However, it's very common for patients to be on things like amitriptyline or nortriptyline because those things can be used for migraine prophylaxis, pain, and insomnia. And sometimes, we run into the challenge of being on too many serotonergic medications. So we had to think about polypharmacy and serotonin syndrome and things like that.
Patients may have a strong belief against antidepressants, and they want to use more natural ways. And I think that involves a little bit of discussion and education.
CAUTION TOWARDS BENZODIAZEPINES
Benzodiazepines are highly effective. Patients frequently want this medication, but we have to understand the risks and explain it. The only risk is not addiction or tolerance.
We have to think about the effects on cognition. There are some studies showing long-term use may be associated with dementia in women. Now, that's not a causal relationship, but we have to think about the long-term effects.
There is an increased risk of falls, we think, in older patients. There is an increased risk of sedation if there are other sedating medications, and you have to tell the patient that it can be very difficult to get off these medications once the patient gets used to it, has a relief of their anxiety, and gets sleeping better. They continue taking it, and they could develop tolerance.
And we know that benzodiazepine withdrawal, like alcohol withdrawal, can be medically serious. Especially with the opioid epidemic and knowing some longer-term risks, I think, for most of us, our practice has changed.
Here's another take-home point with the benzos. It's probably not right to say we never prescribed them, but we also can't overprescribe them. So thinking about your practice, patient population, and where you are on the spectrum of prescribing benzodiazepines is important.
GAD IN CHILDREN
Anxiety in children. There's a couple of differences in the diagnosis, but not too much. You know, school refusal and somatic symptoms would make you think about an anxiety disorder.
SSRIs, when a medication is indicated, are still going to be the first line for childhood anxiety disorders. SSRIs alone, however, or medications alone, are really not a good evidence-based treatment plan. CBT should always be part of the treatment plan.
As so many times, I see anxiety that persists. But the patient may have persistent life stressors, or there's something in the realm of social determinants of health that needs to be addressed.
GENERALIZED ANXIETY DISORDER & RACISM
I think we have to address that, along with the anxiety, where social work or community health workers may come into play.
I think a lot of patients may not be comfortable with the primary care setting and may not be comfortable with SSRIs. And many times, patients from different backgrounds or cultural groups may not see the illness or the treatment the same way.
And so we may need to ask about that. And we need to recognize the impact of racism, discrimination, or historical distrust that certain groups may have. The GAD-7 and the PHQ-9 for depression both come in various languages.
DOES WEED HELP WITH ANXIETY?
Another common question is cannabis use. And the bottom line is we just don't have enough answers. Many patients self-medicate with marijuana. Many states have medical marijuana in Minnesota. PTSD is a qualifying condition, but it's hard to find the real evidence that's effective.
SUMMARY
We need to be very careful thinking about the risks and the side effects of benzodiazepines. Self-medication among patients with GAD was about 35%. Again, you're going to find a range on that number. But the takeaway point is it's a lot.
And if you have a patient using a substance like alcohol, you may want to ask about anxiety. This is a challenging diagnosis, but hopefully, with the things we went over, it'll help you think about the diagnosis.
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