The Rise of Generalized Anxiety Disorder 

Anxiety is pervasive in the world today. All of us including me know what it’s like to be anxious. We have all read recent articles about how the COVID-19 pandemic increased anxiety around the world, and this has placed a lot of focus on anxiety as a psychiatric diagnosis. Anxiety in my opinion is not an independent disease the way the diagnostic and statistical manual (DSM) would lead you to believe. Anxiety is a symptom that has various potential causes and that’s what we are here to talk about today. 

This is inspired by a real case where I needed to do a deep drive into the literature to understand the root of anxiety and its treatments. I hope you guys enjoy the topic.

Introduction 

Generalized Anxiety disorder has been revised significantly over the years by the DSM. It seems like no one knowns what GAD is, or if it’s an independent disease state. The DSM only provides descriptive criteria and does not comment on the underlying cause of anxiety. Prior DSM criteria from DSM III focused more heavily on autonomic and motor symptoms of anxiety. In these editions, what is now GAD was referred to as psychoneurosis an old Freudian term that fell out of favor as we moved away from psychoanalysis. Interesting fact, if you look up the indication for hydroxyzine in anxiety it still states “for tension associated with psychoneurosis.” The more recent updates in DSM have stepped away from these physical symptoms and focused more on the mental state of chronic and excessive worry. If we attempt to apply older studies on anxiety treatment to the current DSM criteria, they may not be valid. 

What I want to stress, is worrying is the core symptom of GAD now with at least 3 out of 6 of the following: 

-Restlessness 

-Being easily fatigued 

-Difficulty concentrating 

-Irritability 

-Muscle tension 

-Sleep disturbance include insomnia 

When I look at the criteria, they look a lot like depression to me. I often argue to my residents and medical students that it’s hard to separate depression and anxiety, but they usually disagree, so this video is for them as well. 

Causes of Anxiety 

We should try and figure out what the potential underlying causes are for anxiety. Since the DSM does not guide us here, we need to think through each possible cause. 

Personality: people often underestimate the importance of personality traits in psychiatry. One personality trait that is part of the “big 5” is neuroticism. We all have anxiety as a personality trait, some individuals have more some have less, but for the most part there is a normal distribution in the population. If you have more, you tend to get diagnosed as having a “anxiety disorder.” Most people fall in the middle we have some anxiety under specific circumstances but not enough for it to be identified as pathology. 

Depression: As I stated before there is a lot of overlap in the criteria for depression and generalized anxiety disorder. In fact, the same medications are used to treat both disorders. Depression can clearly be a cause of anxiety. 

Mania: people often mistakenly believe that people in manic states are having fun and love being that way. This is not true, and anxiety can be one of the potential symptoms associated with manic states. 

Psychosis: Schizophrenia or schizoaffective disorder can be anxiety provoking disorders 

PTSD: Excessive worry can be a part of PTSD 

Eating Disorders

Substance Use Disorders 

OCD

Other environmental factors can cause anxiety independent of those listed above: life stages, divorce, death of a loved one, diagnosis of severe physical illness, significant loss of physical function from an injury 

The point here is there are many things that could result in a state of high anxiety. What you should start to see here is once we rule out all these causes for anxiety there would be no way to diagnose an independent anxiety disorder. 

Just describing the symptoms of anxiety checking the boxes for the criteria and labeling someone as having “anxiety disorder” does not have much meaning. We have to say what the underlying cause of the anxiety is to treat the symptoms effectively. 

Myths About Medication in Anxiety Disorders

People often believe that anxiety responds faster to medication than depression. This is not true the response to medication takes the same amount of time for both anxiety and depression. This provides another layer of evidence that GAD can be driven by depressed states. Trials of medications such as SSRIs can last several weeks as doses are titrated until the individual has an acceptable level of response to the medication. 

There is also no established dose dependent response in GAD. Some believe that GAD responds better to higher doses of SSRIs, say 40 mg of escitalopram. This has not been established in the research literature. This may also indicate that the underlying cause is OCD which traditionally requires higher doses and longer duration of treatment. 

Many people presenting with anxiety will be started on an SSRI. In the past paroxetine was favored by primary care because it had the FDA indication for use in anxiety disorders. I never think paroxetine is the correct choice for anxiety due to the side effect profile which includes risk for withdrawal and harm during pregnancy. Citalopram has suffered a similar fate as dose dependent QTc prolongation limits the doses we can use in clinical practice. Escitalopram can prolong QTc at higher dose above the approved maximum but there is significantly less risk at standard doses. 

How effective are these medications for anxiety disorders? Not very, a meta-analysis found that SSRIs have an effect size of 0.33 falling into the low range. 

Part Two:

Part two of this series will be coming soon. I had way too much to say about the diagnosis of GAD that I didn’t leave any time to discuss treatment. Part two will included a detailed analysis of medications for GAD.

Medication Side Effects: “I feel nauseous”

Introduction:

Did you know that the researchers that conduct drug trials do not ask patients about specific side effects? Rather, they ask a generic question such as “are you having adverse reactions to the medication” the patient then has to self-report any specific side effects they are having. Sometimes physicians during medication management sessions will use a similar question when asking about side effects. Some physicians also make statements when prescribing the medication such as “don’t worry most people do not have side effects with this medication.” This is egregious, considering we know these medications have side effects as all medications do. What I want to do over the next several posts, is discuss the common side effects of SSRIs and what you can do about them. The biggest issue we face with psychiatric medications is adherence, and many times side effects play a role. 

I want to start with the most common side effects and work our way down. Nausea is one of the early side effects that is disturbing to patients and may result in discontinuation of the medication. Several things can be done to reduce the risk of nausea. 

Medication Starting Dose and Titration

One simple step could be to start the medication at the lowest possible dose and titrate slowly. Titrating the dose over one week has been shown to cut the risk of nausea in half. Another potential intervention is to split the dose and give the split dose with separate meals. If possible, use sustained/extended release preparations of the medication. For example, starting a patient on escitalopram 5 mg instead of 10 mg might help reduce the risk of nausea. Another simple change could be the timing of medication administration. Taking the medication after a meal may be helpful. Many patients find that food helps reduce the nausea and most of these medications can be taken with or without food. 

Ginger Is Good

If the above interventions fail to help you can consider ginger root. This dietary supplement can be purchased over the counter from your local health food store. Ginger root 550 mg one to two capsules up to three times per day if the slow titration and other intervention are ineffective. 

If All Else Fails

Finally, if the nausea does not respond to the above interventions then anti-nausea medications are appropriate. The two most commonly used at ondansetron and Mirtazapine which also blocks 5HT-3 receptors leading to reduced nausea. 

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