It never ceases to astonish me when I encounter a young patient who has been prescribed 2 mg of alprazolam daily for years under the guise of treating an “anxiety disorder.” The situation becomes even more concerning when they’re simultaneously taking 30 mg of Adderall. Discussing the risks of long-term benzodiazepine use or proposing an evidence-based tapering plan over 6–12 months often elicits a defensive or negative reaction. However, I make it a point to emphasize that my approach is rooted in evidence and science, which do not support the long-term use of benzodiazepines for anxiety disorders. As clinicians, we have a responsibility to address this widespread prescribing practice, educate patients about the associated risks, and prioritize safer, evidence-based treatments.
RCT Evidence
Duration of Trials:
Most RCTs investigating BZDs in anxiety disorders are short-term, typically lasting 4–12 weeks. Very few extend beyond 6 months, leading to a scarcity of long-term controlled data.
Efficacy:
BZDs, such as diazepam, alprazolam, and clonazepam, are effective in the short term for managing anxiety symptoms in generalized anxiety disorder (GAD), panic disorder (PD), and social anxiety disorder (SAD).
Studies often show comparable short-term efficacy between BZDs and SSRIs or SNRIs, though BZDs act faster.
Tapering and Relapse:
Long-term RCTs involving tapering strategies suggest that discontinuation often leads to relapse of anxiety symptoms, which can complicate the interpretation of their role in maintaining anxiety control versus masking symptoms.
Some studies (e.g., long-term diazepam use in GAD) found sustained symptom relief in individuals maintained on the medication compared to those tapered off, but these are limited and subject to biases such as withdrawal effects.
Combination with Other Treatments:
Some RCTs have explored BZDs as adjunctive therapy, particularly during the initiation of antidepressants, to mitigate early anxiety exacerbation. Long-term data, however, are sparse, and most combination studies focus on the acute phase.
Concerns with Long-Term Use:
Tolerance and Dependence:
Long-term BZD use is associated with tolerance (requiring higher doses for the same effect) and dependence, with withdrawal symptoms often mimicking anxiety.
This complicates distinguishing between anxiety relapse and withdrawal during tapering in long-term trials.
Cognitive Effects:
Chronic BZD use is linked to potential cognitive impairment, particularly in attention and memory, which may persist even after discontinuation.
Risk of Misuse:
Prolonged use carries a risk of misuse, particularly in populations with comorbid substance use disorders.
Lack of Evidence-Based Guidelines:
While short-term efficacy is well-documented, there is insufficient RCT evidence to strongly support long-term BZD use as a monotherapy for anxiety disorders.
Clinical Implications:
Indications for Long-Term Use:
Long-term use may be justified in select patients, such as those who fail other treatments, have contraindications to antidepressants, or require intermittent use for episodic anxiety (e.g., situational SAD).
Guidelines and Best Practices:
Professional guidelines typically recommend using BZDs as a short-term bridge or for situational anxietywhile prioritizing SSRIs, SNRIs, or CBT for long-term management.
If BZDs are used long-term, clinicians should aim for the lowest effective dose, regularly reassess the risk-benefit ratio, and educate patients about dependence.
Anxiety is a very real and powerful force that can take a toll on both your mind and body. In today’s fast-paced world, it’s easy to feel trapped in an anxiety prison, with stressors constantly surrounding us. The weight of it all can be overwhelming, leaving you exhausted mentally and physically. Remember, you’re not alone in this struggle. Take moments for self-care, reach out for support, and know that breaking free from anxiety’s grip is possible. Small steps can lead to big changes.
Anxiety manifests in many ways, and one of the most dangerous is when it turns into anger. Imagine living on edge all day—from the moment you wake up until you finally get home. The constant tension builds as you’re stuck in traffic, stressed at work, and juggling a million thoughts. By the time you walk in the door, your emotional reserves are empty. A simple spilled drink can set you off, leading to an outburst your partner doesn’t understand. It seems small, but the anxiety has been simmering all day, and that moment was its breaking point.
How can we prevent ourselves from reaching this boiling point?
Here are some practical tips to stop anxiety in its tracks:
Grounding Techniques
5-4-3-2-1 Exercise: Focus on 5 things you can see, 4 you can touch, 3 you can hear, 2 you can smell, and 1 you can taste. Bring your mind back to the present moment.
Use Your Senses: Engage with something textured, calming sounds, or soothing scents like lavender.
Deep Breathing
Box Breathing: Inhale for 4 seconds, hold for 4, exhale for 4, pause for 4. Repeat until you feel more grounded.
Diaphragmatic Breathing: Breathe deeply into your diaphragm to activate relaxation.
Mindfulness and Meditation
Focus on the Now: Anxiety often pulls us into future worries. Mindfulness can help center you in the present.
Body Scan: Consciously relax your muscles, releasing any tension.
Positive Self-Talk
Challenge anxious thoughts and replace them with calming affirmations like “I can handle this” or “This feeling will pass.”
Physical Activity
A short walk, yoga, or stretching releases endorphins, naturally easing anxiety.
Progressive Muscle Relaxation
Tense and release muscle groups, starting from your toes up to your head, to calm both body and mind.
Cold Water Splash
Splash your face with cold water or use an ice pack on your neck to stimulate your vagus nerve, which helps slow your heart rate.
Limit Caffeine and Sugar
These can worsen anxiety. Switch to decaf or water when you’re feeling on edge.
Visualization
Picture a peaceful place in your mind. Close your eyes and immerse yourself in the calming details.
Talk to Someone
Reach out to a friend, partner, or therapist. Sometimes simply sharing what you’re feeling makes all the difference.
By implementing these strategies, we can manage anxiety before it escalates into something harmful. You deserve peace—and taking these steps can help you find it.
This reminds me a lot of the depression question. Patients often tell me, “Dr. Rossi, you don’t know what it’s like to be anxious.”
I usually have a quiet chuckle to myself because anxiety is something everyone experiences. It’s a natural part of life. We all have areas where we feel competent, and others where we feel out of our depth. It’s in those areas, the places where we feel uncertain or inadequate, that anxiety can really interfere with our ability to function.
My most challenging personal experience with anxiety happened during the infamous 4th term of medical school at St. George’s University. By this point, you’ve survived the first year and are well into the second. However, this term is notorious, and it often feels like the school uses it to weed out students—which, in my opinion, is a bit unethical. The structure of my routine completely changed. More requirements, longer lab hours, and less time to study. The familiar rhythm I had relied on to keep up was suddenly turned on its head.
Throughout that term, I was constantly on edge, overwhelmed by the pressure that all my hard work could slip away at any moment. I still vividly remember the first time I experienced a panic attack. It was early morning; I woke up drenched in sweat, my heart racing, and I couldn’t catch my breath. I was scared enough to go to the university clinic, and that’s when I found out it was a panic attack.
That experience taught me firsthand what anxiety truly feels like. It’s not just a fleeting worry—it can become physical, paralyzing, and all-consuming. When I talk to patients about anxiety, it’s from a place of understanding. Anxiety doesn’t discriminate, and it certainly doesn’t mean we’re incapable—just human.
When treating anxious depression, SSRIs and SNRIs may not always provide sufficient relief. In such cases, I consider adding medications like quetiapine, which has a significant effect size for generalized anxiety disorder (GAD) and is FDA-approved as an augmentation strategy for depression at doses of 150–300 mg. However, due to its side effect profile, it’s advisable to limit the duration of quetiapine use when possible.
The tried-and-true approach of recommending Cognitive Behavioral Therapy (CBT) along with a serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) doesn’t work for everyone. So, what are the alternatives? One often-overlooked option is hydroxyzine, which has effect sizes (0.4–0.5) similar to benzodiazepines but with a lower risk, particularly in older adults. For those seeking natural remedies, Silexan, available over the counter, is another possibility. Other medications that have shown efficacy in treatment-resistant depression include pregabalin, quetiapine, and eszopiclone. When it comes to social anxiety disorder, I’m a bit old-fashioned but still favor MAOIs in this area.
As many might know there is a new Netflix documentary called Take Your Pills: Xanax and it combines interview footage from physicians, patients, and journalists about anxiety and the use of Xanax. For the most part I thought there were a lot of reasonable discussions about anxiety, its treatment, and the role of medication. I feel like this is an appropriate way to cap off our recent discussions about anxiety disorders and treatment.
Fear and Anxiety: Are They the Same Thing?
The documentary made it seem like anxiety and fear are the same thing and that the exact same neurobiology is involved in each case. I think about anxiety and fear as two separate things that require different approaches.
Anxiety is what an individual feels when they are worried about something that could potentially happen in the future. If you watched my other videos on generalized anxiety disorder (GAD) then you know the Diagnostic and statistical manual (DSM) has made excessive worry the hallmark of GAD.
Fear is a core emotion along with sadness, anger, joy, excitement, and disgust. It’s different than anxiety, which is a fear of some future event happening. Fear is triggered in the moment. When you see that bear walking on the hiking trail or hear the rattle of a snake the fear centers of our brain are activated immediately in that moment. It’s not that we are obsessing about some future outcome, there is something present in the environment that is threatening and demands immediate action.
The Fear Center of The Brain
In humans the fear center of the brain is called the amygdala which stands for almond and that’s because they taste like almonds. No, wait that isn’t right, it’s because they are shaped like an almond. The amygdala is what fires when you see that bear in the woods. This triggers the fight or flight response which leads to things like increase blood flow to the muscles, and increased energy. It prepares the body to run away or fight if necessary.
Benzodiazepines MOA
Benzodiazepines enhance GABA activity by acting as allosteric modulators of the GABA-A receptors. This is the major inhibitory neurotransmitter in the body, and it acts to dampen everything down. Benzodiazepines increase the frequency of opening of chloride ion channels which in turn inhibits the cell and prevents the neuron from firing.
Anxiety Is a Part of Life
As I’ve said before we all have anxiety under certain circumstances. It’s not always a bad thing to have anxiety. In many ways anxiety reminds us that this situation is important, and we need to be appropriately prepared. A healthy amount of anxiety is a good thing overall.
Things go sideways when the anxiety is chronic, persistent, and severe. As I’ve stated in the previous videos some people are just more prone to anxiety. These individuals are high in the big 5 personality trait of neuroticism. While most of us will fall somewhere in the middle there will be outliers on either side with some having significantly less anxiety and others having significantly more.
The one thing that made this documentary hard to follow is that they combined all the anxiety disorders together, at one point they were describing panic attacks, social anxiety, and GAD as if they are all part of the same disease process. While there is significant overlap, the course of illness, and treatment plans will vary greatly which is why proper diagnosis is so important.
Xanax Works great for Physical Symptoms of Panic Attacks
When the interviewees start talking about Xanax it’s in the context of people experiencing panic attack. This is an important distinction to note as most of the symptoms of panic attacks are physical and thus will have a greater response to benzodiazepines. If we are talking about GAD, or social anxiety the anxious thoughts will still be there, and the benzodiazepine may be less effective.
Why Temperament and Environment Deserves More Attention
Much of our baseline temperament is genetic and will be part of the story that determines if you will have more or less anxiety. The other part of the story is environment. The experiences we have matter a lot too. In child psychiatry, there has been this huge focus on minimizing adverse childhood events (ACES). We discovered that things like sexual abuse, physical abuse, and loss of a parent can result in significant risk for poor health outcomes in the future. Baseline temperament that predisposes someone to anxiety combined with significant lifetime trauma could set the table for a future anxiety disorder.
The Prevalence of Benzodiazepine Use
In this documentary they make it seem like benzodiazepine prescriptions have skyrocketed over the last several decades. These prescriptions have increased but we need to explore why. One thing I see all the time is primary care providers prescribing benzodiazepines for patients early in treatment for depression and anxiety. Before exploring psychotherapy or other medication options the person walks out with a Xanax prescription. There is a reason the research tells us most people who see a primary care provider for depression and anxiety do not get better. In fact, as few as 20% of those started on antidepressants by primary care will show significant clinical improvement. This is not a knock on primary care, it’s more that they have been thrown into a mental health crisis and are usually the first person to encounter a patient with anxiety.
The important trends I would like people to pay more attention to is the risk of prescribing opioids and benzodiazepines in combination. This can result in increased risk for overdose death and a significant risk for severe respiratory depression. In addiction treatment people often feel very anxious when stopping opioids and it’s common to want to address that anxiety as a doctor. What ends up happening is people are on medication treatment for opioid use disorder, a benzodiazepine for anxiety, and gabapentin for that little extra relief. All these medications in combination put the patient at risk for adverse outcomes. Another thing to pay attention to is where all the opioid prescriptions are coming from. The highest rates are in many southern states and in places like West Virginia where the opioid epidemic hit the hardest. The final item to discuss is the increased rates of benzodiazepine prescribing in the elderly. There seems to be an increase in benzodiazepine use in this population which is more dangerous due to the risk of falls, altered mental status, and possibly dementia.
There has been a lot of talk over the years about the increased risk of dementia associated with benzodiazepine use. There data has been mixed, but I would say it’s largely in favor of using caution when prescribing benzodiazepines in older populations and avoiding the long-term use of benzodiazepines in all populations.
Social Media and Anxiety
I think social media has done as much harm as it has good for people’s mental health. If you believe everything you see on social media, the impression is everyone you know, or follow is winning, and you are losing. In the past you only had to compare your life to people in your community. Now, we get to compare our lives to the world. Not only are we comparing our lives to large pool of people, but we are also comparing them to people who have created online personas under false pretenses. These are individuals rent house for photo shoots to make you believe that is where they live, or people taking steroids then asking you to buy some supplement that does not provide the results it promises. We all like to think we are immune to these types of schemes, but we are not. In our minds we are comparing our worst moments to other people’s best moments and assuming that this is reality. This is clearly a recipe for anxiety and depression.
Dangerous Coping Strategies for Anxiety
I do not think using alcohol or drugs to alter one’s state of consciousness is exclusive to the past. People have been doing this forever, and it remains a poor way to cope with anxiety. I think one of our problems is attempting to cure the stresses of life. In my practice I do not believe that taking a medication or using alcohol are ways to “cure” anxiety. Most individuals need to take a long hard look at their life and see where the anxiety is coming from and where life changes can be implemented to reduce the tension. When someone takes time to systematically dissect the cause of their anxiety, they often already know what they should do. Take more time off work, practice better self-care, exercise, eat healthy, and sleep better these examples all come to mind for most patients. Most people feel trapped and do not believe they can carve out the time to do these things and that is part of the reason they turn to medication or drugs/alcohol to cope.
While I still believe benzodiazepines can be useful in the right context, they are designed to be used short term. I set limits with my patients early in the process letting them know up front that we are not using this as a long-term solution for their anxiety.
Potential Side Effects of Benzodiazepine use
They did a nice job of describing the changes in memory that occur because of benzodiazepine use. The ability to laydown new memories is impaired when using benzodiazepines that is why I caution anyone with PTSD who is in trauma-based psychotherapy to avoid the use of benzodiazepines. They also focused on the disinhibition caused by increased GABA-A activity. This is less a side effect and more a response that should be expected from the medication. Most individuals with anxiety are wound too tight and have trouble relaxing. The problem with this response occurs when that disinhibition is excessive resulting in embarrassment or inability to work for example.
Withdrawal from these medications can be deadly. There is risk for seizure, rebound anxiety, rebound insomnia all of which can be very distressing. The problem with benzodiazepine withdrawal is the variability in terms of patient’s tolerance to dose reductions. Some patients can tapper off very quickly and have no issue, others need to be tapered slowly over months to years. While I would say it’s rare to have someone who is very sensitive to dose adjustments it can happen and tapering slowly while watching for withdrawal symptoms is important. The example of the guy pipetting a liquid microdose of alprazolam would not be a normal situation, and if you just watch this documentary, you may think everyone who tries to come off these medications must go through a similar process. Benzodiazepines can be safely reduced under the guidance of doctor.
Conclusion
What we see in the end is more of the same recommendations most of my patients would tell “doc I already know this.” They talked about using complementary and alternative medicine which I am a big fan of, diet, exercise, mindfulness, and psychotherapy to find the underlying causes of the excessive worry. They introduce the idea at the end that the world is broken and defective and we should not have to accept the world as it is. This is fine but significant change on a massive scale takes time and it still leaves people asking the question “what do I do right now.” I’m personally active in advocacy work at the local and state level, which is one approach, but it takes a lot of time and resources to affect policy changes and not every patient will have the time or desire to engage in such activities. The only true way out of anxiety is through it. Daily life is painful, and we need to accept that to some degree. Medicating away feelings that are part of life is certainly not the solution and can be the reason we find ourselves in trouble.
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.
