The Universe of Anxiolytics: Which One Might Help Me Best?

– I’ve been diagnosed with anxiety. Which is the best anxiolytic?

+ Let’s take it easy and start from the beginning.

– And what is the beginning?

+ Well, even from the Bible, the beginning is always the word: «anxiolytic» literally means something that calms anxiety. However, nowadays, we use many different medications from various pharmacological groups.

– Are there that many?

+ Yes, quite a few. Antidepressants like sertraline or escitalopram; antipsychotics, such as olanzapine or quetiapine; antihistamines (hydroxyzine); antiepileptics (pregabalin, gabapentin); beta-blockers (propranolol); and finally, what most people understand by anxiolytics without any qualifier, though they are also known as hypnotic-sedatives, are benzodiazepines (alprazolam, lorazepam, diazepam). For historical interest, although they are no longer used for anxiety but are still beloved by the media, let me mention the barbiturates.

– Wow, that’s a lot of names. You doctors must be something special to be able to remember all these terms.

+ And pronounce them without biting our tongues, yes 😉

– Could you explain to me how medications are named, since we’re on the topic of words?

+ Very briefly. When a drug is in the development phase, and it’s not yet known whether it will be useful or not, it’s given a “code name,” consisting of letters and numbers, such as UK-92,480. Once its efficacy is confirmed, it receives a name related to its chemical structure and the family it belongs to (let’s imagine lormetazepam): this name is the “generic” or “international nonproprietary name,” by which it will be known worldwide, with slight variations depending on the language. Finally, when the company markets it, it assigns a brand name made up by the marketing department or based on some of its characteristics (e.g., Atarax – hydroxyzine – an antihistamine with anxiolytic properties, from the Greek ataraxia, meaning imperturbability, serenity). I should also point out that the brand names I’ll be using here are for educational purposes only and do not reflect any commercial interest (I have no ties to the pharmaceutical industry).

– I understand now. Back to my initial question, out of all those options, which is the best for anxiety?

+ That will depend on many factors.

– Such as…

+ The first and probably most important is the type of clinical presentation. I’d also like to remind you that psychotherapy is the most appropriate treatment for mild anxiety disorders and should be combined with pharmacological treatment for moderate cases.

– So, not everyone with anxiety should take medication, right?

+ Exactly. You might not even need to do anything at all—remember that anxiety is an innate emotion (we are born with it) and can even be adaptive. For instance, normal anxiety the first day at a new job pushes us to do better. However, when it’s so exaggerated that it paralyzes us or has very negative consequences on life, leading to unnecessary suffering, it obviously needs to be treated.

– So, which is the best medication? Antidepressants, despite their name?

+ Probably yes. Nowadays, most anxiety disorders are treated with antidepressants. Regarding specific diagnoses, panic disorder (with or without agoraphobia), social anxiety disorder, and generalized anxiety disorder, the most common ones, have antidepressants as their first line of treatment.

– Without being depressed at all? Isn’t it that most cases involve a mix of anxiety and depression?

+ There’s some truth to that. But even in pure anxiety, without any depressive component, antidepressants are the first-line treatment.

– Do all antidepressants work?

+ Almost all of them. The most notable exception is bupropion, which is not effective. The most commonly used nowadays are the well-known SSRIs (selective serotonin reuptake inhibitors), and among these, current guidelines recommend sertraline as the first option. Other widely used ones include escitalopram, fluoxetine, and paroxetine.

– So, I just take a pill, and my anxiety will go away forever?

+ Well, magic belongs to others, unfortunately. Antidepressants work differently: you need to take the treatment every day, and gradually, the anxiety will decrease. Also, it’s not uncommon for it to get worse at the beginning.

– How gradually? How long does it take for the antidepressant to work?

+ Here, I’m afraid, you need to be a “patient” patient. In all cases, we’re talking about weeks to achieve full remission, and although there is considerable interindividual variability, a minimum of about 2 weeks is required to see effects.

– But if I’m feeling really bad, how do I survive that time until the antidepressant kicks in?

+ That’s where the other groups I mentioned come into play. Let’s start with the main one, benzodiazepines—benzos for short. They are pure anxiolytics (meaning they are not antidepressants), but they also have other actions, the most well-known being that they are good muscle relaxants, hypnotics (sleep-inducing, making you sleep), and even antiepileptics. They take effect immediately, last for hours, and then are eliminated, but…

– If they’re so good, that “but” must be the size of a mammoth.

+ BUT, as I said, they make you sleepy (which is bad if we intend to take them during the day and lead a normal life), slow you down, decrease reflexes and balance, impair memory while under their effects, are lethal in overdose, have potential for abuse and addiction, and can be diverted for illicit purposes as well.

– So they’re terrible! How can they be among the best-selling medications?

+ Because they’re truly effective for their intended purpose, which is to eliminate anxiety, and when used properly, they are extremely useful. The most well-known include bromazepam (the famous Lexatin, as in the popular expression “Lexatin omelette”), lorazepam (Orfidal), and alprazolam (one of the strongest benzodiazepines, with a brand name in Spain that alludes to its action, Trankimazin -it’s known as Xanax in US, nice name anyway).

– How should they be taken?

+ Exactly as prescribed by the doctor… to avoid the risks we mentioned earlier. With this medication, it’s especially important to follow the prescribed regimen and inform your healthcare provider if you deviate from it. In panic disorder, for example, benzodiazepines are often used initially along with the antidepressant to cover the time it takes for the latter to start working, and then they are tapered off within weeks.

– What happens when they are prescribed “SOS”?

+ It’s also called “as needed,” “rescue,” “PRN” or “if necessary.” It’s a very useful way to take benzodiazepines. It means they are not scheduled, not taken daily or anything close to that, but only when the person feels they can’t control the anxiety or are in the middle of a crisis. Often, just carrying around the pill is enough to provide reassurance and avoid taking it, almost like a talisman. To draw an analogy, it’s similar to having paracetamol at home. Not every time we have a headache do we take it; we know that sometimes just sleeping or doing something entertaining will make it go away, but if we need it, it’s there, and that’s enough.

– Which one is the best then?

+ There isn’t really a best or worst. They differ in terms of the speed of action, strength (the amount needed to exert its effect), duration of effect, probability of “rebound” anxiety, metabolism… depending on what you’re looking for, you’ll choose the appropriate compound.

– And the other types of drugs you mentioned?

+ Some antihistamines (first generation, which cross into the brain) produce a non-specific “sedation” and a sense of calm: the most commonly used is hydroxyzine. Certain antipsychotics (mainly olanzapine and quetiapine) are also used for their sedative effects, as well as antiepileptics called gabapentinoids, pregabalin, and gabapentin, which share with benzodiazepines their action in favor of the calming neurotransmitter, gamma-aminobutyric acid (GABA). All of these are certainly useful, especially when, for some reason, we want to avoid using benzodiazepines. The most common reason being the risk of addiction.

– Without having a crystal ball, how do you know if someone is going to become addicted to benzos?

+ Indeed, we can’t know for sure, but remember that the best predictor of future behavior is past behavior: someone with a history of substance use is likely to have problems. This is especially true with alcohol: the combination of alcohol and benzodiazepines is one of the most dangerous in my field.

– Are the other drugs better and safer than benzodiazepines?

+ The other drugs also have their own side effects and issues; no medication is free of them. Even water itself is dangerous in excess. But they certainly offer several advantages, especially in terms of their zero potential for addiction and misuse.

– You haven’t mentioned that other drug with the difficult name, propranolol.

+ Propranolol, and a few others in its group, the beta-blockers, are indicated for a very specific form of anxiety, “performance anxiety.” In certain circles, it’s known as the “exam pill,” and it’s also very popular among those giving a lecture or, more modernly, a presentation.

– How does it work?

+ It’s the only one of all the medications we’ve discussed that doesn’t cross the blood-brain barrier, meaning it doesn’t reach the brain. Its action is to reduce all the “peripheral” anxiety symptoms, i.e., those related to the body rather than the mind: tachycardia, sweating, tremors, dry mouth… and in this way, we convince ourselves that we’re not anxious. It’s ideal for oral exams, theatre actors, and all those situations where the sedative effects of other drugs are not desirable. Obviously, antidepressants don’t sedate either, but as we said at the beginning, they’re not effective in the moment.

– We’ve really covered pharmacology. Any final message?

+ The usual: listen to your doctor and trust Sinews, we’re here to help.

– Wait, I almost forgot, what about herbal remedies? That trendy one with the difficult name?

+ Phytotherapy is probably better left for another day; it’s getting late today.

Alicia Fraile is a psychiatrist at SINEWS with more than 20 years of experience in general clinical psychiatry. She has worked in brain damage, Mental Health Centers, occupational psychiatry, work accidents and their repercussion in psychiatry (post-traumatic stress disorder, adaptive disorders), patients with chronic health problems and of course with the most frequent pictures of our field: anxiety, depression, insomnia, obsessive-compulsive disorder.