Anxiety disorders are the most common class of psychiatric disorders. Their US prevalence is about 20%. They’re also among the least recognized and least treated. We have sort of finally beaten into people’s thick skulls that depression isn’t just being sad, and you can’t just turn your frown upside down or something – but the most common response to anxiety disorders is still “Anxiety? So what, everyone gets that sometimes.”

But it’s hard to describe how disabling anxiety can be. A lot of people with nominally much worse conditions – depression, bipolar, even psychosis – will insist that they want their anxiety treated before anything else, because they can live with the rest. On the other hand, while a lot of people with psychosis have enough other problems that treating the psychosis barely puts a dent in their issues, a lot of people with anxiety would be happy and productive if they could just do something about it.

Since I’ve gotten some positive comments on my discussion of depression treatments I thought I’d go through some of the things I’ve seen used to treat anxiety. I’ll include the same disclaimer:

This will be inferior to reading official suggestions, but you will probably not read official suggestions, and you may read this. All opinions here are my own, they are not endorsed by the hospital I work at, they do not constitute medical advice, I have a known habit of being too intrigued by extremely weird experimental ideas for my own good, and you read this at your own risk. I am still a resident (new doctor) and my knowledge is still very slim compared to more experienced professionals. Overall this is more of a starting point for your own research rather than something I would expect people to have good results following exactly as written.

I’ll mostly be talking about what’s called generalized anxiety disorder, with some applicability to panic disorder. Social anxiety, specific phobias, et cetera are their own thing, as is anxiety secondary to other illnesses – but some of the advice may cross over. I’m not going to get too into diagnosis, because generalized anxiety disorder is pretty much exactly what you think it is and a lot (though not all) of this will be applicable for subclinical anxiety as well.

I. Diet And Lifestyle

You didn’t think you were going to get out of this part, did you?

Pretty much every study – epidemiological or experimental, short-term or long-term, has shown that exercise decreases anxiety. The effect seems limited to aerobic exercise like walking, running or swimming, preferably for longer than twenty minutes. Various mechanisms have been postulated including norepinephrine, endogenous opioids, and decreased inflammation.

There’s less agreement on diet. The people who hate fat says high-fat diets cause anxiety. The people who hate carbs say high-carb diets cause anxiety. The people who hate processed food say processed foods cause anxiety. The people who recommend fish oil for everything say insufficient fish oil causes anxiety. None of it seems super credible, but Mayo Clinic has some suitably bland advice.

The one very important connection – if you drink too much coffee, or any other source of caffeine, that will make you anxious. I once had a patient come to me with severe recurrent anxiety. I asked her how much coffee she drank, and she said about twenty cups per day. Suffice it to say this was not a Dr. House-caliber medical mystery.

Also needless to say: get enough sleep. Seriously. Get enough sleep.

Many people find that various breathing exercises or other sorts of mindfulness activities can be helpful in the short term and sometimes build skills useful for the long term. My hospital gives people these handouts on breathing techniques and progressive muscle relaxation. I’ve made fun of HeartMath in the past, but I only learned about them because many people find some success, probably placebo-ish, with their quick coherence technique. If you’re an overachiever and want to get really into this sort of stuff, people always say good things about yoga and especially pranayama breathing. Studies seem to back this up (1, 2, 3) though you’ve got to be careful to weed out the studies by very religious Hindus trying to prove they’ve been right all along.

Meditation has similarly positive results. Here’s a study showing that an intervention to teach patients meditation resulted in decreased anxiety with p < 0.001 even three years later. Here's a meta-analysis of 39 studies finding an effect size of about 0.6 (medium) in the general population, and an effect size of about 1.0 (large) in people with anxiety disorders. But here’s an equal and opposite review that found only “equivocal” results. As far as I can tell, most people investigating meditation think it works pretty well. The meditation techniques that seem to work best are mindfulness meditation and transcendental meditation. You can learn a little about mindfulness meditation here. In order to learn about Transcendental Meditation, send a check made out for $5000 to Maharishi Mahesh Yogi, PO Box….

II. Therapy

Cognitive-behavioral therapy works okay for anxiety just like it works okay for everything else. The Big Graph O’ Effect Sizes says that psychotherapy on average has an effect size of 0.51 in generalized anxiety, compared to medication’s 0.31. This shouldn’t be taken too seriously – the confidence intervals overlap and there’s a wide range of efficacy for different medications – but you won’t be doing any worse by going for the therapy first. Even the Cochrane Review, famous for never drawing any conclusion other than “more research is needed”, is tentatively willing to say that psychotherapy works for anxiety disorders. Their study trends towards finding that cognitive behavioral therapy works better than supportive therapy, but is unable to prove significance – apparently more research is needed.

Exposure therapy can also be useful for panic attacks or specific phobias. This is where they expose you to the thing you’re scared of (or deliberately initiate a panic attack) and keep doing it until you stop being scared and start being bored. According to a bunch of studies it works neither better nor worse than cognitive-behvioral therapy for most things, but my unsupported impression has always been that it’s better at least for panic disorder. Cognitive-behavioral therapy seems clearly superior for social phobia.

You can get psychotherapy from any qualified psychotherapist, a category including counselors, social workers, psychologists, and sometimes psychiatrists. Ones who use “a school” (for example, describe themselves as practicing cognitive behavioral therapy) are usually considered better than those who don’t (“Oh, I do a little of everything with every patient”). If you can’t find (or don’t want to find) a good therapist, there is preliminary evidence that a good self-help therapy workbook (“bibliotherapy”) is about as good as real therapy – including for anxiety (study, other study, yet another study).

I have no special insight into which self-help workbooks are any good, but The Cognitive Behavioral Workbook for Anxiety: A Step-By-Step Program seems to get pretty good ratings.

III. Medications

To be tried after diet and lifestyle interventions when possible.

Medication can work either instead of or in addition to therapy. There are at least seven categories of commonly used conventional anxiety medications: SSRIs, SNRIs, antihistamines, antipsychotics, anticonvulsants, benzodiazepines, and azapirones. These can be divided into mostly-acute (antihistamines and benzos) and mostly-long-term (SSRIs, SNRIs, anticonvulsants, azathioprines), with antipsychotics kind of being a tossup. Depending on whether you just need to get through the occasional panic attack or whether you’re in a chronic unremitting anxiety state, you might want one, the other, or both.

You probably know antihistamines (example: Benadryl) from the many common over-the-counter members of this class. They have some mild short-term anti-anxiety effects. Benadryl will work in a pinch if you need something without a prescription, but the most commonly used anxiolytic antihistamine is hydroxyzine (“Vistaril”, “Atarax”), which is a bit more powerful and less likely to make you fall asleep. As far as anxiolytics go it’s pretty safe as long as it doesn’t make you too sleepy. If you just need something to take the edge off the occasional anxiety attack, this works fine.

Benzodiazepines (examples: Xanax, Ativan, Valium, Klonopin) are very effective in the short-term but also very controversial. In some people they are very habit-forming and can produce a picture very similar to addiction to alcohol (which they chemically resemble). Keep in mind how bad an idea it might be to become extremely addicted to prescription pills that you may suddenly lose access to depending on how your doctor is feeling (you might expect doctors would take the difficulty of coming off these drugs into account, but you might expect a lot of things from doctors that don’t always happen). Studies suggest benzodiazepines can sometimes build tolerance, and that after a month or two of frequent use, they lose their positive effect and you need them just to feel normal. That having been said, a subset of patients – and I can’t tell at this point if it’s a majority or a minority – go on benzodiazepines, do very well, stay on them for long periods without getting dependent, and never have anxiety again. It’s kind of a crapshoot. The most generally recognized “safe” use of benzos is the occasional Xanax to deal with rare but very stressful situations (for example, flying on an airplane if you’re scared of heights). Other people say Klonopin is safer than some of the others and that it’s worth a shot as long as you realize that “Klonopin dose gradually creeping upwards” is a sign that you’re getting into a bad place and need to react immediately. Most people recommend trying other things first before you come here, but once you’ve exhausted other options these can be a powerful last resort.

SSRIs (examples: Prozac, Celexa, Lexapro, Zoloft) are the mainstay of chronic anxiety treatment just like they’re the mainstay of chronic everything-else treatment. As usual, they have real but modest effects after about a month or so, more in some people and less in others. As usual, if one SSRI doesn’t work for you, you might want to try another. These are pretty safe aside from the sexual side effects. Some people get mild withdrawals if they go off these too quickly, so don’t do that. A lot of people use both an SSRI for chronic treatment, plus either an antihistamine or benzo for “break-through” anxiety.

SNRIs (examples: Effexor, Cymbalta) are like SSRIs, but for two neurotransmitters instead of one. This is supposed to make them a little bit more effective. Maybe they are, maybe they aren’t. Fewer sexual problems than SSRIs, but worse discontinuation syndrome. They’re a good second-line chronic medication if SSRIs don’t work. Effexor is probably the best.

Azapirones (example: BuSpar) is, unusually, a rare drug which is specifically targeted at anxiety, rather than a being a repurposed antidepressant or something. BuSpar is very safe, not at all addictive, and rarely works. Every so often somebody comes out with a very cheerful study saying something like “Buspar just as effective as benzodiazepines if given correctly!” and everybody laughs hysterically and goes back to never thinking about it.

Anticonvulsants (examples: Depakote, Neurontin, Tegretol, Lyrica) are seizure medications that sometimes sort of work for anxiety. Most of them have strong side effects and limited utility. The exception is Lyrica (pregabalin), which is pretty new but has shown excellent safety and efficacy in studies. It doesn’t have an FDA indication for anxiety and it’s pretty expensive, so you might have a hard time getting it, but it is at least a well-kept secret.

Atypical antipsychotics (examples: Seroquel, Zyprexa, Abilify, Geodon) are, as always, overused. Most of them either make you gain lots of weight, put you at increased risk for heart rhythm problems, make you feel terrible, put you at risk of permanent movement disorders, or all of the above. They do often treat anxiety, sometimes very well, and psychiatrists like them because they’re good all-purpose no-nonsense drugs with big advertising budgets, but unless you’re also psychotic consider trying some other things first before you try these.

An article in Journal of Psychopharmacology tries to compare the efficacy of all of these classes of drugs and gets the following effect sizes (bigger number = bigger effect):

Pregabalin: 0.5

Antihistamine: 0.45

SNRI: 0.42

Benzo: 0.38

SSRI: 0.36

Azapirone: 0.17

Alternative medicine: -0.31

(remember, other studies suggest psychotherapy is around 0.5)

I heavily challenge the claim that antihistamines are more effect than (or anywhere near as effective as) benzos. I don’t know the confidence intervals on these numbers, so I would suggest reading it as “Everything is about equally effective, except azapirones which aren’t as good”. Their “alternative medicine” category was mostly kava and homeopathy, and I have no idea why it came out negative (kava’s pretty good, and homeopathy shouldn’t separate from 0).

There are also some less commonly used drugs that might help people who don’t respond to any of these.

As usual, MAOIs are very effective, moderately dangerous, and super hard to get. They seem to work especially well for panic disorder and social anxiety.

Clonidine is a medication usually used to control blood pressure. It’s somewhat effective against anxiety and some people think it should be used more. But it can cause you to become too sedated (abnormally low heart rate) and in some people it makes anxiety worse for some reason.

Beta-blockers (example: propranalol) are another blood pressure medication. It is especially effective against somatic symptoms of anxiety – racing heartbeat, shaking, et cetera – and sometimes getting rid of those can make the anxiety go away entirely. It’s most famous for its use against performance anxiety: about a third of musicians use them in concerts, and I’ve heard similar rumors about public speakers, actors, et cetera. I used to think this was a little-known piece of trivia, but whenever I bring it up to doctors (“Hey, did you know some people use beta-blockers for performance anxiety”) the usual response is “Oh, yeah, I prescribe myself some of that when I have to give a presentation at grand rounds.” They don’t seem quite as good for longer-term anxiety disorders, though some people have had good results with them.

I once saw an excellent psychiatrist whom I deeply respect try everything on a patient with severe treatment-resistant anxiety with no results whatsoever until finally he came to Thorazine. This treated the patient’s anxiety pretty well, at the cost of provoking quite a bit of anxiety in the doctor.

Without meaning to give medical advice, and with the caveat that you should ask your doctor for their opinion – one good pharmacological treatment algorithm for anxiety disorders is:

If you just have occasional outbursts that bother you, take occasional doses of hydroxyzine.

If you have a longer-term problem, start with an SSRI. If that doesn’t work, either try more SSRIs and SNRIs, or go to Lyrica. You might as well be on BuSpar somewhere in the process too. If none of that works, choose your poison (or have it chosen for you) among MAOIs, benzos, clonidine, or antipsychotics.

IV. Alternative Treatments

To be used out of curiosity or desperation only – you have other options and these are not guaranteed safe or effective.

Massage therapy, acupuncture, aromatherapy, and everything else in the category of “unnecessarily medicalized relaxing thing” all perform very well as long as you don’t look too hard for a suitable control group. Yes, these are probably placebo, but they’re very effective placebos and if they both work I would rather take a placebo than an antipsychotic.

Inositol and l-theanine are both found in small quantities in the diet (inositol in some vegetables, theanine in tea) and supplementing them has been inconsistently found to help with anxiety. Inositol had some preliminary evidence for effectiveness in panic disorder, but a more recent meta-analysis was unimpressive. I can only say that I have some anecdotal evidence of extremely positive reactions to inositol, but we all know what they say about anecdotal evidence. Keep in mind that the dose used in studies is way larger than the dose anyone will give you – usually corresponding to about 20 of those 500 mg inositol pills a day. This makes it expensive and inconvenient, and most people just compromise by taking so little inositol it shouldn’t possibly be able to have any effect. L-theanine also has a lot of small studies in support, although there’s some question on whether it works on its own or whether it just has useful synergistic effects with caffeine. Sun-theanine is generally considered the most effective form, and recommended dose is about 100 – 400 mg. Both these supplements are afaik very safe and a good option for people who want to test things that might or might not work but have minimal risk. Magnesium should also be in here somewhere.

GABA is the main inhibitory neurotransmitter in the nervous system, and a lot of these other interventions are attempts to convince the brain to release more GABA or potentiate the GABA that’s already released. Can we just cut out the middleman and ingest GABA pills directly? The supplement industry would like you to think so, and you can certainly buy them anywhere supplements are sold, but it’s generally believed that orally ingested GABA can’t cross the blood-brain barrier. The Russians have developed a modified version of GABA that doesn’t have this problem; called picamilon, it seems to be a pretty popular anxiety treatment on the other side of the Pharmacological Iron Curtain. It’s pretty easy to get as a non-prescription supplement here in the West. There are very few studies on it, the ones that exist are in Russian, and I have nothing to go on but a couple of anecdotal reports, most of which are positive (though I personally noticed no effects). But the mechanism of action is plausible, and the long history of successful Russian use at least suggests it probably won’t kill you immediately. Most common dosage seems to be about 100 – 300 mg.

The nootropics/supplement/nutraceutical community also suggest ashwagandha and bacopa for anxiety; various low-quality studies support the use of both (ashwagandha meta-analysis, bacopa study 1, bacopa study 2, bacopa study 3). Bacopa may take several months of frequent use before it starts working; I tried it briefly and had to stop because of gastrointestinal side effects, which are pretty common. There’s also some worry around heavy metal contamination. Swanson’s and Nootropic Depot’s are two that have third-party testing showing they’re uncontaminated.

Kava is a traditional drink from various Pacific islands with anxiolytic properties. Multiple meta-analyses including a Cochrane review find it to be an effective anxiety treatment, but its safety is in question after reports of several cases of liver failure caused by the plant. This may be yet another case of people exaggerating freakishly rare side effects; the risk has been estimated at less than one in a million doses (though remember that if you take it daily for ten years, that number bcomes 1/300). Others suggest a rate as low as one in a hundred million but this assumes zero underreporting; others challenge this assumption. Possibly it is only poorly prepared kava causes liver problems; for traditionally prepared kava, look for preparations that specify they are made from root/rhizome material only. The American Academy of Family Physicians recommends that:

Physicians who supervise patients taking kava for the treatment of GAD should take care to avoid the following: (1) high dosages (more than 300 mg per day); (2) combining kava with hepatoactive agents; (3) using non-root preparations; and (4) exposure for longer than 24 weeks. Use of WS1490 standardized kava extract is also recommended. If these safety precautions are followed, kava can be appropriate therapy for selected patients diagnosed with GAD

Don’t take kava if you have any liver problems, if you’re on any medications that might interact with it, or if you plan on drinking alcohol at the same time. Consider talking about it with your doctor first and getting plans to check liver enzymes regularly.

Selank is an experimental Russian anti-anxiety medication going through their version of clinical trials. It’s a bit high-maintenance – you have to keep it refrigerated or else it decays, and the only two functional means of administration are injection or nasal spray – but anecdotal evidence is extraordinarily positive. No side effects have been found thus far, but needless to say by the time you get to “injecting experimental Russian medications into yourself” we have left the point where we can entirely guarantee this is a good idea. Ceretropic sells a nasal spray version, which is probably more convenient than having to inject it.

Phenibut is another Russian anti-anxiety medication. It is potentially addictive and dangerous. I do not want to actively recommend against it, because it can be very useful if used infrequently and carefully. Discussing exactly how to use it infrequently and carefully is beyond the scope of this article. Please do not use this unless you have looked into it carefully and understand the risks and benefits.

Overall, the best evidence seems to be for l-theanine (especially if you drink coffee) and bacopa (especially if you’re willing to wait months for any effect), with picamilon also worth your time to try and Selank as an option for the very adventurous.

V. Conclusions

No treatment stands out as extremely effective, and the best route to dealing with anxiety probably depends on many factors like your amount of free time, your motivation, your access to medical care, and your willingness to put up with side effects. After you’ve fixed lifestyle issues, I think any of “self-help workbook”, “start SSRIs”, or “try l-theanine” are good first options. On the other hand, benzodiazepines, antipsychotics, and kava are all options I would hold off on until you’ve tried a couple of other things.

Like with the depression post, the most important conclusion you can take from this is that you have lots of options. Please don’t let people give you an SSRI and then give up. Work with your doctor. Anxiety actually has a pretty good prognosis if people work on it, but it can be a difficult and frustrating process. Just remember: there are lots of options.

PS: Relevant Onion