Ketamine’s Breakthrough Role in Treating Anxiety Disorders: A Paradigm Shift in Psychiatric Care

Anxiety is the most common mental health or emotional disorder, affecting about 25% of the population globally. (1) These are massive numbers. What is worrisome is that the number of people complaining about severe anxiety is rising. Though many medications might help manage the condition, most treatments are insufficient and unsatisfactory. Thus, the search for effective treatment continues. Breakthrough ketamine therapy now offers hope, providing quick and prolonged relief.

Emotional disorders like anxiety are more common in females. Most likely, female hormones make them prone to emotional disorders. (2)

Anxiety is not essentially a disorder. It is normal for people to worry and become anxious when facing some threat. However, it is a disorder when the worry is excessive and debilitating. Moreover, in those living with anxiety disorders, this excessive worry is often a perceived threat and not essentially a realistic threat – that is why it is called a disorder.

Fortunately, about half of the anxiety disorders are mild and benefit from lifestyle changes. However, half of all anxiety cases are moderate or severe, requiring regular medical treatment. But, due to a lack of awareness, about one-fourth of those living with moderate to severe anxiety only seek treatment. Another reason for not seeking treatment is that medical drugs often fail to help sufficiently and cause many side effects.

Signs and Symptoms of Anxiety

Anxiety is an emotional disorder that produces both physical and non-physical signs. If left untreated, it may harm health in multiple ways. Its signs and symptoms would also depend on the anxiety type. Anxiety occurs for different reasons in different people.

One of the most common anxiety types is generalized anxiety disorder (GAD). It causes restlessness, fatigue, difficulty concentrating, irritability, headaches, stomach aches, difficulty controlling worries, and sleep issues. These problems often occur for no apparent reason or even in the absence of any realistic threat. Quite often, these responses are to minor issues. (3)

Others might develop panic attacks with pounding heart, sweating, trembling, chest pain, and feeling down and out of control. Such attacks may occur several times a day.

Another common anxiety type is social anxiety. These people have a fear of being judged by others. So, they experience excessive sweating, blushing, pounding heart, and become excessively self-conscious. They often have trouble performing specific kinds of jobs. Further, their life suffers as they avoid gatherings, speaking in front of others, and more.

Yet, another anxiety type is phobias. This simply means excessive fear of something, like a spider, falling from heights, etc. As one can guess, such fears are normal to a certain degree. However, in those living with these conditions, such fears are excessive and debilitating.

Traditional Treatment Approaches

Before we explore one of the innovative approaches to managing the conditions, let’s explore how doctors generally treat anxiety. It is possible to overcome anxiety, but not in all the cases. One can only overcome the conditions through non-pharmacological means. Drugs can only help a bit by lowering the feeling of anxiousness and reducing panic attacks. Moreover, drugs work only as long as one keeps taking those pills. All this means that though overcoming anxiety is possible, it is challenging.

When it comes to treating anxiety, non-pharmacological means remain the treatment of choice. This is generally about teaching patients to counter their fears and overcome them. However, in reality, that is pretty challenging, even with the help of psychotherapists and medications. This is because rewiring the brain requires prolonged and persistent efforts.

Non-Pharmacological Approach

First-line anxiety treatment still remains non-pharmacological means. These methods can be quite effective for mild to moderate anxiety. This means learning about the condition, dietary changes, practicing mindfulness, exercising, and being assertive. (4)

Specialists and support groups can also help make behavior changes. Cognitive behavior therapy can help alter thinking patterns and responses to stress. Other ways to counter anxiety could be breathing exercises.

Medications to Manage Anxiety

Despite the best of the efforts, non-pharmacological approaches fail in most instances. It is quite challenging to control anxiety and fear, even if a person is aware of the issue. Hence, most moderate to severe patients need medical support.

The first-line treatment pharmacological treatment for the condition is using anti-depressants. These medications boost serotonin levels in the brain and have other benefits. However, anti-depressants act slowly and take weeks to start working. They are also highly toxic and cause numerous side effects. Sometimes, their side effects might be so severe that it may beat the purpose of prescribing these drugs. Moreover, these drugs are not known to cure the condition, and all they do is stabilize the mood a bit. (5)

Another group of drugs commonly used to manage anxiety is benzodiazepines. These drugs are known to be highly addictive and cause dependence and sedation. They mainly help by stabilizing mood, but sedation is a frequent issue. Another problem with these drugs is that patients develop a tolerance to these medications. Thus, doctors need to keep increasing their dosages. Simply said, they are quite toxic, and yet they only provide symptomatic relief and are not a cure for the condition. (5)

Of course, doctors might experiment with many other psychoactive compounds with unproven efficacy. Thus, they might prescribe antiseizure drugs, beta-blockers, melatonin-based medications, and other drugs. Most of these therapeutic options are not proven to work, though they might provide some symptomatic relief.

Issues with Traditional Anxiety Treatment

As one can see from the discussion above, there are a few issues with the traditional anxiety treatment approach. The treatment does not cure the condition; even worse, it fails to provide relief in many instances.

The second issue with most of those medications is that they are pretty unsafe and cause many side effects. Some of those medications are even addictive. A person can develop tolerance to most of those drugs, so even if they help initially, they stop helping at the later stages. Even worse, some of those medications may ultimately make the condition worse.

So, it would be right to say that though there are many medical drugs, they are not very effective and cause significant toxicity. Hence, there is a need to find an effective anxiety treatment urgently.

Introducing Innovative Treatment: Ketamine Therapy

One such emerging innovative treatment is ketamine therapy. It is a pretty old drug, which was introduced way back in the 1950s. It is an anesthetic and analgesic drug. However, due to its psychic effect, it is also a recreational drug. (6) Well, it means that it also has a potent impact on the working of the brain, and that is why researchers have recently started exploring its role in managing anxiety.

Interestingly, though the drug has been in use for so long, its mechanism of action is not fully understood yet. However, science knows that it mainly works by affecting the so-called NMDA receptors in the brain along with HCN1 receptors. However, now science shows that it also affects other pathways like the opioid system, cholinergic, and aminergic, which may explain its role in anxiety. (7)

There is a reason why ketamine therapy is becoming popular for managing emotional issues. It acts quickly and appears to provide prolonged relief. It can reset the brain and its emotional responses. Moreover, it also promotes brain rewiring. This means that when it is combined with psychotherapy, it makes patients more receptive, thus altering emotional responses. Hence, it provides hope for permanent or at least prolonged relief from the condition – that is why people are calling it breakthrough therapy for anxiety!

The good thing about ketamine therapy is that patients do not essentially need to take this medication daily. Instead, doctors would give it slow IV infusion in the clinic. One would, of course, need to stay in the clinic, as it causes some euphoria. However, once the person is at home, she feels much better without any drug therapy. Patients may need multiple sessions for optimal results. Researchers are also experimenting with ketamine maintenance therapy using other routes like sub-lingual tabs and nasal sprays.

Ketamine Therapy: Benefits, Efficacy & Scientific Evidence

So, as we have learned about what this therapy is, it is time to look into the clinical studies. As one can see, one of the good things about ketamine is that it has been in clinical use for a really long. It means that science has much understanding of its safety profile.

Before we further explore this topic, it is vital to understand that ketamine is a DEA Schedule III controlled substance. It is not readily available. It is a US FDA-approved anesthetics agent. Hence, its use for managing anxiety is still off-label. Therefore, one can only expect to get ketamine therapy in specialized clinics. (8)

On the encouraging side, it is now a subject of many clinical trials for managing mood and emotional disorders, and the results are incredibly encouraging. Hence, it is pretty likely that we will see the US FDA approving it for managing anxiety so that it can be used more frequently. At present, doctors would only use it in clinics, under medical supervision, and only for refractive anxiety. This means that it is mostly used for moderate to severe anxiety that would not respond to other treatment methods.

However, what has perplexed researchers is its mechanism of action. They are still unsure of how these drugs act so quickly and how to explain their long-lasting action. They know that it is causing some brain changes, but they cannot understand how. Moreover, studies show that such brain changes are not seen with other anesthetics and analgesics. (9)

Thus, for example, doctors did a comparative study of ketamine and midazolam for managing resistant cases of generalized anxiety disorder. Ketamine resulted in significant benefits, but not midazolam. Additionally, electroencephalography (EEG) study found that its ability to reduce the so-called medium-low (theta) frequency at right frontal sites was predictive of its antianxiety action. Hence, the study confirmed that it alters brain waves and thus provides anxiety relief in resistant cases. (10)

One thing also important to note is that these actions of ketamine are not due to euphoria, which only lasts for a few hours. However, its antianxiety effect lasts for several weeks, even after a single IC infusion.

Thus, in one of the studies, researchers injected 0.5 mg/kg of ketamine slowly over 40 minutes into a group of patients to manage their social anxiety. They compared ketamine’s effect to placebo and found that ketamine was much more effective. Thus, for example, after two weeks of ketamine therapy, the response rate on the Liebowitz Social Anxiety Scale (LSAS) was 33.33% for the ketamine group, compared to 0% in the placebo group. The findings were similar when they used other ways to measure the benefits of ketamine therapy in anxiety. Hence, they concluded that ketamine is effective in reducing social anxiety. (11)

As there are now many studies, researchers have also done a few systemic reviews. These are special kinds of studies that combine the findings of multiple studies. Thus, one of the systemic reviews looked at the effectiveness of ketamine for refractory anxiety spectrum disorders. It analyzed data from six clinical trials. It found that ketamine was especially good for managing social anxiety disorder, though not so good for PTSD. Further, they also found that low-dose ketamine maintenance therapy was a good and safe way to maintain the effect. (12)

Yet another more extensive systemic review and meta-analysis analyzed 931 research articles. In their final study, published in 2022, the authors included a total of 40 research studies focusing on resistant cases of mood disorders. They concluded that there is sound evidence that ketamine is suitable for refractive instances of mood disorders. (13)

How Safe is Ketamine

It is a DEA Schedule III controlled substance, which means that it is mind-altering and has the potential to cause addiction and dependence. However, that is possible only if one uses ketamine regularly. However, as one can notice from the studies above, doctors do not prescribe ketamine for prolonged use for managing anxiety. Instead, patients are given ketamine infusion in clinics, which results in prolonged benefits, and this almost rules out the possibility of drug abuse. Moreover, abusing it will only make things worse and may rather cause emotional disorders.

Many high-quality studies show that if ketamine is used as intended, it is pretty safe and does not cause any severe side effects. Thus, if it is given as an infusion for anxiety, it might cause some issues like an increase in blood pressure. It also commonly causes nausea, dizziness, and blurred vision. All these side effects are transient. Hence, if the therapy is done in clinics, it is safe and poses no health risk. (14)

Of course, apart from the above side effects, one would also experience some strange feelings, dissociation, and more. However, most of those adverse effects peak at 30 minutes post-therapy and are almost gone after 60 minutes. That is why one must stay in a clinic for a short time post-therapy. (13)

Of course, doctors would carry out extensive testing before starting therapy. Such a treatment is not given when the patient is intoxicated, for example, consumed alcohol. This therapy is not for pregnant and breastfeeding women and those living with severe mental health issues.

Simply said, to safely use the therapy, it must be done in specialized clinics only.

Finally, one should not forget that most drugs used to manage anxiety, like anti-depressants, anxiolytics, and antiseizure drugs, might have much graver side effects. Especially considering that they are used consistently for months and years.

The Bottom Line

So, now we have looked at what ketamine is, how it is used, and what is the clinical evidence in favor of its use. After analyzing all the studies, we can confidently say that it is emerging as one of the most effective treatments with many benefits over the traditional approaches.

Of course, any anxiety treatment should still start with lifestyle interventions. However, the experience shows that those measures are barely enough to control mild anxiety. Most of those methods fail in moderate to severe anxiety.

Further, data shows that drug therapy has a limited benefit. Those medications have many downsides, like they act slowly over the weeks, do not work for many, and cause many side effects. Even if those medications like benzodiazepines work initially, patients soon develop tolerance.

Ketamine therapy has multiple advantages over the traditional approach. It is effective even for refractory or resistant cases. Moreover, it is worth noticing that it has been mostly tested in severe patients who would not respond to other treatments. Thus, its efficacy would be even higher in patients who were not earlier treated with other drugs.

What is good about ketamine is that it works very quickly. Since a session of infusion therapy may provide benefits lasting for several weeks. It also means that ketamine therapy is relatively safe as its side effects only last for a few hours, but its effects for several weeks.

What is encouraging about ketamine is its ability to alter brain waves and help reprogram and rewire the brain. When combined with other methods like psychological help and cognitive behavior therapy, it might benefit most anxiety patients.

References

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