Anxiety and depression are two of the most common mental health problems in the United States. Anxiety disorders affect more than 40 million people in the U.S. every year. Major depressive disorder affects more than 16 million Americans each year. 

While there are several treatment options for both of these disorders, some people are resistant to typical treatment paths. Ketamine may be an option for people who have tried other approaches with limited results. Learn more about ketamine treatment and its use in treating anxiety and depression.

What Is Ketamine?

Ketamine is a drug that’s primarily used in anesthesia, but it has also been used to treat pain, seizures, depression, and anxiety. As a sedative, ketamine is used to start and maintain anesthesia. It’s helpful in helping people fall asleep and remain relaxed. Other drugs may be used alongside ketamine in anesthesia, but ketamine remains a popular substance all over the world. 

It may be used in surgeries, and it also sees a lot of use in veterinary medicine. It has also been used in extraordinary circumstances, including the 2018 cave rescue of the Thai youth soccer team. The boys were given ketamine as they were transported out of the cave so that they could remain calm and avoid panic during critical moments during the rescue. 

Ketamine is a unique anesthetic because of its ability to sedate people without hindering airflow and breathing. Many other sedatives like barbiturates and benzodiazepines can slow down and restrict breathing. It also increases heart function like your pulse and blood pressure, rather than slowing them down. Those factors make it a helpful drug in a cave rescue, but it can also be useful in anesthesia. 

Ketamine has also been used as an illicit recreational drug. Sedatives are often used as recreational substances for people who are seeking a relaxing high. Ketamine can also cause dissociative effects, which means it can cause a person to have out-of-body experiences. Dissociative episodes are often frightening and unpleasant. You may feel disconnected from your body and your sense of self. 

You may feel like you’re not in control of your body, movements, or your ability to speak. In high doses, ketamine users experience what is called a K-hole, a period of severe dissociation, hallucinations, and heavy sedation. You may feel like you’re in between waking consciousness and dream-like perception. K-holes are usually seen as unpleasant. However, recreational ketamine users may seek to use the drug despite the risk of dissociative effects. 

As recently as 2019, the Food and Drug Administration (FDA) approved a nasal spray analog of ketamine called esketamine for the purpose of treating depression. Esketamine is similar to ketamine, though there are some differences. 

How Does Ketamine Work?

Ketamine is a complicated drug when it comes to pharmacodynamics or how it works in the brain. Ketamine doesn’t just affect one type of chemical or receptor in the brain; it works in multiple areas of the brain. For that reason, it’s very complex, and it can have a wide variety of effects. One of the most significant ways ketamine affects the brain is by working with a chemical called glutamate. Glutamate is one of the essential chemicals in your brain because it facilitates communication between nerve cells, which is how your brain functions. 

In high doses, ketamine is able to block glutamate all over the brain, which slows down nervous system communications. This is why ketamine is useful as a sedative. When your brain’s communication networks start to slow down, you feel sedated or fall asleep. However, ketamine’s effects of glutamate seem to be dose-dependent, which means the amount of the drug you take can change certain effects. In low doses, ketamine can actually increase glutamate levels, which facilitates more communications between neurons. This can cause many different effects and side effects. 

One of the effects may be to help alleviate problems that are caused by poor communication between neurons. Depression may be one of those problems. Chronic stress and mood disorders like depression can cause you to lose certain neural connections. This may be why people with depression lose interest in activities, isolate themselves, and become more apathetic about the world around them. However, esketamine may increase communication and help people with depression recover those lost connections. 

However, increased glutamate may also contribute to dissociative symptoms, hallucinations, and psychosis. While the use of ketamine to treat anxiety and depression seems promising, it may also come with some uncomfortable and disturbing side effects. 

What Are the Acute Side Effects of Ketamine?

The side effects you might experience after taking ketamine will depend on the dose you take and the purpose for which you are taking the drug. If you’re taking ketamine as a recreational drug, you will likely take a smaller dose than someone that’s receiving an anesthetic. One of the main reasons recreational users take ketamine in smaller doses is that it fails as a recreational drug if you pass out and sleep through it. Plus, smaller doses may produce physical and psychological euphoria. However, recreational doses can produce some unpleasant side effects, including:

  • Impaired cognitive function
  • Dehydration
  • Dysphoria
  • Motor control impairment
  • Dizziness
  • Sexual dysfunction
  • Hallucinations
  • Delusions 
  • Derealization
  • Depersonalization 
  • Sleep disturbances
  • Nightmares 

Symptoms of dissociation are associated with higher recreational doses, but they can be disturbing. Depersonalization is the loss of your sense of self. You may feel separated from your body or that you have no individual identity at all. 

Depersonalization may make you feel like you’re a disembodied observer, and it’s often frightening. Derealization is a similar but separate symptom that’s characterized by a feeling that the world around you is distant, distorted, or unreal. Some people who experience this feel like they are looking at the world through a filter or through a pane of glass. Others feel like the world around them is fake or a fabrication. 

Along with hallucinations and delusions, these symptoms can be dangerous for people with mental health issues that cause psychosis. People with schizophrenia and similar disorders may experience these symptoms that trigger a worsening of their disorder. For people without psychotic disorders, severe symptoms may still be frightening and potentially traumatic.

If you’re using ketamine as an anesthetic, there are some other potential symptoms. You may experience some of the above symptoms, especially when you’re coming out of anesthesia. Anesthesia emergence symptoms include strange dreams, dysphoria, hallucinations, and delirium. In some cases, you could experience tonic-clonic movements as you might experience during a seizure. 

What Are the Long-Term Side Effects of Ketamine?

Ketamine can be toxic in very high doses. It’s particularly dangerous for people who use it in high doses for long periods. Like alcohol, ketamine can pose a threat to your liver after frequent heavy use. Your liver is designed to filter toxins out of your blood. Limited therapeutic and medical uses of ketamine may not be enough to cause significant damage, but excessive use may be more than your liver can handle. 

Frequent users may also experience bladder problems and kidney failure. A condition called ketamine-induced cystitis is common among chronic recreational users. Symptoms of ketamine-induced cystitis include frequent urination, painful urination, and the strong and urgent need to urinate. 

Long-term ketamine use can also lead to issues like chemical dependence and addiction. Ketamine dependence may be possible after prolonged, regular use, but the drug’s potential for dependence isn’t fully understood. Animal research has shown that the drug can cause habit-forming behaviors and has abuse potential. The FDA warns that esketamine may also be riskier for people with a history of substance use problems. The FDA points out a study that was done to test the abuse potential of esketamine and ketamine. Participants were more likely to say they liked the ketamine and esketamine in the moment and would take them again when compared to a placebo. 

The FDA reported that there were no withdrawal symptoms reported in four weeks after esketamine treatment. However, people that use the drug consistently for several weeks or months may experience some withdrawal effects when they stop using. For that reason, it’s wise to tell your doctor whenever you would like to alter your dose or stop taking medication. 

How Is Ketamine Different from Other Antidepressants?

Ketamine for anxiety

Ketamine works in a way that’s different from other medications used to treat depression. The most popular antidepressants are selective serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI). Both of these classes of medication work with a chemical in the brain called serotonin. Serotonin is an important chemical messenger in the brain that’s involved in your mood, energy levels, and motivation. 

Serotonin is thought to be involved in mood disorders like depression. Low levels of the important chemical may contribute to low mood, loss of interest in activities, and other common symptoms of depression. Most antidepressants stop a process called reuptake which removes serotonin from your system. SSRIs and SNRIs allow serotonin to build up in the brain, lifting your mood.

However, traditional antidepressants and therapy options don’t work for everyone with depression. Around 10% to 30% of patients with depression don’t see improvement with antidepressant treatment, or they only see limited improvement. Even though traditional antidepressants are relatively safe and well-tolerated by patients, many doctors and therapists are excited by the prospects of new options that may be able to help people with treatment-resistant depression. 

Ketamine affects different parts of the brain and different chemical messengers. Since it primarily works with glutamate, ketamine may produce results in people who have tried other antidepressants with no success. However, ketamine is still reserved for people who have already tried other options. Since ketamine works in different ways all over the brain, it may have different effects on different people. Ketamine may also be more likely than other antidepressants to be misused or abused. 

What Is Ketamine Infusion Therapy?

Ketamine infusion therapy is an off-label use of ketamine to treat mental health problems like depression. Infusion refers to the fact that ketamine is administered in an intravenous solution rather than a pill. Infusion therapy began in the United States before there was FDA approval for drugs like esketamine. While ketamine infusion therapy was legal since the drug was FDA-approved for use as an anesthetic, its off-label use to treat depression was not usually covered by insurance. 

Ketamine infusion therapy lowers improved depression symptoms after four hours and peaks around 24 hours. However, the effects may begin to wear off after seven days. Patients may need to return for therapy after ten days to two weeks. While a single infusion produces longer-lasting effects than a single dose of a traditional antidepressant, infusion requires outpatient visits to a clinic with each dose. For that reason, infusion therapy is similar to maintenance programs. FDA-approved esketamine, sold as Spravato, offers home treatment options.

Ketamine infusion is also used to treat chronic pain symptoms. Ketamine is used in hospital settings among people with pain that is difficult to treat with traditional methods. It may be used alongside morphine or other opioids, but it may also be used on its own. 

Can Ketamine Be Used to Treat Anxiety?

While depression and anxiety seem like opposites, they’re often interconnected. Some people who experience severe anxiety struggle with depression and vice versa. Many of the same treatments for depression are also used to treat anxiety. 

Proponents of ketamine treatment for anxiety disorders like PTSD point to the drug’s dissociative effects as a positive. While dissociation is often a side effect for people taking the drug as an anesthetic or even for recreation, it may help people with anxiety disorders gain a distanced perspective on their problems. In fact, brief dissociative episodes are thought to be a function of the brain’s ability to cope with trauma. Ketamine may be used to treat anxiety that’s resistant to other forms of treatment, as it is used for depression. 

A 2018 study compared the use of ketamine to a placebo in a double-blind trial with 18 participants with social anxiety disorder. They found that ketamine significantly improved anxiety symptoms more than the placebo. 

What Are the Drawbacks of Using Ketamine to Treat Mental Health Issues?

One of the major drawbacks to the use of ketamine in mental health is the lack of understanding of ketamine’s long-term effects. Ketamine is known as a particularly safe anesthetic drug. But people who use it as an anesthetic only take the drug during a medical procedure, not regularly over a long period of time. Treatment for anxiety and depression may require many doses over a longer period of time. 

Ketamine’s effects are also difficult to study. Since it acts on so many receptors in the brain, it’s much more complicated than drugs that are older and more thoroughly studied. If you take ketamine in frequent therapeutic doses for a few weeks, the effects may be hard to predict. It’s important to communicate with your doctor and talk about any new, worsening, or persistent side effects.

Other Anxiety Disorder Treatments

Since anxiety is one of the most common health issues in the United States, there are several treatment options available. There are many different types of anxiety disorders, including generalized anxiety, post-traumatic stress disorder, obsessive-compulsive disorder, and social phobia. The first step in getting the right treatment is to get an accurate diagnosis. Each of the different types of anxiety disorders may have a unique treatment path. 

Getting the right treatment will mean working with your doctor or therapist and exploring possible treatment approaches. It’s also important to note that there isn’t any single treatment option that is equally effective for every person. Finding the right therapy or medication may require a trial and error process. In many cases, a combination of medications and therapy is the best option. 

Since ketamine is a relatively new option for treating anxiety and depression, it may be reserved as a last resort after other options have been tried. Here are some other options that you may go through before or in conjunction with ketamine treatment:

  • Antidepressants. Antidepressants are a first-line medication to treat depression, but they can also be used to alleviate symptoms of anxiety. Antidepressants can lift your mood and help with problems like catastrophization and feeling overwhelmed. You may also feel more energized and ready to take on challenges that you face. 
  • Anxiolytics. Benzodiazepines are an example of a class of drugs called anxiolytics that can directly relieve anxiety. These drugs work with a chemical called gamma-Aminobutyric acid (GABA). This chemical is tied to sleep and relaxation in the brain. Anxiolytics make GABA more effective, facilitating relaxation and a release of anxiety. Anxiolytics like benzodiazepines can also be helpful in facilitating sleep in people with insomnia.
  • Cognitive behavioral therapy. Cognitive behavioral therapy (CBT) is one of the most versatile therapy options available. It involves identifying thoughts and behaviors that lead to ineffective coping responses. One of the main goals of CBT is to improve your sense of self-efficacy by creating effective coping strategies. CBT can also be used to treat other mental and behavioral health problems that may be co-occurring. 
  • Stress management. Stress is a major factor in your overall mental health. In fact, it can also contribute to problems related to your physical health. Managing stress is an important way to address anxiety problems. CBT and general talk therapy may help you find stress management techniques. 
  • Lifestyle changes. In many cases, treatment can be aided by some specific lifestyle changes, including diet and exercise. Sometimes improving cardiovascular health improves anxiety symptoms. Avoiding alcohol and reducing caffeine intake can also help reduce anxiety. Plus, drugs like anxiolytics require you to avoid alcohol intake anyway. 

Other Mood Disorder Treatments

There are many types of depression that all fall under the category of mood disorders. Major depression is one of the most common mood disorders that’s characterized by a major depressive episode that lasts for a few weeks before going away. Major depressive episodes may come and go throughout your life. If left untreated, they can significantly disrupt your life. 

Other examples of mood disorders include bipolar disorder, seasonal depression, perinatal depression, and persistent depressive disorder. The treatment you go through will depend on the specific type of mood disorder you have. Getting a diagnosis will involve going through a physical exam, lab tests, and a psychological evaluation. 

  • Antidepressants. Antidepressants like SSRIs and SNRIs are often the first-line defense for mood disorders. They target serotonin levels to lift your mood. It’s common to take several doses over a period of a few days before you start to see results, but some people are resistant to treatment with antidepressants and need to explore other options. Antidepressants are used first because of their general safety over other options.
  • General talk therapy. Talk therapy can help you discuss your symptoms and frustrations with a therapist. In many cases, unpacking day-to-day problems helps alleviate some issues as you go through a depressive episode. 
  • Cognitive behavioral therapy. CBT is useful in treating depression, just like it is for anxiety. Increasing your sense of self-efficacy may be very important in addressing issues related to depression. Depression often causes feelings of worthlessness and a loss of interest in important activities. CBT may help you develop coping strategies to get through periods of depression. 
  • Antipsychotics. Some mood disorders, like bipolar disorder and major depressive disorder, can cause psychotic symptoms. Psychosis can occur as your mood drifts into extremes. Bipolar disorder can cause a manic episode which causes a very high mood that can come with delusional thinking. In some cases, major depressive episodes can cause you to have persecutory delusions or the feeling that everyone dislikes you, even strangers. Antipsychotics can help alleviate those symptoms. 
  • Mood stabilizers. Mood disorders like bipolar disorder involve both high and low moods. In some cases, a mood stabilizer is used to keep your mood in the normal range and avoid depressive and manic episodes. Examples include carbamazepine, which is an anticonvulsant medication that’s used to treat epilepsy, though it can also be used to treat manic-depressive issues. 

If you explore the use of ketamine to treat depression, you may have already attempted some of the treatments above. However, ketamine treatment may also be used alongside CBT and other psychotherapeutic options. Since ketamine is a relatively new and unpredictable option, you should meet with your doctor or therapist regularly to talk about your progress and any side effects you may have.

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