Ketamine for Treating Depression and PTSD: Science 101

Depression and stress disorders are common. In this article, we will look at the research on using ketamine to treat depression and PTSD, including how it works, how well it works, and any potential side effects.

These mental health conditions can make it hard for people to enjoy their lives, and cope with stress. There are many different ways to treat depression and PTSD, including therapy, medication, and lifestyle changes. But, for some, depression and anxiety become chronic, long-standing, and resistant to traditional treatment.

Ketamine has become a promising treatment option for these conditions. Ketamine is a medication that was first used as an anaesthetic, and is now known widely for its use in alleviating the symptoms of hard to treat depression and stress disorders.  When standard treatments like therapy-only, SSRIs-only, or a combination of therapy and SSRIS do not work, other psychiatric interventions, like Ketamine treatment, offer new hope.  

What is ketamine?

For many ketamine is a familiar word, but not always for it’s medicinal use. While ketamine has reputation for being a club drug, and like other medications, has been abused in uncontrolled settings, for medical purposes and with the correct dosage and administration it is a safe and highly effective treatment. Ketamine has been used for decades as an anaesthetic. In human medicine Ketamine has historically been used as a means of sedation and for pain management. In fact Ketamine is on the WHO’s list of essential medications for pain management and anesthesia.  

While in an active phase of treatment, Ketamine makes people feel detached or dissociated from their surroundings and themselves.  However, the impact of ketamine on the brain is now believed to last after the immediate effects have worn off, and the benefits in a psychiatric setting can build overtime and with continued treatment.

How does ketamine work for depression and PTSD?

As is the case with many medications research is always deepening the understanding scientists and doctors have on the how & why psychological change occurs with Ketamine treatment.  What is known is that  ketamine does help with depression and PTSD especially when other treatments have failed to bring about lasting relie, and the way it works in the brain is different than how traditionally prescribed SSRIs work.

Ketamine targets the glutamate system in the brain, which plays an important role in healthy brain functioning. Glutamate is a highly abundant neurotransmitter, responsible for facilitating signals between nerve cells. Through the target of the glutamate system scientists theorize that Ketamine works by blocking a protein called the NMDA receptor in nerve cells and activating another protein called the AMPA receptor, which helps with forming and saving memories. This interaction between the NMDA and AMPA receptors may lead to the quick and sustained improvement in mood and behavior seen with ketamine treatment. Ketamine may also increase the production of BDNF, a protein that helps nerve cells grow and survive, and change the activity of neurotransmitters like serotonin, norepinephrine, and dopamine, which are involved in mood regulation.

Interestingly, the pain relief and mood improvement can last even after the drug has left the body. This might be because ketamine changes how the brain’s cells talk to each other, which can help the brain form new connections that last longer than the drug’s effects. Often this concept of being able to change and create new connections is called neuroplasticity. 

Evidence for using ketamine for depression and PTSD

There is a lot of evidence showing that ketamine can be used to treat depression and PTSD. Many studies have shown that ketamine can quickly and effectively reduce symptoms of depression and PTSD.

One study published in the American Journal of Psychiatry found that a single IV infusion of ketamine improved mood and suicidal thoughts in patients with treatment-resistant depression. Another study published in the Journal of Clinical Psychiatry found that a series of six IV ketamine infusions reduced symptoms of PTSD in military veterans.

Several studies that look at many studies together, called meta-analyses, have also shown that ketamine is a safe and effective treatment for depression and PTSD. A meta-analysis published in the Journal of Affective Disorders found that ketamine was more effective than a dummy treatment at reducing symptoms of depression, with a large effect size and a quick onset of action. A systematic review published in the Journal of Clinical Psychiatry similarly found that ketamine was effective at reducing symptoms of PTSD, with a moderate to large effect size.

What are the potential side effects of ketamine?

Like any medication, ketamine can cause side effects. The most common side effects of ketamine are dizziness, drowsiness, nausea, and vomiting.  Ketamine will also impair your ability to drive or operate machinery which is why Heading requires patients have transportation to and from treatment. Other potential side effects include hallucinations, changes in blood pressure, and respiratory problems, which is why Heading recommends treatment be in-person and under the direct supervision of medical professionals. It is important to talk to a healthcare provider about the risks and benefits of ketamine treatment before starting treatment.

More research

There are a number of studies that discuss the use of ketamine for the treatment of depression.  Here are a few examples of scientific resources that may be of interest.

Zarate, C. A., Jr., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., … Charney, D. S. (2006). A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Archives of General Psychiatry, 63(8), 856–864. https://doi.org/10.1001/archpsyc.63.8.856

• This study found that a single intravenous (IV) infusion of ketamine was associated with a rapid and significant improvement in mood and suicidal thoughts in patients with treatment-resistant depression.

Feder, A., Parides, M. K., Murrough, J. W., Perez, A. M., Morgan, J. E., Saxena, S., … Charney, D. S. (2014). Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: A randomized clinical trial. JAMA Psychiatry, 71(6), 681–688. https://doi.org/10.1001/jamapsychiatry.2014.30

• This study found that a series of six IV ketamine infusions was associated with a significant reduction in symptoms of PTSD in military veterans.

Caddy, C., Giaroli, G., White, T. P., & Tracy, D. K. (2019). Ketamine as a treatment for depression: A systematic review and meta-analysis. Journal of Affective Disorders, 245, 959–973. https://doi.org/10.1016/j.jad.2019.03.053

• This meta-analysis concluded that ketamine is a safe and effective treatment for depression, with a large effect size and a rapid onset of action.

Bremner, J. D., Vythilingam, M., Vermetten, E., Adil, J., Khan, S., Nazeer, A., … Krystal, J. H. (2008). Pilot study of repeat-dose intravenous ketamine in treatment-resistant posttraumatic stress disorder. Biological Psychiatry, 63(3), 339–341. https://doi.org/10.1016/j.biopsych.2007.05.028

• This study found that a series of IV ketamine infusions was associated with a significant reduction in symptoms of PTSD in a small group of patients

Unlike with most antidepressants, patients considering ketamine have to consider different methods of receiving the medication as well as the location for treatment: at home or in a clinic under the supervision of a medical professional. 

While at-home treatments have the advantage of convenience and accessibility, there are aspects of the in-clinic process that cannot be duplicated at home. Some experts even argue an in-clinic treatment is essential for safety and efficacy.  From the added sense of security to access to a well-oiled integrated care team, every part of the in-clinic experience is thoughtfully designed to optimize therapeutic outcomes.

By exploring the benefits of in-clinic treatments below, you’ll be well-suited to make an educated decision on which option is right for you.

Access to Different Ways of Taking Ketamine

Ketamine is available in several forms or routes of administration, including oral tablets, nasal sprays, and IV infusions. While oral tablets are commonly prescribed for at-home use, others must be administered at a clinic. At Heading, we offer Spravato® (intranasal esketamine) and intramuscular (IM) ketamine. In both instances, you need a medical provider’s support and supervision.

“Each method of receiving ketamine treatment has its benefits and drawbacks, many of which are unique to individual patients,” shares Dr. Tyson Lippe, an Austin-Texas-based psychiatrist here at Heading Health. “However, patients taking Spravato®, which is FDA-approved to treat treatment-resistant depression, will need to come into the clinic – it’s a requirement.” 

Dr. Arif Noorbaksh highlights that cost is a key reason in favor of having access to all the ketamine forms and routes of administration.

Spravato®, which is delivered intranasally, is FDA-approved to treat treatment-resistant depression. And for the vast majority of these patients that we see at Heading, this also means that insurance will play a part in covering the expense. 

While our team at Heading has worked hard to ensure we can also provide coverage for IM ketamine, we are unique in this respect. At other clinics, Spravato® may be a patient’s best bet for getting their treatment covered.

Optimal Set and Setting for Mental Health Improvement

With any intervention that has the potential to produce psychoactive effects, the set and setting (i.e., the patient’s mindset and treatment environment) are vital. Most immediately, how you feel going into the treatment can impact how you feel during it. If you go in confident and calm, you’ll be more likely to have a pleasant experience.

Aside from being valuable in its own right, positive ketamine experiences can result in other good outcomes. For example, studies have found that pleasant ketamine experiences are associated with better treatment outcomes, while scary ones can undermine ketamine’s antidepressant effects. Knowing that a care team is steps away can help ease nerves about treatment, and may put patients at ease knowing help is available should they experience any adverse side effects.

While everyone has their own unique preferences regarding set and setting, an environment that supports feelings of safety and security is essential. Ketamine treatment centers are well-equipped to provide this. 

With physicians and therapists on-site, patients can feel confident that a competent professional is there to help. As Dr. Noorbaskh shares:

Patients receiving ketamine in a clinic or medical center receive an entire team of people who are supporting the best possible outcomes. Safety is, of course, paramount. Patients also take comfort in knowing that they have a medical team who can immediately make them more comfortable and answer any questions or concerns they may have in real-time. And these are also the same people you will see time and time again. Developing therapeutic relationships requires trust, and building trust over time with your care team enhances the experience. 

Being in the hands of a team of professionals isn’t the only way clinics can support a positive mindset. Clinics often take great care to design the treatment rooms so they are conducive to feelings of calmness and relaxation. For example, they may include soft ambient and natural lighting, cozy chairs, fresh greenery, and ample space to help you settle in and focus on your journey.

Improved Patient-Provider Relationship

At-home ketamine therapies are sometimes paired with telehealth tools to help guide patients through their treatments. However, while telehealth increases access and flexibility, there are situations where in-person treatments offer irreplaceable benefits, especially for individuals experiencing loneliness and isolation. 

As Dr. Tyson Lippe shares:

I see patients through telehealth, and I also see patients in person. Telehealth certainly increases accessibility, which is incredibly valuable. That said, loneliness and isolation are significant mental health concerns. Anytime we are able to connect directly with people who truly care about our health and well-being, there is a benefit. Offering care in a more hybrid fashion with telepsychiatry and in-clinic treatment administration opens up accessibility while also maintaining great care.

Behavioral Activation

Aside from helping patients combat loneliness and isolation, in-person treatment centers can lead to better outcomes simply by providing patients with a regularly scheduled outing and a chance to interact with friendly staff. In fact, in one evidence-backed form of psychotherapy called behavioral activation, practitioners help patients engage in pleasurable activities that get them moving and socializing to alleviate symptoms of their depression. 

By offering patients a reason to go out, enjoy the company of physicians they’ve grown close to, and undergo a relaxing treatment on a consistent basis, ketamine clinics are able to supplement the therapeutic effects of ketamine itself with the benefits of behavioral activation. 

Comprehensive, Integrated Care

Ketamine often works best when combined with other interventions. For example, Janssen Pharmaceuticals, the maker of Spravato®, recommends combining the treatment with an oral antidepressant. Similarly, researchers have found that psychotherapy can extend the therapeutic effects of ketamine. 

Dr. Noorbaksh highlights how, for a holistic approach to work seamlessly, providers from different disciplines and areas of expertise must develop close working relationships that facilitate the delivery of comprehensive, integrated care:

An important aspect of medicine is developing relationships with other healthcare professionals. At Heading, our approach is hybrid with telehealth for psychiatry and therapy services and in-person visits for interventional treatments like TMS and ketamine. When it comes to combining services, I don’t have to go far to help my patients find great therapists. I’m able to directly communicate with my patients’ therapists, nurses, and care coordinators. Direct communication means there’s less time that my patients and I are waiting for treatment notes to be reviewed or changes in care to take place.

Accountability

Though ketamine can alleviate symptoms far more rapidly and with less frequent maintenance than other interventions, repeated visits are often necessary to sustain the full benefits of the treatment. However, the mental health conditions that ketamine can be used to treat can make it more difficult for patients to stay on schedule.

When asked how in-person treatment centers are well-equipped to address this issue, Dr. Noorbaksh emphasized the value of the interpersonal connections and support patients receive from their care team:

The human interaction and support patients receive from the clinical team during treatment are tremendously valuable. Psychiatric care nurses, medical assistants, and the psychiatrist providing care all get to know their patients and facilitate touch points that simply can’t be replicated in the same way remotely.

In other words, providers at in-person treatment centers can draw on their close connections with and deep understanding of their patients to help mitigate any motivational barriers to receiving treatment. 

Aside from interpersonal connections, clinics are well-equipped to take over the logistical obstacles that might otherwise make scheduling and receiving treatment overwhelming for individuals suffering from anxiety and depression. Dr. Lippe shares that:

Mental health conditions like anxiety and depression can make it hard to keep engaging in activities that are beneficial to health and well-being. But having a clinical team that schedules appointments, offers reminders, and conducts follow-up visits helps keep patients on track. This is vital as we know that staying on track with treatment and in therapy can lead to faster and more durable outcomes. 

Finding the Best Option for You

Ketamine is a powerful psychiatric intervention that can alleviate symptoms of the most severe cases of depression. Specialized clinics designed to optimize each part of the treatment process are likely the best place to undergo ketamine therapy and maximize its therapeutic potential. Some of the most important benefits treatment centers are better suited to provide include:

• The ability to choose the most effective and affordable type of ketamine and route of administration
• A tailored environment carefully crafted to support feelings of confidence, safety, and security
• Close patient-provider relationships that use the power of social connection to build on ketamine’s effects
• Behavioral activation through consistent appointments, which provide individuals with depression with a regularly scheduled relaxing outing and the opportunity to socialize
• Comprehensive, integrated care supported by efficient communication among healthcare professionals
• Added accountability due to interpersonal connections with staff and a competent team ready to take care of all the logistics of planning appointments.