Ketamine For Anxiety – What it is & How it helps Anxiety and Depression ?

Anxiety disorders are one of the most prevalent mental health issues in the United States. People of all ages are affected by a wide range of debilitating anxiety disorders, such as phobias, panic disorder, post-traumatic stress disorder, and other mental health issues that include anxiety as a prominent and distressing symptom.

Anxiety disorders can be treated.A combination of medication and psychotherapy can help alleviate the associated symptoms in many cases. .Unfortunately, even after trying several different types of treatment, 30-40% of people with anxiety are unable to find relief through standard therapeutic approaches.

Fortunately, treatment for anxiety and other mental health issues is evolving, and off-label medications and treatments can have positive results.

One such example is ketamine treatment. Ketamine, which was originally approved by the FDA as an anaesthetic, is increasingly being used to help manage the symptoms of treatment-resistant depression. Ketamine has recently shown promise in the treatment of anxiety.

Ketamine is best known today as a hallucinatory street drug, but it was first used as a rapid-acting intravenous anaesthetic drug in the 1960s and has been used off-label in the treatment of depression since the 1990s.

What is Ketamine?

Unlike traditional depression treatments, which focus on increasing brain chemicals to improve the patient’s mood, ketamine repairs neuron synapses and increases glutamate levels in the brain, resulting in a faster improvement than antidepressants.

Depression and anxiety frequently coexist, and one reason for this could be that both disorders involve glutamate system abnormalities.

Ketamine and other drugs that affect the glutamate and GABA (Gamma-aminobutyric acid) systems have been studied extensively in the treatment of anxiety and depression—and Ketamine has proven effective in many cases.

In one double-blind study, ketamine infusion rapidly and significantly reduces symptom severity in patients with PTSD.(Source)

Another randomised controlled trial (RCT) of 15 patients with OCD discovered that the anti-OCD effects of a single intravenous dose of ketamine lasted for more than a week in some patients with constant intrusive thoughts.(Source)

A study of patients with anxious and non-anxious bipolar depression discovered that ketamine had significant antidepressant effects in both anxious and non-anxious patients with bipolar depression.

Scientists are still trying to figure out how ketamine reduces anxiety and depression, but they do know that, unlike antidepressants, which take weeks to work, ketamine starts working immediately and provides long-term symptom relief.

How Does Ketamine Work?

A growing body of evidence suggests that glutamate, a widely distributed excitatory neurotransmitter, plays a role in mediating stress response and the formation of traumatic memories.

Ketamine is an antagonist of the glutamatergic N-methyl-d-aspartate (NMDA) receptor.

Its antidepressant and anti-anxiety effects are thought to be mediated by increasing brain-derived neutrophic factor translation and secretion, as well as by inhibiting glycogen synthase kinase-3 and activating mammalian target of rapamycin signalling.

Although brain-derived neutrophic factor plays a role in behavioural responses to antidepressants, the effect on synaptic plasticity may take several weeks to manifest.

Ketamine-mediated synaptic plasticity changes, on the other hand, appear to occur within hours of ketamine administration.

“The current thinking is that dendritic growth and increased synaptic connections occur 6 to 12 weeks after starting treatment with traditional antidepressants, but with ketamine, these can occur within 24 hours of the infusion,” Dr Masand explained.

Ketamine and Anxiety: A Growing Body of Evidence

“Ketamine has been studied and shown to be effective with a variety of anxiety disorders, including SAD, GAD, and PTSD, although data on its effectiveness in obsessive compulsive disorder (OCD) is more mixed,” Dr Masand observed.

GAD/SAD

A small study of 12 patients with GAD and/or SAD compared three ascending ketamine doses to midazolam. Each was given at 1-week intervals, with midazolam dosing position counterbalanced across patients.Ketamine was discovered to improve Fear Questionnaire scores in a dose-dependent manner. (Source)

Furthermore, its effect on decreasing theta frequency in the right frontal sites as measured by electroencephalogram (EEG) was comparable to that of conventional anxiolytics.

Glue et al used an ascending single-dose at weekly intervals study design to assess the efficacy and safety of ketamine in 12 patients with refractory GAD and/or SAD who were not currently depressed. Patients reported reduced anxiety within 1 hour of dosing, which lasted up to 7 days.

A follow-up study looked at the impact of ketamine maintenance treatment in patients with GAD and/or SAD (n=20), and found that 18 of the 20 patients reported ongoing improvements in social and/or work functioning during treatment.

The researchers came to the conclusion that maintenance therapy “might be a therapeutic option for patients with treatment-refractory GAD/SAD.”

“What’s attractive about any of this study is that the impact of just one infusion lasted for 14 weeks, proposing that patients with anxiety disorders may have longer upkeep of response than patients with major depression, where the response has only been maintained for one week,” Dr Masand said.

What exactly is Ketamine IV therapy?

Ketamine IV therapy entails a carefully dosed infusion of ketamine in a medical setting. Patients typically receive three treatments in the first week, two in the second week, and one a week for the next three weeks.

Ketamine IV therapy takes about 90 minutes per visit and includes an observation period before the patient is sent home.

Unlike traditional antidepressants, which can take weeks to work, ketamine symptom relief begins within a few hours of treatment.

Some people find that ketamine therapy is sufficient to completely alleviate their symptoms, while others find that it works best in conjunction with other medications and treatments.

Ketamine has the chance to aid manage symptoms and significantly improve quality of life in someone who has tried but failed to find relief via other treatment methods.

Effects on Brain

Ketamine may also act in other ways in the brain.

To communicate with one another, some nerve cells (neurons) in the brain that are involved in mood use a chemical (neurotransmitter) called glutamate.

To participate in this communication, nerve cells require glutamate receptors (think of them as glutamate catcher’s mitts).

Those nerve cells in the brains of some people suffering from depression are no longer stimulated by glutamate.

It’s as if the glutamate receptors, or catcher’s mitts, have been deactivated or weakened.

However, when people with this problem are given ketamine, their nerve cell connections are restocked with new glutamate receptors.

It’s as if ketamine aids in the formation of new catcher’s mitts for glutamate, allowing nerve cells to respond to it once more.

According to research, while ketamine’s main action is in glutamate receptors, it also requires opioid receptors to have antidepressant effects.(Source)

That’s concerning for psychiatrist Alan Shatzberg, MD, who conducted some of the research that led to this discovery.

“It may not matter, but the fact that ketamine works through an opioid mechanism concerns me,” he says.

The concern, which has been expressed by other researchers in ketamine studies, is that people may require larger and larger doses of ketamine over time in order to feel its effects, as is the case with opioid painkillers. Treatments should be spread out and tapered over time to help reduce this risk.

Of course, any comparative to opioids raises the issue of addiction risk.

“I believe it is less addictive than opioids, but it is not without risks,” says Shatzberg, the director of Stanford University’s Mood Disorders Center. Indeed, case studies have detailed individuals who displayed signs of addiction or abused the drug.

Because it is an unapproved treatment, it is unclear whether the risk of addiction or tolerance outweighs benefits.

However, some recommendations suggest that it may not be safe for people with a history of substance abuse.

People with substance abuse issues have been barred from participating in many clinical trials.

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References :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729569/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8679040/

https://www.nature.com/articles/npp2013150

https://onlinelibrary.wiley.com/doi/abs/10.1111/bdi.12277

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