Ketamine Nasal Spray Drug for Depression

A recent press release through NPR has stated that the Food and Drug Administration will approve esketamine as a treatment option for depression, through a nasal spray. Esketamine is chemically related to ketamine (as an enantiomer), a similar drug known best as an anesthetic and a party drug. Both ketamine and esketamine are known as recreational dissociative hallucinogens. Furthermore, both drugs have a series of known risks associated with them, including the fact that they both have effects on the brain’s dopaminergic pathways – a known mechanism for substance dependence and addiction.

So why is esketamine being prescribed for the treatment of depression? Evidence suggests that it may be an effective antidepressant for people struggling with treatment-resistant depression, a form of depression found is a many as 30 percent of patients seeking relief from depressive symptoms through conventional treatments. These patients are unable to find relief through methods such as SSRIs and therapy. But, is the risk worth it?

 

What Is Ketamine?

Ketamine, and by extension esketamine, is a general anesthetic and a common party drug. It’s usually taken either intravenously or through a nasal spray, with the latter being currently prescribed for depression. While esketamine has been approved by the FDA, ketamine has also been considered an option in the fight against depression, with several studies and trials investigating the effects of ketamine, esketamine, and ketamine’s opposite enantiomer arketamine on patients with treatment resistant depression.

Ketamine as both a hallucinogen and an anesthetic are potentially effective in the treatment of depression because they soothe pain and induce relaxation in a therapeutic state. Ketamine is popularly used as a general anesthetic, especially in third-world countries or places where the maintenance and storage of more expensive anesthetics is not an option. Ketamine is approved as an anesthetic for a variety of operations, including skin grafts, orthopedic procedures, and minor surgical interventions. As an anesthetic, one of its valuable traits is the fact that it does not lower a person’s blood pressure or breathing rate, making it less dangerous than drugs that could potentially induce respiratory failure.

As a hallucinogen, ketamine shares similar properties to drugs like dextromethorphan (DXM), phencyclidine (PCP), and nitrous oxide. It has been abused both as a party drug and as a date rape drug. According to the American Psychological Association, “While ketamine may be beneficial to some patients with mood disorders, it is important to consider the limitations of the available data and the potential risk associated with the drug when considering the treatment option.”

Until recently, ketamine has often been used as an off-label depression treatment, not approved by the FDA. Today, however, ketamine’s chemical cousin esketamine has become an approved form of treatment for treatment-resistant depression.

 

Why Is Ketamine an Option for Depression?

Some studies have come out showing the efficacy of ketamine for depression treatment. Others, however, have pointed out that there is conflicting data. Other studies show that the drug is too risky and not always effective. Some trials have been stopped due to severe side effects in patients. While ketamine is a powerful antidepressant, it can easily be dangerous.

Esketamine has recently been approved by the FDA, but there are many strings attached to that approval, such as only nasal sprays being approved, the fact that esketamine is typically only prescribed after other conventional options have failed, and the fact that these drugs cannot be brought home and can only be administered by a doctor. There are still risks involved with the use of esketamine and ketamine.

 

What Are the Risks Involved?

Every drug has risks, and it is only when the benefits far outweigh the risks that a drug is considered an option for treatment. Ketamine is the same, and its hallucinatory effects and overall chemical structure may induce several potential side effects. For one, patients with glaucoma, brain lesions/tumors or some form of brain swelling cannot receive ketamine, due to the potential increase in intracranial pressure (brain pressure) from ketamine use.

Although ketamine does not lower blood pressure, it may increase it, making it risky on patients with a heart condition, high blood pressure, chest pains, or aneurysms. Patients with an addiction to alcohol or other drugs are also advised not to take ketamine if it is avoidable. Because some drugs don’t agree with individuals, it’s important to approach a doctor with your full medical history to help determine if you might have an allergy to the drug.

Past these side effects, ketamine is also an addictive drug. Because it induces relaxation and euphoria and affects the dopamine levels in a person’s brain, repeated recreational use can lead to a physical dependence on the drug, as well as a series of dangers associated with overusing hallucinogens, including more serious forms of dissociation and mental health problems, as well as potential for accidental self-harm and death while under the effects of a high dose of ketamine.

Currently, the FDA has approved the prescription of esketamine through nasal spray for patients with treatment-resistant depression, but only in a clinical setting, because the side effects are severe enough that patients may endanger themselves if they take the drug without regulation from a doctor, or anywhere other than in the safe comfort of their own home or the doctor’s office. After an intense high, ketamine can induce problems in coordination, mental and cognitive function, and physical senses for up to 24 hours. Long-term problems related to overuse include kidney and bladder issues and even memory loss and psychosis.

Many fear that prescribing ketamine will lead to an increase in ketamine abuse. Prior to the approval, statistics show that ketamine abuse among teens has been on a decline since 2002, when 2.6 percent of 12th graders reported using the drug recreationally versus 1.4 percent in 2014. This number may increase over the coming years.

 

What Other Options Exist?

Treatment-resistant depression is a serious issue that plagues many Americans who seek treatment for depression and do not feel that any of the conventional treatments are effective. While ketamine and esketamine are two options, others exist. Aside from selective serotonin reuptake inhibitors (SSRIs), other antidepressants that are usually prescribed before other options are considered include serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs).

Transcranial magnetic stimulation is another option employed against treatment-resistant depression – it is a non-invasive treatment involving a special machine that sends magnetic waves into a portion of the frontal lobe associated with mood regulation, improving, and eliminating depressive symptoms over the course of 20-30 sessions within a short 4-6-week period.

Depression treatment is not instant, and relief takes time. Progress is difficult to measure and often slow, which is why many psychiatrists and therapists recommend the use of journaling and other techniques to keep track of day-to-day emotional changes, and thus have a better more truthful overview of how treatment helps on a month-to-month basis. Most antidepressants take up to a month to begin influencing a person’s mental health, and many other treatments take time to work as well. While treatment choices matter, it’s just as important to have the right environment and a support system for treating depression. It takes a multimodal approach and relying on one treatment or another is not the right way.

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