Those with mental illness are likely familiar with the treatment routine of psychotherapy and antidepressants, but did you ever think about treating depression with a nasal spray, like you would treat an allergy?

On March 5th, the Food and Drug Administration approved a new form of depression treatment, which comes in the form of a nasal spray. The drug, which goes by the brand name Spravato, is intended for those suffering from treatment-resistant depression.

Although the FDA has given its stamp of approval on Spravato for depression, they informed their audience of some caveats. There are a few conditions one must meet before being prescribed the drug, and the drug can only be administered “through a restricted distribution system,” according to the FDA.

We’re going to break down this news into a few different pieces to help understand the implications of this drug:

• Treatment-resistant depression
• What is Spravato
• What to expect when taking Spravato
  

Read on to find out what to consider when it comes to Spravato.

Treatment-resistant Depression

While most people who suffer from major depressive disorder see their symptoms improve with psychotherapy and/or an antidepressant, that is not always the case. Roughly 30 percent of those with depression suffer from treatment-resistant depression (TMD). The FDA says Spravato should be used in addition to an antidepressant for those with TRD.

It can be difficult to define and diagnose TRD. According to Jaskaran Singh, M.D., of Janssen Pharmaceuticals, there are some general guidelines one can use.

“A patient is generally considered to have [treatment-resistant depression] if the individual hasn’t responded to adequate doses of two different antidepressants taken for a sufficient duration of time, which is usually six weeks,”

Certain conditions and traits increase the risk for TRD in patients with depression:

• Overall health. Other preexisting conditions, such as thyroid disease and chronic pain, put patients with depression at a higher risk for TRD than those without.
• Age and gender. Women and senior citizens tend to have higher rates of TMD than other demographics with depression.
• Symptom Frequency. Those who experience depressive symptoms more frequently and/or at a more severe level are more vulnerable to TRD.

TRD or Unresponsive to Antidepressants?

While it may be easier to point a finger at TRD, there are a few reasons why an antidepressant might not be working for someone. It can be a bit of a process finding the right antidepressant and dosage that works best for you, since it doesn’t always click with the first prescription. Additionally, it’s important to wait for that 6-8 week benchmark, because that is how long it takes for an antidepressant to kick in.

Another thing to think about when it comes to your relationship with antidepressants comes from recent scientific breakthroughs. Professionals have begun to theorize that low levels of neurotransmitters like serotonin and norepinephrine—which are associated with mood—might not be the sole cause of depression. Because most antidepressants only target these neurotransmitters, antidepressants aren’t enough.

While low levels of serotonin and norepinephrine are the predominant causes of depression in the medical community, professionals still aren’t entirely sure of the exact problem or it’s solution.

What is Spravato?

Spravato is the brand name for the nasal spray that was recently approved by the FDA to treat treatment-resistant depression, esketamine. You may have read that last sentence as a red flag upon seeing the word ketamine. That initial reaction may not be entirely off-base. Esketamine is chemically related to ketamine, the drug intended for sedation which has previously been associated with the culture of party drugs. The two chemicals have a similar makeup, but it’s their molecular arrangement that gives each drug a different name.

There exists previous research which began in the 2000s on the use of small doses of ketamine to treat depression, although it lacks formal FDA approval. Ketamine is known to induce a  hallucinogenic response in addition to its sedative effect.

The chemical cousins do share the fast-acting sedation associated with ketamine. Compared to other antidepressants, which take six to eight weeks to take effect, a patient will feel the effects of Spravato in about an hour after the dose has been given. Because of this immediacy, ongoing research is exploring the idea of giving Spravato to patients that had been hospitalized for suicidal intentions.

While other antidepressants, such as Prozac and Zoloft, boost neurotransmitters serotonin and norepinephrine, Spravato targets glutamate in the brain, a different neurotransmitter that is overly abundant in the brains of those with depression. More specifically, Spravato inhibits NMDA receptors, which interact with glutamine. This individuality has caused esketamine’s approval to get so much press—there’s nothing like it currently on the market to treat depression. Aside from Spravato, there are few options intended specifically for cases of treatment-resistant depression.

What to expect with Spravato

You can receive eskatamine via a nasal spray or intravenously, but Spravato is given in the form of a nasal spray, which the patient will self-administer with provider supervision and instruction. Depending on the person, sessions will occur once a week or once every other week. Treatment can cost anywhere from $590 to $900 per session.

It is important to note that Spravato will be prescribed in addition to an antidepressant, and is only administered in certain offices with explicit conditions in place. The availability of the drug is subjected to a Risk Evaluation and Mitigation strategy (REMS) by the FDA, which says the prescriber and the patient both have to sign a Patient Enrollment Form that advises the patient to “make arrangements to safely leave the health care setting to get home” and not to “drive or use heavy machinery for the rest of the day on which they receive the drug.” After receiving Spravato, a health care provider needs to monitor the patient for at least two hours, but the provider will determine when exactly the patient is ready to leave.

Similarly, the FDA says a patient receiving a Spravato treatment must be given a Medication Guide, which lists the drug’s implications.

After testing the efficacy of Spravato in three short-term trial sessions, the FDA noted a few potential side effects:

• Disassociation
• Dizziness
• Nausea
• Sedation
• Vertigo
• Decreased feeling or sensitivity (hypoesthesia)
• Anxiety
• Lethargy
• Increased blood pressure
• Vomiting
• Feeling drunk
• Impaired attention, judgement, and/or thinking
  

Because of these potential side effects, the FDA advises that a Spravato patient shouldn't drive until the next day. Someone receiving Spravato should not be breastfeeding, and it’s advised that contraception be used during treatment. Similarly, certain pre-existing disorders could increase the patient’s risk of cardiovascular or cerebrovascular side effects from Spravato.

In addition to the previous side effects, there are a few other details a patient might want to consider. For one thing, professionals are not sure if Spravato is appropriate for long-term use.  Previous studies on the long-term use of ketamine in mice have shown dangerous side effects, such as bladder toxicity, cognitive problems, and brain lesions. There is also uncertainty regarding the potential for abuse or misuse of the drug; the FDA included in its Boxed Warning that patients are at risk for abuse and misuse of the drug, as well as suicidal thoughts.

Spravato is certainly making headlines in the medical community, but this drug is still new. While the drug is helpful for those experiencing an episode of major depressive disorder, professionals are not entirely certain on the long-term benefits of the drug.

If you think you or someone you know may be suffering from depression, speak to a mental healthcare provider as soon as possible, and ask them about treatment options for depression. If it is a mental health emergency, call 911.

What other questions do you have about Spravato? Let us know in the comments!