How Spravato® Works Differently than Traditional Antidepressants

Gallup News reported in May 2023 that the percentage of U.S. adults diagnosed with depression at some point during their lifetime reached 29%, almost 10 percentage points higher than the first report in 2015. The percentage of those being treated for depression also increased, to 17.8%, an increase of around seven points over the same period.

Depression can be treated with psychotherapy and antidepressant medications like the selective serotonin reuptake inhibitors (SSRIs) and the selective norepinephrine reuptake inhibitors (SNRIs). Though not created for depression, these drugs are used “off label” to treat the symptoms of depression.

So, what happens when you don’t respond to these medications? What else is there to try?

At Interventional Psychiatry Group, serving the Memphis area in Cordova, Tennessee, Dr. Jim Pang Jr. offers Spravato® as an alternative to treatment-resistant depression. The nasal spray is one component of the anesthetic drug ketamine, and it works differently than traditional antidepressants, offering hope of relief to many.

How do traditional antidepressants work?

SSRIs are a widely used type of antidepressant and often the first line medications given to treat major depressive disorder (MDD), since they carry fewer side effects than most other types. They’re often used in combination with cognitive behavioral therapy (CBT), a form of psychotherapy, to approach the problem from different angles.

It's believed that SSRIs work by increasing serotonin levels in the brain. Serotonin is a neurotransmitter, a molecule that carries messages between the nerve cells in the brain, and it’s thought to have a positive  influence on mood, emotion, and sleep.

After delivering its message, serotonin is usually reabsorbed by the nerve cells (called "reuptake"), to be used again. The SSRIs work by inhibiting the reuptake, making the existing molecules readily available to pass on more messages.

Low serotonin levels play a role in depression and related mental health conditions, so a rise in those levels can improve symptoms and make people respond better to other forms of treatment, such as CBT.

SSRIs are usually taken in tablet form and need to be taken for at least two to four weeks before you can tell if you’re receiving any benefit from the medication. You can expect some mild side effects when you get started, but you shouldn’t discontinue the medication unless your provider tells you to. Side effects generally dissipate quickly.

And now the bad news: Not everybody responds to medications like the SSRIs and SNRIs. In fact, treatment-resistant depression affects about 30% of people diagnosed with major depressive disorder. That’s a lot of people not getting better. Fortunately, there’s an alternative.

Ketamine and Spravato

Ketamine started life as a veterinary anesthetic, then was approved for use on battlefields and in operating rooms for its dissociative properties in the early 1970s. EMTs in the field noticed that it calmed agitated patients, and so it next found a use in treating mental health disorders. It’s become commonly used for depression and pain conditions, though only “off label,” as it hasn’t been FDA approved for those uses.

Enter Spravato (esketamine), a derivative of ketamine available in a nasal spray. In March 2019, the FDA approved it, “in conjunction with an oral antidepressant, for the treatment of depression in adults who have tried other antidepressant medicines but have not benefited from them,” according to the press release.

Because of the potential for abuse and misuse of the drug, it’s only available through a restricted distribution system, which means it must be administered in a certified medical office where the provider can monitor the patient throughout the treatment process.

Spravato is the first FDA-approved medication specifically for treatment-resistant depression and to treat depressive symptoms in adults with MDD with suicidal thoughts or actions. 

Spravato, like ketamine, doesn’t work with the serotonin system. Instead, it works on glutamate, another neurotransmitter that has effects on mood, pleasure, and reward.

It also plays a key role in synaptic plasticity (building new nerve connections to support elevated mood) and neural communication. This unique mechanism is believed to contribute to its ability to alleviate depression symptoms where other treatments have failed.

Esketamine also brings about rapid, sustained relief from depressive symptoms. Unlike the two to four weeks of waiting with the SSRIs to see a benefit, esketamine has been shown to produce results within hours to days.

If you’re interested in finding out more about Spravato and how it can help your depression symptoms, call Interventional Psychiatry Group at 901-752-4900, or book online with us today.