About 30% of the 15 million Americans with major depressive disorder (MDD) are not responding adequately to their current antidepressants. This condition is known as Treatment Resistant Depression (TRD). The problem is compounded by the fact that multiple, repeated antidepressant trials offer little additional benefit. When patients fail 2 trials of standard antidepressant therapy, the chances of remission with the third antidepressant are less than 15% and less than 5% with the fourth.
Until recently, there were only a few choices if standard antidepressants did not work: augmentation with atypical antipsychotics, transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT). For many patients, logistical factors, time commitments and the risk of permanent side effects made these treatments unappealing. Recently, ketamine and esketamine (marketed as Spravato®) have become alternatives to TMS, ECT and adjunctive antipsychotic medications. Ketamine is not approved by the FDA but has been shown in studies to be effective in TRD, Bipolar Depression, PTSD, OCD, and substance use disorders. Spravato® is FDA approved for use in depression.
Spravato® is esketamine, an isomer of ketamine, and it is used to treat major depression. It is the more potent isomer of ketamine which allows it to be delivered effectively and comfortably by nasal spray. Spravato® was approved by the FDA in 2019 as it was shown in clinical trials to be safe and effective in patients with treatment resistant depression.
Spravato® is FDA approved for treatment resistant depression in adults in conjunction with another antidepressant. Treatment resistant depression is now defined as depression that does not respond to adequate trials of two antidepressants. Spravato® has been recently approved for use in adults with major depressive disorder who have suicidal ideation. These patients do not have to fail adequate trials of 2 antidepressants, they can proceed directly to Spravato® treatment.
Like many antidepressants, we don’t know the exact mechanism of action. We do know that Spravato® interacts with the NMDA receptor, a subtype of glutamate receptor. This is different from most of the current antidepressants which interact with receptors involved with norepinephrine, serotonin, and dopamine.
In clinical trials, 70% of patients with TRD responded. Many of these patients failed 3-5 antidepressants and had suicidal ideation as one of their depressive symptoms. Clinically there are three main advantages to Spravato® treatment: it works when other antidepressants do not, it works quickly (in days to weeks instead of months), and there are virtually no medication side effects between treatments.
If you or someone you love is suffering from Depression that is not responding to treatment, we encourage you to reach out to Avance Psychiatry. Please call 919-375-0142 to make an appointment with us.