FDA Approves First-Ever Standalone Therapy For Treatment-Resistant Depression

MDD is one of the most common mental health conditions in the US, affecting an estimated 21 million adults. Of those, around a third experience a treatment-resistant form of the condition; this means that their symptoms haven’t significantly alleviated after receiving standard treatments, such as at least two antidepressants and psychotherapy.

While there are existing avenues for such cases, including transcranial magnetic stimulation, researchers have also been exploring the possibility of using alternative antidepressant medications – that’s where the newly-approved nasal spray comes in.

Called SPRAVATO®, the nasal spray contains esketamine, a drug that is the chemical mirror-image (enantiomer) of the anesthetic drug ketamine. It had previously been FDA-approved back in 2019 – with some controversy, given the addictive nature of ketamine – for use with oral antidepressants.

Now, according to its manufacturer Johnson & Johnson, fresh clinical trial data has shown that the spray is effective on its own; at week 4 of the study, 22.5 percent of the patients taking SPRAVATO® had achieved remission from their treatment-resistant MDD, compared to 7.6 percent of the placebo group.

Like other antidepressants, the exact mechanism by which esketamine works to reduce depressive symptoms is unknown. However, esketamine increases levels of glutamate, an excitatory neurotransmitter.

Given the potential for abuse, there’s also some controversy over the use of esketamine as a treatment for depression. However, its approval doesn’t mean that it’ll be handed out with reckless abandon – the spray will only be available through a restricted program and can only be administered in a healthcare setting.

Patients will then have to be monitored by a healthcare provider for at least two hours for serious side effects – despite its apparent effectiveness, esketamine can still have side effects. According to Johns Hopkins Medicine, these can range from nausea and a headache all the way through to dissociation and hallucinations, though they tend to peak at around 40 minutes after the drug is administered and decrease thereafter.

Nonetheless, those behind the development of the spray are hopeful that its approval will make a difference to people with MDD.

“Treatment-resistant depression can be very complicated, especially for patients who do not respond to oral antidepressants or cannot tolerate them. For too long, healthcare providers have had few options to offer patients much-needed symptom improvement,” said Dr Bill Martin, Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Innovative Medicine, in a statement.

Now, Martin continued, “patients may experience improvements in depressive symptoms as early as 24 hours and at 28 days – without the need for daily oral antidepressants.”

If you or someone you know is struggling, help and support are available in the US via the 988 Suicide & Crisis Lifeline which can be contacted by dialing 988. In the UK and Ireland, the Samaritans can be contacted on 116 123. International helplines can be found at SuicideStop.com.