Depression - Intranasal Glutamatergic Antidepressants
(Esketamine)
Esketamine is a new type of antidepressant medication. Unlike typical antidepressants, it targets the brain’s glutamatergic system, stimulating the release of glutamate in brain nerves, which rapidly increases the number and strength of connections between neurons. With more active connections between neurons than before, a person’s mood and motivation are consequently improved.
-
What’s the difference between glutamate medications and serotonin? The new drug Esketamine as one of the options for treatment-resistant depression
-
The pros and cons of Esketamine! Be sure to read carefully before deciding on treatment
-
Prescription process revealed! Turns out Esketamine is inhaled?
-
Suspect you have depression? The PHQ-7 questionnaire can help!
What’s the Difference Between Glutamate Medications and Serotonin? The New Drug Esketamine as One Option for Treatment-Resistant Depression
There are many causes of depression, and most treatments are based on the Monoamine Hypothesis: the brain lacks sufficient serotonin and other neurotransmitters, and taking oral antidepressants to replenish these substances can alleviate depression symptoms.
However, for some patients, depression is a stubborn, treatment-resistant condition. Even after trying various antidepressants, their symptoms persist. These lingering symptoms affect their daily life and work performance, significantly increasing the risk of depression relapse.
When facing treatment-resistant depression (TRD), psychiatrists typically explore alternative approaches. This might involve switching to different types of antidepressants, trying TMS (Transcranial Magnetic Stimulation), or, in more severe cases, admitting the patient for ECT (Electroconvulsive Therapy).
Esketamine is a new type of antidepressant. Unlike traditional antidepressants, it targets the brain’s glutamatergic system, stimulating the release of glutamate in brain nerves. This rapidly increases the number and strength of connections between neurons. With more active neural connections than before, a person’s mood and motivation improve accordingly.
Notably, Esketamine is quite similar in composition to ketamine (commonly known as “K” among recreational drug users). Esketamine is the S-enantiomer of ketamine, but it has a higher affinity, resulting in a stronger effect on the glutamatergic system.
Some people worry that Esketamine might lead to abuse issues like ketamine. However, Esketamine is not addictive. According to clinical trial data, no patients exhibited abusive behavior, nor did they experience withdrawal symptoms after stopping treatment. During treatment, no one requested an increase in dosage or frequency. While many ketamine abusers develop bladder inflammation, no patients in clinical trials reported interstitial cystitis.
Reference:
-
FDA approves first treatment for people with treatment-resistant depression
-
Esketamine for treatment-resistant depression: a new tool for psychiatrists
-
Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants
The Pros and Cons of Esketamine! Must Read Carefully Before Deciding on Treatment
As mentioned earlier, Esketamine, as a new glutamate-based medication, is a great option for treating treatment-resistant depression. However, before choosing to undergo Esketamine treatment, it’s essential to thoroughly understand its benefits and drawbacks.
Esketamine is approved in the United States for treating treatment-resistant depression and for reducing acute suicidal thoughts in patients with depression. Generally, patients can feel the treatment’s effects as early as 24 hours after taking Esketamine, with more than half achieving symptom remission within 28 days of starting treatment. For those who complete a full course of Esketamine, the long-term risk of relapse is reduced by 70% compared to those taking traditional antidepressants, and over half of patients remain in remission a year after completing the course.
However, where there are benefits, there are also downsides. According to current guidelines, Esketamine users must also take a traditional antidepressant like an SSRI or SNRI. This doesn’t mean Esketamine’s effectiveness depends on these drugs—it’s just that in past studies, patients prescribed Esketamine were already on antidepressants. As a result, there isn’t enough data to prove that Esketamine alone can effectively treat treatment-resistant depression.
After taking Esketamine, some patients may experience various side effects, such as dizziness, nausea, headaches, fatigue, vomiting, urinary symptoms, or reduced taste and sensation. However, these side effects typically last only a very short time. According to studies, only 3.8% of patients discontinued treatment within 48 weeks due to these side effects.
It’s important to note that not every depression patient is suitable for Esketamine. If a patient has ever had an allergic reaction to any of its components, or has a history of conditions like aneurysms, brain hemorrhage, or a heart attack within the past 6 weeks, doctors should not prescribe Esketamine. Additionally, we do not recommend its use for patients who are pregnant.
Compared to typical antidepressants, Esketamine is also more expensive. Patients need to spend more time at the clinic for treatment—during the initial phase, they must attend twice-weekly sessions, each lasting two hours. For the average working person, this could be a significant limitation.
Reference:
-
FDA approves new nasal spray medication for treatment-resistant depression
-
Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants
-
Esketamine for the treatment of treatment-resistant depression
-
Efficacy and safety of intranasal esketamine in treatment-resistant depression
Prescription Process Revealed! Turns Out Esketamine Is Inhaled?
Esketamine is unlike other antidepressants. This medication is delivered through a nasal spray device, and before use, healthcare professionals will demonstrate how to use the nasal spray to the patient.
Before using the nasal spray, the patient should first wipe their nose, then lean back comfortably in a chair. Once seated properly, the patient inserts the device’s tip into one nostril, presses the other nostril closed with a finger, pushes the plunger of the nasal spray upward while inhaling, and then removes the device. After that, they should gently sniff to ensure the medication stays in the nose.
Repeat the process for the other nostril. Once finished, the healthcare professional will check the nasal spray device to confirm the medication has been fully used. The patient needs to rest for 5 minutes before using another device, if required. The number of devices used depends on the doctor’s decision, with dosage adjusted based on the patient’s emotional state.
After using Esketamine, the patient must remain at the clinic for 1.5–2 hours. The doctor will provide a calm and quiet environment for the patient to rest. Healthcare staff will also periodically measure the patient’s blood pressure, and if it becomes too high, they will promptly provide appropriate treatment.
As mentioned earlier, Esketamine is a glutamate-based medication. Taking Esketamine stimulates neurons to release glutamate, rapidly increasing the number and strength of connections between brain neurons in a short time.
References:
-
FDA approves new nasal spray medication for treatment-resistant depression
-
The neurobiology of depression, ketamine, and the rapid-acting antidepressant response
-
Efficacy and safety of intranasal esketamine in treatment-resistant depression
Suspect You Have Depression? The PHQ-9 Questionnaire Can Help!
We might worry about whether we have depression. Before seeing a doctor, complete the following questionnaire, and the computer will automatically calculate your score, giving you an additional reference point.
