This new therapeutic option seems reestablishing neural connections that are reduced or diminished, thus helping patients to respond better to therapy. Its innovation lies in the fact that it is a glutamate receptor modulator, which helps restore synaptic connections in brain cells in people with major depressive disorder. For acting on a different neurotransmitter, the US Food and Drug Administration (FDA) granted it Breakthrough Therapy Designation in November 2013.
The drug, which has already been studied in approximately more than 1800 patients in five global trials, showed that when administered together with an oral antidepressant, it offers a significant improvement in depressive symptoms and long-term relapse prevention. Asked about its coverage in social and prepaid works, Johnson & Johnson’s Janssen laboratory, which launches the spray in the country, pointed out that “The type of coverage will vary according to the health system that each patient has.”
Esketamine, which is launched this Thursday in the country, is already on the market and according to studies, in addition to the basic antidepressant, shows results in a matter of hours, while that most conventional antidepressants can take 3 to 6 weeks to work.
One of the professionals who know the most about this new therapeutic option in the country is the Dr. Daniel Mosca, psychiatrist, coordinator of the Traumatic Stress service at Hospital Alvear and coordinator of the SAME Human Factors team. In dialogue with Ambit, cleared up doubts about the nasal spray.
Journalist: Why a nasal spray?
Daniel Mosca: The first presentation of this drug was an intravenous injection, which was never available in Argentina. But the spray has pharmacokinetic characteristics that improve absorption and reduce the number of procedures and discomfort.
Q .: What characteristics does the drug have?
D.M: It is an antidepressant that works by a completely different mechanism of action than those that hit the market in the last 40 or 50 years. All antidepressants work on amines, such as serotonin, norepinephrine, or dopamine. This new drug has a different mechanism of action associated with glutamate, which is another neurotransmitter in the brain.
Q .: Does the fact that it is a spray make its effect faster?
D.M.: It is faster not because it is a spray, but because of the characteristics of the drug. With conventional antidepressants we have to wait two weeks to see a full effect and, in many cases, we have to start changing strategies or increasing doses when we realize that the drug did not work. In contrast, with esketamine, this is seen in the first four hours of administration, because it has a much lower latency than conventional antidepressant therapies.
Q .: Why is it indicated as a third line of treatment?
D.M.: It is given as the third line because the studies were done on patients with resistant depression, which are those who did not respond to the first two lines of treatment. At no time was it thought of as the first line of treatment because between 60 and 70% of patients will respond to the usual drugs, which have a much simpler route of administration that consists of taking a tablet every morning. But between 30 and 40% do not respond, so we are going to think about esketamine, with a more complex form of administration than oral.
Q .: How is the spray administered and how often?
D.M.: The nasal spray is self-administered by the patient, but supervised by a physician. In other words, the patient will not be able to go to the pharmacy to buy this intranasal device, but the drug will go directly to the center where it is administered and to where the patient has to move. Regarding the frequency, at first it is administered twice a week during the first month, in the second week it becomes weekly and there, based on the response of the patient, if he recovered emotionally and functionally, we begin in a stage maintenance every two weeks or in some patients, up to four weeks.
Q .: Why is it given with an oral antidepressant together?
D.M.: Because it was studied that way. The trials were conducted by administering a conventional antidepressant plus placebo or an antidepressant plus esketamine and were approved by the FDA and ANMAT. In fact, we now have one of the studies that is still ongoing in Argentina (because we participate in the international development program for this drug) in which the traditional antidepressant may not be administered.
Q .: This drug works in hours. Can this be considered an advantage over other drugs?
D.M.: Surely. And this is anecdotal, but when we evaluate medications, we use scales that measure how depressive symptoms decrease. And we had to modify one of the scales of clinical studies in suicidal patients, in which symptoms are usually taken in the last 7 or 14 days. We modified it because in many patients improvement of the symptoms was seen within 24 hours from an application-
Q .: What adverse effects does esketamine have?
D.M.: To a lesser extent, the adverse effects of the drug may be drowsiness and feeling dizzy, but the most common are dissociative symptoms and increased blood pressure. Before each administration, the parameters that one must take are the blood pressure and the partial pressure of oxygen that is taken with an oximeter. If at the time of administration, blood pressure is above normal values, wait to see if this is attributable to nerves, but if it does not drop, it warrants a cardiology consultation. Both adverse effects, such as increased blood pressure and dissociative symptoms, may peak around 30 or 40 minutes after administration. But after 60 or 90 minutes, the patient is regularized and these manifestations disappear, as well as dizziness and drowsiness. The duration of adverse effects is also another important difference compared to other antidepressants, in which the adverse reactions specific to each drug can last for days or even the entire time of taking.
Q .: Who cannot receive this nasal spray?
D.M.: The uncontrolled hypertensive, but it can be administered to those who take the medication and have controlled previous blood pressure levels. Neither are patients who have a partial pressure of oxygen lower than 93, which are those who suffer from severe Chronic Obstructive Pulmonary Disease (COPD), patients who have psychiatric comorbidities and those who present unstable medical comorbidities (the latter is a condition must have for any medication).