A breakthrough study finds esketamine nasal spray may deliver meaningful improvement for treatment-resistant depression within hours. For decades, patients struggling with major depressive disorder (MDD) have had to wait weeks sometimes months for antidepressant medications to show effects. For roughly one in three people, even after trying multiple drugs, relief never comes. This group, known as treatment-resistant depression (TRD), faces limited and often frustrating options.

Now, a new clinical trial suggests there may be another path, esketamine nasal spray. Researchers report that when used as a standalone treatment, esketamine provided rapid and sustained relief for adults with TRD. Unlike traditional antidepressants that take weeks to work, improvements appeared within 24 hours and lasted throughout the study’s four-week duration. The findings were published in JAMA Psychiatry.

Ketamine, a compound first approved in the 1970s as an anesthetic, has drawn increasing attention for its antidepressant effects at lower doses. Esketamine, a chemically refined version, works on similar pathways but is more targeted.

In 2019, the U.S. Food and Drug Administration approved SPRAVATO, an esketamine nasal spray, for use alongside oral antidepressants in TRD. Until now, it was unclear whether the spray could stand on its own. This new phase 4 trial offers the strongest evidence yet that esketamine may be effective without an added oral drug.

The study enrolled 378 adults across 51 U.S. outpatient centers between 2020 and 2024. To qualify, participants had to show a history of poor response—defined as less than 25% improvement—to at least two antidepressants during their current depressive episode.

Key features of the trial included:

Design: randomized, double-blind, placebo-controlled

Groups: fixed doses of either 56 mg or 84 mg esketamine, or a placebo spray

Treatment schedule: twice-weekly dosing for four weeks

Primary measure: changes in Montgomery-Åsberg Depression Rating Scale (MADRS) scores, which capture depression severity

Most participants were women (61%), and the average age was 45. All entered the study with moderate-to-severe depression.

How Esketamine Nasal Spray Works?

Within a single day of treatment, both esketamine groups reported noticeable improvements compared to placebo. By day 28, those on 56 mg showed a 5.1-point greater reduction in symptom scores versus placebo.

The 84 mg group had an even stronger effect, with a 6.8-point advantage. For perspective, traditional antidepressants often take six to eight weeks to yield measurable changes. Esketamine’s speed is one of the factors making it so promising for TRD patients, many of whom live with intense, persistent distress.

Patients who continued into the optional 12-week open-label phase—where all participants received esketamine—maintained or further improved their scores. This suggests the drug’s benefits may extend beyond the initial four weeks.

The “number needed to treat,” a measure of clinical significance, was around 6–7 for symptom response. This means that for every six or seven patients treated, at least one more experienced a meaningful reduction in depression compared to placebo. For a psychiatric intervention, that is a robust effect size.

Are There Any Side Effects of the Nasal Spray?

Like other ketamine-based therapies, esketamine is not without side effects. In this trial, the most common were nausea, dizziness, headache, and dissociation, a temporary feeling of detachment from one’s surroundings.

Importantly, these effects were short-lived, generally resolving within hours of dosing. Safety monitoring also showed no increase in suicidal thinking compared to placebo, an encouraging finding in depression research. No treatment-related deaths were reported.

Still, the psychoactive nature of the drug meant some participants could guess whether they had received esketamine or placebo, a limitation that researchers acknowledged.

For the estimated 280 million people worldwide living with major depressive disorder, and especially the one-third who don’t respond to conventional drugs, esketamine represents a potential paradigm shift.

Traditional antidepressants work by altering serotonin, norepinephrine, or dopamine. Esketamine instead targets the glutamate system, offering a novel mechanism of action. That difference matters- before SPRAVATO, psychiatry hadn’t seen a new treatment pathway in over 30 years.

Adam Janik, medical director at Johnson & Johnson and lead author of the study, emphasized the scale of the problem: “The size and scope of the global depression epidemic is staggering. Significant unmet needs remain for these patients.”

While the findings are promising, experts caution against premature conclusions. The trial population was not racially diverse, and individuals with certain psychiatric conditions were excluded. That raises questions about how well the results will apply across broader patient groups.

For decades, patients with treatment-resistant depression have cycled through medications, therapies, and hospitalizations, often with little relief. This study adds weight to a growing body of evidence that esketamine could break that cycle. While it is not a cure, the possibility of meaningful relief within hours rather than weeks could be life-changing for millions.

The NHS has issued a caution on its website for anyone taking a commonly prescribed medication for high blood pressure. Also known as hypertension, this condition affects roughly one in three adults in the UK, many of whom may not even be aware they have it. Since uncontrolled high blood pressure can raise the risk of stroke, heart disease, and kidney problems, early treatment is essential.

This is where blood pressure–lowering medications come in. As of 2025, amlodipine (a calcium channel blocker) and ramipril (an ACE inhibitor) rank among the most commonly prescribed drugs in the UK. Recently, the NHS has highlighted some warnings regarding these medications. Let’s look at why and what precautions patients taking them should follow.

What Is Amlodipine?

Amlodipine is a calcium channel blocker that helps manage high blood pressure. A single dose works for over 24 hours, so it only needs to be taken once daily. It is also prescribed for people experiencing chest pain. According to the Cleveland Clinic, amlodipine relaxes blood vessels and eases the workload on the heart. Each year, more than 30 million prescriptions are written for this medication. Many patients take amlodipine for long periods or even for life. It is usually recommended when lifestyle changes alone are insufficient to control blood pressure or when genetic factors make medication necessary.

How Amlodipine Works?

Amlodipine helps prevent future heart problems, including heart disease, heart attacks, and strokes. It is also used to relieve chest pain caused by angina. The drug lowers high blood pressure by relaxing and widening blood vessels, which makes it easier for the heart to pump blood throughout the body. In angina, chest pain occurs because arteries leading to the heart are narrowed and stiff. Amlodipine improves blood and oxygen flow to the heart, easing these symptoms. It is available only with a prescription and comes as a tablet or a liquid that is swallowed.

Why Is the NHS Warning Against Amlodipine?

Patients taking amlodipine should avoid one particular drink. The NHS website states: "Do not take amlodipine with grapefruit juice. Consuming large amounts of grapefruit or grapefruit juice can raise amlodipine levels in your body and worsen side effects. If affected, you may need to avoid grapefruit or grapefruit juice while on this medication."

It adds: "Tell your doctor if you experience increased side effects, such as dizziness, flushing, or headaches, after consuming grapefruit or grapefruit juice. Otherwise, you can continue to eat and drink normally while taking amlodipine."

Amlodipine Side Effects

These side effects occur in more than one in 100 people. They are usually mild and temporary, and there are ways to manage them:

• Headaches: Rest and stay hydrated. Limit alcohol intake. Your pharmacist can suggest a suitable painkiller. Headaches usually ease within the first week of starting amlodipine. Contact your doctor if they persist or are severe.
• Feeling dizzy: Sit or lie down until the dizziness passes. Avoid driving, cycling, or operating machinery until you feel better.
• Flushing: Reduce coffee, tea, and alcohol consumption. Keep your environment cool, use a fan, spray your face with cool water, or sip cold drinks. This usually resolves in a few days; consult your doctor if it persists.
• Pounding heartbeat: Take amlodipine when you can rest or sit down if symptoms occur. Reducing alcohol, smoking, caffeine, and heavy meals may help.

The White House on Friday shared a memo from President Donald Trump’s physician detailing his latest visit to Walter Reed Army Medical Center, where he received both a COVID-19 booster and a flu shot.

In the one-page summary, Dr. Sean P. Barbarella noted that the former president “continues to be in excellent health, showing strong cardiovascular, respiratory, neurological, and overall physical function.”

According to the memo, Trump’s stop at Walter Reed was a “scheduled follow-up.” White House press secretary Karoline Leavitt had earlier in the week described it as part of his “routine annual check-up,” even though it marks his second visit this year following a full physical examination.

Why Donald Trump Took the COVID Shot?

The memo explained that the former president’s visit involved preventive health screenings and immunizations, which included his annual flu vaccine and an updated COVID-19 booster. It also mentioned that Trump has suggested plans to travel to Egypt in connection with the Israel-Gaza peace efforts.

In addition, the document noted that “comprehensive laboratory tests conducted during the visit showed outstanding results, with stable metabolic, blood, and heart indicators.” The report concluded that Trump continues to maintain excellent overall health.

Access to COVID Shots Narrows Under Trump Administration

COVID-19 vaccines have become more difficult to access during the Trump administration. On Monday, the Centers for Disease Control and Prevention revised its vaccination guidelines, now recommending the shots only for individuals aged 65 and above or for those with existing health conditions, and only after consulting a healthcare provider such as a doctor, nurse, or pharmacist.

This update follows months of differing state-level vaccine rules, which created a confusing patchwork of policies nationwide. As a result, many people are finding it increasingly challenging to get vaccinated, depending on where they live.

CDC Says People Must Consult a Health Professional Before COVID Shot

Acting CDC Director Jim O’Neill has approved new COVID-19 vaccine recommendations proposed by Health Secretary Robert F. Kennedy Jr.’s selected Advisory Committee on Immunization Practices, which convened in September.

During a previous meeting held in June, vaccine advisers to the CDC had discussed revising the vaccination process. Under the new rules, people are now required to speak with a doctor, pharmacist, or another healthcare provider about the potential risks and benefits before receiving the shot. This added step, referred to as “shared decision-making” or “individual-based decision-making,” is highlighted in the CDC’s official statement.

The updated policy represents the final step needed to enforce the new vaccination guidelines, influencing who can receive and administer the COVID-19 vaccine and determining whether it will be covered by private or public insurance plans without additional copayments.

Final Recommendations Were Delayed

The approval followed an unusual two-week delay between the time CDC advisers issued their recommendations and when the agency formally accepted them. With this decision now in place, the CDC can begin distributing vaccines to doctors, clinics, and other healthcare providers under the Vaccines for Children Program, which supplies free vaccines to about 40 percent of children in the United States.

Hellofresh: As the listeria outbreak continues to spread across the United States, more products are being identified as contaminated. The U.S. Food and Drug Administration (FDA) has issued a recall for certain frozen spinach items found to contain Listeria monocytogenes. The affected spinach was sold under two names, Del Mar 35-pound Bulk Organic Frozen Spinach and Sno-Pac Organic Frozen Cut Spinach in 10-ounce packs, distributed to consumers across the country.

Each year, millions of Americans deal with food sensitivities and allergies. According to the FDA, the nine main food allergens in the United States include eggs, milk, fish, wheat, soybeans, crustacean shellfish, sesame, tree nuts, and peanuts.

HelloFresh Meals Contaminated With Listeria

Federal health officials have advised the public not to eat certain HelloFresh subscription meals containing spinach that may be contaminated with listeria. In connection with the same concern, Sno Pac Foods, Inc. has also recalled both its Sno Pac and Del Mar brands of organic frozen spinach products due to fears of Listeria monocytogenes contamination.

The recalled Del Mar Bulk Organic Frozen Spinach was sold in 35-pound boxes with an expiration date of January 1, 2027, and the following lot numbers: 250107A, 250107B, 250107C, 250107D, 2501071, and 2501073.

The Sno Pac Organic Frozen Cut Spinach came in 10-ounce containers with these lot codes and “best by” dates: SPM1.190.5 (best by July 9, 2027), SPC1.160.5 (best by June 9, 2027), SPC2.160.5 (best by June 9, 2027), and SPM1.097.5 (best by April 7, 2027).

The official notice warns: “Healthy individuals may experience short-term symptoms such as high fever, severe headache, stiffness, nausea, abdominal pain, and diarrhea. However, Listeria infection can lead to miscarriages and stillbirths in pregnant women.”

For more details, consumers can view the recalled product labels on the FDA website. Anyone who has these frozen spinach products at home is urged not to eat them. Instead, they should dispose of the items safely or return them to the store for a full refund.

Previous Listeria Outbreaks

Just last month, FreshRealm confirmed that tests showed pasta used in certain linguine dishes sold at Walmart carried the same strain of listeria linked to an earlier outbreak in June. That outbreak, which initially involved chicken fettuccine Alfredo, resulted in at least four deaths and 20 reported illnesses, the most recent occurring on September 11.

What Is Listeria Monocytogenes?

According to the National Institutes of Health, Listeria monocytogenes is a type of bacteria that causes the infection known as listeriosis. It is a facultative anaerobic organism, meaning it can survive with or without oxygen. The bacterium can live and multiply inside the body’s cells, making it one of the most dangerous foodborne pathogens known.

Listeria Symptoms

A listeria infection can be especially serious for older adults, pregnant women and their newborns, and individuals with weakened immune systems. Common symptoms include fever, muscle aches, headache, stiff neck, confusion, loss of balance, and convulsions.

The Centers for Disease Control and Prevention (CDC) estimates that around 1,600 people become ill from listeria infections each year, and roughly 260 die. Federal agencies said in December that they were revising safety procedures to prevent further outbreaks following several major incidents, including one linked to Boar’s Head deli meats that caused 10 deaths and more than 60 illnesses last year.