At a veterans event in Kentucky last week, President Donald Trump touted what he called an "incredible" new drug he says could help American veterans struggling with depression.
The drug, called esketamine and marketed as Spravato, was produced by Johnson & Johnson subsidiary Janssen Pharmaceuticals and billed as a breakthrough treatment for patients who have not responded to other antidepressants.
The Food and Drug Administration approved Spravato in March, although some uncertainties remain about its effectiveness, risks and long term effects, according to experts.
However, those concerns were absent when the president ordered Department of Veterans Affairs last week to purchase it and "get as much of it as you can from Johnson & Johnson."
"It really has an incredible effect for a lot of people," Trump told an audience at the AMVETS National Convention in Louisville, Kentucky, on Wednesday.
In light of the burden of severe depression among veterans and the alarming rate of suicide -- with 20 veterans dying each day by suicide -- Trump is not the only one who feels the imperative of a timely solution.
What is Spravato?
Spravato is a nasal spray based on the drug ketamine, which has been used as an anesthetic for over half a century since its introduction in the 1960s and has played an emerging role in the treatment of chronic pain and treatment-resistant depression by doctors.
Typically given in IV form, ketamine was reformulated as Spravato for people with treatment-resistant depression, and it boasts quicker and easier delivery with fewer side effects.
A series of clinical trials have shown that the drug, when given in conjunction with a typical antidepressant, such as a selective serotonin reuptake inhibitor, can improve people's depressive symptoms.
Results in one out of three randomized controlled trials used by the FDA to fast-track the drug showed positive efficacy, but the size of the drug's impact on depressive symptoms has been critiqued. In the study used by the FDA, there was just a 4-point improvement in depression symptoms on a 60-point scale used by some clinicians to measure depression.
"The clinical trials of esketamine were completely underwhelming," said Dr. Wesley Boyd, psychiatrist at Cambridge Health Alliance and an assistant professor of psychiatry at Harvard Medical School who was not involved in the studies.
"I'm open to giving esketamine consideration, but given the data we have and its high cost, there are other drugs and therapies we can maximize first," he added.
Boyd cautioned about trials supported by the pharmaceutical industry, like those used for Spravato, though it is not uncommon for pharmaceutical companies to sponsor trials. The two trials that had positive results used by the FDA in their approval of Spravato were funded and conducted by Janssen.
Another refrain among experts is that there is too little data to assess the medication's long term effects, including potential harms, and it has not shown to be efficacious in treating individuals over the age of 65 -- a population of particular relevance to the veteran community. It was also mainly tested in white people.
Long-term studies and reporting of adverse events associated with the use of the drug are ongoing.
A treatment for America's veterans?
Despite the limited research on esketamine, the FDA green-lighted Spravato because there's been a long-standing need for more effective treatments for treatment-resistance depression, which is considered a life-threatening condition, according to the FDA.
Used in conjunction with oral antidepressants, Spravato is administered by medical professionals who are required to monitor a patient for two hours after receiving treatment. Possible side effects of the drug include sedation, nausea and increased blood pressure.
Additionally, black box warnings include the risk of drug abuse and suicide in pediatric and young adult patients. While suicide warnings are seen with other antidepressants, Boyd notes that box warnings are not generic, saying, "A box warning would have to be a result of people during clinical trials who experienced suicidal thinking while taking the drug."
Although, severely depressed people may already have suicidal thoughts before starting treatment, he added.
"I applaud VA efforts to get good treatments into the hands of veterans -- not just the hottest treatment, but the whole menu of options" said Dr. Jonathan Avery, director of Addiction Psychiatry at Weill Cornell Medical College who completed his training at the VA but was not involved in the clinical trials for Spravato. "There's a lot of hope for esketamine, but we should be sure the VA is equipped with all the well-studied medications and psycho-social treatments that we have, including cognitive behavioral therapy."
In response to mounting rates of suicide among veterans, the VA has reformed its guidelines to reflect new data on best practices for screening, evaluating and treating veterans with increased suicide risks.
New recommendations suggest a combination of medication and cognitive behavioral therapy with routine medical visits, frequent outreach, and a "safety" or "crisis response" plan for those at greatest risk. The recommendations also address "lethal means" safety, including restricting people’s access to firearms, poisons, medications and installing barriers to prevent jumping from lethal heights.
Getting Spravato to veterans
A VA advisory panel in June decided the use of Spravato would require justification prior to use -- an authorization not unusual for an expensive and powerful new drug.
Still, Spravato is now available to veterans enrolled in VA care "based on an individualized treatment plan developed by their provider in collaboration with the veteran," a VA spokesperson said.
The department has developed guidelines for Spravato's use "to promote thoughtful patient selection and safe administration practices."
VA Secretary Robert Wilkie, who described Spravato as in its "opening stages" during a Fox News interview on Thursday, said the drug is being used by veterans under the supervision of anesthesiologists at the VA who can monitor any side effects patients experience after taking the drug.
The VA spokesperson told ABC News that the department will continue to monitor the drug's use "to more fully understand its relative safety and effectiveness as compared to other available treatments. Based on this information, the VA may revise its clinical guidance and formulary status if warranted."
Trump pushes Spravato
While there is excitement in the medical community about the promise of Spravato, the president's public promotion of the drug's prescription for veterans has raised eyebrows.
The Center for Public Integrity, a nonprofit investigative news organization, reported in June that Trump was pushing VA officials for quicker adoption of Spravato, and, according to Bloomberg News, the president personally offered to help the VA negotiate purchases of the drug from Janssen.
Trump's ambassador to the United Kingdom Robert Wood "Woody" Johnson IV is the great-grandson of the co-founder of Johnson & Johnson and heir to the "consumer products fortune," owning over 1.5 million shares in the company, according to Bloomberg.
Johnson donated $1 million to Trump's inaugural campaign and was nominated to the ambassadorship in 2017.
Prior to departing for Louisville on Wednesday, the president said the VA would get Spravato "at a very good cost." But hours later at the AMVETS event, he suggested Johnson & Johnson should give the drug to the department for "free" because they "have done so well in this country and they have made so much money."
Janssen spokesperson Kaitlin Meiser told ABC News, "We have not had any conversations with President Trump regarding Spravato."
"Information regarding contracts with payers, including the VA, is proprietary," Meiser said, but "the VA is offered the lowest price in the country."
The VA also declined to say how much the purchase of Spravato would cost the department.