Nasal spray for depression is promising, but precautions should be taken

Nasal spray for depression is promising, but precautions should be taken
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On Tuesday March 5, the U.S. Food and Drug Administration approved a nasal spray called esketamine, a molecular variation of ketamine, which can alleviate symptoms of treatment-resistant depression in just a few hours. While ketamine has attracted criticism and controversy over the years, there are numerous reasons to celebrate this development, even if it’s with some caution.

Depression is a common mental health disorder that carries a heavy personal and public health burden. People who are clinically depressed often don’t function as well in their jobs or in their lives. They have higher rates of attempted and completed suicide than those without the disorder. They also take more sick days and leaves of absence from work, and consume more health care services.


Most people with symptoms of depression have the expectation that if they seek medical attention, their physician will prescribe an antidepressant, like Prozac or Zoloft. Those medications typically take at least a few weeks to reach their full effect. While many people who receive an antidepressant follow this recovery path, others do not. Those with treatment-resistant depression are individuals who’ve had persisting symptoms of depression, despite at least two full treatment episodes with different antidepressants. For individuals with such depression, and for their loved ones, this fast-acting nasal spray is a potential breakthrough.

Ketamine, first developed in 1962 as an anesthetic, has a storied experimental past, including as a combat-zone anesthetic and party drug known as “Special K.” Arguing that the effects of ketamine were similar, but less intense than phencyclidine (PCP), the Drug Enforcement Administration, in 1999, classified ketamine as a Schedule III controlled substance. That attempt to curb recreational use, fortunately didn’t stop scientists from studying the drug.

Dr. John Krystal, professor and chair of the Yale department of psychiatry, has been studying ketamine and its effects in humans for over 25 years. This work and research by other investigators across the country has now led to the FDA approve esketamine. Dr. Krystal and his colleagues have called ketamine a paradigm shift in the treatment of depression.

He explains that, “All prior antidepressant treatment for depression have targeted the monoamine systems of the brain, neural systems that use chemicals like dopamine, serotonin, and norepinephrine for neural communication. Ketamine targets a different system, the glutamate system. Because it works through a different chemical signaling system than the standard antidepressants, people who do not respond to standard antidepressant medications may still respond to ketamine.”

Of course, there are always additional angles to think about as the practice of this new treatment unfolds. Sharon Wise, a mental health advocate and artist in Washington, DC, believes this is exciting news. “This is exactly what some folks need,” Sharon exclaimed. But then half-jokingly adds, “It’s better than a lobotomy.” She has struggled with poorly treated mental illness for most of her childhood, and parts of her adulthood. Sharon knows the horrors of un-treated as well as under-treated depressive symptoms. Even though Sharon is enthusiastic about this advance, she can’t help but wonder if, when, and how it will be made available to those who are financially disadvantaged. “I hope it’s not just for those who can afford it or have good insurance. I bet you must get all kinds of Medicaid approvals before a poor person can access it.” For sure, effective mental health treatments need to be available and accessible to all persons.

Dr. David Susman, a clinical psychologist who worked for over two decades at a public psychiatric hospital in Kentucky and has an award-winning blog on mental health, wellness and recovery brings up another good point. “Like all medicines, it won’t repair your relationships, make you a better person, or fix all your problems.

That’s why psychotherapy is so important.” It is true that medications do not offer individuals social support systems and skills for more effective living. But if someone has had two full courses of traditional antidepressants, and still wears a thick-coat of self-loathing, can’t get out of bed or make eye contact with loved ones, this new medication, with appropriate supervision and caution, could be a game-changer. And, if it helps individuals with treatment-resistant depression gain meaningful improvement in a relatively short period of time, it may give them the energy and hope to engage in other forms of healing, including evidence-based psychotherapies.

So, what are the cautions and how should esketamine be administered? Dr. Krystal believes, “People should be carefully prepared for the possible subjective effects of ketamine, such as drowsiness, nausea or confusion. They should be supervised by a licensed health care professional when administered ketamine to help them manage the effects of the drug.

And they should be debriefed after they receive ketamine to make sure that they understand what they experienced. I believe that the addiction risks of ketamine can be managed effectively by limiting the administration of ketamine to clinic settings. I am very concerned that if people took home large amounts of ketamine to use as they saw fit, that they would be vulnerable to developing addiction or other complications of ketamine treatment.”

Though the therapeutic effects of ketamine have been best studied for the treatment of depression symptoms in the context of major depression or depression symptoms associated with bipolar disorder, other exciting research is on the horizon. The effects of ketamine are currently being studied for those with PTSD, borderline personality disorder, obsessive compulsive disorder, generalized anxiety disorder, and other conditions.

This new nasal spray delivery system promises to make ketamine treatment available to a much wider group of patients. In so doing, it could have a profound impact on the lives of people who suffer with persisting symptoms of depression. For now, this nasal spray has to be administered at a physician’s office and not at home. Of course, more studies are warranted, and precautions should be taken. But, no doubt, this is a huge step forward for science and for those who suffer.

Joan Cook is a psychologist and associate professor at Yale University who researches traumatic stress and clinically treats combat veterans, interpersonal violence survivors and people who escaped the former World Trade Center towers on 9/11.