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NIH MedlinePlus the Magazine, Trusted Health Information from the National Institutes of Health


For the First Time, Life Seems Worth Living

Drug in research shows promise

Beck first tried to commit suicide when she was just 12 years old. It wasn't her last attempt.

Over the next decade, Beck (not her real name) sought help for what was diagnosed by psychiatrists and other health professionals as extreme depressive disorder, post-traumatic stress disorder (PTSD), and generalized anxiety disorder.

"All through adolescence, I had feelings of hopelessness," she says. Although she became a talented musician and an artist, she could feel no pleasure or fulfillment in any of her accomplishments.

"I have been able to navigate through the world, for the most part, without being seen as a sick person."

"I have been able to navigate through the world, for the most part, without being seen as a sick person."

But none of the medications and other treatments she underwent over the years made any difference in her severe depression, suicidal thoughts, and feelings of worthlessness. Finally, she approached the National Institute of Mental Health (NIMH) at NIH, desperate for help. Now in her mid-20s, she was admitted into a research study run by Dr. Carlos Zarate that was testing a medication called ketamine.

"I got an intravenous infusion of ketamine, which took a couple of hours. After the experience, I felt very neutral and calm—kind of cleaned out a little bit. The first moment that I felt ketamine had acted as an antidepressant was when I felt proud of having gotten through the infusion.

"I've accomplished a lot of things in my life, but I've never really felt proud of myself before. That was a really unique experience," she says. "And I could tell there was something a little different in my brain after that. The week after the infusion, I felt self-esteem for the first time. There were moments when I wasn't thinking anything at all, rather than having a non-stop barrage of negative thoughts. Those were important experiences for me, and ones I hope to build on."

It's unlikely that ketamine, in its current form, will become a practical treatment for most cases of depression. It must be administered through infusion (intravenously), requiring a hospital setting, and can potentially trigger adverse side effects. Patients also typically relapse after treatment ends. But research is continuing.

Dr. Carlos Zarate: "The research on ketamine is very exciting."

Carlos A. Zarate, MD

Carlos A. Zarate, MD, is a pioneer and award-winning expert on developing novel medications for treatment-resistant depression and bipolar disorder.

He is Chief of the Experimental Therapeutics and Pathophysiology Branch and Section on the Neurobiology and Treatment of Mood Disorders at the National Institute of Mental Health, and Clinical Professor of Psychiatry and Behavioral Sciences at George Washington University.

Dr. Zarate spoke recently to NIH MedlinePlus magazine about depression and the promising treatment of the drug ketamine.

What should people do if they think they or a loved one might suffer from depression?

If someone just has a sad mood or if something bad happens, but their low mood doesn't last longer than a few weeks, it might not be depression. If someone has persistent symptoms, for more days than not for several weeks, then they may need to seek help.

How do you seek help? There are many places to get information, including the web. One place with information you can trust is the National Institute of Mental Health, of course.

For the most part, everyone should have a primary care provider. They are trained to identify symptoms of depression, and have questionnaires. So, you should feel free to bring up the topic of depression with your primary care provider. Your health care professional will evaluate you to see if the symptoms need evaluation.

Tell us about ketamine, which has been seen to be a fast-acting medicine for those with severe clinical depression?

The limitation of our current psychotherapy and medications for depression is that there is a considerable lag—weeks, if not months—for the full effects to take place. Many people do benefit, but it takes a long time, and not everybody gets better.

We've been studying ketamine for about a decade. It's an anesthetic, but in very low doses ketamine works as a rapid antidepressant. This discovery fundamentally changes our understanding of how an antidepressant mechanism works.

When ketamine works—and it doesn't work for everybody—the patient responds within a few hours. It also has rapid anti-suicidal effects. Within 40 minutes, suicidal thoughts seem to be gone or rapidly improved. It also seems to have an effect on anhedonia (a form of depression that robs a patient of any pleasure in life). If we just focus on depression and suicide, ketamine's reactions for patients within a few hours to a day, at most, is remarkable.

If it's so remarkable, what is the issue with ketamine?

As an anesthetic agent, it has to be closely monitored, because it may cause changes in blood pressure and pulse. Also, during the infusion of ketamine, people experience symptoms of dissociation; you are disconnected from your senses. So, smells, light, and sounds might be distorted. The patient might hear voices or see things that are not there. Also, if not used correctly, there could be a potential of abuse with ketamine.

Despite that, there has been a surge of worldwide ketamine use with very ill patients. The research on ketamine is very exciting. And we are working to develop a safer form of ketamine, without ketamine's side effects.

Read More "Depression" Articles

Dealing with Depression / Depression Strikes… Anyone / For the First Time, Life Seems Worth Living | Dr. Carlos Zarate / Understanding Depression | Research Update

Winter 2017 Issue: Volume 11 Number 4 Page 5-6