Millisecond brain signals predict response to fast-acting antidepressant

October 03, 2008

Images of the brain's fastest signals reveal an electromagnetic marker that predicts a patient's response to a fast-acting antidepressant, researchers have discovered.

"Such biomarkers that identify who will benefit from a new class of antidepressants could someday minimize trial-and-error prescribing and speed delivery of care for what can be a life-threatening illness," said Carlos Zarate, M.D., of the National Institute of Mental Health (NIMH), Mood and Anxiety Disorders Program.

In the new study at the National Institutes of Health in Bethesda, MD, depressed patients showed increasing activity in a mood-regulating hub near the front of the brain while viewing flashing frightful faces - the more the increase, the better their response to an experimental fast-acting medication called ketamine. By contrast, healthy controls showed decreasing activity in this brain area under the same conditions.

Zarate, Giacomo Salvadore, M.D., Brian Cornwell, Ph.D., and NIMH colleagues report on their discovery online in Biological Psychiatry September 24, 2008.

Two years ago, Zarate and colleagues reported that ketamine, which targets the brain chemical glutamate, can lift depressions in just hours, instead of the weeks it takes conventional antidepressants, which work through the brain chemical serotonin. Evidence suggests that glutamate likely acts closer to the source of the depression than serotonin, and is not dependant on slower mechanisms, such as the synthesis of new neurons.

Earlier imaging studies with conventional antidepressants had hinted that increased activity of the mood-regulating hub, called the anterior cingulate cortex (ACC), signals a better response.

To find out if ACC activity might also forecast response to glutamate-targeting medications, the NIMH researchers imaged the brain activity of 11 depressed patients and 11 healthy participants, using magnetoencephalography (MEG). This imaging technology can non-invasively detect brain electromagnetic activity lasting only milliseconds - the speed of communications in neural circuits - whereas other functional brain imaging techniques can only capture activity that last seconds or minutes, and some involve radiation exposure.

This precise timing enabled the MEG scanner to capture the brain's split-second responses to rapidly flashing pictures of fearful faces, a task known to activate the ACC. While healthy participants' ACC activity dropped off as they quickly habituated to the faces, patients' ACC activity showed an opposite trend. The more robust this increase, the more symptoms improved just four hours after a patient received a single infusion of ketamine.

"The ACC may be slow to respond, but not completely impaired, in patients who respond to ketamine," explained Cornwell.

The lag in ACC activity could be a window into the dysfunctional workings of the glutamate-related circuitry targeted by the medication, the researchers suggest. Ketamine's side effects make it a poor candidate for becoming a practical antidepressant, but the new findings are helping to focus the search for new treatments that work through the same mechanism, they say.

NIH/National Institute of Mental Health

---

---

	Coming of Age on Zoloft: How Antidepressants Cheered Us Up, Let Us Down, and Changed Who We Are by Katherine Sharpe (Author) When Katherine Sharpe arrived at her college health center with an age-old complaint, a bad case of homesickness, she received a thoroughly modern response: a twenty-minute appointment and a prescription for Zoloft—a drug she would take for the next ten years. This outcome, once unlikely, is now alarmingly common. Twenty-five years after Prozac entered the marketplace, 10 percent of Americans over the age of six use an SSRI antidepressant. In Coming of Age on Zoloft, Sharpe blends deeply personal writing, thoughtful interviews, and historical context to achieve an unprecedented portrait of the antidepressant generation. She explores questions of identity that arise for people who start medication before they have an adult sense of self. She asks why some individuals find a diagnosis of...
	The Antidepressant Solution: A Step-by-Step Guide to Safely Overcoming Antidepressant Withdrawal, Dependence, and "Addiction" by Joseph Glenmullen (Author) With the FDA's warning that antidepressants may cause agitation, anxiety, hostility, and even violent or suicidal tendencies, these medications are at the forefront of national legal news. Harvard physician Joseph Glenmullen has led the charge to warn the public that antidepressants are overprescribed, underregulated, and, especially, misunderstood in their side and withdrawal effects. Now he offers a solution! More than twenty million Americans -- including over one million teens and children -- take one of today's popular antidepressants, such as Paxil, Zoloft, or Effexor. Dr. Glenmullen recognizes the many benefits of antidepressants and prescribes them to his patients, but he is also committed to warning the public of the dangers associated with overprescription. Dr. Glenmullen's...
	The Emperor's New Drugs: Exploding the Antidepressant Myth by Irving Kirsch Ph.D. (Author) Irving Kirsch has the world doubting the efficacy of antidepressants. Based on fifteen years of research, The Emperor's New Drugs makes an overwhelming case that what the medical community considered a cornerstone of psychiatric treatment is little more than a faulty consensus. But Kirsch does more than just criticize: He offers a path society can follow to stop popping pills and start proper treatment.
	Taking Antidepressants: Your Comprehensive Guide to Starting, Staying On, and Safely Quitting by Michael Banov (Author) Antidepressants are the most commonly prescribed class of medications in this country ¬ 190 million prescriptions per year have been written since 2005. Yet, consumers have few available resources to educate them in a balanced fashion about starting and stopping antidepressants. People want to know if antidepressants are really safe, whether they are addictive, and how they may affect their personality. In this book, triple board-certified psychiatrist Dr. Michael Banov walks the reader through a personalized process to help them make the right choice about starting antidepressants, staying on antidepressants, and stopping antidepressants. He includes specific guidelines on how to safely reduce and ultimately stop taking antidepressants, if it is appropriate to do so. Readers will...
	The Anti-Depressant Fact Book: What Your Doctor Won't Tell You About Prozac, Zoloft, Paxil, Celexa, and Luvox by Peter R. Breggin (Author) Known as "the Ralph Nader of psychiatry," Dr. Peter Breggin has been the medical expert in countless court cases involving the use or misuse of psychoactive medications. This unusual position has given him unprecedented access to private pharmaceutical research and correspondence files, information from which informs this straight-talking guide to the most prescribed and controversial category of American drugs: antidepressants. From how these drugs work in the brain to how they treat (or don't treat) depression and obsessive-compulsive, panic, and other disorders; from the documented side and withdrawal effects to what every parent needs to know about antidepressants and teenagers, The Anti-Depressant Fact Book is up-to-the minute and easy-to-access. Hard-hitting and enlightening, every...
	The Prescriber's Guide: Antidepressants: Stahl's Essential Psychopharmacology by Stephen Stahl (Author), Meghan M. Grady (Editor), Nancy Munter (Editor) This spin-off from Stephen Stahl's new, completely revised, and fully updated fourth edition of the Prescriber's Guide covers the most important drugs in use today for treating depression. Now established as the indispensable formulary in psychopharmacology, easy to navigate and easy to use, the Prescriber's Guide combines evidence-based information with clinically-informed guidance to support clinicians in making the most effective prescribing decisions for the good of their patients. Incorporating information on the newest indications, new formulations, new recommendations and new safety data, this edition continues to provide the essential practical support required by anyone prescribing in the field of mental health.
	The Antidepressant Antidote: Five Steps to Get Off Antidepressants Safely and Effectively by Bethany Butzer Ph.D. (Author) Do you want to get off antidepressants and move toward a more full and balanced life? Have you tried several times to get off antidepressants, only to end up right back on them? If so, this book is for you. In The Antidepressant Antidote: Five Steps to Get Off Antidepressants Safely and Effectively, Bethany Butzer, Ph.D. provides practical and proven techniques to help you get off antidepressants once and for all. This life-enhancing 5-step program will teach you: • How to get the support you need as you taper off antidepressants. • Tips to deal with the withdrawal effects that can arise when reducing your antidepressant dose. • Techniques to let go of stress, anxiety, sadness, and depression. • Smart choices to move you toward the type of life you...
	Tarascon Primary Care Pocketbook Card: Antidepressants by Joseph S. Esherick (Author) Measuring only 5.5 x 3.25 inches, this quick and handy laminated card tucks neatly into your Tarascon books to provide you with immediate access to the most frequently used tables in your Tarascon Primary Care Pocketbook.
	The Antidepressant Era by David Healy (Author) When we stop at the pharmacy to pick up our Prozac, are we simply buying a drug? Or are we buying into a disease as well? The first complete account of the phenomenon of antidepressants, this authoritative, highly readable book relates how depression, a disease only recently deemed too rare to merit study, has become one of the most common disorders of our day--and a booming business to boot. The Antidepressant Era chronicles the history of psychopharmacology from its inception with the discovery of chlorpromazine in 1951 to current battles over whether these powerful chemical compounds should replace psychotherapy. An expert in both the history and the science of neurochemistry and psychopharmacology, David Healy offers a close-up perspective on early research and clinical trials,...
	The Antidepressant Survival Guide: The Clinically Proven Program to Enhance the Benefits and Beat the Side Effects of Your Medication by Robert J. Hedaya (Author) "Now patients can have the best of both worlds -- freedom from depression and freedom from side effects. Dr. Robert Hedaya offers a wealth of wisdom drawn from years of clinical experience, research, and teaching. This book is a much-needed lantern in the darkness." -- Norman Rosenthal, M.D., author of St. John's Wort: The Herbal Way to Feeling Good * Restore the vital vitamins, minerals, and hormones necessary to maintain good health. * Optimize your body's metabolic system. * Restore your ability to experience pleasure in life. An estimated twenty-five million Americans take antidepressants to combat depression, but most continue to cope with a host of debilitating side effects that equal, and sometimes outweigh, the medication's obvious benefits. Many doctors...