Antidepressants need new nerve cells to be effective, UT Southwestern researchers find

August 28, 2008

Researchers at UT Southwestern Medical Center have discovered in mice that the brain must create new nerve cells for either exercise or antidepressants to reduce depression-like behavior.

In addition, the researchers found that antidepressants and exercise use the same biochemical pathway to exert their effects.

These results might help explain some unknown mechanisms of antidepressants and provide a new direction for developing drugs to treat depression, said Dr. Luis Parada, chairman of developmental biology and senior author of a study in the Aug. 14 issue of the journal Neuron.

In animals, it was already known that long-term treatment with antidepressants causes new nerve cells to be generated in a part of the brain called the dentate gyrus. Exercise, which can also relieve the symptoms of depression, stimulates the generation of new nerve cells in the same area.

"We would never claim that what we study in mice directly relates to how antidepressants work in humans, but there are interesting features in parallel," Dr. Parada said. "The study unifies different observations that point to the brain's dentate gyrus region and to creation of nerve cells as being important in depression."

Antidepressants act very quickly to increase levels of natural compounds, called neurotransmitters, which nerve cells use to communicate. It takes several weeks to several months, however, for the patients who respond to such treatments to feel less depressed. Dr. Parada said this implies that some other long-term mechanism is also at work.

The current study was designed to test several phenomena that have long been observed in animal studies but have not been studied together to see if they are linked, Dr. Parada said.

The researchers focused on a molecule called TrkB, or Track-B, which is found on the surface of nerve cells and responds to several growth factors to cause new nerves to grow in the dentate gyrus.

They genetically engineered mice to lack TrkB specifically in the stem cells that give rise to new neurons, then gave them antidepressants for several weeks or allowed them to run on wheels. When the mice were tested for depressive behavior, the tests revealed that neither the antidepressants nor the exercise had helped them, and the animals also had not grown new nerve cells in the dentate gyrus.

"At least in mice, this result directly links antidepressants and voluntary exercise with TrkB-mediated creation of nerve cells," Dr. Parada said.

The results also showed that antidepressants required TrkB to stimulate the growth of new nerve cells.

Matching the timeframe for medicated patients to feel less depressed, it takes several weeks for new nerve cells to grow, Dr. Parada said. This parallel effect, he said, may mean that antidepressants need to stimulate growth of new cells in the dentate gyrus in order to achieve their full effect.

"We can get biochemical, physiological, behavioral and anatomical results in animal models," Dr. Parada said. "These all resonate with the human condition, so perhaps you have a physiological relevancy.

"There could be a way to stimulate growth of nerve cells to fight depression, for example."

UT Southwestern Medical Center

---

---

	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 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.
	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...
	America Fooled: The Truth About Antidepressants, Antipsychotics And How We've Been Deceived by Timothy Scott (Author) America Fooled is the non-sensational, fact-filled story of how Americans have come to believe that depression and other mental problems are caused by chemical imbalances which can be fixed with pills. It reveals how the drug studies used to achieve FDA approval are designed, paid for and written by the drug companies themselves and are purposely deceptive. Part 1 of America Fooled is focused on antidepressants, their effectiveness, and their side effects including the permanent brain damage that results from long-term use about which so few Americans have any knowledge (including those who prescribe and those who take antidepressants). Part 2 deals with the various approaches used throughout history to treat more serious mental problems including the use of antipsychotics. The side...
	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 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...
	Is It Me or My Meds?: Living with Antidepressants by David A. Karp (Author) By the millennium Americans were spending more than 12 billion dollars yearly on antidepressant medications. Currently, millions of people in the U.S. routinely use these pills. Are these miracle drugs, quickly curing depression? Or is their popularity a sign that we now inappropriately redefine normal life problems as diseases? Are they prescribed too often or too seldom? How do they affect self-images? David Karp approaches these questions from the inside, having suffered from clinical depression for most of his adult life. In this book he explores the relationship between pills and personhood by listening to a group of experts who rarely get the chance to speak on the matter--those who are taking the medications. Their voices, extracted from interviews Karp conducted, color the...
	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 Evidence-Based Guide to Antidepressant Medications by Anthony J. (Author), Rothschild (Author) The second book in the Evidence-Based Guides series, The Evidence-Based Guide to Antidepressant Medications, provides a clear reference to the current knowledge and evidence base for the use of antidepressants among a variety of patients across a wide range of disorders. Today, in part due to the newer antidepressants, which have fewer side effects and less toxicity in overdose, many non mental health professionals feel comfortable prescribing antidepressants. Antidepressants are prescribed for many patients in addition to those who have major depressive disorder, including patients with bipolar disorder, posttraumatic stress disorder, schizophrenia, and personality disorders, as well as those with medical illnesses. In addition, antidepressants are increasingly being prescribed by...
	Prozac, Paxil, Zoloft and Other Antidepressants: Pros and Cons by Do It Now Foundation Discusses Prozac, Paxil, Zoloft, and other antidepressant drugs known as selective serotonin reuptake inhibitors. Topics include actions and effects, adverse reactions, and possible links to suicide and violence.