First generation antipsychotic drugs as effective as newer ones in some children

September 15, 2008

CHAPEL HILL - Nearly every child who receives an antipsychotic medicine is first prescribed one of the second-generation, or "atypical" drugs, such as olanzapine and risperidone. However, there has never been evidence that these drugs are more effective than the older, first-generation medications.

Now a study from the University of North Carolina at Chapel Hill School of Medicine suggests that molindone, a first-generation drug, is as effective as the newer ones and should be used as a first line of therapy in some children with schizophrenia or schizoaffective disorder.

"People thought the second-generation drugs were superior because they had no side effects. We found that molindone works as well as newer drugs, and in some cases it's safer," said Lin Sikich, M.D., associate professor in the department of psychiatry at UNC and lead author of the study, titled the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study.

"The guidelines are going to have to be rewritten because of this study," Sikich said. A report of the study is published Monday in the Sept. 15, 2008 edition of the American Journal of Psychiatry. Co-author Jeffrey Lieberman, M.D., led the earlier CATIE trial at UNC, a landmark study that compared antipsychotic medications in adults. Lieberman is now at Columbia University Medical Center.

The study is the largest head-to-head trial comparing the newer drugs, which became available in the 1990s, to the older ones, which have been around since the 1950s.

Between 2002 and 2006 the study randomly assigned 119 people aged 8 to 19 years to receive molindone, olanzapine or risperidone over an eight-week period at four sites: UNC; McLean Hospital and Cambridge Health Alliance at Harvard Medical School; Seattle Children's Hospital and the University of Washington; and Case Western Reserve University.

A decline in symptoms was similar across the three medications. But the drugs caused very different types of side effects, Sikich said. Both olanzapine and risperidone were associated with significant weight gain and could put young patients at risk of developing heart disease and diabetes. In fact, the National Institute of Mental Health, which sponsored the study, halted recruitment into the olanzapine arm of the study because of the weight gain problem and the resulting increase in cholesterol and glucose levels.

"Olanzapine should not be a first-line therapy in adolescents," Sikich said.

Both the older "typical" antipsychotics and newer "atypical" ones block dopamine receptors in the brain, but the newer drugs also interact with serotonin receptors and cause fewer muscle side effects, including stiffness, muscle cramps, restlessness and involuntary movements. With some older drugs, the involuntary movements can lead to permanent physical disabilities.

There were more reported cases of restlessness with molindone treatment than with either of the two newer treatments. Participants treated with molindone were also required to receive another drug, benztropine, to decrease muscle cramps and stiffness.

Brandon Constantineau, 18, of Wilmington, N.C., enrolled in the TEOSS study about four years ago. He was initially prescribed olanzapine but quickly began gaining weight, ultimately adding more than 45 pounds over 36 weeks. He was switched to molindone and gained about 8 pounds over the next 31 weeks and saw improvements similar to those with olanzapine. But, probably as a result of being on olanzapine, Sikich said, Brandon developed fatty liver disease and was ultimately prescribed two other medications.

Brandon's case also highlights two other points Sikich makes in the study: the benefits of proper diagnosis and the need for more effective medications.

"He was treated when he was very young, about 3, for ADHD," said Brandon's father, Richard Constantineau. But medications and other therapies didn't help, and Brandon grew violent.

"At the point when we went to see Dr. Sikich, when Brandon was 14, I was getting phone calls from the school because he was making threats against teachers," said Brandon's mother, Darlene Wilson. This coincided with violent threats against his parents and, Brandon said, "at one point in time I thought I was seeing angels with halos and wings, like in the Bible."

A psychiatrist Brandon had been seeing was not helpful, Wilson said, so a pediatrician referred them to Sikich.

Late diagnosis is a common problem with many children who develop early onset schizophrenia or schizoaffective disorder, and the diseases usually develop more severely when they begin in childhood, Sikich said.

Brandon is now doing well on an even newer drug, ziprasidone. But in the TEOSS trial only half of all of the participants responded to any medication.

"Medications make a vast difference in peoples' lives, but we need better treatment options," Sikich said. The trial will next compare outcomes after a one-year course of treatment.

Brandon and his family appreciate first-hand the challenges and advances.

"It's working well for him and we need to enjoy the good times, because it's not always good times," Wilson said. "We just have to enjoy what we have right now."

University of North Carolina School of Medicine

---

---

	Antipsychotics and Mood Stabilizers: Stahl's Essential Psychopharmacology, 3rd edition (Essential Psychopharmacology Series) by Stephen M. Stahl (Author) Relying upon the best-selling third edition of Stahl's Essential Psychopharmacology, Dr. Stephen M. Stahl has revised chapters covering antipsychotics and mood stabilizers for this third edition of Antipsychotics and Mood Stabilizers. More than one-third longer than the previous edition, Antipsychotics and Mood Stabilizers is essential reading for professionals treating psychosis and students learning the mechanisms of drug reactions. This updated edition includes advances in neurobiology and recent clinical developments to explain the concepts underlying drug treatment of psychiatric disorders. The fully revised text is complemented by many new illustrations and enhanced to reflect new knowledge and topics not covered in the previous edition. Intended as a primer text covering all...
	THE PROMISE OF ATYPICAL ANTIPSYCHOTICS: Fewer side effects mean enhanced compliance and improved functioning First-line second-generation drugs are approved ... new formulations. (Postgraduate Medicine) by JTE Multimedia Five new antipsychotic drugs introduced in the United States in the last decade offer physicians the ability to treat patients with schizophrenia and bipolar mania without the adverse effects of the first-generation antipsychotics. In this article, the authors discuss the advantages and side effects of these agents and present a guide to help physicians choose the optimal drug in the most favorable formulation for each patient. Citrome L, Volavka J. The promise of atypical antipsychotics: fewer side effects mean enhanced compliance and improved functioning. Original Publication Date: October 2004
	Antipsychotic long-acting injections by Peter Haddad (Author), Tim Lambert (Author), John Lauriello (Author) Antipsychotic long-acting injections (LAIs) were introduced in the 1960s to improve treatment adherence in schizophrenia. Subsequently, first-generation antipsychotic LAIs became widely used in many countries. Recently there has been a resurgence of interest in LAIs that partly reflects the introduction of several second-generation antipsychotic LAIs. This book brings together clinical and research findings on LAIs in a comprehensive volume, with chapters being written by international experts. Though the book concentrates on the use of LAIs in schizophrenia, the emerging evidence base for the use of LAIs in bipolar disorder is also discussed. A repeated theme throughout the book is the importance of prescribing decisions - whether for oral medication or an LAI, reflecting a...
	Safety of Antipsychotics.: An article from: Family Practice News by Lee Cohen (Author) This digital document is an article from Family Practice News, published by International Medical News Group on May 15, 2001. The length of the article is 709 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser. Citation Details Title: Safety of Antipsychotics. Author: Lee Cohen Publication: Family Practice News (Magazine/Journal) Date: May 15, 2001 Publisher: International Medical News Group Volume: 31 Issue: 10 Page: 27 Distributed by Thomson...
	LC-MS in Drug Bioanalysis by Q. Alan Xu (Editor), Timothy L. Madden (Editor) Clinical pharmacology plays an important role in today’s medicine. Due to the high sensitivity, selectivity, and affordability of a mass spectrometer (MS), the high performance liquid chromatography – mass spectrometry (LC-MS) analytical technique is widely used in the determination of drugs in human biological matrixes for clinical pharmacology. Specifically, LC-MS is used to analyze: anticancer drugs antidementia drugs antidepressant drugs antiepileptic drugs antifundal drug antimicrobial drugs antipsychotic drugs antiretroviral drugs anxiolytic/hypnotic drugs cardiac drugs drugs for addiction immunosuppressant drugs mood stabilizer drugs This book will primarily cover the various methods of validation for LC-MS techniques and applications used in modern clinical pharmacology.
	Essential Psychopharmacology of Antipsychotics and Mood Stabilizers (Essential Psychopharmacology Series) by Stephen M. Stahl (Author), Nancy Munter (Illustrator)
	Drug Induced Movement Disorders by Stewart Factor (Editor), Anthony Lang (Editor), William Weiner (Editor) An invaluable addition to the library of any neurologist, this book updates and presents the current state of the art clinical approaches to this subject, assisting neurologists and physicians alike in this difficult but increasingly common situation.
	Antipsychotics and their Side Effects (Cambridge Medicine) by David M. Gardner (Author), Michael D. Teehan (Author), Ross Baldessarini (Foreword) With the remarkable expansion in the use of antipsychotics, concerns about their immediate, intermediate, and long-term adverse effects have intensified. Despite this, studies consistently show that monitoring of patients taking antipsychotics can be inadequate, haphazard, or worse. This book provides a comprehensive review of the adverse effects of this pharmacologically complex therapeutic class, covering all commonly used conventional and atypical agents. In the first section, each chapter provides background information about an adverse effect, reviews the evidence linking the effect to various antipsychotics, and provides specific detection and monitoring recommendations. The second section provides unique monitoring guides for each antipsychotic. The third section provides the...
	A Guide to the Extrapyramidal Side Effects of Antipsychotic Drugs by D. G. Cunningham Owens (Author) Antipsychotic drugs have revolutionized the management of major psychiatric disorders and the outcomes of those who suffer from them. However, they often contribute to a range of adverse effects, among the most frequent and distressing of which are those resulting in disturbance of voluntary motor function. Extrapyramidal side effects--or EPS--are still poorly recognized and frequently misattributed. Despite vast research literature, there have been few attempts to bring together both the descriptive clinical elements of these disorders and major research conclusions pertinent to routine practice. This very readable and well-illustrated book seeks to rectify this problem in the hope of increasing clinicians' awareness of the issues and acknowledgement of their impact. This is a task made...
	Clinical handbook of antipsychotic drug therapy by Aaron S Mason (Author)