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                DEPARTMENT OF HEALTH AND HUMAN SERVICES

 

                      FOOD AND DRUG ADMINISTRATION

 

                CENTER FOR DRUG EVALUATION AND RESEARCH

 

 

 

              PSYCHOPHARMACOLOGIC DRUGS ADVISORY COMMITTEE

 

                    WITH THE PEDIATRIC SUBCOMMITTEE

 

             OF THE ANTI-INFECTIVE DRUGS ADVISORY COMMITTEE

 

 

 

 

 

                        Monday, February 2, 2004

 

                               8:00 a.m.

 

 

 

                          Holiday Inn Bethesda

                          Versailles I and II

                         8120 Wisconsin Avenue

                           Bethesda, Maryland

 

                                                                 2

 

                              PARTICIPANTS

 

      Matthew Rudorfer, M.D., Chair

      Anuja M. Patel, M.P.H., Executive Secretary

 

      PSYCHOPHARMACOLOGICAL DRUGS ADVISORY COMMITTEE

           MEMBERS

                Tana Grady-Weliky, M.D.

                Irene E. Ortiz, M.D.

                Richard P. Malone, M.D

                Wayne K. Goodman, M.D.

                James J. McGough, M.D.

                Jean E. Bronstein, R.N., M.S.

                  (Consumer Rep)

                Andrew C. Leon, Ph.D.

                Philip S. Wang, M.D. M.P.H., Dr. P.H.

                Dilip J. Mehta, M.D., Ph.D.,

                  (Industry Rep)

 

      ANTI-INFECTIVE DRUGS ADVISORY COMMITTEE

           MEMBERS

 

                Steven C. Ebert, Pharm. D. (Consumer Rep)

                Mary P. Glode, M.D.

                Samuel D. Maldonado, M.D., M.P.H.

                  (Industry Rep)

 

      PEDIATRIC SUBCOMMITTEE OF THE ANTI-INFECTIVE DRUGS

      ADVISORY COMMITTEE MEMBERS

 

                P. Joan Chesney, M.D.

                Mary Glode, M.D.

                Steven Ebert, Pharm. D. (Consumer Rep)

                Robert Nelson, M.D., Ph.D.

                Richard Gorman, M.D., FAAP

                Robert J. Fink, M.D.

                Susan Fuchs, M.D.

                David Danford, M.D.

                Victor Santana, M.D.

                Mark Hudak, M.D.

                Judith R. O'Fallon, Ph.D.

 

      SGE CONSULTANTS (VOTING)

 

                Elizabeth B. Andrews, Ph.D.

                Norman Fost, M.D., M.P.H.

                Charles E. Irwin, Jr., M.D.

                Lauren K. Leslie, M.D., FAAP

                James M. Perrin, M.D.

                Cynthia R. Pfeffer, M.D.

 

      SGE PATIENT REPRESENTATIVE (VOTING)

 

                Gail W. Griffith

 

                                                                 3

 

                        PARTICIPANTS (Continued)

 

      GOVERNMENT EMPLOYEE (non-voting)

 

                Daniel S. Pine, M.D.

 

      FDA

 

                Robert Temple, M.D.

                Russell G. Katz, M.D.

                Thomas Laughren, M.D.

                M. Dianne Murphy, M.D.

                Susan Cummins, M.D., MPH

                Anne Trontell, M.D., MPH

 

                                                                 4

 

                            C O N T E N T S

                                                              PAGE

      Call to Order and Opening Remarks:

                Matthew Rudorfer, M.D.                           6

 

      Introductions                                              8

 

      Conflict of Interest Statement:

                Anuja M. Patel, MPH                             15

 

      Overview of Issues:

                Russell Katz, M.D.                              19

 

      Pediatric Drug Development Program:

                Dianne Murphy, M.D.                             26

 

      Pediatric Depression and Its Treatment:

                Cynthia R. Pfeffer, M.D.                        39

 

      Suicide and Related Problems in Adolescents:

                David Shaffer, FRCP (Lond) FRC Psych            60

 

      Open Public Hearing

                Irving Kirsch and David Antonuccio              79

                Lisa Van Syckel                                 82

                Ann Blake Tracy, Ph.D.                          83

                Tom Woodward                                    85

                Mark Miller                                     87

                Corey and Jay Baadsgaard                        90

                Joyce Storey                                    91

                Jame Tierney                                    93

                Donna and Mark Taylor                           95

                Shannon Baker                                   97

                Dawn Rider                                      98

                Sara Bostock                                   100

                Vera Hassner Sharav                            103

                Cynthia Brockman                               104

                Todd and Eileen Shivak                         107

                Andy Vickery                                   109

                Rosie Carr Meysenburg                          111

                Rachel Adler                                   112

                Pepper Draper                                  115

                Donald Marks, M.D., Ph.D.                      117

                Leah Harris                                    119

                Donald Farber                                  121

                Lorraine Slater                                123

                Matthew Piepenberg                             125

                Terri Williams                                 127

                Glenn McIntosh                                 129

                Delnora Duprey                                 132

                Joe Pittman                                    133

                Richard Mack                                   135

                Noah Wright Smith                              137

                Marion Goff                                    139

 

                                                                 5

 

                      C O N T E N T S (Continued)

 

                                                              PAGE

      Open Public Hearing (Continued)

                Gary Cheslek, M.D.                             142

                Sherri Walton                                  144

                Peter R. Breggin, M.D.                         146

                Robert Fritz                                   148

                Lawrence Greenhill, M.D.                       151

                Suzanne Vogel-Scibilia, M.D.                   152

                Dennis Winter                                  155

                Steve Cole                                     157

                Allan Routhier                                 158

                Daniel J. Safer, M.D.                          161

                Julie Magno Zito, M.D.                         163

                Joseph Glenmullen, M.D.                        164

                Linda Cheslek                                  165

                Jeff Avery                                     167

                Harry Skigis                                   169

                Pamela Wild                                    170

                Karen Barth Menzies                            172

                Amy Coburn                                     174

                Sharon McBride                                 175

                Thomas Moore, M.D.                             178

 

      Pediatric and Adolescent Antidepressant Drug Use

      in the U.S.:

                Gianna C. Rigoni, Pharm.D., M.S.               181

 

      One-Year Post-Exclusivity-Mandated Adverse Event

      Review for Paroxetine and Citalopram:

                Solomon Iyasu, M.D., MPH                       195

 

      Office of Drug Safety Data Resources

      for the Study of Suicidal Events:

                Andrew D. Mosholder, M.D., MPH                 215

 

      Open Public Hearing

                David Fassler, M.D.                            225

                Lawrence Diller                                227

 

      Regulatory History on Antidepressants and

      Suicidality and Update on Current Plans for

      Analysis of Pediatric Suicidality Data:

                Thomas Laughren, M.D.                          230

 

      Suicidality Classification Project:

                Kelly Posner, Ph.D.                            265

 

      Plans for Analysis of Patient Level Data

      for Pediatric Studies:

                Tarek Hammad, M.D., Ph.D., M.Sc., M.S.         273

 

      Open Committee Discussion                                291

 

                                                                 6

 

  1                Call to Order and Opening Remarks

 

  2             DR. RUDORFER:  I am Dr. Matthew Rudorfer,

 

  3   a research psychiatrist at the National Institute

 

  4   of Mental Health, today wearing my hat as Chair of

 

  5   the Advisory Committee.

 

  6             As you settle in, please take this

 

  7   opportunity to put into silent mode your cell

 

  8   phones and any other devices that ring, beep, or

 

  9   play show tunes.

 

 10             I have some official language to read.

 

 11   All committee members and consultants have been

 

 12   provided with copies of background materials from

 

 13   the FDA and with copies of letters from the public

 

 14   that were received by the January 26th deadline.

 

 15   The background materials have been posted on the

 

 16   FDA web site.  Copies of all these materials are

 

 17   available for viewing at the FDA desk outside this

 

 18   room.

 

 19             We have a large table and a full house as

 

 20   you can see and a very important and exciting topic

 

 21   to discuss, so we would like to start with a few

 

 22   rules of order.  FDA relies on its advisory

 

 23   committees to provide the best possible scientific

 

 24   advice available to assist us in a discussion of

 

 25   complex topics.  We understand that issues raised

 

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  1   during the meeting may well lead to conversations

 

  2   over breaks or during lunch.

 

  3             However, one of the benefits of an

 

  4   advisory committee meeting is that discussions take

 

  5   place in an open and public forum.  To that end, we

 

  6   request that members of the committees not engage

 

  7   in off-record conversations on today's topic during

 

  8   the breaks and lunch.

 

  9             Whenever there is an important topic to be

 

 10   discussed, there are a variety of opinions.  One of

 

 11   our goals today is for this meeting to be conducted

 

 12   in a fair and open way where every participant is

 

 13   listened to carefully and treated with dignity,

 

 14   courtesy, and respect. Anyone whose behavior is

 

 15   disruptive to the meeting will be asked to leave.

 

 16             We are confident that everyone here is

 

 17   sensitive to these issues and can appreciate that

 

 18   these comments are intended as a gentle reminder.

 

 19   We look forward to a productive and interesting

 

 20   meeting.

 

 21             Just to reiterate a couple of points.

 

 22   This is an unusual meeting in that we have two

 

 23   advisory committees represented here,

 

 24   Psychopharmacologic Drugs and a subcommittee that

 

 25   is equivalent of a Pediatric Drugs Advisory

 

                                                                 8

 

  1   Committee chaired by Dr. Joan Chesney here to my

 

  2   left.

 

  3             Suppose we begin by going around the table

 

  4   for introductions.  Can we start at that end,

 

  5   please.

 

  6                          Introductions

 

  7             DR. TEMPLE:  I am Bob Temple.  I am the

 

  8   Office Director for Office of Drug Evaluation I.

 

  9             DR. KATZ:  Russ Katz, Division Director of

 

 10   the Division of Neuropharmacological Drug Products,

 

 11   FDA.

 

 12             DR. LAUGHREN:  Tom Laughren, Psychopharm

 

 13   Team Leader in the Neuropharm Division.

 

 14             DR. MURPHY:  Dianne Murphy, Office

 

 15   Director, Office of Counterterrorism and Pediatric

 

 16   Drug Development.

 

 17             DR. CUMMINS:  Susan Cummins, Medical Team

 

 18   Leader with the Division of Pediatric Drug

 

 19   Development.

 

 20             DR. TRONTELL:  Anne Trontell, Deputy

 

 21   Director, Office of Drug Safety.

 

 22             DR. FUCHS:  Susan Fuchs, member of the

 

 23   Pediatric Subcommittee of the Anti-Infective Drugs

 

 24   Advisory Committee.

 

 25             DR. FINK:  Bob Fink, pediatric

 

                                                                 9

 

  1   pulmonologist, Dayton, Ohio.

 

  2             DR. ORTIZ:  Irene Ortiz, geriatric

 

  3   psychiatrist, Albuquerque VA and the University of

 

  4   New Mexico.

 

  5             DR. LESLIE:  Lauren  Leslie, behavioral

 

  6   and developmental pediatrician and health services

 

  7   researcher in San Diego.

 

  8             DR. LEON:   Andrew Leon, Professor of

 

  9   Biostatistics and Psychiatry at Cornell Medical

 

 10   College.

 

 11             DR. GOODMAN:  Wayne Goodman, Professor and

 

 12   Chairman, Department of Psychiatry at the

 

 13   University of Florida.

 

 14             DR. PFEFFER:  Cynthia Pfeffer, Adolescent

 

 15   Psychiatrist and Professor of Psychiatry at Weill

 

 16   Medical College of Cornell University.

 

 17             DR. GORMAN:  Rich Gorman, pediatrician in

 

 18   private practice in Ellicott City and member of the

 

 19   Pediatric Advisory Subcommittee.

 

 20             DR. GLODE:  Mary Glode, Professor of

 

 21   Pediatrics, Pediatric Infectious Disease Specialist

 

 22   at Children's Hospital, University of Colorado at

 

 23   Denver.

 

 24             DR. HUDAK:  Mark Hudak, neonatologist and

 

 25   Professor of Pediatrics, University of Florida at

 

                                                                10

 

  1   Jacksonville, and member of the Pediatric

 

  2   Subcommittee.

 

  3             DR. MALONE:  Richard Malone, child

 

  4   psychiatrist, Drexel University, College of

 

  5   Medicine, and I am a member of the Psychopharm

 

  6   Advisory Committee.

 

  7             DR. SANTANA:  Victor Santana, pediatric

 

  8   hematologist/oncologist, St. Jude's Children's

 

  9   Research Hospital and University of Tennessee at

 

 10   Memphis, Tennessee.

 

 11             MS. PATEL:  Anuja Patel, Executive

 

 12   Secretary, Advisors and Consultants Staff.

 

 13             DR. RUDORFER:  Dr. Matthew  Rudorfer,

 

 14   Acting Chief, Adult Interventions Branch, National

 

 15   Institute of Mental Health and Chair of the