Antidepressants and Suicidality in Adults: Data Overview

1. Antidepressants and Suicidality in Adults:Data Overview M. Lisa Jones MD, MPH Medical Reviewer Division of Psychiatry Products Psychopharmacologic Drugs Advisory Committee December 13, 2006

2. Antidepressants Studied

3. FDA Data Request Letters • FDA analysis based on randomized, controlled trial datasets provided by the sponsors of the antidepressant drugs: • FDA sent four data request letters to sponsors from Dec. 2004 to Aug. 2005 • Resulting sponsor datasets received by the FDA from Sept. 2005 to Sept. 2006

4. Selecting Trials for the Dataset • FDA letter provided the following guidance to sponsors on the studies to include in the dataset: • Randomized, placebo-controlled trials only • Trials for any indication • Trials of any length • Trials with at least 20 subjects per treatment arm • Sponsors submitted a listing of the trials they intended to include/exclude, and the FDA provided feedback on the trials to be included in the final datasets

5. Study Indication Groups • Major depressive disorder (MDD) • Other depressive disorders • Other psychiatric disorders • Behavioral disorders • Other disorders • Trials categorized by reviewer consensus • MDD and Non-MDD datasets submitted separately Non-MDD Indications

6. Other Depressive Disorders • MDD or Bipolar Disorder • Premenstrual Dysphoric Disorder • Post Natal Depression • Seasonal Affective Disorder • Atypical Depression • Bipolar Disorder • Depression (Unspecified) • Depression (Non-MDD) • Dysthymia • Dysthymia or Major Depression

7. Other Psychiatric Disorders • ADHD • Adjustment Disorder • Anxiety Disorders • Alzheimer’s Disease • Bulimia • Generalized Anxiety Disorder • Generalized Social Phobia • Negative Symptoms Of Schizophrenia • Neurasthenia • Non-Depressed OCD • Obsessive Compulsive Disorder • Pain Disorder • Panic Disorder • Post-traumatic Stress Disorder • Social Anxiety Disorder

8. Other Behavioral Disorders • Obesity / Diabetes or Glucose Intolerance • Smoking Cessation • Weight Loss • Weight Maintenance • Alcoholism • Insomnia • Insomnia and Anxiety Preceding Surgery • Obesity • Obesity and Hypertension • Obesity, Hypertension and Diabetes

9. Other Disorders • Stress Urinary Incontinence • Sexual Dysfunction • Sleep in Healthy Volunteers • Urge Urinary Incontinence • Diabetic Neuropathy • Fibromyalgia • Mixed Urinary Incontinence • Migraine Prophylaxis • Neuropathic Pain • Non-Ulcer Dyspepsia • Premature Ejaculation

10. Trial Disposition

11. Event Identification • To identify potentially suicide-related adverse events (PSRAEs), sponsors were asked to search the trial preferred terms, verbatim terms and comments for suicide-related text strings (e.g. “accident-,” “attempt,” “burn,” “cut,” “gun”) • Search strictly limited to the double-blind period • Subjects with events pre-dating baseline were not excluded. Events were counted if they recurred during the trial.

12. Event Adjudication • Adjudication of PSRAEs as per the Columbia Classification Algorithm of Suicide Assessment (C-CASA) • Due to the large number of subjects in the adult suicidality analysis, adjudications were performed by the sponsors and were not overseen by the FDA • “False positive” events identified by the text string search (e.g. gas/epigastric pain) were excluded

13. C-CASA Event Classification The numbering above represents a ranking of event severity, and only the most severe event per patient was submitted in the datasets

14. Dataset Variables

15. Dataset Variables