# Presentation: 143565

## 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

## Antidepressants Studied

| SSRIs | 1.  Citalopram  (Celexa®)
2.  Escitalopram (Lexapro®)
3.  Fluoxetine  (Prozac®)
4.  Fluvoxamine (Luvox®)
5.  Paroxetine (Paxil®)
6.  Sertraline 	(Zoloft®) |
| --- | --- |
| Non-SSRIs | 7.  Bupropion (Wellbutrin®)
8.  Duloxetine (Cymbalta®)
9.  Mirtazapine (Remeron®)
10.  Nefazodone (Serzone®) 
11. Venlafaxine (Effexor®) |

## 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

## 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

## 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

## 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

## Other Psychiatric Disorders

- Neurasthenia
- Non-Depressed OCD
- Obsessive Compulsive Disorder
- Pain Disorder
- Panic Disorder
- Post-traumatic Stress Disorder
- Social Anxiety Disorder

- ADHD
- Adjustment Disorder
- Anxiety Disorders
- Alzheimer’s Disease
- Bulimia
- Generalized Anxiety Disorder
- Generalized Social Phobia
- Negative Symptoms Of Schizophrenia

## 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

## 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

## Trial Disposition

| Disposition |   | Number of Trials |  |
| --- | --- | --- | --- |
| Included |  |  | 372 |
| Excluded | Exclusion Reason |  | 26 |
|  | Fewer than 20 subjects per arm in test-drug or placebo arms  | 23 |  |
|  | Data not available for most subjects | 3 |  |
| Duplicate trials  |  |  |                    6 |
| Total  |   |   | 404 |

## 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.

## 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

## 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

| Events
Completed suicide
Suicide attempt
Preparatory acts 
Suicidal ideation
Self-injurious behavior, intent unknown
Not enough information (Fatal)
Not enough information (Non-Fatal) | Coding
1
2
3
4
5
6
9 |
| --- | --- |

## Dataset Variables

| Trial identifiers
 | Trial and subject identifiers, trial indication |
| --- | --- |
| Trial-related | Setting (Inpt. or Outpt.), Location (North America or not), Premature Discontinuations |
| Subject
demographics | Age, Gender, Race |
| Treatment-related | Treatment group, information on the active control drug (if any) |

## Dataset Variables

| Disease-
related
 | Prior Attempt, Prior Ideation, Symptom Scale (Scale name, Baseline and Final Scores), Response |
| --- | --- |
| Outcome-related | Suicidality Event, Time to Event or Time on Study Drug |
| Subject Deaths | Death by any cause occurring within 90 days after the intended treatment  |