# Presentation: 371854

## Overview of Psychiatric Disorders

- Douglas Jacobs, MDAssociate Clinical Professor of Psychiatry
- Harvard Medical School

**Notes:**
Introduction
- Psychiatrist and Suicidologist
- studied the problem of suicide for over 25 years
- I developed National Depression screening day, the first National   program screening for depression
- has reviewed the records of over 300 suicides applying principles of   psychological autopsy
- has edited 3 textbooks on suicide
- still actively treat depressed and suicidal patients

I will present a clinical context for understanding the psychiatric conditions described in the spontaneous reports, specifically suicide and depression first in the general population, then in the major Accutane population (Ages 15-24).  This context will focus on the question of Accutane’s relationship to and or impact on these conditions and will examine the dual use of the term depression as an illness vs depression as a symptom, particularly as it relates to medications
Dr. Nelson will then provide an epidemiologic analysis - and then I will close with a clinical analysis of the suicide reports.
In order to address the questions about the relationship of Accutane to the suicide reports, one must understand the factors underlying any suicide.

## Overview of Clinical Context of Spontaneous Reports

- Suicide
- clinical and demographic correlates
- clinical features
- Suicidal Behavior
- definitional issues as they relate to spontaneous reports
- Depression
- definitions - illness vs symptoms
- relationship to medications
- relationship to suicide
- Depression and Suicide in Ages 15-24
- diagnostic issues
- epidemiology and risk factors

## Suicide:  A Multi-Factorial Event - Adult

**SUICIDE**

**Neurobiology**

- Severe Medical
- Illness

**Impulsiveness**

- Access To Weapons

- Hopelessness

- Life Stressors

- Family History

**Suicidal**
**Behavior**

- Personality Disorder/Traits

- No **apparent**psychopathology

- Substance Use/Abuse

**Psychiatric Illness****Co-morbidity**

**Suicide:  A Multi-Factorial Event - Adult**

## Incidence of Suicide

- 30,000 suicides per year in the US
- 0.01% annual incidence rate (11.4/100,000)
- 80% suicides are in males (4:1 m/f ratio)
- Third leading cause of death in the 15-24 age group representing 20% of suicides (approximately 6,000)

## Suicide:  Clinical Features

- Associated with severe depression
- Majority not in mental health treatment
- 75% have seen a physician in previous six months
- No one factor predictive of suicide
- 60% suicide on first attempt
- No medication has ever been proven to cause suicide

## Profile of the Suicides in the Accutane Medwatch Reports

- 30,000 suicides per year in the US
- 0.01% annual incidence rate (11.4/100,000)
**80% suicides are in males (4:1 m/f ratio)**
- Third leading cause of death in the 15-24 age group representing 20% of suicides

- Associated with severe depression
**Majority not in mental health treatment**
**75% have seen a physician in previous six months**
- No one factor predictive of suicide
**60% suicide on first attempt**
- No medication has ever been proven to cause suicide

## Definitional Issues - Suicidal Behavior

**Suicidal Ideation:**
- A) nonspecific -- thoughts of death
- B)  specific -- the thought of death includes an intent to die with a plan of action
- Prevalence of suicidal ideation = 2.6%
- Thoughts of death = 28.2%
- Suicidal ideation (definition B) is associated with a psychiatric disorder, primarily depression

**Suicide Attempts:**** **
- A) (U.S.) Potential or actual self-injurious behavior accompanied by intent to die
- B) (Europe) Parasuicide -- a self-harmful act with nonfatal outcome -- intent not included in definition
- (U.S.)  Current prevalence estimates: 0.3 to 0.8%
- Male/Female ratio 1:3 (inverse of suicides)
- Attempts/completion 18/1
- Higher incidence of attempts in 15-24 age population: 100/1 (parasuicide)
- Serious suicide attempts indicative of severe psychiatric illness

## Overview of Suicidal Behavior

- Ideators: 5,000,000*
- Attempters:  600,000*
- Completers:  31,284 (1995)

- Suicide Ideators (2.6%)

- Suicide Attempters

- Completers

****estimate***

- Thoughts of death (28%)

- Self Destructive Behavior

**Overview of Suicidal Behavior**

## Depression:   Epidemiology

- Prevalent disorder 12% annually - 20 million people
- Undertreated and Underdiagnosed - Only 20% with recent episodes in treatment;  40% lifetime.
- 20% appear in general medical practices; 50% undiagnosed
- Decreased age of onset since WW II
- Male/Female ratio 1:2

## Depression:  The Illness VersusDepressive Symptoms - (The Blues)

- Essential distinction:	An illness	A normal reaction		to life situations
- Prevalence:	12%	25%
- Symptoms:	Multiple: mood,	Single:  mood	thoughts, bodily	functions
- Duration:	Persists, episodic	Temporary
- Suicide Potential:	Can result in	Rarely produces	suicide	suicidal thoughts
- Treatment:	Requires specific	Requires a good	medical/psychiatric	listener and/or	treatment	time to heal

**Depression****	****The Blues**

## The Issue of Medications and “Depression”

- Are medications that are reported to cause depression (approximately 100) associated with diagnosed depressive disorders or depressive symptoms?
- Case reports vs empirical evidence
- Majority of evidence suggests association with depressive symptoms and **not** depressive disorders
- Clinical significance of depressive symptoms is minimal

## Adolescent Depression - Clinical Features

**Increased moodiness, irritability, argumentativeness**
- Poor concentration
- Sleep and appetite changes
**Increased self-criticism**
- Despair, sadness, emptiness
- Loss of energy
- Lack of interest in usual activities and friends
**Increased talk of death and dying**
**Threats of suicide**

## Why Adolescent Depression Is Undiagnosed

- Normal adolescents often moody, frequently argue
- Symptoms of depression overlap with traits of normal adolescence
- Parents, teachers and other adults label it “troubled teenage behavior”
- Adolescents conceal symptoms from parents and care givers

## Adolescent Depression - Relationship to Stressful Events

- Depression can occur after a stressful event or in teenagers who have not experienced a stressful event (50-50)

## Suicide Rates for All Persons and Persons Aged 15 to 24, U.S., 1900-1995

- Adapted from:  Rosenberg  et al, 1987.  The Emergence of Youth Suicide: An Epidemiologic Analysis and Public Health Perspective.  Annual Review of Public Health, 8:417-44
- Updated from National Center for Health Statistics Center

- Year

- SuicideRate(per 100,000)

- PSY 110, (1063), 7/18/00

- _Ages 15-24_1950 = 41980 = 12.3

- 13.35

- 11.9

**1950**

**1980**

## Suicide:  A Multi-Factorial Event - Adolescent

**SUICIDE**

**Neurobiology**

**Impulsiveness**

**Family History**

**Suicidal**
**Behavior**

**Conduct Disorder**

- No **apparent**psychopathology

**Substance ****Use/Abuse**

**Psychiatric Illness****Co-morbidity**

**Age Specific**
** ****Stressors**

**Self-esteem/image**
**Academic Problems**
**Disciplinary Crisis/   **** Humiliation**

**Exposure to ****Suicide**

**Access To Weapons**

**Hopelessness**

**Severe Acne**

**Suicide:  A Multi-Factorial Event - Adolescent**

## No Apparent Psychopathology

**No Apparent Psychopathology**

- Psychological autopsy studies reveal risk factors:
- subsyndromal psychopathology
- past suicidality
- familial psychiatric disorder
- legal/disciplinary problems
- presence of firearm (or other lethal method)

## Clinical Analysis of Spontaneous Reports

- Dr. Jacobs

## Questions Addressed

- Is there any pattern to suicide reports in relationship to Accutane?
- e.g., gender distribution and on/off Accutane
- What is the significance of the temporal association with “depression”?
- Does Accutane exacerbate underlying psychopathology and lead to suicide?
- Does Accutane cause impulsive suicides?

## Categories of Suicides in Medwatch Reports

- Relationship to Accutane Use
- Concealment of symptoms
- Confounding factors e.g. pre-existing psychiatric history
- No apparent psychopathology
- Miscellaneous

## Suicide:  On/Off Accutane

- 30 cases were on Accutane, including 4 that were on over 6 months
- 24 cases were off Accutane
- 10 unknown
- No evidence of predominance of on/off factor
- Gender -- total males = 53, total females = 11
- total suicides consistent with known demographics
- on/off ratio the same, regardless of gender

## Case Example: Relationship to Accutane

_**Off Accutane 9 Months**_

_**Analysis**_**:  No consistent relationship to Accutane**

**Case Example: Relationship to Accutane**

- 22 year-old male
- Firearm
- No relevant findings

- 19 year-old male
- Firearm
- History of psychosis
- School stressors
- Duration 6 months

## “Depression” Occurring While On Accutane

- 17 out of 64 reports
- 10 cases committed suicide on Accutane
- 7 cases committed suicide off Accutane
- Only one case had psychiatric treatment

## 14 year-old male
Committed suicide 2 months on Accutane
Psychiatric History -- none reported
No depression or suicidal ideation noted while on Accutane

- Committed suicide 2 months on Accutane
- Psychiatric History -- none reported
- No depression or suicidal ideation noted while on Accutane

- Pre existing depression and suicidal ideation -- revealed by diary found after suicide
- Depression with suicidal ideation requires psychiatric treatment
**    **_**Analysis**_:  Depression and suicidal ideation concealed from family and physician

**Case Example ****– Concealment of Symptoms**

- _Case Description_

- _Case Analysis_

## Prior Psychiatric History Related to On/Off Accutane

- Question:  What is the impact of Accutane on this at-risk group for exacerbation of underlying illness leading to suicide?
- Results:  9 cases on Accutane               12 cases off Accutane

## Reports With Prior Psychiatric History That Represent “Controls”

-   > 6 mo
-      9 mo
-    18 mo
-      6 yrs
-      6 yrs
-      8 yrs
- ~ 10 yrs
-    10 yrs

-  None of these reports developed    symptoms of underlying illness 		while on Accutane
-  Accutane did not precipitate 		symptoms in persons at-risk
-  Suicide unrelated to Accutane
**   **_**Analysis**_**: **Suicide related to 		underlying psychiatric disorder

-   8 mo
-   6 mo
-   4 mo
-   6 mo
-   3 mo
- 18 mo
-   6 mo
-   1 yr

_**Time Off**_

_**Duration**_

## 18 year-old male
On Accutane < 1 month
No history of depression, mood swings or stressors
Suicide by inhaling pellets placed in a canister, attached to tubing and a face mask

- On Accutane < 1 month
- No history of depression, mood swings or stressors
- Suicide by inhaling pellets placed in a canister, attached to tubing and a face mask

- Engaged in risky behavior
- Method suggestive of “getting high”
- 	_**Analysis**_: Suicide intent not established, possible accidental death

- _Case Description_

- _Case Analysis_

**Case Example ****–**** No Apparent Psychopathology**

## Case of Murder-Suicide

- _Case Analysis_

**Case of Murder-Suicide**

- Duration = 8 months
- Off Accutane 4 months
- Method = killed self and child by drowning (child not exposed to Accutane)
- Prior history = post-partum depression
- Accutane stopped because of “delirium”
- Hospitalization offered but refused

- Infanticide consistent with psychotic depression
- Post-partum depression occurs in manic-depressive illness
- “Delirium” most likely was psychotic episode
- 	_**Analysis**_:  Events related to severe underlying psychiatric disorder

## 21 year-old male
Psychiatric history
Patient had been in and out of substance abuse rehabilitation treatment
On Accutane, 6 months
No report of depressive symptoms nor of drug relapse
Committed suicide 1 year off Accutane

- Psychiatric history
- Patient had been in and out of substance abuse rehabilitation treatment
- On Accutane, 6 months
- No report of depressive symptoms nor of drug relapse
- Committed suicide 1 year off Accutane

- Substance abusers are at-risk for mood disorders and impulsive behavior
- Accutane did not cause relapse, mood symptoms, or impulsive actions
**     **_**Analysis**_:  Suicide was related to pre-existing psychiatric conditions and happened a considerable amount of time after discontinuation of Accutane

- _Case Description_

- _Case Analysis_

**Case Example ****–**** Substance Abuse/Impulsive Behavior**

## Summary of Clinical Analysis

- No alteration of gender distribution
- No impact of on/off Accutane
- No significant relationship to concurrent “depression”
- No exacerbation of underlying psychiatric disorders
- Lack of warning signs consistent with youth suicide
- No evidence of impulsive factor