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Overview of Psychiatric Overview of Psychiatric DisordersDisorders

Douglas Jacobs, MDDouglas Jacobs, MDAssociate Clinical Professor of PsychiatryAssociate Clinical Professor of Psychiatry

Harvard Medical SchoolHarvard Medical School

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Overview of Clinical Context of Overview of Clinical Context of Spontaneous ReportsSpontaneous Reports SuicideSuicide

– clinical and demographic correlatesclinical and demographic correlates– clinical featuresclinical features

Suicidal BehaviorSuicidal Behavior– definitional issues as they relate to spontaneous reportsdefinitional issues as they relate to spontaneous reports

DepressionDepression– definitions - illness vs symptomsdefinitions - illness vs symptoms

relationship to medicationsrelationship to medications– relationship to suiciderelationship to suicide

Depression and Suicide in Ages 15-24Depression and Suicide in Ages 15-24– diagnostic issuesdiagnostic issues– epidemiology and risk factorsepidemiology and risk factors

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SUICIDSUICIDEE

Neurobiology

Severe MedicalIllness

Impulsiveness

Access To WeaponsHopelessness

Life Stressors

Family History

SuicidalBehavior

Personality Disorder/Traits

No apparentpsychopathology

Substance Use/Abuse

Psychiatric Illness

Co-morbidity

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

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Incidence of SuicideIncidence of Suicide

30,000 suicides per year in the US30,000 suicides per year in the US

0.01% annual incidence rate (11.4/100,000) 0.01% annual incidence rate (11.4/100,000)

80% suicides are in males (4:1 m/f ratio) 80% suicides are in males (4:1 m/f ratio)

Third leading cause of death in the 15-24 age Third leading cause of death in the 15-24 age group representing 20% of suicides group representing 20% of suicides (approximately 6,000)(approximately 6,000)

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Suicide: Clinical FeaturesSuicide: Clinical Features

Associated with severe depressionAssociated with severe depression

Majority not in mental health treatmentMajority not in mental health treatment

75% have seen a physician in previous six months75% have seen a physician in previous six months

No one factor predictive of suicideNo one factor predictive of suicide

60% suicide on first attempt60% suicide on first attempt

No medication has ever been proven to cause suicideNo medication has ever been proven to cause suicide

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Profile of the Suicides in the Accutane Profile of the Suicides in the Accutane Medwatch ReportsMedwatch Reports 30,000 suicides per year in the 30,000 suicides per year in the

USUS

0.01% annual incidence rate 0.01% annual incidence rate (11.4/100,000) (11.4/100,000)

80% suicides are in males (4:1 80% suicides are in males (4:1 m/f ratio)m/f ratio)

Third leading cause of death in Third leading cause of death in the 15-24 age group the 15-24 age group representing 20% of suicidesrepresenting 20% of suicides

Associated with severe depressionAssociated with severe depression

Majority not in mental health Majority not in mental health treatmenttreatment

75% have seen a physician in 75% have seen a physician in previous six monthsprevious six months

No one factor predictive of suicideNo one factor predictive of suicide

60% suicide on first attempt60% suicide on first attempt

No medication has ever been proven No medication has ever been proven to cause suicideto cause suicide

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Definitional Issues - Suicidal BehaviorDefinitional Issues - Suicidal BehaviorSuicidal Ideation:Suicidal Ideation:

– A) nonspecific -- thoughts of death A) nonspecific -- thoughts of death – B) specific -- the thought of death includes B) specific -- the thought of death includes

an intent to die with a plan of action an intent to die with a plan of action

Prevalence of suicidal Prevalence of suicidal ideation = 2.6%ideation = 2.6%

Thoughts of death = 28.2% Thoughts of death = 28.2%

Suicidal ideation (definition B) is associated Suicidal ideation (definition B) is associated with a psychiatric with a psychiatric disorder, primarily depressiondisorder, primarily depression

Suicide Attempts:Suicide Attempts: – A) (U.S.) Potential or actual self-injurious A) (U.S.) Potential or actual self-injurious

behavior accompanied by intent to diebehavior accompanied by intent to die– B) (Europe) Parasuicide -- a self-harmful B) (Europe) Parasuicide -- a self-harmful

act with nonfatal outcome -- intent not act with nonfatal outcome -- intent not included in definitionincluded in definition

(U.S.) Current prevalence estimates: (U.S.) Current prevalence estimates: 0.3 to 0.8%0.3 to 0.8%– Male/Female ratio 1:3 (inverse of Male/Female ratio 1:3 (inverse of

suicides)suicides)– Attempts/completion 18/1Attempts/completion 18/1

Higher incidence of attempts in 15-24 age Higher incidence of attempts in 15-24 age population: 100/1 (parasuicide)population: 100/1 (parasuicide)

Serious suicide attempts indicative of severe Serious suicide attempts indicative of severe psychiatric illnesspsychiatric illness

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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 BehaviorOverview of Suicidal Behavior

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Depression: EpidemiologyDepression: Epidemiology

Prevalent disorder 12% annually - 20 million peoplePrevalent disorder 12% annually - 20 million people

Undertreated and Underdiagnosed - Only 20% with Undertreated and Underdiagnosed - Only 20% with recent episodes in treatment; 40% lifetime. recent episodes in treatment; 40% lifetime.

20% appear in general medical practices; 50% 20% appear in general medical practices; 50% undiagnosedundiagnosed

Decreased age of onset since WW IIDecreased age of onset since WW II

Male/Female ratio 1:2Male/Female ratio 1:2

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Depression: The Illness VersusDepression: The Illness VersusDepressive Symptoms - (The Blues)Depressive Symptoms - (The Blues)

Essential distinction:Essential distinction: An An illnessillness A A normalnormal reactionreactionto life situationsto life situations

Prevalence:Prevalence: 12%12% 25%25%

Symptoms:Symptoms: Multiple: mood,Multiple: mood, Single: moodSingle: moodthoughts, bodilythoughts, bodilyfunctionsfunctions

Duration:Duration: Persists, episodicPersists, episodic TemporaryTemporary

Suicide Potential:Suicide Potential: Can result inCan result in Rarely producesRarely producessuicidesuicide suicidal thoughtssuicidal thoughts

Treatment:Treatment: Requires specificRequires specific Requires a goodRequires a goodmedical/psychiatricmedical/psychiatric listener and/orlistener and/ortreatmenttreatment time to healtime to heal

DepressionDepression The BluesThe Blues

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The Issue of Medications The Issue of Medications and “Depression”and “Depression”

Are medications that are reported to cause depression Are medications that are reported to cause depression (approximately 100) associated with diagnosed (approximately 100) associated with diagnosed depressive disorders or depressive symptoms?depressive disorders or depressive symptoms?

Case reports vs empirical evidenceCase reports vs empirical evidence

Majority of evidence suggests association with Majority of evidence suggests association with depressive symptoms and depressive symptoms and notnot depressive disorders depressive disorders

Clinical significance of depressive symptoms Clinical significance of depressive symptoms is minimalis minimal

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Adolescent Depression - Clinical FeaturesAdolescent Depression - Clinical Features Increased moodiness, irritability, argumentativenessIncreased moodiness, irritability, argumentativeness

Poor concentrationPoor concentration

Sleep and appetite changesSleep and appetite changes

Increased self-criticismIncreased self-criticism

Despair, sadness, emptinessDespair, sadness, emptiness

Loss of energyLoss of energy

Lack of interest in usual activities and friendsLack of interest in usual activities and friends

Increased talk of death and dyingIncreased talk of death and dying

Threats of suicideThreats of suicide

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Why Adolescent Depression Is UndiagnosedWhy Adolescent Depression Is Undiagnosed

Normal adolescents often moody, Normal adolescents often moody, frequently arguefrequently argue

Symptoms of depression overlap with traits of Symptoms of depression overlap with traits of normal adolescencenormal adolescence

Parents, teachers and other adults label it “troubled Parents, teachers and other adults label it “troubled teenage behavior”teenage behavior”

Adolescents conceal symptoms from parents and Adolescents conceal symptoms from parents and care giverscare givers

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Adolescent Depression - Relationship to Adolescent Depression - Relationship to Stressful EventsStressful Events

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

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

0

2

4

6

8

10

12

14

16

18

Year 1900 1905 1910 1915 1920 1925 1930 1935 1940 1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995

Ages 15-24

All Ages

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

YearYear

SuicideSuicideRateRate

(per 100,000)(per 100,000)

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

Ages 15-24Ages 15-241950 = 41950 = 41980 = 12.31980 = 12.3

13.3513.35

11.911.9

1950 1980

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SUICIDESUICIDE

Neurobiology

Impulsiveness

Family History

SuicidalBehavior

Conduct Disorder

No apparentpsychopathology

Substance Use/Abuse

Psychiatric Illness

Co-morbidity

Age Specific Stressors

•Self-esteem/imageSelf-esteem/image

•Academic ProblemsAcademic Problems

•Disciplinary Crisis/ Disciplinary Crisis/ Humiliation Humiliation

Exposure to Suicide

Access To Weapons

Hopelessness

Severe Acne

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

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Note: Cases 15, 29, 1, 61, 14, 8 (patient had 2 courses of Accutane,argues against impulsive rx to Accutane

No Apparent PsychopathologyNo Apparent Psychopathology

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

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Clinical Analysis of Clinical Analysis of Spontaneous ReportsSpontaneous Reports

Dr. JacobsDr. Jacobs

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Questions AddressedQuestions Addressed

Is there any pattern to suicide reports in relationship Is there any pattern to suicide reports in relationship to Accutane?to Accutane?– e.g., gender distribution and on/off Accutanee.g., gender distribution and on/off Accutane

What is the significance of the temporal association What is the significance of the temporal association with “depression”?with “depression”?

Does Accutane exacerbate underlying Does Accutane exacerbate underlying psychopathology and lead to suicide?psychopathology and lead to suicide?

Does Accutane cause impulsive suicides?Does Accutane cause impulsive suicides?

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Categories of Suicides in Categories of Suicides in Medwatch ReportsMedwatch Reports

Relationship to Accutane UseRelationship to Accutane Use

Concealment of symptomsConcealment of symptoms

Confounding factors e.g. pre-existing Confounding factors e.g. pre-existing psychiatric historypsychiatric history

No apparent psychopathologyNo apparent psychopathology

MiscellaneousMiscellaneous

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Suicide: On/Off AccutaneSuicide: On/Off Accutane

30 cases were on Accutane, including 4 that were on 30 cases were on Accutane, including 4 that were on over 6 monthsover 6 months

24 cases were off Accutane24 cases were off Accutane

10 unknown10 unknown

No evidence of predominance of on/off factorNo evidence of predominance of on/off factor

Gender -- total males = 53, total females = 11Gender -- total males = 53, total females = 11 total suicides consistent with known demographics total suicides consistent with known demographics on/off ratio the same, regardless of genderon/off ratio the same, regardless of gender

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On Accutane < 1 MonthOn Accutane < 1 Month Off Accutane 9 MonthsOff Accutane 9 Months

AnalysisAnalysis: No consistent relationship to Accutane: No consistent relationship to Accutane

Case Example: Relationship to AccutaneCase Example: Relationship to Accutane

22 year-old male22 year-old male

FirearmFirearm

No relevant findingsNo relevant findings

19 year-old male19 year-old male

FirearmFirearm

History of psychosisHistory of psychosis

School stressorsSchool stressors

Duration 6 monthsDuration 6 months

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““Depression” Occurring While Depression” Occurring While On AccutaneOn Accutane

17 out of 64 reports17 out of 64 reports

10 cases committed suicide on Accutane10 cases committed suicide on Accutane

7 cases committed suicide off Accutane7 cases committed suicide off Accutane

Only one case had psychiatric treatmentOnly one case had psychiatric treatment

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14 year-old male14 year-old male

Committed suicide 2 months Committed suicide 2 months on Accutaneon Accutane

Psychiatric History -- none Psychiatric History -- none reportedreported

No depression or suicidal No depression or suicidal ideation noted while on ideation noted while on AccutaneAccutane

Pre existing depression and Pre existing depression and suicidal ideation -- revealed by suicidal ideation -- revealed by diary found after suicidediary found after suicide

Depression with suicidal Depression with suicidal ideation requires psychiatric ideation requires psychiatric treatmenttreatment

AnalysisAnalysis: Depression and : Depression and suicidal ideation concealed suicidal ideation concealed from family and physicianfrom family and physician

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

Case DescriptionCase Description Case AnalysisCase Analysis

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Prior Psychiatric History Related to Prior Psychiatric History Related to On/Off AccutaneOn/Off Accutane

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

Results: 9 cases on AccutaneResults: 9 cases on Accutane 12 cases off Accutane 12 cases off Accutane

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

> 6 mo> 6 mo

9 mo9 mo

18 mo18 mo

6 yrs6 yrs

6 yrs6 yrs

8 yrs8 yrs

~ 10 yrs~ 10 yrs

10 yrs10 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 mo8 mo

6 mo6 mo

4 mo4 mo

6 mo6 mo

3 mo3 mo

18 mo18 mo

6 mo6 mo

1 yr1 yr

Time OffDuration

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18 year-old male18 year-old male

On Accutane < 1 monthOn Accutane < 1 month

No history of depression, No history of depression, mood swings or stressorsmood swings or stressors

Suicide by inhaling pellets Suicide by inhaling pellets placed in a canister, placed in a canister, attached to tubing and a attached to tubing and a face maskface mask

Engaged in risky behaviorEngaged in risky behavior

Method suggestive of Method suggestive of “getting high”“getting high”

AnalysisAnalysis: Suicide intent : Suicide intent not established, possible not established, possible accidental deathaccidental death

Case DescriptionCase Description Case AnalysisCase Analysis

Case Example Case Example –– No Apparent No Apparent PsychopathologyPsychopathology

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Case DescriptionCase Description Case AnalysisCase Analysis

Case of Murder-SuicideCase of Murder-Suicide

Duration = 8 monthsDuration = 8 months

Off Accutane 4 monthsOff Accutane 4 months

Method = killed self and child by Method = killed self and child by drowning (child not drowning (child not exposed to Accutane)exposed to Accutane)

Prior history = post-partum Prior history = post-partum depressiondepression

Accutane stopped because Accutane stopped because of “delirium”of “delirium”

Hospitalization offered Hospitalization offered but refusedbut refused

Infanticide consistent with Infanticide consistent with psychotic depressionpsychotic depression

Post-partum depression occurs Post-partum depression occurs in manic-depressive illnessin manic-depressive illness

““Delirium” most likely was Delirium” most likely was psychotic episodepsychotic episode

AnalysisAnalysis: Events related to : Events related to severe underlying psychiatric severe underlying psychiatric disorderdisorder

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21 year-old male21 year-old male

Psychiatric historyPsychiatric history

Patient had been in and out of Patient had been in and out of substance abuse rehabilitation substance abuse rehabilitation treatmenttreatment

On Accutane, 6 monthsOn Accutane, 6 months

No report of depressive symptoms No report of depressive symptoms nor of drug relapsenor of drug relapse

Committed suicide 1 year off Committed suicide 1 year off AccutaneAccutane

Substance abusers are at-risk for Substance abusers are at-risk for mood disorders and impulsive mood disorders and impulsive behaviorbehavior

Accutane did not cause relapse, Accutane did not cause relapse, mood symptoms, or impulsive mood symptoms, or impulsive actionsactions

AnalysisAnalysis: Suicide was related to : Suicide was related to pre-existing psychiatric conditions pre-existing psychiatric conditions and happened a considerable and happened a considerable amount of time after discontinuation amount of time after discontinuation of Accutaneof Accutane

Case DescriptionCase Description Case AnalysisCase Analysis

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

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Summary of Clinical AnalysisSummary of Clinical Analysis

No alteration of gender distributionNo alteration of gender distribution

No impact of on/off AccutaneNo impact of on/off Accutane

No significant relationship to concurrent “depression”No significant relationship to concurrent “depression”

No exacerbation of underlying psychiatric disordersNo exacerbation of underlying psychiatric disorders

Lack of warning signs consistent with youth suicideLack of warning signs consistent with youth suicide

No evidence of impulsive factorNo evidence of impulsive factor