FOOD AND DRUG ADMINISTRATION FDA Meeting SUICIDE AND

FOOD AND DRUG ADMINISTRATION FDA Meeting SUICIDE AND RELATED PROBLEMS IN ADOLESCENCE February 2, 2004 9: 00 A. M. Washington, D. C. David Shaffer, F. R. C. Psych. Columbia University/New York State Psychiatric Institute 1051 Riverside Drive, New York, NY 10032

1 EPIDEMIOLOGY

LEADING CAUSES OF DEATH IN 15 - TO 19 -YEAR-OLDS — U N I T E D S T A T E S, 2001 — CAUSE # OF DEATHS Accidents Homicide Suicide Cancer Heart Disease Congenital Anomalies Chronic Lower Respiratory Disease Stroke Influenza and Pneumonia Blood Poisoning Anderson & Smith 2003 6646 1899 1611 732 347 255 74 68 66 57 1599 C. E 14

SUICIDE METHODS: CHILDREN AND OTHERS — % O F A L L S U I C I D E S, U N I T E D S T A T E S, 2000 — 5– 19 Years ≥ 20 Years M F ALL (N=1, 595) (N=333) (N=1, 928) (N= 22, 016) (N=5, 399) (N=27, 415) Firearms 55 37 52 62 37 57 Hanging/ Suffocation 35 40 36 19 15 18 Ingestion 3 13 5 7 31 12 CO poisoning 2 2 2 5 6 5 Jumping from a Height 2 3 2 Cutting . 4 0 . 3 1 1 1 Other 3 5 3 4 7 5 CDC Wonder 2003 (11/13)

SUICIDE RATES BY RACE PER 100, 000 LIVING POPULATION 100, 000 Rate per — U N I T E D S T A T E S , A L L A G E S, 2001 — Age CDC 2003 (WISQARS) C. E 1. XX

SUICIDE RATES DURING ADOLESCENCE 100, 000 Rate per — U N I T E D S T A T E S , A G E S 10– 24, 2001 — Age CDC 2003 (WISQARS) C. E 3

TEEN SUICIDE RATES IN COUNTRIES WITH EFFECTIVE REPORTING — M A L E S A G E 15– 19 — COUNTRY* YEARS 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1997– 1998– 1999 1998– 1999 1997– 1998– 1999 1996– 1997 1999– 2000 1998– 1999 1997– 1998 1996– 1997 1995– 1996 Russian Federation New Zealand Kazakhstan Estonia Lithuania Finland Latvia Belarus Canada Austria Ukraine Croatia Australia Ireland Switzerland 16 USA 17 Belgium RATE** 34. 5 33. 2 30. 7 28. 8 28. 5 24. 2 22. 1 21. 4 19. 1 18. 6 17. 7 17. 5 16. 0 15. 2 1997– 1998 14. 9 1994– 1995 14. 6 COUNTRY* YEARS RATE** 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 1995– 1996– 1997 1999– 2000 1997– 1998– 1999 1995– 1996 1997– 1998 1996– 1997 1998– 1999 1996– 1997– 1998 14. 4 14. 0 12. 2 11. 9 11. 5 9. 4 8. 7 7. 6 6. 8 6. 6 6. 3 5. 9 5. 2 4. 9 1997– 1998 3. 9 2. 3 Poland Norway Hungary Bulgaria Czech Republic Germany Sweden Denmark France Japan Romania United Kingdom Netherlands Italy Spain China (selected urban and rural) 34 Greece Pelkunen & Marttunen 2003; *available from WHO 3/5/2003; **2 -year average per 100, 000 population

TEEN SUICIDE RATES IN COUNTRIES WITH EFFECTIVE REPORTING — F E M A L E S A G E 15– 19 — COUNTRY* 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 New Zealand Kazakhstan Lithuania Russian Federation Estonia Norway China (selected urban and rural) Latvia Belarus Finland Australia Switzerland Croatia Austria Canada Ireland Ukraine YEARS RATE** COUNTRY* YEARS RATE** 1997– 1998– 1999 1997– 1998– 1999 1996– 1997 17. 1 10. 3 8. 5 7. 6 7. 0 18 19 20 21 1997– 1998 1994– 1995– 1996 1998– 1999 4. 5 3. 4 3. 3 1997– 1998– 1999 1997– 1998 1995– 1996 1998– 1999– 2000 1996– 1997 1999– 2000 6. 4 5. 9 5. 6 5. 4 5. 3 4. 9 4. 8 4. 6 Bulgaria Belgium Sweden Romania 22 USA 23 24 25 26 27 28 29 30 31 32 33 34 Czech Republic Hungary France Japan Netherlands Poland Germany Denmark United Kingdom Spain Italy Greece 1997– 1998 3. 2 1998– 1999– 2000 1997– 1998 1996– 1997 1998– 1999 1995– 1996 1998– 1999 1997– 1998 1996– 1997– 1998 3. 1 2. 9 2. 8 2. 0 1. 6 1. 5 0. 5 Pelkunen & Marttunen 2003; *available from WHO 3/5/2003; **2 -year average per 100, 000 population

FREQUENCY OF SUICIDAL IDEATION AND ATTEMPTS — U. S. HIGH-SCHOOL STUDENTS, AGE 15– 19, YRBS —— (2001, N=13, 601) RATE N Ideation 19. 0% 3. 8 million Attempt 8. 8% 1. 8 million Attempt received medical attention 2. 6% 520, 000 SUICIDE (age 15– 19)* . 008% * Anderson 2002; Grunbaum et al. 2002 (YRBS), U. S. Census 2000 1, 611 C. E 15. XX

TEEN ATTEMPTERS ATTEMPTS PER YEAR (2001, YRBS, N=13, 601) 1 2 or 3 4 or More 53% 30% 17% § Similar findings in patient studies § 1 attempt increases risk of another 15 -fold Barter et al. 1968, Brent 1993, CDC 2002 (YRBS 2001 Codebook), Goldacre & Hawton 1985, Goldston et al. 1999, Hawton et al. 1982, Hulten 2001, Kotila 1992, Lewinsohn et al. 1994, Mc. Intire et al. 1977, Spirito 1992, Spirito et al. 2003, Wichstrom 2000 SA 42. XX

TEEN IDEATORS EPISODES OF IDEATION* PER YEAR (N=981) 1 45% 2 24% 3 or More 31% Reifman & Windle 1995; *“How often have you thought about killing yourself? ”; past year, N=698; last 6 months, N=283) SI 19. XX

HOW ARE SUICIDAL ADOLESCENTS EXCLUDED FROM PSYCHOPHARM STUDIES? STUDY Sertraline (Wagner et al. 2003) EXCLUSION CRITERIA “previous attempt or posing significant suicidal risk” Fluoxetine (Emslie et al. 2002) “serious suicidal risk” Fluoxetine (Emslie et al. 1997) not specified Paroxetine (Keller et al. 2001) “current ideation with intent or specific plan OR history of attempts by drug overdose” Citalopram (Wagner et al. 2001) not specified SI 22. XX

20 TH-CENTURY - CHANGES IN YOUTH SUICIDE RATES Rate per 100, 000 — U N I T E D S T A T E S , A G E S 15– 24 — Year Anderson 2002, CDC Wonder 2003, USDHEW 1956, Vital Statistics U. S. 1954– 1978 C. E 16. XX

2 CAUSES OF SUICIDE

PSYCHIATRIC DISORDER IN ADOLESCENT SUICIDE —PSYCHOLOGICAL-AUTOPSY STUDIES— LOCATION N YEARS % Israel 43 mid-1980 s 90% *New York 120 1984– 1986 90% Finland 53 1987– 1988 94% *Pittsburgh 140 1984– 1994 82% Apter 1993, Shaffer 1996, Marttunen 1991, Brent 1999; *case-control studies C. D 6. XX

MOST COMMON DIAGNOSES IN TEEN SUICIDESS MALE (N=213) FEMALE (N=46) Depression 50% 69% Antisocial 43% 24% Substance Abuse 38% 17% Anxiety 19% 48% 66% of 16 - to 19 -Year-Old Male Suicides Have Substance/Alcohol Abuse Brent et al. 1999, Shaffer et al. 1996 C. D 8. XX

SUICIDALITY IN DEPRESSED CHILDREN AND TEENS At Time of Diagnosis STUDIES SUBJECTS IDEATION ATTEMPT 6 1265 60% 30% During Follow-Up STUDIES SUBJECTS IDEATION ATTEMPT 3 466 ? 24% Andrews & Lewinsohn 1992, Fombonne et al. 2001, Haavisto et al. 2003, Kovacs et al. 1993, Larson & Ivarsson 1998, Ryan et al. 1987, Weissman et al. 1999, Wichstrom 2000 DE 21. XX

OTHER FACTORS THAT PREDISPOSE TO SUICIDE § Imitation § Biological abnormalities that ? predispose to impulsive response to stress § A family history of suicide 2004 January

HOW SUICIDES OCCUR —PATHWAYS TO AND FROM IDEATION— COGNITIVE SET SUICIDAL IDEATION (Hopelessness) ACTIVE DISORDER e. g. Mood Disorder Substance Abuse Alcohol Abuse e. g. Trouble with Law/School Loss Humiliation FACILITATION SOCIAL STRESS EVENT INHIBITION UNDERLYING “IMPULSIVE” TRAIT Religiosity Available Support Difficult Access to Method Consider Effect on Others ACUTE MOOD CHANGE e. g. Anxiety – Dread Hopelessness Anger MENTAL STATE Slowed Down IMPACT OF ALCOHOL SOCIAL Recent Example Weak Taboo Being Alone METHOD AVAILABILITY/ COMPETENCE MENTAL STATE Agitation SURVIVAL SUICIDE C. MO 1. XX

3 CHANGING RATES

20 TH-CENTURY - CHANGES IN YOUTH SUICIDE RATES Rate per 100, 000 — U N I T E D S T A T E S , A G E S 15– 24 — Year Anderson 2002, CDC Wonder 2003, USDHEW 1956, Vital Statistics U. S. 1954– 1978 C. E 16. XX

TEEN SUICIDE RATES IN INDUSTRIALIZED NATIONS — M A L E S 15– 24, 1988– 2001 — Declining Rates § § § § § Australia Austria* Canada England & Wales France Germany* Hong Kong Ireland Italy § § Japan New Zealand Spain Switzerland* Stable/Rising Rates § Scotland World Health Organization 2003; *decline started before 1988

POSSIBLE REASONS FOR DECLINING SUICIDE RATES 1 § Economic Prosperity BUT • Rates also decline in high-youthunemployment countries • relationship between SES and suicide not strong § Less drug and alcohol abuse BUT • use and abuse rates have not changed [DR 13. XX]

POSSIBLE REASONS FOR DECLINING SUICIDE RATES 2 § Reduced firearm availability BUT • proportion of suicides by firearm unchanged • declines noted in countries with very few firearm suicides [DR 13. XX]

POSSIBLE REASONS FOR DECLINING SUICIDE RATES 3 § More psychotherapeutic treatment BUT • psychotherapy has declined § More psychopharmacologic treatment § Better recognition of adolescent depression § Some combination of the above [DR 13. XX]

4 TREATMENT CONSIDERATIONS

EFFECTIVE TREATMENT OF SUICIDE ATTEMPTERS —META-ANALYSIS OF 23 RCTs— Outcome = Repeated Attempts PSYCHOTHERAPY § DBT (adult borderlines) MEDICATION § Flupenthixol (Navane) in multiple attempts § Lithium in bipolar § Clozaril in schizophrenia Meltzer et al 2003, Montgomery & Montgomery 1982, Tondo & Baldessarini 2000 C. Rx 3

TEENS WHO SUICIDE RECEIVE LESS TREATMENT THAN ADULTS Adults STUDY RECENT TREATMENT Ulster United Kingdom 30% 56% Canada 50% Teens STUDY Finland Pittsburgh New York City Norway RECENT TREATMENT 23% 15% 21% 7% Marttunen et al. 1992 Brent et al. 1993, Shaffer et al. 1996, Groholt et al. 1997, Foster et al. 1997, Appleby et al. 1999, Lesage et al. 1994 C. Rx 18. XX

DEPRESSED TEENS WHO COMMIT SUICIDE DO NOT TAKE THEIR MEDICATIONS — U T A H Y O U T H S U I C I D E S T U D Y, N = 49 — Prescribed antidepressants 24% Antidepressants found at autopsy 0% Gray et al. 2003 DR 30. XX

SUICIDALITY DURING THE TREATMENT OF TEEN DEPRESSION Cautions & Considerations -1 § Ideation and attempts are common in depressed teens and recur frequently. § Teens often conceal ideation and attempts unless asked about them directly. Self report facilitates disclosure. § Event Reports may be influenced by mode of elicitation. They are not used with a glossary, misclassification can occur. 2004 February

SUICIDALITY DURING THE TREATMENT OF TEEN DEPRESSION Cautions & Considerations -2 § “Self harm” is a heterogeneous descriptor - not all types of self harm are associated with suicidal intent. § There have been no direct studies -with frequent and careful measurements examining whether SSRI’s increase, decrease or have no effect on suicidal ideation and behavior. 2004 February

SUICIDALITY DURING THE TREATMENT OF TEEN DEPRESSION Cautions & Considerations -3 § After increasing for 35 years teen suicide rates have been declining consistently in many countries. § During this period there has been a marked increase in exposure of teens to SSRI antidepressants. § These trends could be related. We do not - currently - have a better explanation for the turnabout of a condition that led to the death of tens of thousands of young people. 2004 February