1. Teen Depression andTeen Depression and
SuicideSuicide
Carlo G. Carandang, M.D.Carlo G. Carandang, M.D.
Attending Child PsychiatristAttending Child Psychiatrist
Maine Medical CenterMaine Medical Center
PortlandPortland
Clinical Assistant Professor of PsychiatryClinical Assistant Professor of Psychiatry
University of Vermont College of MedicineUniversity of Vermont College of Medicine
BurlingtonBurlington

2. DisclosureDisclosure
 Grant/Research Support:Grant/Research Support:
• Maine Medical Center Research InstituteMaine Medical Center Research Institute
• GlaxoSmithKlineGlaxoSmithKline

3. HypothesisHypothesis
 Early identification and aggressiveEarly identification and aggressive
treatment of depression intreatment of depression in
adolescents will decrease the overalladolescents will decrease the overall
suicide rate in young persons.suicide rate in young persons.

4. ObjectivesObjectives
 Learn clinical presentation ofLearn clinical presentation of
adolescent depressionadolescent depression
 Learn course and prognosis ofLearn course and prognosis of
pediatric depressionpediatric depression
 Learn treatment of pediatricLearn treatment of pediatric
depressiondepression
 Discuss controversy ofDiscuss controversy of
antidepressant medications in youthantidepressant medications in youth
and suicidalityand suicidality

5. Youth Depression: PrevalenceYouth Depression: Prevalence
 Common ConditionCommon Condition
 Point Prevalence:Point Prevalence:
• 1-3% of children1-3% of children
• 3-9% of adolescents3-9% of adolescents
 Lifetime Prevalence: 20-25% by endLifetime Prevalence: 20-25% by end
of adolescence (Kessler et al. 2001)of adolescence (Kessler et al. 2001)
 Prevalence increases with agePrevalence increases with age

6. Youth Depression: Cohort EffectYouth Depression: Cohort Effect
 Cohort EffectCohort Effect
 Successive generations after 1940 at greater riskSuccessive generations after 1940 at greater risk
 Younger age of onset in more recent generationsYounger age of onset in more recent generations
 Increased recognition and diagnostic accuracyIncreased recognition and diagnostic accuracy
• Less controversial diagnosis, particularly forLess controversial diagnosis, particularly for
childrenchildren
 Higher actual ratesHigher actual rates
• Biological factors: earlier menarche, geneticBiological factors: earlier menarche, genetic
anticipationanticipation
• Environmental factors: dietary changes,Environmental factors: dietary changes,
familial/societal disruption, academicfamilial/societal disruption, academic
expectations, increased exposure to adverse lifeexpectations, increased exposure to adverse life
eventsevents

7. Youth Depression: Gender andYouth Depression: Gender and
PubertyPuberty
 Gender DistributionGender Distribution
• 1:1 before puberty1:1 before puberty
• 2:1 female predominance after, similar2:1 female predominance after, similar
to adultsto adults
• Ratio equalizes after menopauseRatio equalizes after menopause

8. Youth Depression: ClinicalYouth Depression: Clinical
PresentationPresentation
 SIGECAPS for 2+ weeksSIGECAPS for 2+ weeks
 Dysthymia: 1 vs 2 year criterion)Dysthymia: 1 vs 2 year criterion)
• SSleep Disturbanceleep Disturbance
• IIrritabilityrritability (core symptom in youth, not adults)(core symptom in youth, not adults)
• GGuiltuilt
• EEnergynergy
• CConcentrationoncentration
• AAppetite/weight (in youth, failure to maintainppetite/weight (in youth, failure to maintain
expected weight gains)expected weight gains)
• PPsychomotor Agitation or Retardationsychomotor Agitation or Retardation
• SSuicidalityuicidality

9. Youth Depression: DiagnosticYouth Depression: Diagnostic
IssuesIssues
 For adult depression, interview focused onFor adult depression, interview focused on
the patientthe patient
 For youth depression, interview focused onFor youth depression, interview focused on
multiple informants:multiple informants:
• Patient, parents, teachers, pediatricianPatient, parents, teachers, pediatrician
 Disagreement on symptoms often occursDisagreement on symptoms often occurs
between youth and parentbetween youth and parent
• Use the “OR” rule: count the positiveUse the “OR” rule: count the positive
symptoms from either source towardssymptoms from either source towards
diagnostic criteriadiagnostic criteria

10. Youth Depression: AssessmentYouth Depression: Assessment
 Clinical historyClinical history
• Child, family, school and other sourcesChild, family, school and other sources
 Standardized clinical instrumentsStandardized clinical instruments
(e.g. K-SADS)(e.g. K-SADS)
 Rating scalesRating scales
• Self: Childhood Depression Inventory (CDI)Self: Childhood Depression Inventory (CDI)
 Clinical cutoff value for CDI: 10Clinical cutoff value for CDI: 10
• Clinician: Childhood Depression Rating ScaleClinician: Childhood Depression Rating Scale
(CDRS-R)(CDRS-R)
 Baseline value 17 / Clinical cutoff: 35Baseline value 17 / Clinical cutoff: 35

11. Youth Depression: ComorbidityYouth Depression: Comorbidity
 DysthymiaDysthymia
• Dysthymia as “gateway” disorderDysthymia as “gateway” disorder
 Anxiety disordersAnxiety disorders (often precedes(often precedes
depression in youth)depression in youth)
 Disruptive disordersDisruptive disorders (attention deficit,(attention deficit,
oppositional defiant, conduct)oppositional defiant, conduct)
 Substance abuseSubstance abuse
 Eating DisordersEating Disorders
 Learning DisabilitiesLearning Disabilities

12. Depression vs. Bipolar DisorderDepression vs. Bipolar Disorder
 Pediatric Bipolar DisorderPediatric Bipolar Disorder
• Depression may be the firstDepression may be the first
presentation of underlying Bipolarpresentation of underlying Bipolar
DisorderDisorder
• Mixed states are common in youthMixed states are common in youth
• ““Switch” rates are reported to be asSwitch” rates are reported to be as
high as 40%high as 40%
• Legitimate “switches” may be hard toLegitimate “switches” may be hard to
interpret in the face of treatment orinterpret in the face of treatment or
concurrent substance useconcurrent substance use

13. Risk Factors/Correlates forRisk Factors/Correlates for
DepressionDepression
 Biological CorrelatesBiological Correlates
• Genetics: twin studies, offspring studies andGenetics: twin studies, offspring studies and
family history studies show that depressionfamily history studies show that depression
aggregates in familiesaggregates in families
• Temperament: no evidence to dateTemperament: no evidence to date
• Hormonal: puberty increases risk of depressionHormonal: puberty increases risk of depression
for females; thyroid and growth hormonefor females; thyroid and growth hormone
abnormalitiesabnormalities
• Sleep: sleep disruption can lead to moodSleep: sleep disruption can lead to mood
disruptions and functional impairmentdisruptions and functional impairment

14. Risk Factors/Correlates forRisk Factors/Correlates for
DepressionDepression
 Psychological CorrelatesPsychological Correlates
• Cognitive Factors: pessimistic view ofCognitive Factors: pessimistic view of
the world (dysfunctional attitudes) andthe world (dysfunctional attitudes) and
viewing negative events as beyondviewing negative events as beyond
one’s controlone’s control
• Negative Life Events: often triggersNegative Life Events: often triggers
onset of depression (loss, failure, abuse)onset of depression (loss, failure, abuse)

15. Risk Factors/Correlates forRisk Factors/Correlates for
DepressionDepression
 Social/Environmental CorrelatesSocial/Environmental Correlates
• Poverty: a risk factor for mental illnessPoverty: a risk factor for mental illness
in generalin general
• Parenting Environment: parentalParenting Environment: parental
transmission of depression to offspring;transmission of depression to offspring;
depressed parent emotionallydepressed parent emotionally
disengaged, and model cognitivedisengaged, and model cognitive
distortions, negativity, and behaviorsdistortions, negativity, and behaviors
• Peers: rejection and bullying increasePeers: rejection and bullying increase
risk for depressionrisk for depression

16. Youth Depression: Clinical CourseYouth Depression: Clinical Course
 Typical episode duration: 7-9 monthsTypical episode duration: 7-9 months
• Childhood onset MDD has a 60-70% riskChildhood onset MDD has a 60-70% risk
of recurrence in adulthoodof recurrence in adulthood
• 20-40% of youth with depression20-40% of youth with depression
develop bipolar disorder within 5 yearsdevelop bipolar disorder within 5 years
(Weller and Weller 2000)(Weller and Weller 2000)

17. Youth Depression: Clinical CourseYouth Depression: Clinical Course
 Protracted, chronic course in ~10%Protracted, chronic course in ~10%
of cases.of cases.
 Risk factors of chronic depression:Risk factors of chronic depression:
• Earlier onsetEarlier onset
• Number and severity of prior episodesNumber and severity of prior episodes
• Poor compliance/ lack of treatmentPoor compliance/ lack of treatment
• Psychiatric illness in parentsPsychiatric illness in parents
• Adverse life eventsAdverse life events

18. Youth Depression: Clinical CourseYouth Depression: Clinical Course
 Disruption in several domains:Disruption in several domains:
• School performanceSchool performance
• Peer relationshipsPeer relationships
• Family interactionsFamily interactions
 Long term sequelae:Long term sequelae:
• Suicidal behaviorSuicidal behavior
• Academic problemsAcademic problems
• Negative self-imageNegative self-image
• Substance abuseSubstance abuse
• Relationship problems (peers and family)Relationship problems (peers and family)
• Antisocial behaviorsAntisocial behaviors
• Psychiatric hospitalizationPsychiatric hospitalization

19. Teen Depression and SuicideTeen Depression and Suicide
 Between 1964 and 1990, the suicideBetween 1964 and 1990, the suicide
rate for teens 15-19 in the USrate for teens 15-19 in the US
increased more than 3-fold (4 to 11increased more than 3-fold (4 to 11
per 100,000)per 100,000)
 Between 1990 and 2000, the suicideBetween 1990 and 2000, the suicide
rate for teens 15-19 in the USrate for teens 15-19 in the US
decreased by over 20% (11 to 8 perdecreased by over 20% (11 to 8 per
100,000)100,000)
 Prozac first marketed in 1988, andProzac first marketed in 1988, and
antidepressant Rx increase for youthantidepressant Rx increase for youth

20. (Shaffer et al., 1996)(Shaffer et al., 1996)
Psychopathology and Suicide inPsychopathology and Suicide in
YouthYouth
 Over 90% of suicide victims orOver 90% of suicide victims or
suicide attempters have a psychiatricsuicide attempters have a psychiatric
illnessillness
• 60% of all suicides occur in youth with60% of all suicides occur in youth with
mood disorders (depression and bipolarmood disorders (depression and bipolar
disorderdisorder
• The other 30% of all suicides occur inThe other 30% of all suicides occur in
youth with schizophrenia, conductyouth with schizophrenia, conduct
disorder, substance abuse, eatingdisorder, substance abuse, eating
disorders, anxiety disordersdisorders, anxiety disorders

21. (Brent et al., 1993)(Brent et al., 1993)
Psychological Autopsy StudyPsychological Autopsy Study
 Case-control studyCase-control study
• 67 adolescent suicide victims compared67 adolescent suicide victims compared
to 67 age and demographically matchedto 67 age and demographically matched
community-based controlscommunity-based controls
 Relative risks (RR) for youth suicideRelative risks (RR) for youth suicide
secondary to psychopathologysecondary to psychopathology

22. (Brent et al., 1993)(Brent et al., 1993)
Psychological Autopsy StudyPsychological Autopsy Study
RRRR 95% CI95% CI
Major DepressiveMajor Depressive
D/OD/O
27.027.0 1.6-199.81.6-199.8
Bipolar D/O, mixedBipolar D/O, mixed 9.09.0 1.1-71.01.1-71.0
Substance abuseSubstance abuse 8.58.5 2.0-36.82.0-36.8
Conduct D/OConduct D/O 6.06.0 1.8-20.41.8-20.4
Hx suicide attemptHx suicide attempt 17.017.0 2.3-127.72.3-127.7
SI with planSI with plan 21.021.0 2.8-156.32.8-156.3

23. (Brent et al., 1993)(Brent et al., 1993)
Psychological Autopsy StudyPsychological Autopsy Study
 Results of Brent 1993 study suggestResults of Brent 1993 study suggest
an important means of reducingan important means of reducing
suicide rates in youth is to identifysuicide rates in youth is to identify
and treat youth with Mood Disordersand treat youth with Mood Disorders
(especially Major Depressive(especially Major Depressive
Disorder) and Substance AbuseDisorder) and Substance Abuse

24. (Brent et al., 1988)(Brent et al., 1988)
Study of Youth Suicidal BehaviorStudy of Youth Suicidal Behavior
 Comparative study of adolescent suicide victimsComparative study of adolescent suicide victims
and adolescent psychiatric inpatients whoand adolescent psychiatric inpatients who
attempted suicideattempted suicide
 Both groups were highly associated withBoth groups were highly associated with
depressiondepression
 Bipolar D/O more common in suicide victims thanBipolar D/O more common in suicide victims than
among suicidal inpatients (RR 13.7; 95% CI 2.1-among suicidal inpatients (RR 13.7; 95% CI 2.1-
89.9)89.9)
 Suicide victims more likely to have firearms in theSuicide victims more likely to have firearms in the
home than suicidal inpatients (RR 2.7; 95% CIhome than suicidal inpatients (RR 2.7; 95% CI
1.1-6.4)1.1-6.4)
 This study suggests that removing firearms fromThis study suggests that removing firearms from
the home and addressing cycling mood disordersthe home and addressing cycling mood disorders
might be suicide-preventive strategiesmight be suicide-preventive strategies

25. Studies of Suicidal BehaviorStudies of Suicidal Behavior
Associated with Youth Bipolar D/OAssociated with Youth Bipolar D/O
 Most studies have not highlighted the riskMost studies have not highlighted the risk
of suicide among bipolar youthof suicide among bipolar youth
• Low prevalenceLow prevalence
• Controversy regarding diagnosisControversy regarding diagnosis
 However, when samples of bipolar youthHowever, when samples of bipolar youth
are described, suicidal risk is elevated forare described, suicidal risk is elevated for
youth with bipolar D/O, especially rapid-youth with bipolar D/O, especially rapid-
cyclingcycling
 A preventative strategy for suicide mightA preventative strategy for suicide might
be to identify youth with rapidly cyclingbe to identify youth with rapidly cycling
mood statesmood states

26. (Weissman et al., 1999)(Weissman et al., 1999)
Longitudinal StudyLongitudinal Study
 73 adolescents with depression and 3773 adolescents with depression and 37
adolescents without psychiatric disordersadolescents without psychiatric disorders
were followed up 10 to 15 years laterwere followed up 10 to 15 years later
 Result: 7.7% of adolescents withResult: 7.7% of adolescents with
depression SUICIDED, while none of thedepression SUICIDED, while none of the
healthy adolescents didhealthy adolescents did
 This study suggests that adolescentThis study suggests that adolescent
depression associated with significant riskdepression associated with significant risk
of completed suicideof completed suicide

27. (Klimes-Dougan et al., 1999)(Klimes-Dougan et al., 1999)
Family StudyFamily Study
 A comparative study of 192 children ofA comparative study of 192 children of
mothers with depression, and mothersmothers with depression, and mothers
without depressionwithout depression
 Results: children of depressed mothersResults: children of depressed mothers
significantly more likely to exhibit suicidalsignificantly more likely to exhibit suicidal
ideations and attempts, compared toideations and attempts, compared to
children of healthy motherschildren of healthy mothers
 This study suggests that it is important toThis study suggests that it is important to
identify family history of mood disorders,identify family history of mood disorders,
as this imparts mood disorder risk andas this imparts mood disorder risk and
hence suicide riskhence suicide risk

28. Prevention of Suicidal BehaviorPrevention of Suicidal Behavior
 Identification of youth at risk for moodIdentification of youth at risk for mood
disorders (especially depression) may bedisorders (especially depression) may be
the best primary preventive methodthe best primary preventive method
• Offspring of parents with mood disordersOffspring of parents with mood disorders
 Identification and treatment of youth withIdentification and treatment of youth with
mood disorders (especially depression)mood disorders (especially depression)
 Decrease access of firearms and toxicDecrease access of firearms and toxic
medications (Tylenol) to youth (mostmedications (Tylenol) to youth (most
common method of suicide)common method of suicide)

29. Assessing Suicide RiskAssessing Suicide Risk
 Predisposing factorsPredisposing factors
• Previous suicide attemptsPrevious suicide attempts
• Depression, Bipolar D/ODepression, Bipolar D/O
• Panic attacksPanic attacks
• Substance abuseSubstance abuse
• Family history of suicideFamily history of suicide
• Impulsive and aggressive behaviorImpulsive and aggressive behavior
• Caucasian malesCaucasian males
 MeansMeans
• Always inquire about firearm availabilityAlways inquire about firearm availability
 Keeping guns separate from bullets: false reassuranceKeeping guns separate from bullets: false reassurance
• Secure toxic medications: TylenolSecure toxic medications: Tylenol

30. Teen Depression: Initial TreatmentTeen Depression: Initial Treatment
PlanPlan
 Always assess for safetyAlways assess for safety
• Assess suicide risk, substance abuse,Assess suicide risk, substance abuse,
firearms in the house, medicationsfirearms in the house, medications
secured (esp. Acetaminophen andsecured (esp. Acetaminophen and
Ibuprofen)Ibuprofen)
 Family involvement crucialFamily involvement crucial
 Modified school planModified school plan

31. Depression: PsychotherapyDepression: Psychotherapy
 PsychoeducationPsychoeducation
• ““Is it adolescence or is it depression?”Is it adolescence or is it depression?”
 Cognitive-Behavioral TreatmentCognitive-Behavioral Treatment
(CBT, Brent)(CBT, Brent)
• Cognitive distortions, generalization,Cognitive distortions, generalization,
overattributionoverattribution
 Interpersonal Psychotherapy (IPT,Interpersonal Psychotherapy (IPT,
Mufson)Mufson)
• Areas of loss and grief, interpersonalAreas of loss and grief, interpersonal
roles and disputes, role transitionsroles and disputes, role transitions

32. Depression: PsychotherapyDepression: Psychotherapy
 Dialectic Behavioral Therapy (DBT,Dialectic Behavioral Therapy (DBT,
Linehan)Linehan)
• Strategies helpful in treatment ofStrategies helpful in treatment of
parasuicidal behaviors, comorbidparasuicidal behaviors, comorbid
personality disorders (teens)personality disorders (teens)
 Psychodynamic PsychotherapyPsychodynamic Psychotherapy
(Fonagy)(Fonagy)

33. Depression: PsychotherapyDepression: Psychotherapy
 CBT most frequently investigatedCBT most frequently investigated
treatment for depression in youthtreatment for depression in youth
• Depressed children and CBT: 4 of 5 childDepressed children and CBT: 4 of 5 child
CBT studies demonstrate short-termCBT studies demonstrate short-term
efficacy; 1 study demonstrated efficacyefficacy; 1 study demonstrated efficacy
maintained 9 months latermaintained 9 months later
• Depressed adolescents and CBT: 7 of 9Depressed adolescents and CBT: 7 of 9
adolescent CBT studies demonstrateadolescent CBT studies demonstrate
short-term efficacyshort-term efficacy
(Curry 2001)(Curry 2001)

34. Depression: PsychotherapyDepression: Psychotherapy
 IPT: 2 controlled studies showIPT: 2 controlled studies show
efficacy short-termefficacy short-term
 Combination of CBT and medicationCombination of CBT and medication
is most effective in youth depressionis most effective in youth depression
(March et al. 2004)(March et al. 2004)

35. Depression: PsychotherapyDepression: Psychotherapy
SummarySummary
 Characteristics of effectiveCharacteristics of effective
psychotherapy for acute depressionpsychotherapy for acute depression
in youth:in youth:
• Focus on “here and now”Focus on “here and now”
• Focus on specific problemFocus on specific problem
• Practical and concrete solutionsPractical and concrete solutions
• Alliance with family, schoolAlliance with family, school

36. Depression: PharmacotherapyDepression: Pharmacotherapy
 Medication not usually first-line,Medication not usually first-line,
except:except:
• Severe symptoms or suicidal riskSevere symptoms or suicidal risk
• Psychotic and bipolar depressionsPsychotic and bipolar depressions
• Symptoms prevent participation inSymptoms prevent participation in
psychotherapypsychotherapy
• Adequate psychotherapy trial ineffectiveAdequate psychotherapy trial ineffective
• Chronic or recurrent depressionChronic or recurrent depression

37. Pharmacotherapy of YouthPharmacotherapy of Youth
Depression: TCA’sDepression: TCA’s
 Tricyclic antidepressants (TCA’s)Tricyclic antidepressants (TCA’s)
• Efficacy not better than placeboEfficacy not better than placebo
• Anticholinergic and cardiovascular sideAnticholinergic and cardiovascular side
effectseffects
• Lethal in overdoseLethal in overdose

38. SSRI’s: FDA Blackbox WarningSSRI’s: FDA Blackbox Warning
 Selective Serotonin Reuptake InhibitorsSelective Serotonin Reuptake Inhibitors
(SSRI’s)(SSRI’s)
 FDA: SSRI’s associated with increased riskFDA: SSRI’s associated with increased risk
of suicide in youthof suicide in youth
 UK: SSRI’s banned in youthUK: SSRI’s banned in youth
 Columbia pooled analysis of 24 clinicalColumbia pooled analysis of 24 clinical
trials involving 4,400 youthtrials involving 4,400 youth
• 4% suicidal events on medication versus 2%4% suicidal events on medication versus 2%
on placeboon placebo
• Statistically significant p<0.05Statistically significant p<0.05
• No completed suicides in trialsNo completed suicides in trials

39. FDA Blackbox and SSRI’sFDA Blackbox and SSRI’s
 Methodological problemsMethodological problems
• Studies were not designed to measure suicideStudies were not designed to measure suicide
outcomesoutcomes
• Most studies only had spontaneous reporting ofMost studies only had spontaneous reporting of
suicide behaviors, with no prospective methodsuicide behaviors, with no prospective method
for monitoring suicide behaviorsfor monitoring suicide behaviors
• Definition of suicide not uniform across studiesDefinition of suicide not uniform across studies
 Includes activation, agitation, in addition to actualIncludes activation, agitation, in addition to actual
suicidal ideations/behaviorssuicidal ideations/behaviors

40. FDA Blackbox and SSRI’sFDA Blackbox and SSRI’s
 FDA initially stated that SSRI’s canFDA initially stated that SSRI’s can
causecause suicide in youthsuicide in youth
 Recently, FDA announced that SSRI’sRecently, FDA announced that SSRI’s
increases the risk of suicide in short-increases the risk of suicide in short-
term studiesterm studies

41. FDA Blackbox on SSRI’sFDA Blackbox on SSRI’s
 Blackbox on all antidepressants inBlackbox on all antidepressants in
youth <18 years old for ANYyouth <18 years old for ANY
indicationindication
 Includes all antidepressants: SSRI’s,Includes all antidepressants: SSRI’s,
bupropion (Wellbutrin), venlafaxinebupropion (Wellbutrin), venlafaxine
(Effexor), mirtazepine (Remeron),(Effexor), mirtazepine (Remeron),
nefazodone (Serzone )and TCA’snefazodone (Serzone )and TCA’s
 Duloxetine (Strattera) was notDuloxetine (Strattera) was not
included (Why Not???)included (Why Not???)

42. Risk Ratio of Serious Suicide-Risk Ratio of Serious Suicide-
Related Event on SSRI’sRelated Event on SSRI’s
N (drug)N (drug) N (PBO)N (PBO) Risk RatioRisk Ratio
ProzacProzac 249249 209209 0.920.92
PaxilPaxil 642642 549549 2.652.65
ZoloftZoloft 281281 279279 1.481.48
CelexaCelexa 210210 197197 1.371.37
EffexorEffexor 339339 342342 4.974.97
RemeronRemeron 170170 8888 1.581.58
SerzoneSerzone 279279 189189 No eventsNo events
Total allTotal all
trialstrials
1.781.78

43. Treatment of Youth DepressionTreatment of Youth Depression
 Few pharmacokinetic & dose-rangeFew pharmacokinetic & dose-range
studiesstudies
 SSRI’s may induce mania,SSRI’s may induce mania,
hypomania, behavioral activationhypomania, behavioral activation
(impulsive, silly, agitated, daring)(impulsive, silly, agitated, daring)
 No long-term studies of treatment ofNo long-term studies of treatment of
depression; long-term effects ofdepression; long-term effects of
SSRI’s not knownSSRI’s not known

44. Published Placebo- ControlledPublished Placebo- Controlled
Studies: SSRI’s in YouthStudies: SSRI’s in Youth
DepressionDepression
 Emslie et al (1997): modest fluoxetine efficacy:Emslie et al (1997): modest fluoxetine efficacy:
fluoxetine 58%, placebo 32%fluoxetine 58%, placebo 32%
 Keller et al (2001): paroxetine efficacy:Keller et al (2001): paroxetine efficacy:
paroxetine 63%, imipramine 50%, placebo 46%,paroxetine 63%, imipramine 50%, placebo 46%,
1 of 2 primary outcome measures was significant;1 of 2 primary outcome measures was significant;
2 other studies were negative2 other studies were negative
 Emslie et al (2002): fluoxetine efficacy: effectsEmslie et al (2002): fluoxetine efficacy: effects
modest (fluoxetine 41%, placebo 20%) & not allmodest (fluoxetine 41%, placebo 20%) & not all
outcome measures were significantly differentoutcome measures were significantly different
than placebothan placebo
 Wagner et al (2003): sertraline efficacy:Wagner et al (2003): sertraline efficacy:
sertraline 69%, placebo 59%sertraline 69%, placebo 59%

45. TADS: Combination Treatment ofTADS: Combination Treatment of
Depression in TeensDepression in Teens
 NIMH sponsored “The Treatment ofNIMH sponsored “The Treatment of
Adolescents with Depression Study”Adolescents with Depression Study”
 N=439, 12-17 year olds with depression,N=439, 12-17 year olds with depression,
12 weeks12 weeks
 CGI-Improvement of 1 or 2CGI-Improvement of 1 or 2
• Fluoxetine+CBT: 71%Fluoxetine+CBT: 71%
• Fluoxetine alone: 61%Fluoxetine alone: 61%
• CBT alone: 43% (not significant)CBT alone: 43% (not significant)
• Placebo: 35%Placebo: 35%
 Fluoxetine+CBT also the best at reducingFluoxetine+CBT also the best at reducing
suicidalitysuicidality

46. Why Prescribe Antidepressants inWhy Prescribe Antidepressants in
Youth with these Suicide Risks?Youth with these Suicide Risks?
 For Prozac, need to treat just 3For Prozac, need to treat just 3
patients to see significant responsepatients to see significant response
 In contrast, need to treat over 50In contrast, need to treat over 50
patients in order to see SSRI-inducedpatients in order to see SSRI-induced
suicidal ideationssuicidal ideations
 AACAP finds this an acceptable risk-AACAP finds this an acceptable risk-
benefit ratio for the treatment ofbenefit ratio for the treatment of
pediatric depressionpediatric depression

47. Recommendations for SSRI’s inRecommendations for SSRI’s in
Youth DepressionYouth Depression
 Mild to moderate depression: CBTMild to moderate depression: CBT
 Moderate to severe depression: SSRI +Moderate to severe depression: SSRI +
CBT (esp. for suicidality)CBT (esp. for suicidality)
 Consider Prozac as first-line treatmentConsider Prozac as first-line treatment
 Monitor weekly, watching for anxiety,Monitor weekly, watching for anxiety,
agitation, impulsivity, akathisia, maniaagitation, impulsivity, akathisia, mania
 Spend more time with families on risk-Spend more time with families on risk-
benefit discussion before treatmentbenefit discussion before treatment

48. Effect of Blackbox on Public HealthEffect of Blackbox on Public Health
 Questions:Questions:
• Effect on suicide rates?Effect on suicide rates?
• Effect on treatment delivery?Effect on treatment delivery?
 Will families avoid seeking treatment?Will families avoid seeking treatment?
 Will Pediatricians and Family PractitionersWill Pediatricians and Family Practitioners
stop prescribing SSRI’s?stop prescribing SSRI’s?
 Can Child Psychiatrists handle the burden ofCan Child Psychiatrists handle the burden of
treating youth depression alone?treating youth depression alone?
• Will the FDA eventually ban SSRI’s inWill the FDA eventually ban SSRI’s in
youth?youth?

49. Effect of Blackbox on Public HealthEffect of Blackbox on Public Health
 Youth prescribed less antidepressantsYouth prescribed less antidepressants
 Medco Health Solutions, Inc. coversMedco Health Solutions, Inc. covers
12,374,932 patients under 1812,374,932 patients under 18
• 10% DECREASE in antidepressant Rx in 200410% DECREASE in antidepressant Rx in 2004
to youth under 18to youth under 18
• This contrasts to almost 9% INCREASE inThis contrasts to almost 9% INCREASE in
antidepressant Rx in 2003 to youth under 18antidepressant Rx in 2003 to youth under 18
(start of controversy in May 2003)(start of controversy in May 2003)
• Only a 0.66% prescribing rate ofOnly a 0.66% prescribing rate of
antidepressants in youthantidepressants in youth
• Expect continued decrease in prescribing, withExpect continued decrease in prescribing, with
possible increase in suicide rate in youthpossible increase in suicide rate in youth

50. Treatment-Resistant Depression:Treatment-Resistant Depression:
Mood StabilizersMood Stabilizers
 Augmentation, combinationAugmentation, combination
• Lithium augmentation: open-label prospectiveLithium augmentation: open-label prospective
(Strober et al. 1992)(Strober et al. 1992)
 Imipramine + Lithium helpfulImipramine + Lithium helpful
 N=24, mean age 15.4, dosing variable, 3 weeksN=24, mean age 15.4, dosing variable, 3 weeks
• Lamotrigine (Lamictal) augmentation: case seriesLamotrigine (Lamictal) augmentation: case series
(Carandang et al., 2003)(Carandang et al., 2003)
 LTG augmentation helpful for refractory depressionLTG augmentation helpful for refractory depression
 N=9, ages 14-18, dosing 25-200mg dailyN=9, ages 14-18, dosing 25-200mg daily
 1 patient developed benign rash1 patient developed benign rash

51. Treatment-Resistant Depression:Treatment-Resistant Depression:
MonoAmine Oxidase Inhibitors (MAOIs)MonoAmine Oxidase Inhibitors (MAOIs)
• Phenelzine* (Nardil), IsocarbozacidePhenelzine* (Nardil), Isocarbozacide
(Marplan) & Tranylcipromine (Parnate)(Marplan) & Tranylcipromine (Parnate)
• Tyramine reaction + dietary restrictionsTyramine reaction + dietary restrictions
• Serotonin syndrome: long “moratorium”Serotonin syndrome: long “moratorium”
before introducing 5HT-enhancingbefore introducing 5HT-enhancing
agentsagents

52. Treatment-Resistant Depression:Treatment-Resistant Depression:
Electroconvulsive Treatment (ECT)Electroconvulsive Treatment (ECT)
 Last resort treatmentLast resort treatment
 Perhaps under-utilized, especially inPerhaps under-utilized, especially in
psychotic or seriously suicidal casespsychotic or seriously suicidal cases
 Safety and acceptance of treatmentSafety and acceptance of treatment
well establishedwell established
• Meta analysis of close to 400 casesMeta analysis of close to 400 cases
(Walter & Rey 1997)(Walter & Rey 1997)

53. Depression MaintenanceDepression Maintenance
TreatmentTreatment
 MaintenanceMaintenance
• Single episode: 6 - 12 monthsSingle episode: 6 - 12 months
• Multiple or severe episodes: 1 - 5+Multiple or severe episodes: 1 - 5+
years?years?
 Weigh exposure risk to those ofWeigh exposure risk to those of
untreated illnessuntreated illness
 Alliance with youth and familyAlliance with youth and family
 Optimize school programOptimize school program

54. Summary: Treatment Approach toSummary: Treatment Approach to
Suicidal YouthSuicidal Youth
 Treat current illness (medication andTreat current illness (medication and
psychotherapy)psychotherapy)
 Reduce hopelessnessReduce hopelessness
• Ask about anything that is keeping them aliveAsk about anything that is keeping them alive
 Target distortions related to precipitant orTarget distortions related to precipitant or
motivationmotivation
• ““My family is better-off without me”My family is better-off without me”
 Teach problem-solving skills; address how toTeach problem-solving skills; address how to
regulate emotionsregulate emotions
 Address family conflictAddress family conflict
• Enlist help of family membersEnlist help of family members
 Secure lethal agents (guns, medications, carSecure lethal agents (guns, medications, car
keys, alcohol, knives)keys, alcohol, knives)
 Atypical antipsychotics and lithium may be last-Atypical antipsychotics and lithium may be last-
resort options for severe suicidal ideationsresort options for severe suicidal ideations

55. Summary: Prevention of SuicidalSummary: Prevention of Suicidal
Behavior in YouthBehavior in Youth
 Identification of youth at risk for moodIdentification of youth at risk for mood
disorders (especially depression) may bedisorders (especially depression) may be
the best primary preventive methodthe best primary preventive method
• Offspring of parents with mood disordersOffspring of parents with mood disorders
 Identification and treatment of youth withIdentification and treatment of youth with
mood disorders (especially depression)mood disorders (especially depression)
 Decrease access of firearms to youthDecrease access of firearms to youth
(most common method of suicide)(most common method of suicide)
 Be aware of contagion effect of suicide,Be aware of contagion effect of suicide,
especially with adolescentsespecially with adolescents
• Avoid sensationalized coverage of suicidesAvoid sensationalized coverage of suicides

56. Teenage Depression StudiesTeenage Depression Studies
at Maine Medical Centerat Maine Medical Center
Please call for more information:Please call for more information:
Betsy Mullany, RNBetsy Mullany, RN
Research Nurse CoordinatorResearch Nurse Coordinator
Pediatric Affective Disorder ServicesPediatric Affective Disorder Services
Maine Medical CenterMaine Medical Center
216 Vaughan St.216 Vaughan St.
Portland, ME 04102Portland, ME 04102
(207) 662-5287 voice(207) 662-5287 voice
mullae@mmc.orgmullae@mmc.org