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Transcript TASA Site Training
Long-term Effects of Mental
Health Interventions in Children
Benedetto Vitiello, M.D.
Roma, 11 May 2012
Disclosure
I have no financial conflicts of interest
The views here presented are not official
statements of NIMH/NIH
Prominence of mental illness in childhood
Leading causes of burden of disease for age
under 15 years, in high-income countries:
1.
Neuropsychiatric disorders
2.
Perinatal conditions
3.
Unintentional injuries
(WHO 2004)
Psychopathology during development
Autism spectrum disorders affect about 0.5%
of children
Anxiety disorders often start in childhood
About one third of all cases of schizophrenia
start below age 18
Age of onset of mood disorders
(Kessler et al., 2005)
Depression In 25% of cases, onset by age 19
In 10% of cases, onset by age 14
In 5% of cases, onset by age 12
Bipolar
In 25% of cases, onset by age 17
In 10% of cases, onset by age 13
In 5% of cases, onset by age 11
Most common causes of
hospitalization in the U.S.
Age 10-14 yr:
(Lasky et al. 2011)
Age 15-17 yr:
1.
Appendicitis
1.
Mood disorders
2.
Mood disorders
2.
Obstetrics
3.
Asthma
3.
Traumas
Aims of this presentation:
To review the developmental context for
mental health interventions
To discuss the effectiveness of commonly used
child psychiatry treatments
To highlight areas of ongoing research
Importance of a long-term perspective
Most psychiatric disorders are chronic or
recurrent, and require long-term treatment
Early intervention may be the only opportunity
to improve life long prognosis
Chronic treatment can have unwanted effects
We need to consider the trajectory of
psychopathology in order to:
To understand the meaning of the symptom
To plan targeted therapeutic interventions
ADHD trajectory with age (Faraone et al. 2006)
Treatment effectiveness:
the best source of evidence
Type I: strong evidence from at least one
systematic review of multiple well-designed
randomized controlled trials (RCT)
Type II: strong evidence from at least one
properly designed RCT of appropriate size
[Gray, 1997]
Treatment effect size (vs. a control)
0.3
small effect size
0.5
medium effect size
0.8
large effect size
Effective treatments of ADHD
Effect size
medium
NNT
Behavior therapy
6
Stimulants (methylphenidate, amphet.) large
3
Atomoxetine
medium
6
Alpha-2 agonists
medium
6
Stimulants are highly effective
at decreasing ADHD symptoms
Highest level of evidence:
Type I: strong evidence from meta-analyses and
systematic reviews of multiple RCTs.
Well documented by numerous placebo-controlled studies
(both crossover and parallel-group designs)
Methylphenidate: Effects
•
•
Effect size vs. placebo:
•
Teacher-rated inattention/hyperactivity: 1.31
•
Parent-rated inattention/hyperactivity: 0.63
Response rate: 77% on MPH
12.5% on Placebo
NNT=1.5
[MTA Study]
Pediatric stimulant use in the U.S., 1987-2008
(Zuvekas & Vitiello, 2012)
6
Number of Users per 100 Population
5
4
0-5
6-1
130-1
3
2
1
0
1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
Year
14-Month Outcomes
Teacher SNAP-Inattention
3
Time x Tx: F=10.6, p<.0001
Site x Tx: F=0.9, ns
Site: F=2.7, p<.02
2.5
CC
Beh
Average Score
MedMgt
2
Comb
1.5
1
Comb, MedMgt > Beh, CC
0.5
0
0
100
200
300
400
Assessment Point (Days)
Normative comparison group
Treatment of ADHD
Effective at improving attention and decreasing
impulsivity/hyperactivity
Effective at improving performance on academic work and tests
How effective at improving learning?
How effective in changing the trajectory of psychopathology and
improve distal prognosis?
ADHD Medication and School Achievement
(Scheffler et al. 2009)
Early Childhood Longitudinal Study
N=594 children with ADHD
5 surveys between kindergarten and 5th grade
Children treated with medication had a mean
math score greater than untreated children,
after controlling for confounding variables
Stimulant medication improves
driving on simulator (Kay et al., 2009)
Stimulant improves road driving
(Verster et al., 2008)
N=18
Randomized, placebo-controlled cross-over
Methylphenidate 10-30 mg
Primary measure: weaving of the car (SD of
lateral position: 21.1 on placebo vs. 18.8 on MPH
(p=.004)
Long-term safety of stimulants
Stimulants and growth
Group
Rx Dose
Height Growth
(mean mg/day)
(mean cm/14 months)
Beh
0
6.19
CC
23
5.68
Comb
31
4.95
Med only
38
4.75
Behav - Med = 1.23 cm/year
[MTA Cooperative Group, Pediatrics 2004;113:762-9]
Chronic MPH in juvenile male rhesus
monkeys (Mattison et al., 2011)
Methylphenidate 2.5 mg/kg/day (N=10)
Plasma levels: 4-14 ng/mL
Methylphenidate 12.5 mg/kg/day (N=10)
Plasma levels: 50-200 ng/mL
Control: saline (N=10)
Treatment: 5 days a week
Duration: 33 months
Pubertal delay in male monkeys treated with
methylphenidate (Mattison et al., 2011)
Stimulants and cardiovascular function
Average increase in:
•
Heart rate: 2-6 bmp
•
Systolic BP: 2-4 mmHg
•
Diastolic BP: 1-3 mmHg
Stimulants treatment for 10 years (Vitiello et al., 2012)
Average increase in:
•
Heart rate: 2-6 bmp
•
Systolic BP: 2-4 mmHg
•
Diastolic BP: 1-3 mmHg
during chronic treatment
Stimulants and risk for hypertension
after 10 years of treatment (Vitiello et al., 2012)
50
40
30
Hypertension
Pre-hypertension
20
10
0
Currently on stimulant (N=18)
Previously on stimulant
(N=275)
Never on stimulant (N=50)
Normative comparison
(N=211)
Cumulative 10-year exposure to stimulant
and risk for hypertension (Vitiello et al., 2011)
Cumulative dose
N
%
95% C.I.
0
50
18.0
6.2 - 29.8
1-7,898
26
19.2
2.4 - 36.1
7,899-43,460
100
23.0
13.6-32.4
>43,460
169
21.3
14.3-28.3
After 10 yrs of stimulant treatment
(Vitiello et al., 2011)
Current N
HR
SD
use
No med
No
50
68.9
11.0
Cum < 7,898 mg
No
26
70.2
14.7
Cum 7,899-43,460 mg
No
98
68.1
11.3
Yes
2
82.0
5.7
No
145
70.7
11.1
Yes
24
73.7
10.4
Cum >43,460 mg
Depression and development
When negative thoughts become depression
Often preceded by anxiety disorder
Much more common after puberty
–
Episodic and recurrent
–
1.4% at age 8-11 vs. 3.2% at age 12-15
cumulative prevalence: 11.7% by age 18)
Predicts mood disorder in adulthood
Natural history of self-harm: a populationbased cohort study
(Moran et al., 2012)
Treatment of depression in youth:
how effective?
CBT:
ES=0.34
SSRIs:
ES=0.25 (Bridge et al. 2007)
(Weisz et al. 2006)
Response rate: 61% on med. vs. 50% on placebo NNT=10
TADS (N=439, age 12-17)
Mean CDRS Score - Adjusted
60
COMB
50
FLX
CBT
PBO
40
30
Baseline
Week 6
Week 12
TAD S
Depression scores over 9 months
65
Mean CDRS-R Score
OC: Unadjusted Data
55
COMB
FLX
45
CBT
PBO
35
25
Base
Wk6
Wk12
Wk18
Assessment
Wk24
Wk30
Wk36
TAD S
Antidepressant in children:
how safe?
(Bridge et al. 2007)
Rate of suicidal ideation/suicide attempts:
SSRI: 3% (CI 95%, 2 to 4%)
PBO:
2% (CI 95%, 1 to 2%)
NNH=112
Bipolar disorder (“extreme mood
dysregulation”) and its treatment
TEAM: randomized trial of risperidone, lithium, and
valproate
N=279
–
6-15 yr (mean 10), 50% males, 73% white
Five U.S. universities
8 weeks
Open but with blinded clinical raters at baseline and
end of study (week 8)
TEAM: Improvement rate at week 8
(Geller et al. 2012)
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
65.6%
34.4%
Risperidone
(n=93)
Lithium
(n=93)
23.1%
Divalproex
(n=104)
Schizophrenia: a developmental disorder
Progressive brain volume loss
in the early phase of schizophrenia
(Sporn et al., 2003)
Can early antipsychotic treatment improve
the prognosis of schizophrenia?
•
Duration of untreated psychosis predicts
outcome
•
Prognosis depends on level of functioning at
time of treatment
•
But, antipsychotics do not stop the brain loss…
Conclusions
There are effective psychiatric treatments for
children with ADHD, mood and anxiety
disorders
These treatments can improve symptoms and
functioning, but their long term impact is
unclear
Research is ongoing to develop disease
modifying treatments