Antipsychotika: Nebenwirkungsprofile und unterschiedliche ...
Transcript of Antipsychotika: Nebenwirkungsprofile und unterschiedliche ...
Antipsychotika: Nebenwirkungsprofile und
unterschiedliche Indikationen
Prof. Dr. med. Christoph U. Correll
Professor of Child and Adolescent PsychiatryCharité – Universitätsmedizin Berlin
Berlin, Germany
Professor of Psychiatry and Molecular Medicine
The Donald and Barbara Zucker School of Medicine at Hofstra/NorthwellNew York, USA
For Personal Use Only
Disclosures: Christoph U. Correll
I have an interest in relation with one or more organizations that could be perceived as a possible conflict of interest in the context of this presentation.
The relationships are summarized below:
Interest Name of organization
Grants Bendheim Foundation, Center for Medicaid and Medicare, National Institute of Mental Health (NIMH), Patient-Centered Outcomes Research Institute, Otsuka, Takeda, Thrasher Foundation
Shares No share holdings in pharmaceutical companies
Paid positions, honoraria and advisory boards
Alkermes, Forum, Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, Medavante, Medscape, Neurocrine, Otsuka, Pfizer, ProPhase, Sunovion, Supernus, Takeda,
and Teva.
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Overview Schizophrenia
Bipolar Disorder
Autism/Aggression
Tourette’s Disorder
Adverse Effects
Adverse Effect Monitoring and Management
Conclusions
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The Effectiveness Pyramid
Functional Capacity
Quality of Life
Subjective Well-being
Adherence/Alliance
Tolerability
Efficacy
Medication
Psycho-
EducationPsycho-
Therapy
Correll CU. J Clin Psychiatry. 2011;72(suppl 1):9-13.
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Schizophrenia Spectrum Disorders
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Δin
PA
NS
S T
ota
l S
co
re (
LO
CF
)
PBO ARI
10
mg
30
mg
PBO
n=98
OLA
n=99
n=97
RIS
1-3
mg4-6
mg
n=54
n=54
n=50
PBO
*
***
******
Baseline PANSS:
95 94 9595 96 93 95 93
RIS
0.15-0.6
mg
1.5-6
mg
n=141
n=138
***
2.5-20
mg
n=35
n=72
QUE
400
mg
800
mg
PBO
n=73
n=73
n=74
* **
98 98 97
ZIP
6/12
mg
40-160
mg
PBOPALI
1.5
mg
3/6
mg
PBO
*
n=54
n=48
n=47
n=51
n=183
n=86
91 92 91 9193 96
Mean Improvement in PANSS Total Score from 9
6-Wk RCTs in Pediatric Schizophrenia (13-17 Yrs)
Adapted from: Correll CU et al. J Clin Psychiatry. 2011 May;72(5):655-670.
*p<0.05 vs placebo, **p<0.01 vs placebo, ***p<0.001 vs placebo;
PBO, placebo; OLA, olanzapine; ARI, aripiprazole; RIS, risperidone; QUE, quetiapine; PALI, paliperidone; ZIP, ziprasidone; ASE,
asenapine; LUR, lurasidone
OLA ARI RIS RIS QUE PALI ZIP
LUR
5
mg
10
mg
PBO
n=112
n=108
n=106
LUR
93 94 9487 89
n=102
n=98
n=106
40
mg
80
mg
ASEPBO
ASE
98 97 99
******
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Network Metaanalysis: PANSS Total Score
Reduction with 8 Antipsychotics vs. Placebo
Trial duration=6-12 weeks, age=8-19 years; males=61% Pagsberg AK et al J Am Acad Child Adolesc Psychiatry. 2017 Mar;56(3):191-202.
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Network Metaanalysis: PANSS Total Score
Reduction with 8 Antipsychotics vs. Placebo
and vs Adult Data (Leucht et al, Lancet 2013)
Pagsberg AK et al J Am Acad Child Adolesc Psychiatry. 2017 Mar;56(3):191-202.
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No Antipsychotic Efficacy Differences in Pediatric Schizophrenia, Except CLO
% C
han
ge i
n B
PR
S/ P
AN
SS
To
tal
Sco
re
RIS
P
n
=19
OL
AN
n=
16
HA
LO
n=
15
RIS
P
n=
13
OL
AN
Z
n
=12
RIS
P
n
=41
MO
LIN
n=
40
OL
AN
n
=26
QU
ET
n
=24
RIS
P
n
=11
QU
ET
n
=11
CL
OZ
n
=10
HA
LO
n
=11
CL
OZ
n
=12
OL
AN
n
=13
CL
OZ
n
=18
OL
AN
n
=21
BaselinePANSS:BPRS: 84 85 72 6987 89 53 53
8 W 24 W 6 W8 W 8 WDuration: 12 W 12 W
54
94 93 95 100 100
6 W
5049
106 91
OL
AN
n
=35
*
4.0 12.3 5.0 1.6 8.2 2.8 11.4 60 9.7 533 176 16 327 18.1 403 26.2Mean Dose (mg): 2.9 607
a=significant advantage of CLO vs OLA for negative sxs; b=significant advantage for CLO vs OLA for response
Schimmelmann B, Schmidt SJ, Carbon M, Correll CU. Curr Opin Psychiatry. 2013;26(2):219-30.
a
b
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Paliperidone ER (n=113) vs Aripiprazole (n=114) in Adolescents with Schizophrenia
Savitz AJ et al. J Am Acad Child Adolesc Psychiatry. 2015;54(2):126-137.
Total PANSS PANSS Positive Symptom Subscale
PANSS Negative Symptom SubscaleMean modal dose:
Pali-ER: 6 mg (mean: 7 mg, range:3-9 mg
ARI: 15 mg (mean: 12 mg, range: 5-15 mg
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PANSS Total and Subscale Score Changes
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52-week ARI vs PBO for Relapse Prevention
Time to All-Cause Discontinuation
Age: 15.4 (13-17) years, 65% male with schizophrenia, PANMSS-total: 64, CGI-S=3.1Correll CU et al. J Am Acad Child Adolesc Psychiatry. 2017 Sep;56(9):784-792.
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52-week ARI vs PBO for Relapse Prevention
Time to Impending Relapse
Age: 15.4 (13-17) years, 65% male with schizophrenia, PANMSS-total: 64, CGI-S=3.1Correll CU et al. J Am Acad Child Adolesc Psychiatry. 2017 Sep;56(9):784-792.
*
Relapse: 19.4% vs 34.5% (NNT=7), p=0.018ARI 20-30 mg: 25.0% vs 54.6% (NNT=4), p=0.0064ARI 10-15 mg: 13.0% vs 23.1% (NNT=11), p=0.33
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Treatment of Pediatric Bipolar Disorder
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Acute Efficacy for Mania/Mixed Episodes
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SGAs: YMRS Total Improvement from 6 PBO-
Controlled RCTs in Pediatric BPD (10–17 yrs)
*p<0.01 vs placebo; **p<0.001 vs placebo; ***p<0.0001 vs placebo
1. Tohen M, et al. Am J Psychiatry 2007;164:1547–1556 2. Findling RL et al. J Clin Psychiatry 2009;70:1441–1451.
3. Haas M et al. Bipolar Disord 2009;11:687–700. 4. Pathak RL et al. J Clin Psychiatry. 2013 Jan;74(1):e100-9.
5. Findling RL et al. J Child Adolesc Psychoph. 2013;23(8):545-57. 6. Findling RL et al. J Am Acad Child Adolesc Psychiatry.
2015 Dec;54(12):1032-41.
Mean
ch
an
ge in
YM
RT
S t
ota
l sco
re
PBO ARI2
10
mg
30
mg
PBO
n=99
OLA1
n=98
n=99
RIS3
0.5-2.5
mg
3-6
mg
n=58
n=50
n=61
PBO
******
****
Baseline
YMRS:
31.132.0 33.1 31.0 31.1 30.529.8 29.5
QUE4
400
mg
600
mg
n=93
n=95
**
2.5-20
mg
n=54
n=107
n=89
30.0 29.2 29.2
PBO
**
PBOZIP5
20-160
mg
n=88
n=149
**
27.0 26.2
**
Adapted from Correll CU et al. J Clin Psychiatry. 2011 May;72(5):655-670.
n=101
n=98
n=98
n=98
ASE6
5
mg
10
mg
PBO
20
mg
****
*
29.9 29.5 30.3 30.2
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Mood Stabilizers: YMRS Total Improvement from 5
PBO-Controlled RCTs in Pediatric BPD (6-17 Yrs)
Me
an
ch
an
ge
in Y
MR
TS
To
tal S
co
re
PBO OXC2
1515
mg/d
PBOTPX1
n=
55
n=
55
Baseline
YMRS:30.529.9 31.7 28.8
278
mg/d
n=
27
n=
27
**
PBOVPA6
ER
15-35 mg/d
PBOLi5
30mg/
kg
VPA5
IR
20mg/kg
29.3 27.3 26.6 31.3 31.0
n=
53n=
56
n=
28
n=
70
n=
74
1. DelBello MP et al J Am Acad Child Adolesc Psychiatry. 2005 Jun;44(6):539-47;
2. Wagner KD et al. Am J Psychiatry. 2006 Jul;163(7):1179-86;
3. Findling RL, et al. Pediatrics. 2015 Nov;136(5):885-94.
4. Kowatch RA et al. J Child Adolesc Psychopharmacol. 2015 May;25(4):306-13.
5. Kowatch R et al. AACAP Annual Meeting, October 27, 2007;
6. Wagner KD et J Am Acad Child Adolesc Psychiatry. 2009 May;48(5):519-32.
n=
66n=
31
PBO Li3
30.5mg/
kg
30.0 29.5
*
n=
21
n=
7
30.6 29.8
PBO VPA4
IR
10mg/kgFor Personal Use Only
Antipsychotics-PBO vs. Mood Stabilizer-PBO
Differences in Efficacy
*N = patients on medication or placebo
** = 95% confidence interval crosses 0, which indicates that the difference between treatment group and
placebo is not statistically significant Correll CU et al. Bipolar Disorders 2010;12(2):116-41.
Children and Adolescents Significant Difference
SGA vs MS in Youth
Outcome Second- Generation Antipsychotics
N = 1,118
Mood Stabilizers
N = 494Continuous Outcome Effect
Size95% CI Effect
Size95% CI
YMRS (including TPX among MS)
0.65 0.53– 0.78 0.24 0.06– 0.41 SGA > MS
YMRS (excluding TPX among MS)
0.20 0.02– 0.39 SGA > MS
CGI-BP Overall Illness (including TPX among MS)
0.63 0.50– 0.76 0.471 - N/A
Categorical Outcome NNT 95% CI NNT 95% CIResponse: ≥ 50% ↓YMRS 4.0 3.3– 5.3 7.81 4.7– 24.4 NS
Remission: YMRS </ = 12 3.7 3.1– 4.7 -33.3** -6.8– 10.0 NS
All-cause Discontinuation 12.7 7.5– 41.2 15.6** -7.9–4.3 NS
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Response and Remission in 4 Trials Comparing
Antipsychotics with Mood Stabilizers in PBD
* p<0.05; **p<0.01; ***p<0.001 favoring antipsychotic;
1. DelBello MP, et al. JAACAP 2006;54(3):305-13 – mean age: 15.0 years; 46% with psychosis
2. Pavuluri MN et al. Bipolar Disord 2010;12:593-605 – mean age: 10.9 years; 20% with psychosis
3. Geller B et al. Arch Gen Psychiatry 2012;69:515-28 – mean age: 10.1 years; 77% with psychosis
4. Kowatch RA et al. J Child Adolesc Psychopharmacol. 2015 May;25(4):306-13.
Stu
dy D
efi
ne
d R
es
po
ns
e (
%)
n=
25
n=
25
n=
32
n=
33
n=
89
N
=90
n=
100
n=
25
n=
25
n=
32
n=
33
QUE
101 ug/mL
VPA1
412 mg
RIS
96 ug/mL
VPA2
1.4 mg
RIS
114 ug/mL
VPA3
1.4 mg 1.1 mEg/l
Li QUE
101 ug/mL
VPA1
412 mg
RIS
96 ug/mL
VPA2
1.4 mg
>50%
YMRS ↓↓↓↓< 12 on
YMRS
* **
Response Remission< 12 on
YMRS
**** *
>50%
YMRS ↓↓↓↓
CGI-BP <2
and 8 wk
completer
n=
18
n=
21
RIS VPA4
0.5 mg
CGI-BP <2
81 ug/mL
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TEAM Study: Effect Sizes of Risperidone vs. Lithium *
* On KSADS-Mania Rating Scale Vitiello B et al. J Am Acad Child Adolesc Psychiatry. 2012;51(9):867-78.
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Antipsychotics-PBO vs. Mood Stabilizer-PBO
Differences in Efficacy
*N = patients on medication or placebo
** = 95% confidence interval crosses 0, which indicates that the difference between treatment group and
placebo is not statistically significant Correll CU et al. Bipolar Disorders 2010;12(2):116-41.
Children and Adolescents Significant Difference
SGA vs MS in Youth
Outcome Second- Generation Antipsychotics
N = 1,118
Mood Stabilizers
N = 494Continuous Outcome Effect
Size95% CI Effect
Size95% CI
YMRS (including TPX among MS)
0.65 0.53– 0.78 0.24 0.06– 0.41 SGA > MS
YMRS (excluding TPX among MS)
0.20 0.02– 0.39 SGA > MS
CGI-BP Overall Illness (including TPX among MS)
0.63 0.50– 0.76 0.471 - N/A
Categorical Outcome NNT 95% CI NNT 95% CIResponse: ≥ 50% ↓YMRS 4.0 3.3– 5.3 7.81 4.7– 24.4 NS
Remission: YMRS </ = 12 3.7 3.1– 4.7 -33.3** -6.8– 10.0 NS
All-cause Discontinuation 12.7 7.5– 41.2 15.6** -7.9–4.3 NS
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Acute Efficacy for Bipolar Depression
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Quetiapine (n=93) vs. Placebo (n=100):CDRS-R Change
Age: 10-17 years (mean=14.0), females: 49.5%Response: PBO=55.0% vs QUE: 63.0%; Remission: PBO: 34.0% vs QUE: 45.7%
Findling RL et M al. J Child Adolesc Psychopharmacol. 2014 Aug;24(6):325-35.
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8-Week RCT of OLA/FLU vs PBO
Detke H et al. J Am Acad Child Adolesc Psychiatry. 2015 Mar;54(3):217-24.
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6-Week RCT of Lurasidone vs PBO: CDRS-R
DelBello M et al. J Am Acad Child Adolesc Psychiatry. 2017. Dec;56(12):1015–25.
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Bipolar Disorder Maintenance
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18 Mo Maintenance VPA or Li Trial (N=60)
139 youths (10.8±3.5 yrs) initially treated with Li+/DVPX for 10.7±5.4 weeks. Li+ and DVPX did not differ in survival time until emerging relapse (p=0.55) or all-cause discontinuation (p =0.72).
Findling et al., J Am Acad Child Adolesc Psychiatry. 2005 May;44(5):409-17.
n=30
n=30
p=0.72
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Maintenance: Lamotrigine vs Placebo
Findling RL, et al. J Am Acad Child Adolesc Psychiatry. 2015 Dec;54(12):1020-1031.
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Maintenance: Aripiprazole vs Placebo
Findling RL, et al. Bipolar Disord. 2013 Mar;15(2):138-49.
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Tourette’s Disorder
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Endpoint Yale Global Tic Severity Total Scores
1. Yoo HK et al. J Clin Psychiatry. 2013 Aug;74(8):e772-80; 2. Scahill L et al. Neurology. 2003 Apr 8;60(7):1130-5; 3. Sallee FR et al. J Am Acad Child Adolesc Psychiatry. 2000;39(3):292-9; 4. Sallee FR et al. Am J Psychiatry 1997;154:1057-1062.
En
dp
oin
t Y
GT
S S
To
tal S
co
re
n= 14 n= 12 n= 12 n= 16n= 29 n= 32
PBO ARI1 RIS2
0.5-4
PBO
2-20
PBO ZIP3
5-40Dose (mg/d):
8 Weeks 4 Weeks10 WeeksDuration:
***
**
46.9 46.929.5 28.3 28.5Baseline YGTSS:
PBO HAL PIM4
6 Weeks [3-way x-over study]
*
3.5 3.4
Total n= 22 x-over subjects
* p<0.05; ** p<0.001
28.6 27.0
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Significant Superiority on the Yale Global Tic Severity Score
with Aripiprazole (n=29) vs. Placebo (n=32)
*p<0.05; mean dose 11+/-6 mg (range: 2-20)Yoo HK et al. J Clin Psychiatry. 2013 Aug;74(8):e772-80.
*
*
*
p=0.027
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Aripiprazole low dose (N=44) vs. high dose (N=45) vs. Placebo (44)
Low-dose aripiprazole (5 mg/day if <50 kg; 10 mg/day if ≥50 kg),
high-dose aripiprazole (10 mg/day if <50 kg; 20 mg/day if ≥50 kg)
Sallee F, et al. J Child Adolesc Psychopharmacol. 2017 Nov; 27 (9): 771-781.
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Adverse Effects
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Extrapyramidal Effects
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Inverse Relationship Between Age and Incidence of EPS
Parkinsonism Dystonia Akathisia
Keepers GA et al. Arch Gen Psychiatry. 1983;40:1113-7.
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Neuromotor Side Effects in Youth Naturalistically Treated with 5 SGAs
for 3 Months (n=342)
13.6 years; male=58.2% ; AP-naïve=65.8%
Carbon M et al. J Am Acad Child Adolesc Psychiatry. 2015 Sep;54(9):718-727.
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Participants Treated With 2nd-Generation Antipsychotics
6 times lower 1-Year Incidence Rates of TD with Atypical Antipsychotics vs. Haloperidol
in Adults and 50% lower Risk in Youth
*1 study reported separate rates for TD in adults and in the elderly; Correll CU et al. (2004), Am J Psychiatry
161(3):414; †Correll CU & Kane JM (2007), J Child Adolesc Psychiatry;15(5):647-655.
† 0.8
6.8
5.3
0.4
5.4
0
1
2
3
4
5
6
7
Children
(N=783,
10 Trials)
Adults
(N=1,964,
6 Trials*)
Adults and
Elderly (N=207,
1 Trial)
Elderly (N=521,
4 Trials*)
Haloperidol-
Treated Adults
(N=408,
3 Trials)
Me
an
Ra
te o
fTa
rdiv
e D
ys
kin
es
ia (
%) For Personal Use Only
Alertness/Cognition
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Naturalistic Comparison of Aripiprazole, Olanzapine,
Quetiapine and Risperidone: 3-Month Rates of
Drowsiness in 257 AP-Naïve Youth (SATIETY Study)
257 antipsychotic-naïve youth (13.8±3.6 years, male=57.8%) initiated aripiprazole (n=40), olanzapine
(n=45), quetiapine (n=36), or risperidone (n=135)
Al Dhaher Z et al. J Child Adolesc Psychopharmacol. 2016 Jun;26(5):458-70.
For Personal Use Only
Prolactin and Related Effects
For Personal Use Only
Relative Potency of Antipsychotics in Elevating Serum PRL Prolactin in Youth
• Paliperidone > Risperidone > Haloperidol
> Olanzapine > Ziprasidone
> Quetiapine > Clozapine > Aripiprazole
• Aripiprazole has partial D2-DA agonist
activity, and may suppress PRL below
baseline levels
Correll and Carlson, JAACAP 2006;45: 771-791
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1 Year Prolactin ChangeP
rola
cti
n (
ng
/mL
)
Overall group comparison p<0.0001 at all time points
Wks
†
† 25.7 ng/mL = Hyperprolactinemia
Correll CU et al. ICOSR 2007
N=474N=542 N=307 N=395 N=205 N=147 N=108
For Personal Use Only
% Of Youth With Hyper-Prolactinemia%
Pa
tie
nts
wit
h P
RL
> 2
5.7
ng
/mL
p<.0001 p<.0001 p<.0001 p=.0002
82 178 36 34 9 43 61 40 6 30N 119 58 27 41107 22 5 2619 36
N=522 N=205 N=112N=144
Correll CU et al. ICOSR 2007
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Weight Gain
For Personal Use Only
Weight gain on SGAs vs. PLA
SGAs: second-generation antipsychotics; PLA: placebo; NNH: number-needed-to-harm; ZIP: ziprasidone; ARI: aripiprazole; QUE: quetiapine; RIS: risperidone; OLA: olanzapine; SCZ: schizophrenia; BPD: bipolar I disorder; DBD: disruptive behavior disorderAdapted from: De Hert M, Dobbelaere M, Sheridan E, Cohen D, Correll CU. Eur Psychiatry. 2011 Apr;26(3):144-58.
NNT based on difference in% with >/=7% weight gain
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12-week Cardiometabolic Effects of SGAs in AP-Naïve Youth
Correll CU et al. JAMA 2009;302:1765–1773
*
Fasting Glucose Fasting Triglycerides
Body Weight Fasting Total Cholesterol
Ch
ole
ste
rolch
ange
(mg
/dL
)
Glu
co
se
ch
an
ge
(mg/d
L)
Tri
gly
ce
rid
es
ch
an
ge
(mg/d
L)
For Personal Use Only
Number needed to harm (NNH) for adverse body composition outcomes
Antipsychotic-naïve sample. Total n=272*
*Includes 15 untreated comparison patientsData are presented as NNT +/- 95% Confidence IntervalCalculated from data in Correll CU et al. JAMA 2009;302:1765–1773
Outcome variable
Aripiprazole(n=41)
Olanzapine(n=45)
Quetiapine(n=36)
Risperidone(n=135)
Weight gain >7% 2 (1-3) 1 (1-2) 2 (1-3) 2 (1-3)
Weight gain >14%
6 (3-∞) 2 (1-4) 3 (2-14) 4 (2-31)
Weight gain >21%
20 (6-∞) 4 (2-38) 18 (6-∞) 15 (5-∞)
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2.6-3-fold higher Incidence of Type 2 Diabetes in Youth Exposed to Antipsychotics than in
Healthy Control Youth
Studies=8, 298,803 patients and 463 084 patient-years; cumulative T2DM risk (odds ratio [OR], 2.58; 95%CI,
1.56-4.24; P < .0001) and incidence rate ratio (IRR) (IRR, 3.02; 95%CI, 1.71-5.35; P < .0001)
Galling B et al. JAMA Psychiatry. 2016 Mar 1;73(3):247-59.
For Personal Use Only
1.8-2-fold higher Incidence of Type 2 Diabetes in Youth Exposed to Antipsychotics than in
Psychiatrically Ill Youth
Studies=7, 1,342,121 patients and 2,071,135 patient-years; cumulative T2DM risk (OR, 2.09; 95%CI, 1.50-5
2.90; P < .0001) and IRR (IRR, 1.79; 95%CI, 1.31-2.44; P < .0001).
Galling B et al. JAMA Psychiatry. 2016 Mar 1;73(3):247-59.
For Personal Use Only
Solmi M et al. World Psychiatry 2020;19:214–232.
Proportion of 78 Reported Adverse Events of 80 Psycho-
tropic Drugs in Youth Either Worse / not Different from PBO
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Adverse Effect Monitoring and Management
For Personal Use Only
Psychotropic Side Effect Monitoring in Youths
Assessments Frequency Personal and family history Baseline and Annually
Lifestyle monitoring Every visit
Height, weight, BMI percentile / z-score Every visit
Somnolence/sedation Every visit
Sexual symptoms/signs Baseline, during titration and q 3 mo
Blood pressure, pulse Baseline, 3-months and 6-monthly
Fasting glucose, lipids (if on APs) Baseline, at 3 mo and (6-)12monthly
Liver function tests (if on APs) Baseline, at 3 mo and (6-)12 monthly
EPS, akathisia Baseline, titration, 3 mo and annually
Dyskinesia / TD Baseline, 3 mo and annually
Electrolytes, blood count, renal f’ction On per case basis (except if on CLO)
Prolactin Only when symptomatic
EKG If on ZIP: during titration, at max. dose
If abnormal exam/Hx prior to stimulants
Adapted from: Correll CU. J Am Acad Child Adolesc Psychiatry. 2008;47(1):9-20.
For Personal Use Only
Medical Risk Management Strategies in Antipsychotic-Treated Patients
Treatment Initiation• Healthy lifestyle counseling• Healthy lifestyle intervention
• Start with lower-risk antipsychoticPR
IMA
RY
If Adverse Effect Is Present• Healthy lifestyle counseling/intervention
• Consider changing to lower-risk antipsychotic• Consider weight loss intervention
SE
CO
ND
AR
Y
If Adverse Effect Progresses/Serious• Healthy lifestyle counseling/intervention
• Considering changing to lower-risk antipsychotic• Add targeted treatment for pathological values
• Consider referral to specialist
TE
RT
IAR
Y
PR
EV
EN
TIO
N
Correll CU. CNS Spectr. Vol 12. No 10 (Suppl 17), 2007: 12-20,35.
For Personal Use Only
Pharmacologic Weight Loss (kg) Compared
to Placebo in Antipsychotic-treated Patients
(N=32, n=1482)
Blue squares: significant difference Maayan L, Vakhrusheva J, Correll CU. Neuropsychopharmacology. 2010 Jun;35:1520-30.
Kg Favors Placebo
Favors Intervention
4
2
0
-2
6
-4
-6
WMD
95% CI
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Interventions for Weight Change
Vancamfort D et al., World Psychiatry. 2019 Feb;18(1):53-66.
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Healthy Lifestyle Instruction (HLI) vs Metformin+HLI vs. Antipsychotic Switch+HLI:
BMI Z-Score Change
Correll CU et al. World Psychiatry. 2020 Feb;19(1):69-80.
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Adverse Effects with Overall Group Differences
Correll CU et al. World Psychiatry. 2020 Feb;19(1):69-80.
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Adverse Effects with Overall Group Differences
Correll CU et al. World Psychiatry. 2020 Feb;19(1):69-80.
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Summary
Severe psychiatric disorders not infrequently start before age 18
While some symptom presentations may differ across the age range, the diagnostic criteria are identical for youth and adults
Treatment guidelines are identical for youth and adults, except that dosing may have to be slower and (potentially somewhat) lower, and youth are more sensitive to adverse events
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Summary cont’d
Second-generation antipsychotics have proven efficacy in pediatric schizophrenia, bipolar disorder, irritability associated with autistic disorder, aggression and Tourette’s disorder.
Like in adults, the relative efficacy of antipsychotics seems to be roughly similar, except for clozapine
Pediatric patients are at greater risk for prolactin elevation, sedation, weight gain and metabolic effects
A careful risk-to-benefit evaluation is needed and lowest risk agents and non-pharmacologic treatment options ought to be tried first
Attention should be paid to effects of psychotropics on development and long-term risks and benefits
Stratified and personalized treatment is needed
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