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.


Overview Schizophrenia

Bipolar Disorder

Autism/Aggression

Tourette’s Disorder

Adverse Effects

Adverse Effect Monitoring and Management

Conclusions


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.


Schizophrenia Spectrum Disorders


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

******


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.


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.


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


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


PANSS Total and Subscale Score Changes


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.


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


Treatment of Pediatric Bipolar Disorder


Acute Efficacy for Mania/Mixed Episodes


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


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


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


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.


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


Acute Efficacy for Bipolar Depression


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.


8-Week RCT of OLA/FLU vs PBO

Detke H et al. J Am Acad Child Adolesc Psychiatry. 2015 Mar;54(3):217-24.


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.


Bipolar Disorder Maintenance


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


Maintenance: Lamotrigine vs Placebo

Findling RL, et al. J Am Acad Child Adolesc Psychiatry. 2015 Dec;54(12):1020-1031.


Maintenance: Aripiprazole vs Placebo

Findling RL, et al. Bipolar Disord. 2013 Mar;15(2):138-49.


Tourette’s Disorder


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


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


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.


Adverse Effects


Extrapyramidal Effects


Inverse Relationship Between Age and Incidence of EPS

Parkinsonism Dystonia Akathisia

Keepers GA et al. Arch Gen Psychiatry. 1983;40:1113-7.


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.


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


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.


Prolactin and Related Effects


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


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


% 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


Weight Gain


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


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)


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-∞)


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.


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.


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


Adverse Effect Monitoring and Management


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.


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.


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


Interventions for Weight Change

Vancamfort D et al., World Psychiatry. 2019 Feb;18(1):53-66.



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.


Adverse Effects with Overall Group Differences



Adverse Effects with Overall Group Differences



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


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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Antipsychotika: Nebenwirkungsprofile und unterschiedliche