Overzicht
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Achtergrond
Methodologische problemen
Survey
Resultaten
Aanbevelingen
1
Achtergrond: Diagnose
Niet scherp afgelijnd qua diagnose
Veel comorbiditeit
Hoog risico syndroom,
Onmiddellijke interventie
Geen diagnostische specificiteit
Wisselend verloop en presentatie
Groot hervalrisico
Onmiskenbare relatie met agressie
Quid prodromen
2
Achtergrond: Diagnose
•  Schizofrenie, BPD I/II zijn de meest frequente
comorbide diagnoses
4,5,6
•  Dimensie of categorie in de volgende DSM edities?
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4
Marco CA, Vaughan J. Emergency management of agitation in schizophrenia. Am J Emerg Med. 2005;23(6):767-776.
5
D’Amore J, Hung O, Chiang W, Goldfrank L. The epidemiology of the homeless population and its impact on an urban
emergency department. Acad Emerg Med. 2001;8(11):1051-1055.
6
Zun LS, Downey LV. Level of agitation of psychiatric patients presenting to an emergency department. Prim Care
Companion J Clin Psychiatry. 2008;10(2):108-113.
3
Achtergrond: Epidemiologische data
•  1.7x 10 6 /jaar aanmeldingen voor agitatie1,2
•  10% patienten op spoed hebben risico op
ontwikkeling van agitatie symptomen tijdens
de medische evaluatie3
•
1 Allen MH, Currier GW. Use of restraints and pharmacotherapy in academic psychiatric
emergency services. Gen Hosp Psychiatry. 2004;26(1):42-49.
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2 Marco CA, Vaughan J. Emergency management of agitation in schizophrenia. Am J
Emerg Med. 2005;23(6):767-776.
3 Huf G, Alexander J, Allen MH. Haloperidol plus promethazine for psychosis induced
aggression. Cochrane Database Syst Rev. 2005;(1):CD005146.
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4
Methodologische problemen
•  Welke patiënten komen in (farma)trials?
-  Inclusiecriteria en - instrumenten
-  Ecologische validiteit van RCT
-  Oorzaak van heterogeneïteit in (alle) trials die
interventies in agitatie en agressie bestuderen
5
Methodologie
Wat meten schalen ?
•  Delen vna het klinische syndroom ?
•  Post hoc vs “ in het moment”?
•  Evaluatie door zorgverlener en niet de evaluatie door patiënt?
•  Cross-sectioneel vs longitudinaal ( time series)?
-  Time series = Follow up & predictieve research
6
Voorbeelden
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Brøset Violence Checklist (BVC) 8
Overt Aggression Scale (OAS) 9
Agitated Behavior Scale (ABS) 10
Behavioural Activity Rating Scale (BARS)
Experience Sampling Method (ESM) 12
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11
Almvik R.et al. The Brøset Violence Checklist. Sensitivity, specificity, and interrater reliability. J
Interpersonal Violence. 2000;15(12):1284-1296.
9 The Overt Aggression Scale for the objective rating of verbal and physical aggression. Yudofsky, Stuart C.;
The American Journal of Psychiatry, Vol 143(1), Jan 1986, 35-39.
10 Bogner, J. (2000). The Agitated Behavior Scale. The Center for Outcome Measurement in Brain Injury
11
Swift J, J Psychiatr Res. 2002 Mar-Apr;36(2):87-95.
12 Psychol Med. 2009 Sep;39(9):1533-47. Epub 2009 Feb 12. Experience sampling research in
psychopathology: opening the black box of daily life. Myin-Germeys I,
8
7
Methodologie
•  Diagnose en patiëntinclusie : “ Beauty Agitation
is in the eye of the beholder “
•  Conclusies uit onderzoek: “There is nothing
worse than a sharp image of a fuzzy concept.
(Ansel Adams)
•  Maar: toch worden guidelines gepubliceerd uit
deze research
8
•  LiVio review on interventions in agitation/
agression7 :
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127,550 hits
1,154 included papers
Intervention review
Risk assessment
Analyses
•  Descriptives
•  Bivariate analyses
•  Meta analyses (40 RCTs)
•  Subgroup analyses
7
9
Juliette Hockenhull, submitted
Heterogeneity estimates and effect
sizes of all included RCT (7)
N Analyses
Effect Size
95% CI
Lower
Upper
Two-tailed Test of Null Hypothesis (Homogenous
z
Data)
p
Estimates of Heterogeneity
Q
df Q
p
I2
Effect Size Estimates based on Standardized Mean Difference
95% CI
Two-tailed Test of Null Hypothesis (Homogenous
Data)
Lower
Upper
Z
Model
Fixed Random
40
40
0.59
0.35
0.53
0.26
0.65
0.49
-9.86
-6.29
0.0001
0.0001
278.95
39
0.0001
86.02
-0.29
-0.57
-0.35
-0.23
-9.86
-0.75
-0.39
-6.29
10
11
Type of drugs studied
30
25
28
25
20
15
10
5
5
4
3
2
1
0
12
12
Comparators
12
11
10
8
8
6
5
4
2
2
1
0
NA
Head to head
Placebo
Dosing
TAU
13
13
Outcome measures
7
6
6
5
4
3
2
1
0
1
1
1
0
0
0
14
0
14
Study design
3,5
3
3
2,5
2
2
1,5
1
1
0,5
0
RCT
Concurrent/cross
sectional
Crossover
15
15
Drugs being studied
Author
Clozapine Olanzapine Risperidone Haloperidol
Citrome
20012
Czobor
19953
Kane 20014
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/
2 Citrome, L., J. Volavka, et al. (2001). "Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia." Psychiatric Services 52(11): 1510-1514.
3 Czobor, P., J. Volavka, et al. (1995). "Effect of Risperidone on Hostility in Schizophrenia." Journal of Clinical Psychopharmacology 15(4): 243-249.
4 Kane, J. M., S. R. Marder, et al. (2001). "Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison." Arch Gen Psychiatry 58(10):
965-972.
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Details of studies
Author
Citrome 2001
Czobor 1995
Scale used
PANSS hostility
PANSS hostility BPRS Hostility
open in-patient hospital not stated or
ward
unclear
C= 500 (200-800)
R=2, 6, 10 or 16
Dose (mg)
O=20 (10-40)
H=20
R=8 (4-16)
H=20 (10-30)
Follow up (weeks) 1, 2, 3, 4, 6, 8, 10, 12, 14 2, 4, 6, 8
Setting
Data type
Means
Comment
History of sub-optimal
treatment response
Mean change
Kane 2001
mixed settings
C=500
H=10
5, 11, 17, 29
Means
Partially responsive
patients
17
17
Results
Author
Clozapine
Olanzapine
Risperidone
Haloperidol
Mean
(SD)
Mean
(SD)
Mean
(SD)
Mean
(SD)
Mean
(SD)
Mean
(SD)
Mean
(SD)
Mean
(SD)
Citrome 2001 2.68 (1.58) 2.24 (1.34) 2.35 (1.47) 2.24 (1.73) 2.4 (1.19) 2.49 (1.61) 2.42 (1.26) 2.95 (1.51)
Czobor 1995*
Kane 2001
1.55 (1.30) 3.73 (1.12) 1.00 (1.41) 3.5 (0.72)
8 (3.2)
6 (2)
7.9 (2.7)
7.4 (2.7)
* Mean change
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18
Overview
70
60
61
53
50
40
30
25
20
10
0
8
Population (Schizophrenia Intervention subgroup
or schizo-affective only) (Atypical antipsychotics)
6
3
Outcome (Scale)
19
19
Guidelines; gebaseerd op actueel
(niet-homogene ) onderzoek
•  Haloperidol = lorazepam
•  haloperidol plus lorazepam niet superieur tov lorazepam of
haloperidol in monotherapie
•  Effect van dehydrobenzperidol, risperidone, olanzapine en
aripiprazole is vergelijkbaar met lorazepam of haloperidol.
•  haloperidol plus promethazine : sneller effect dan met
lorazepam, haloperidol or olanzapine alone
•  Zuclopenthixol acutard = te mijden in acute indicaties
-  M. Bak, J. van Os, M. Marcelis. Acute ingrijpmedicatie; literatuuroverzicht
en aanbevelingen. Tijdschrift voor Psychiatrie 53 (2011) 10, 727 – 737
-  TREC studies
20
TREC trials
21
TREC trials x4
1.
Brazil, 2003 (BMJ). n=301. Tranquil/sedated at 20mins. IM
Midazolam vs. IM Haloperidol+promethazine
2.
India, 2004 (BJPsych). n=200. Tranquil/asleep by 4hrs IM
lorazepam vs. IM Haloperidol+promethazine
3.
Brazil, 2007 (BMJ). n=316. Tranquil/asleep at 20mins. IM
Haloperidol vs. IM Haloperidol+promethazine
4.
India, 2007 (BMJ). n=300. Tranquil/asleep at 15mins. IM
olanzapine vs. IM Haloperidol+promethazine
22
Survey: Prescription habits of PSY/ER MD in Flanders
•  Q
-  What are the prescribing habits for psychiatrists
and emergency doctors in agitation.
-  Do these habits differ in both specialties ?
-  Is there concordance with published guidelines?
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METHODOLOGY
•  Cross-sectional online survey, 1/7/12 – 30/9/12
•  All MD in psychiatric hospital/general hospital & all ER
doctors
•  Aantal ziekenhuizen = 89
•  Aantal psychiaters = 281
•  Aantal artsen op spoed = 267
•  110 responses= response rate 20 %
-  Accurate for analysis.
-
-
Visser L. et al.. 1996. “Mail Surveys for Election Forecasting? An Evaluation of the Colombia Dispatch Poll.” Public Opinion
Quarterly 60: 181-227
Holbrook, Allyson, Jon Krosnick, and Alison Pfent. 2007. “The Causes and Consequences of Response Rates in Surveys by
the News Media and Government Contractor Survey Research Firms.” In Advances in telephone survey methodology, ed.
James M. Lepkowski, N. Clyde Tucker, J. Michael Brick, Edith D. De Leeuw, Lilli Japec, Paul J. Lavrakas, Michael W. Link,
and Roberta L. Sangster. New York: Wiley.
•  No missing variables in antwoorden
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Results
Variables
Age
Max. responders 35-50y (norm. Distr)
Sex ( % M/F)
63,6/36,4
Type (% PSY/ER
65,5/34,5
Workplace ( % PH/GH/ER)
39,1/22,7/38,2
Nr pt in treatment/month ( % <10/>10)
64,5/35,5
Use rating scales (%Y/N)
5,5/94,5
First choice for MD
AP>BZD
Second choice for MD
BZD>AP
Monotherapy vs combinations (% Y/N/?)
20,9/79,1/0
POST SECL change (% Y/N)
60,9/39,1
Monotherapy vs combinations in seclusion
(% Y/N/?)
8,3/53,7/38,2
25
Resultaten
•  Agitatie is frequent: 64 % psychiaters & SA >
10 , 21% >20 per maand.
•  Geen duidelijke noch gesystematiseerde
protocollen
•  Alle respondenten AP > BZD
-  NS: olz>lor>clo
-  S: clo>olz>dro
•  Zuclopenthixol à “acutard” ?
26
Resultaten
•  PSY vs SA
-  SA : BZD in s & ns
-  PSY: AP in s & ns
•  Analyse naar specifiek geneesmiddel
-  PSY (ns)QTP ; (s) OLZ ; + effect van ZUC la !!
•  Ouder vs jonger
-  Ouder: meer ZUC la
•  Afwezigheid van effect- en
veiligheidsmonitoring
27
Aanbevelingen
•  Gebrek aan rationale: potentieel probleem voor patiënt- en
stafveiligheid
•  Droperidol: quid cardiale toxiciteit?
•  Complexe relatie met richtlijn (HAL,LOR), maar die differentieert
niet tss agitatie-etiologie of graad van agitatie. Onze
respondenten volgen richtlijn alleen in NS…
•  Acutard gebruik : educatie !
•  Zelfde educatie & communicatie naar SA en PSY is nodig, evt
formulariumaanpassing ?
•  Jongere artsen: andere strategie, toch al effect van educatie ?
•  Dringend nood aan monitoring !
28
•
UPC KULeuven Kortenberg
-  Dr Hella Demunter
-  Prof Dr Guido Pieters
-  Leen Vandenbussche
•
AZ Sint Jan AV , EPSI
-  Dr Jürgen De Fruyt
•
UAntwerpen
-  Dr Chris Bervoets
-  Prof Dr Manuel Morrens
-  Prof Dr Bernard Sabbe
•
AZ Sint Elisabeth Herentals
-  Dr Barry Dekeyser
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