RICERCA CLINICA ED EPIDEMIOLOGIA DEI NEUROLETTICI
Corrado Barbui
Corrado
Barbui
Università di Verona
[email protected]
Sommario della presentazione
Sommario della presentazione
‰ Antipsicotici di vecchia e nuova generazione = crediamo alle metanalisi o ai singoli trial?
‰ Politerapie antipsicotiche = le evidenze randomizzate non raccontano tutta la verità!
‰ Tollerabilità degli antipsicotici = i dati osservazionali
possono indurre in errore…
‰ Che cosa possiamo fare nel nostro servizio psichiatrico?
‰ Antipsicotici di vecchia e nuova generazione = crediamo alle metanalisi o ai singoli trial?
“We compared nine second-generation
antipsychotic drugs with first-generation drugs
for overall efficacy (main outcome),
outcome) positive,
positive
negative and depressive symptoms, relapse,
quality of life, extrapyramidal side
side-effects,
effects,
weight gain, and sedation.”
“We included 150 double-blind, mostly shortterm, studies, with 21 533 participants.”
positive symptoms
negative
g
symptoms
y p
extrapyramidal
side effects
side-effects
weight gain
“Le sperimentazioni cliniche […] non studiano i p
[ ]
miei pazienti, non studiano i miei trattamenti, non valutano gli esiti che cerco di ottenere”
“… not my patients, not my treatments, not what I try to do”
‰ Pazienti non selezionati
non selezionati
‰ Trattamenti simili a quelli erogati in pratica
‰ Indicatori di esito clinicamente rilevanti
‰ Campioni numerosi reclutati in setting rappresentativi
‰ Durata adeguata
‰ Indipendenza da interessi commerciali
TRIAL PRAGMATICI DI EFFECTIVENESS
CATIE: Broad Inclusion and
Mi i l E
Minimal
Exclusion
l i C
Criteria
it i
♦
DSM-IV
DSM
IV schizophrenia,
hi
h i 18-65
18 65 years old
ld
♦ Not first-episode or treatment-resistant
♦ Concomitant medications,
medical illnesses, substance use
disorders allowed
♦ Conducted at 57 geographically,
demographically and organizationally
demographically,
diverse sites
Stroup TS, et al. Schizophr Bull. 2003;29(1):15-31.
Determinants of Drug Effectiveness
Staying
St i on th
the D
Drug IIs C
Critical
iti l
Efficacy
Tolerability
Decision to Stay
on the Drug
Clinician Input
Patient Input
Primary Outcome Measure:
All--Cause
All
C
Treatment
T t
t Discontinuation
Di
ti ti
Efficacy
Tolerability
All-Cause
All
Cause
Discontinuation
Clinician Input
Patient Input
CATIE Phase 1:
D bl -Blinded
DoubleDouble
Bli d d and
d Randomized
R d i d
Olanzapine
7.5-30 mg/day
1460 Patients
With
Schizophrenia
Perphenazine
P
h
i
8-32 mg/day*
Randomi ed
Randomized
Quetiapine
Q
ti i
200-800 mg/day
Risperidone
Ri
id
1.5-6 mg/day
Ziprasidone
Zi
id
40-160 mg/day†
*Persons with TD not assigned to perphenazine.
†Ziprasidone added after 40% sample enrolled.
Stroup TS, et al. Schizophr Bull. 2003;29(1):15-31.
‰ Antipsicotici di vecchia e nuova generazione crediamo alle metanalisi
generazione = crediamo alle metanalisi o ai singoli trial?
=
Uso critico delle evidenze! Esistono sperimentazioni più “vicine” alla p
p
prospettiva clinica
‰ Politerapie antipsicotiche = le evidenze randomizzate non raccontano tutta la verità!
randomizzate non raccontano tutta la verità!
Data Sources: Cochrane Schizophrenia Group register and hand
searches of relevant journals/conference proceedings.
Study Selection: Randomized controlled trials comparing antipsychotic
monotherapy to cotreatment with a second antipsychotic.
Results: 19 studies (1229 patients)
“We calc
calculated
lated the adjusted
adj sted incidence of sudden
s dden cardiac
ca diac death
among current users of antipsychotic drugs in a retrospective
cohort study of Medicaid enrollees in Tennessee.”
“The primary analysis included 44,218 and 46,089 baseline
users of single
g typical
yp
and atypical
yp
drugs,
g respectively,
p
y and
186,600 matched nonusers of antipsychotic drugs.”
Age 30
30-74
74
‰ Non solo uso critico delle evidenze, ma anche…
‰ …Le
Le evidenze randomizzate devono evidenze randomizzate devono
essere supplementate da dati epidemiologici osservazionali
epidemiologici osservazionali
‰ Tollerabilità degli antipsicotici = i dati g
p
osservazionali possono indurre in errore: l’esempio della mortalità da p
antipsicotici
retrospective
i cohort
h study
d involving
i l i 22,890 patients
22 890
i
6
65 years
of age or older who began receiving a conventional or atypical antipsychotic medication
risk of death within 180 days, less than 40 days, 40 to 79 days, and 80 to 180 days after the initiation of therapy with an antipsychotic medication
we controlled for potential confounding
variables
‰ E nelle popolazioni di pazienti con
schizofrenia
hi f i l’esposizione
l’
i i
aglili
antipsicotici è dannosa in termini di
h d outcome
hard
t
((mortalità?)
t lità?)
‰
Nationwide registers in Finland were used to compare the cause‐specific mortality in 66 881 patients versus the total population (5∙2 million) between 1996 and 2006, and to link these data with the use of antipsychotic drugs.
‰
We measured the all‐cause mortality of patients with schizophrenia in outpatient care during current and cumulative exposure to any antipsychotic drug versus no use of these drugs, and exposure to the six most frequently used antipsychotic drugs h
d
d
h i
f
l
d
i
h i d
compared with perphenazine use.
‰
The study population consisted of 30,803 men and 36,078 women with schizophrenia. The
study population consisted of 30 803 men and 36 078 women with schizophrenia
The mean age at the start of follow‐up was 51 years (average follow‐up 8∙6 years)
Risk of death from any cause
Risk of death from suicide
Risk of death from ischaemic heart disease
Risk of death from any cause versus cumulative use of any antipsychotic drug
Long‐term treatment with antipsychotic drugs is associated with lower mortality compared with no antipsychotic use
antipsychotic use.
Second generation drugs are a highly heterogeneous Second‐generation
drugs are a highly heterogeneous
group, and clozapine seems to be associated with a substantially lower mortality than any other antipsychotics.
Restrictions on the use of clozapine should be Restrictions
on the use of clozapine should be
reassessed.
‰ Non solo uso critico delle evidenze, ma anche…
anche
‰ …le evidenze randomizzate devono essere supplementate da dati epidemiologici osservazionali, e ancora…
‰ …uso “ragionato” dei dati osservazionali
EBM
EBP
Contesto normativo
Metodologia per il passaggio dalle evidenze alla pratica
id
ll
i
http://www gradeworkinggroup org/
http://www.gradeworkinggroup.org/
EBM
Linee-guida
contestualizzate alla
realtà locale (valori,
(
preferenze, scelte)
EBP
Aspetti legislativi
EBM
Process and outcome
monitoring
Aspetti organizzativi
Linee-guida
Risorse
e libraries
e-libraries
Formazione
EBP
accountability
Integrazione (MG,
dipendenze, alcol,
disabilità, neurops.)
contesto
Quality Improvement:
migliorare i processi di cura e gli
esiti dei pazienti
ricerca