QUETIAPINA Perfil Psiconeuroinmunoendcrino

1
QUETIAPINAPerfil Psiconeuroinmunoendócrino
ANDREA MARQUEZ LOPEZ MATO PABLO BERETTA Instituto
de Psiquiatría Biológica Integral www.ipbi.com.ar
2
RECEPTOR BINDING
Goldstein 1999
Receptor A1, 2 a1, a2 adrenergic D1,2
dopamine H1 histamine 5HT1A, 2A serotonin M
muscarinic
3
El punto más difícil no es que respondan al
tratamiento sino que continúen tomando la
medicación Lieberman, 90
Ninguna píldora puede ayudarme a lidiar con el
problema de no querer tomarlas
Godwin and Jamison, 90
.
4
SHIFT IN RISK PERCEPTION
Prior Safety Concerns
Current Safety Concerns
Diabetes
Neurologic Side Effects
EPS TD
Weight Gain
Hyper Glycemia
CVD
Insulin Resistance
Weight Gain
Insulin Resistance
EPS
Hyper- lipidemia
QTc
Dyslipidemia
CVD
QTc
Hyper- glycemia
5
THE CONTINUUM OF CARE
Efficacy
Positive symptom relief Hostility,
aggression Smooth IM to PO transition Alleviation
of comorbid depressive/manic symptoms
Negative symptom relief Improve mood and
depressive symptoms Cognitive improvement
Control Behavior (agitation)
Relapse Prevention
1-3 days
7-14 days
6 months
Acute dystonia Sedation Orthostasis QTc
prolongation
EPS Drug-drug interactions QTc prolongation
TD Hyperprolactinemia Weight gain Hyperglycemia QT
c prolongation
Safety
6
SIDE EFFECTS
Maudsley Hospital Prescribing Guidelines
7
PNIE DEL TRATAMIENTO AP

• Desórdenes por extrapiramidalismo
• Desórdenes por hiperprolactinemia
• Desórdenes endócrinos varios
• Desórdenes de aumento de peso
• Desórdenes del metabolismo hidrocarbonado
• Desórdenes del metabolismo lipídico
• Desórdenes del balance hídrico
• Desórdenes metabolismo hepático y cardíaco
• Desórdenes hematológicos e inmunes
• Desórdenes de la sexualidad
• Teratogénesis, carcinogénesis y otros

Lopez Mato. 2002
8
PNIE DEL TRATAMIENTO AP

• Desórdenes por extrapiramidalismo
• Desórdenes por hiperprolactinemia
• Desórdenes endócrinos varios
• Desórdenes de aumento de peso
• Desórdenes del metabolismo hidrocarbonado
• Desórdenes del metabolismo lipídico
• Desórdenes del balance hídrico
• Desórdenes metabolismo hepático y cardíaco
• Desórdenes hematológicos e inmunes
• Desórdenes de la sexualidad
• Teratogénesis, carcinogénesis y otros

Lopez Mato. 2002
9
X
GRADO DI OCCUPAZIONE RECETTORIALE D2 NELLO
STRIATO y EFFETI COLATERALI
A dosaggi terapeutici, gli APT presentano un
grado di occupazione dei recettori dopaminergici
D2 compreso tra il 70 e l 89
occupazione recettoriale efficacia
antipsicotica 60-70
iperprolattinemia gt 70 EPS
gt 80
Lefficacia clinica degli APT è inevitabilmente
associata alliperprolattinemia Laumento della
prolattina è un marker della azione dei farmaci
APT
10
MOVIMIENTOS ANORMALES POR AP
BUTIROFENONAS SULPIRIDA AMISULPRIDE RISPERIDONA PR
OMAZINICOS ARIPRIPAZOL OLANZAPINA ZIPRASIDONA CLOZ
APINA QUETIAPINA
Lopez Mato A., 2003
11
PARKINSONISMO

• Parkinsonismo Motor
• EPS
• Distonía
• Diskinesia tardía
• Parkinsonismo Cognitivo
• Pensamiento enlentecido y pobre
• Sentimiento de vacío
• Dificultades de concentración

Gerlach 98
12
PARKINSONISMO

• Parkinsonismo Social
• Falta de iniciativa
• Disminución de las energías
• Pobreza de contactos sociales
• Parkinsonismo Emocional
• Indiferencia emocional
• Anhedonia
• Falta de placer en las actividades

Gerlach 98
13
LOW EPS RISK
Jibson and Tandon 1998
14
SIMPSON-ANGUS (SEP) CATIE
Lieberman JA, et al. N Engl J Med.
2005353(12)1209-1223.
15
PNIE DEL TRATAMIENTO DE AP

• Desórdenes por extrapiramidalismo
• Desórdenes por hiperprolactinemia
• Desórdenes endócrinos varios
• Desórdenes de aumento de peso
• Desórdenes del metabolismo hidrocarbonado
• Desórdenes del metabolismo lipídico
• Desórdenes del balance hídrico
• Desórdenes metabolismo hepático y cardíaco
• Desórdenes hematológicos e inmunes
• Desórdenes de la sexualidad
• Teratogénesis, carcinogénesis y otros

Lopez Mato. 2002
16
AUMENTO PROLACTINA POR AP
BUTIROFENONAS SULPIRIDA AMISULPRIDE RISPERIDONA PR
OMAZINICOS ZIPRASIDONA ARIPRIPAZOL
OLANZAPINA QUETIAPINA
CLOZAPINA
Lopez Mato A., 2003
17
HYPERPROLACTINEMIA
Sexual dysfunction
Gynaecomastia
Amenorrhoea
Prolactin elevation
Impotence
Osteoporosis
Breast enlargement
Galactorrhoea
Data from Arvanitis et al 1997
18
LA PROLACTINA ES MAS QUEUNA HORMONA DE MATERNAJE

• Función en coping (afrontamiento) al stress
• Función metabólica (hormona anabólica)
• Función sobre SNC (crecimiento dendrital y
• sinaptogénesis)
• Función sobre inmunomodulación
• Función sobre conductas sexual y maternal

Illa G . Lopez Mato A . Psiconeuroinmunoendocrino
logia. 2002
19
BUT PROLACTIN IN UNMEDICATED SCHIZOPHRENIC
PRL levels are not elevated in un medicated
schizophrenic patients But they show a phase
advance of circadian serum prolactin secretion
with the peak serum PRL level being reached 1.5
hours earlier Daytime PRL secretion does not
appear to be enhanced
However, it has been suggested that PRL in the
normal range may be correlated to different
subgroups of disease
20
PRL IN SCHIZOPHRENIA SUBTYPES
F
M
The normal range of serum prolactin levels
seems to obscure significant differences
between specific groups of schizophrenia
patients
F
M
M. Segala, A. et al. Serum prolactin levels in
unmedicated first-episode and recurrent
schizophrenia patients a possible marker for the
diseases subtypes Psychiatry Research 127 (2004)
227 235
21
QUETIAPINE AND PROLACTIN
Data from Arvanitis et al 1997
20

Mean change in prolactin levels (µg/L)
from baseline at endpoint
15
10
5
0
-5
Placebo
75
150
300
600
750
Haloperidol12 mg/day
Seroquel (mg/day)
plt0.01 vs placebo
22
NORMALISATION OF PREVIOUSLY ELEVATED PROLACTIN
LEVELS
Haloperidolup to 20 mg/day (n320)
Seroquelup to 800 mg/day (n429)
LSM change in prolactin levels (µg/L) from
baseline to end of treatment

Meta-analysis of 3 double-blind, randomised trials
Data on file - AstraZeneca
plt0.001 vs haloperidol
23

• HYPERPROLACTINEMIA
• Although an elevation of prolactin levels was
  not demonstrated in clinical trials with
  SEROQUEL, increased prolactin levels were
  observed in rat studies with this compound, and
  were associated with an increase in mammary gland
  neoplasia in rats.

De Seroquel
24
PRL AND BREAST CANCER
Two studies (in 1999 and 2004), from Hankinson's
group demonstrated a clear correlation between
PRL levels and breast cancer risk in gt30,000
postmenopausal women with 306 and 851 breast
cancers respectively Women with PRL levels in
the higher quartile of the normal range had an
increased risk (by a factor of 2) of developing
breast cancer, compared to patients with PRL
levels in the lower quartile of the normal
range) This risk mainly affected ER tumors (RR
of 1.78 95 CI 1.28-2.5) and ER/PR- tumors
(RR 1.94 95 CI 0.99-3.78) Currently
we dont know whether hyperprolactinemic patients
are at high risk of developing cancers (no
large scale studies)

• - Hankinson SE, et al. 1999, Plasma prolactin
  levels and subsequent risk of breast
  cancer in postmenopausal women. J Natl Cancer
  Inst 91629-634
• Tworoger SS, et al. 2004 Plasma prolactin
  concentrations and risk of
  postmenopausal breast cancer. Cancer Res
  646814-6819

25
PRL AND PROSTATE CANCER
One recent study, involving 30,000 men
including 144 prostate cancers (the Northern
Sweden Health and Disease Cohort), concluded
that there is no correlation between PRL levels
and the risk to develop prostate cancer There
is no epidemiological study investigating PRL as
a possible risk factor for developing prostate
hyperplasia. Only one recent report is
available. It is a prospective, case-control
study involving only 20 men with prolactinoma in
which no correlation between
hyperprolactinemia and prostate hyperplasia was
found

• - Stattin P, et al. 2001 Plasma prolactin and
  prostate cancer risk A prospective study. IJ
  Cancer 92463-465
• Colao A, et al. 2004 Prolactin and prostate
  hypertrophy a pilot observational, prospective,
  study in men with prolactinoma. J Clin
  Endocrinol Metab 892770-5

26
PNIE DEL TRATAMIENTO DE AP

• Desórdenes por extrapiramidalismo
• Desórdenes por hiperprolactinemia
• Desórdenes endócrinos varios
• Desórdenes de aumento de peso
• Desórdenes del metabolismo hidrocarbonado
• Desórdenes del metabolismo lipídico
• Desórdenes del balance hídrico
• Desórdenes metabolismo hepático y cardíaco
• Desórdenes hematológicos e inmunes
• Desórdenes de la sexualidad
• Teratogénesis, carcinogénesis y otros

Lopez Mato. 2002
27
Quetiapine is known to have adverse effects on
thyroid function. In clinical trials, about 0.4
(10/2386) of patients treated with quetiapine
experienced TSH elevations, and 6 of these
sujects required thyroid hormone
supplementation.The mechanism of action by which
quetiapine causes hypothyroidism is unknown.
Quetiapine-induced hypothyroidism. Sriram
Ramaswamy, MD, Zakaria Siddiqui, MD, Sahdev
Saharan, MD, Teri L. Gabel, PharmD, BCPP, and
Subhash C. Bhatia, MD. Omaha, Nebraska, USA
HIPOTIROIDISMO
28

• It is expected that TT4 levels will decrease
  during
• quetiapine treatment, and this may possibly
  be related
• to competitive metabolism of thyroid hormones
  and
• quetiapine by UDP-glucuronosyltransferase.
• KELLY Deanna L. CONLEY Robert R., Maryland
  Psychiatric Research Center, University of
  Maryland School of Medicine, Baltimore,
  ETATS-UNIS
• Other mood stabilizers like valproate or
  lithium appear to affect TSH or hormone levels,
  and when combined
• with quetiapine may affect thyroid function
  more
• strongly than any single drug.
• Patients taking lithium and either valproate
  or quetiapine should have serum TSH monitored
  every three months for the first year in
  treatment.
• Aaron Levin. Commonly prescribed
  psychopharmacological agents can cause a range of
  side effects in the endocrine system, but they
  can be managed by aware clinicians. Psychiatric
  News April 15, 2005. Volume 40 Number 8, p. 53.

29
Cortisol decreased after quetiapine
administration from time 150 min to time 240 min.
ACTH secretion showed no difference compared to
placebo. There was a late increase in growth
hormone secretion, significant in comparison with
placebo only at time 210 min.
Neuroendocrine effects of quetiapine in healthy
volunteers Alexandro de Borja Gonçalves Guerra,
Saulo Castel The International Journal of
Neuropsychopharmacology (2005), 8 49-57
30
PNIE DEL TRATAMIENTO DE AP

• Desórdenes por extrapiramidalismo
• Desórdenes por hiperprolactinemia
• Desórdenes endócrinos varios
• Desórdenes de aumento de peso
• Desórdenes del metabolismo hidrocarbonado
• Desórdenes del metabolismo lipídico
• Desórdenes del balance hídrico
• Desórdenes metabolismo hepático y cardíaco
• Desórdenes hematológicos e inmunes
• Desórdenes de la sexualidad
• Teratogénesis, carcinogénesis y otros

Lopez Mato. 2002
31
CLINICA DIARIAAUMENTO DE PESO POR AP
CLOZAPINA OLANZAPINA RISPERIDONA QUETIAPINA ZIPRAS
IDONA HALOPERIDOL ARIPIRAZOL
Nashraldam H, Korn M, Metabolic Disorders in
Schizophrenic. Relation to AA Treatment.
Schizophrenia Medscape Expert Columm, 28-7-04
32
AUMENTO DE PESO

• Mayor incidencia en mujeres
• Mayor incidencia en bipolares
• Mayor aumento cuanto menor BMI
• No dosis dependiente
• Historia personal o familiar de obesidad

33

• El aumento de peso correlaciona con la mejoría
  sintomática, sobre todo con la resocialización
• Desde la era preneuroléptica se correlaciona
  aumento de peso con mejoría de la psicosis

34
PESO Y AA
Acción en Hipotálamo lateral y ventromedial
Cambios en la Sensibilidad a la Leptina
1 Baptista T. Acta Psychiatr Scand.
1999100(1)3-16. 2 Cohen S, et al. J Clin
Psychiatry. 200162(2)114-116. 3 Heiman ML, et
al. Presented at 154th APA Annual Meeting May
5-10, 2001 New Orleans. 4 Mercer LP, et al. J
Nutr. 1994124(7) 1029-1036. 5 Reynolds GP, et
al. Lancet. 2002359(9323)2086-2087. 6 Simansky
KJ. Behav Brain Res.199673(1-2)37-42. 7 Stanton
JM. Schizophr Bull. 199521(3)463-472. 8 Tecott
LH, et al. Nature. 1995374(6522)542-546. 9
Virkkunen M, Pharmacopsychiatry.
200235(3)124-126. 10 Lopez Mato el al, VerteX
.2003
35
PESO Y DOSIS
Change in mean weight from baseline (kg)
300 mg
gt300-500 mg
gt500 mg
343 407
327
Mean duration of treatment (days)
(n103)
(n94)
(n174)
Brecher et al 2000
36
PESO Y TTO CRONICO
Patients ()
80
70
60
50
40
30
20
10
0
Favourable shifta
Unfavourable decrease
Unchanged
Unfavourable increase
?53 weeks Dose up to 800 mg/day(n112) aFavoura
ble increase or decrease
Shift in BMI category from baseline
Data on file - AstraZeneca
37
TTO CRONICO Y OBESIDAD SEVERA
Patients()
80
70
60
50
40
30
20
10
0
Unfavourable decrease
Favourable decrease
Unchanged
Unfavourable increase
Shift in BMI category from baseline
?53 weeks (n20) Dose up to 800 mg/day
Data on file - AstraZeneca
38
PNIE DEL TRATAMIENTO AP

• Desórdenes por extrapiramidalismo
• Desórdenes por hiperprolactinemia
• Desórdenes endócrinos varios
• Desórdenes de aumento de peso
• Desórdenes del metabolismo hidrocarbonado
• Desórdenes del metabolismo lipídico
• Desórdenes del balance hídrico
• Desórdenes metabolismo hepático - cardíaco
• Desórdenes hematológicos e inmunes
• Desórdenes de la sexualidad
• Teratogénesis, carcinogénesis y otros

Lopez Mato. 2002
39
LABORATORY ASSESSMENTS
40
PNIE DEL TRATAMIENTO AP

• Desórdenes por extrapiramidalismo
• Desórdenes por hiperprolactinemia
• Desórdenes endócrinos varios
• Desórdenes de aumento de peso
• Desórdenes del metabolismo hidrocarbonado
• Desórdenes del metabolismo lipídico
• Desórdenes del balance hídrico
• Desórdenes metabolismo hepático - cardíaco
• Desórdenes hematológicos e inmunes
• Desórdenes de la sexualidad
• Teratogénesis, carcinogénesis y otros

Lopez Mato. 2002
41

• CHOLESTEROL AND TRIGLYCERIDE ELEVATIONS
• In schizophrenia trials, Quetiapine-treated
  patients had increases from baseline in
  cholesterol and triglyceride of 11 and 17,
  respectively, compared to slight decreases for
  placebo patients.
• These changes were only weakly related to the
  increases in weight observed in
  Quetiapine-treated patients.

42
PNIE DEL TRATAMIENTO DE AP

• Desórdenes por extrapiramidalismo
• Desórdenes por hiperprolactinemia
• Desórdenes endócrinos varios
• Desórdenes de aumento de peso
• Desórdenes del metabolismo hidrocarbonado
• Desórdenes del metabolismo lipídico
• Desórdenes del balance hídrico
• Desórdenes metabolismo hepático - cardíaco
• Desórdenes hematológicos e inmunes
• Desórdenes de la sexualidad
• Teratogénesis, carcinogénesis y otros

Lopez Mato. 2002
43
CLINICA DIARIA RIESGO DE SIADH POR AP
PROMAZINICOS ZIPRASIDONA QUETIAPINA
???? CLOZAPINA OLANZAPINA OTROS
ANTIPSICOTICOS BUTIROFENONAS
Lopez Mato A, 2003
44
POLIDIPSIA PSICOGENA (Intoxicación Hídrica)

• Frecuente en esquizofrenia crónica
• Con hiponatremia (SIADH)
• Sin hiponatremia
• Exacerbación psicótica con metilfenidato aumenta
  secreción de ADH
• NL aumentan disfunción por acción directa sobre
  ADH acción de AA se desconoce
• Complicación severa convulsiones
• Sospecha aumento diurno gt 2 kilos

Lopez Mato. 2002
45

• Recently risperidone and quetiapine have been
  reported to cause hypokalaemia due to cellular
  shift.

Norden A. Laboratory Endocrinology Investigation
of hypokalaemia. Department of Clinical
Biochemistry, Addenbrookes Hospital, Cambridge.,
UK
Report of an elderly man who developed
hyponatremia after treatment with
quetiapine Atalay, Ayce MD A Case of Syndrome
of Inappropriate Secretion of Antidiuretic
Hormone in Elderly Patient Secondary to
Quetiapine. Southern Medical Jour. 2007. Het
syndroom van inadequate secretie van
antidiuretisch hormoon (SIADH) tijdens het
gebruik van de antipsychotica haloperidol en
quetiapine  Van den heuvel OA Bet P. M.
Nederlands tijdschrift voor geneeskunde  2006, 
46
PNIE DEL TRATAMIENTO DE AP

• Desórdenes por extrapiramidalismo
• Desórdenes por hiperprolactinemia
• Desórdenes endócrinos varios
• Desórdenes de aumento de peso
• Desórdenes del metabolismo hidrocarbonado
• Desórdenes del metabolismo lipídico
• Desórdenes del balance hídrico
• Desórdenes metabolismo hepático - cardíaco
• Desórdenes hematológicos e inmunes
• Desórdenes de la sexualidad
• Teratogénesis, carcinogénesis y otros

Lopez Mato. 2002
47
RIESGO DE EVENTOS HEPATOTOXICOS POR AP

CARBAMACEPINA VALPROICO PROMAZINICOS
OLANZAPINA QUETIAPINA LITIO
Lopez Mato A., 2003
48

• TRANSAMINASE ELEVATIONS
• Asymptomatic, transient and reversible elevations
  -
• -In schizophrenia trials, elevations of gt 3
  times
• 6 for Quetiapine compared to 1 for placebo.
• - In acute bipolar mania trials, elevations of gt
  3 times
• 1 both for Quetiapine and placebo.
• No se necesita interrumpir tratamiento
• .

De Seroquel
49
RIESGO DE EVENTOS CARDIOLOGICOS POR AP
TIORIDAZINA ZIPRASIDONA SERTINDOL PROMAZINICOS Q
UETIAPINA OLANZAPINA

Lopez Mato A., 2003
50
AA Y QT
aPfizer study 54 baseline correctionDoses are
highest total daily doses evaluated
Mean QTcchange from baselinea (msec)
40
35
30
25
20
15
10
5
0
Olanzapine20 mg
Haloperidol15 mg
Risperidone16 mg
Seroquel750 mg
Thioridazine300 mg
-5
Ziprasidone160 mg
(n24) (n25)
(n27) (n27) (n31)
(n30)
Pfizer Study 54, FDA Psychopharmacological Drug
Advisory Committee 19th July 2000
51
CEREBROVASCULAR ADVERSE EVENTS Class warning
for elevated risk of cerebrovascular adverse
events Risperidone (3.8) vs. Placebo (1.5)
N1230 Olanzapine (1.3) vs. Placebo (0.4)
N1882 Aripiprazole (1.3) vs. Placebo (0.6)
N938 Quetiapine (0.3) vs. Placebo (1.9) N568
52
NEW WARNING

• - 17 PCTs reviewed enrolling 5377 elderly pts
  with dementia related behavioral disorders (3611
  drug, 1766 placebo)
• Rate of death
• drug treated patients 4.5
• placebo group 2.6
• -Risk of death 1.6 to 1.7 times bigger
• Cause of death
• heart related or infectious
• Six drugs involved aripiprazole, olanzapine,
  risperidone, quetiapine, ziprasidone,
  haloperidol, clozapine, and olanzapine/fluoxetine

Atypical antipsychotics used to treat
dementia-related psychosis carry an increased
risk of death compared with placebo FDA Warning
on Mortality. April 11, 2005
53
PNIE DEL TRATAMIENTO DE AP

• Desórdenes por extrapiramidalismo
• Desórdenes por hiperprolactinemia
• Desórdenes endócrinos varios
• Desórdenes de aumento de peso
• Desórdenes del metabolismo hidrocarbonado
• Desórdenes del metabolismo lipídico
• Desórdenes del balance hídrico
• Desórdenes metabolismo hepático y cardíaco
• Desórdenes hematológicos e inmunes
• Desórdenes de la sexualidad
• Teratogénesis, carcinogénesis y otros

Lopez Mato. 2002
54
RIESGO DE EVENTOS HEMATOLOGICOS POR AP
CLOZAPINA PROMAZINICOS CARBAMACEPINA LITIO QUETIA
PINA

Lopez Mato A., 2003
55
NEUTROPHIL COUNTS
aResults are presented as number of
patientsNeutropenia defined as a low cell count
lt1.5 x 109 cells/L One patient with one
non-serious AE (neutrophil count decreased)
potentially related to agranulocytosis (defined
as a cell count lt0.5 x 109 cells/L) was reported
and led to discontinuation from the study
56
PNIE DEL TRATAMIENTO DE AP

• Desórdenes por extrapiramidalismo
• Desórdenes por hiperprolactinemia
• Desórdenes endócrinos varios
• Desórdenes de aumento de peso
• Desórdenes del metabolismo hidrocarbonado
• Desórdenes del metabolismo lipídico
• Desórdenes del balance hídrico
• Desórdenes metabolismo hepático y cardíaco
• Desórdenes hematológicos e inmunes
• Desórdenes de la sexualidad
• Teratogénesis, carcinogénesis y otros

Lopez Mato. 2002
57
RIESGO DE DISFUNCION SEXUAL
ANTICOLINERGICOSCLOZAPINA ZIPRASIDONA RISPERIDONA
BUTIROFENONAS QUETIAPINA OLANZAPINA ARIPRIPAZOL

Lopez Mato A., 2003
58
SEXUAL DYSFUNCTION
Randomized open-label study of the impact of
quetiapine versus risperidone on sexual
functioning.(mayor to risperidone) Knegtering
R, Castelein S, Bous H, Department of Psychiatry,
University Hospital Groningen, The Netherlands.
One case of priapism in a patient receiving
Quetiapine has been reported prior to market
introduction. While a causal relationship to use
of Quetiapine has not been established, other
drugs with alpha-adrenergic blocking effects have
been reported to inducepriapism, and it is
possible that Quetiapine may share this capacity.
59
PNIE DEL TRATAMIENTO DE AP

• Desórdenes por extrapiramidalismo
• Desórdenes por hiperprolactinemia
• Desórdenes endócrinos varios
• Desórdenes de aumento de peso
• Desórdenes del metabolismo hidrocarbonado
• Desórdenes del metabolismo lipídico
• Desórdenes del balance hídrico
• Desórdenes metabolismo hepático y cardíaco
• Desórdenes hematológicos e inmunes
• Desórdenes de la sexualidad
• Teratogénesis, carcinogénesis y otros

Lopez Mato. 2002
60
FDA - RIESGO DE EVENTOS TERATOGENICOS POR AP
ANTICOLINERGICOS C BUTIROFENONAS C PROMAZINICOS
C ARIPRIPAZOL C ZIPRASIDONA C RISPERIDONA
C QUETIAPINA C OLANZAPINA CB CLOZAPINA B
Lopez Mato. 03
61
ANTIPSYCHOTICS IN POSTPARTUM

• Prolactin-sparing antipsychotic may be useful,
  e.g., olanzapine and quetiapine.
• Clozapine use is restricted because of the
  haematological risk.
• The risk of relapse of schizophrenia during this
  time is also significant like the mood disorders

Dr. Ahmed Shoka
62
RIESGO DE EVENTOS OFTALMOLOGICOS
POR AP

QUETIAPINA ???? PROMAZINICOS
Lopez Mato A., 2003
63
CATARATAS

• 26 of schizophrenics have lens opacities
• multiple cataractogenic risk factors
• 620,000 Seroquel exposures through May 31 2000
• 32 cases of lens opacities reported
• Most had concomitant risk factors trauma,
  hypertension, diabetes, known cataractogens
• Independent evaluation by ophthalmologist
  consultant did not identify hallmarks suggesting
  lens toxicity attributable to Seroquel

McCarty et al 1999 Laties et al 2000
64
PNIE DEL TRATAMIENTO DE AP

• Desórdenes por extrapiramidalismo
• Desórdenes por hiperprolactinemia
• Desórdenes endócrinos varios
• Desórdenes de aumento de peso
• Desórdenes del metabolismo hidrocarbonado
• Desórdenes del metabolismo lipídico
• Desórdenes del balance hídrico
• Desórdenes metabolismo hepático y cardíaco
• Desórdenes hematológicos e inmunes
• Desórdenes de la sexualidad
• Teratogénesis, carcinogénesis y otros

Lopez Mato. 2002
65
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• Incidence of EPS no different to placebo across
  the full dose range
• Significantly less EPS than haloperidol, even at
  higher doses
• Incidence of EPS does not increase with long-term
  use
• Low risk of tardive dyskinesia
• Low level of sexual dysfunction (prolactin levels
  equivalent to placebo across all doses)
• Significantly lower prolactin levels than
  standard antipsychotics
• Weight neutral in long-term monotherapy
• No clinically significant effect on QT interval -
  ECG monitoring not require
• No requirement for blood or thyroid or liver
  monitoring

Meats 1997 Data on file - AstraZeneca
66
MUCHAS GRACIAS
SEROQUEL ES SEGURIDAD
ANDREA LOPEZ MATOPABLO BERETTA www.ipbi.com.ar