Study type

Study topic

Human medicinal product

Study type

Non-interventional study

Scope of the study

Safety study (incl. comparative)

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Name of medicine, other

First-generation antipsychotics, Second-generation antipsychotics

Anatomical Therapeutic Chemical (ATC) code

(N05A) ANTIPSYCHOTICS
ANTIPSYCHOTICS
(N05AA01) chlorpromazine
chlorpromazine
(N05AA02) levomepromazine
levomepromazine
(N05AA03) promazine
promazine
(N05AA04) acepromazine
acepromazine
(N05AA05) triflupromazine
triflupromazine
(N05AA06) cyamemazine
cyamemazine
(N05AA07) chlorproethazine
chlorproethazine
(N05AB01) dixyrazine
dixyrazine
(N05AB02) fluphenazine
fluphenazine
(N05AB03) perphenazine
perphenazine
(N05AB04) prochlorperazine
prochlorperazine
(N05AB05) thiopropazate
thiopropazate
(N05AB06) trifluoperazine
trifluoperazine
(N05AB07) acetophenazine
acetophenazine
(N05AB08) thioproperazine
thioproperazine
(N05AB09) butaperazine
butaperazine
(N05AB10) perazine
perazine
(N05AC01) periciazine
periciazine
(N05AC02) thioridazine
thioridazine
(N05AC03) mesoridazine
mesoridazine
(N05AC04) pipotiazine
pipotiazine
(N05AD01) haloperidol
haloperidol
(N05AD02) trifluperidol
trifluperidol
(N05AD03) melperone
melperone
(N05AD04) moperone
moperone
(N05AD05) pipamperone
pipamperone
(N05AD06) bromperidol
bromperidol
(N05AD07) benperidol
benperidol
(N05AD08) droperidol
droperidol
(N05AD09) fluanisone
fluanisone
(N05AE01) oxypertine
oxypertine
(N05AE02) molindone
molindone
(N05AE03) sertindole
sertindole
(N05AE04) ziprasidone
ziprasidone
(N05AE05) lurasidone
lurasidone
(N05AF01) flupentixol
flupentixol
(N05AF02) clopenthixol
clopenthixol
(N05AF03) chlorprothixene
chlorprothixene
(N05AF04) tiotixene
tiotixene
(N05AF05) zuclopenthixol
zuclopenthixol
(N05AG01) fluspirilene
fluspirilene
(N05AG02) pimozide
pimozide
(N05AG03) penfluridol
penfluridol
(N05AH01) loxapine
loxapine
(N05AH02) clozapine
clozapine
(N05AH03) olanzapine
olanzapine
(N05AH04) quetiapine
quetiapine
(N05AH05) asenapine
asenapine
(N05AH06) clotiapine
clotiapine
(N05AL01) sulpiride
sulpiride
(N05AL02) sultopride
sultopride
(N05AL03) tiapride
tiapride
(N05AL04) remoxipride
remoxipride
(N05AL05) amisulpride
amisulpride
(N05AL06) veralipride
veralipride
(N05AL07) levosulpiride
levosulpiride
(N05AX07) prothipendyl
prothipendyl
(N05AX08) risperidone
risperidone
(N05AX10) mosapramine
mosapramine
(N05AX11) zotepine
zotepine
(N05AX12) aripiprazole
aripiprazole
(N05AX13) paliperidone
paliperidone
(N05AX14) iloperidone
iloperidone
(N05AX15) cariprazine
cariprazine
(N05AX16) brexpiprazole
brexpiprazole

Medical condition to be studied

Schizophrenia
Bipolar disorder
Mania

Additional medical condition(s)

Depressive disorder with psychotic symptoms
Population studied

Short description of the study population

In the primary analysis, all pregnancies identified in the MBRN (Medical Birth Registry of Norway) for pregnancies lasting ≥12 weeks, and primary and secondary care registries for pregnancies lasting <12 weeks. In the secondary analysis, we will restrict to pregnancies identified in the MBRN.

Age groups

  • Adult and elderly population (≥18 years)
    • Adults (18 to < 65 years)
      • Adults (18 to < 46 years)

Special population of interest

Pregnant women

Estimated number of subjects

860000
Study design details

Study design

Cohort study using nation-wide registry data.

Main study objective

To evaluate the association of exposure to second-generation antipsychotics during pregnancy with the risk of spontaneous abortion.

Setting

We will use Norwegian nationwide registry data, which consist of the Medical Birth Registry of Norway (MBRN), linked to the Norwegian Prescription Database (NorPD) covering all dispensed medications to outpatients, the Norwegian control and payment of health reimbursements (KUHR) covering primary care contacts and the Norwegian Patient Registry (NPR) covering secondary care contacts through the maternal personal identification number.

Comparators

Several comparison groups will be employed: 1. Unexposed, diseased comparison group, 2. First-generation antipsychotics during pregnancy (Active comparator), 3. Exposed to second-generation antipsychotics only prior to pregnancy (Discontinuer).

Outcomes

The primary outcome is defined as spontaneous abortions. Elective termination is considered a competing outcome. The secondary outcomes are preterm birth, small-for-gestational-age (SGA), low Apgar score, transfer to NICU, congenital malformations, gestational diabetes, preeclampsia, caesarean section.

Data analysis plan

In the primary analysis, we will estimate the hazard ratio with 95% CI with each comparator group, while controlling for measured confounders identified using Directed Acyclic Graphs.