Role of α1-adrenergic antagonist activity and 5-HT1A antagonism in the occurrence of ischaemic stroke and TIA within one year after a first prescription of antipsychotics in France: a cohort study in the EGB between 2009 and 2019

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/40829
• EU PAS number:
  EUPAS40828
• Study ID:
  40829
• Official title and acronym:
  Role of α1-adrenergic antagonist activity and 5-HT1A antagonism in the occurrence of ischaemic stroke and TIA within one year after a first prescription of antipsychotics in France: a cohort study in the EGB between 2009 and 2019
• DARWIN EU® study:
  No
• Study countries:
  France
• Study description:
  Antipsychotics are widely prescribed in the French general population. They constitute a heterogeneous pharmacological class, are non-selective, and each antipsychotic binds differently to α1-adrenergic or serotonin 5-HT1A receptors. Cardiovascular adverse effects are a major cause of mortality in patients exposed to antipsychotics, including ischaemic strokes within the first few weeks of prescription. These could be explained by early cardiovascular pharmacodynamic effects (orthostatic hypotension, QT prolongation). However, another class of drugs presents an increased risk of early strokes, particularly ischaemic strokes: alpha-blockers. These drugs act by strongly blocking α1-adrenergic and serotonin 5-HT1A receptors. Moreover, activation of these receptors in the cerebral arteries can lead to vasoconstriction. Blocking these receptors could therefore lead to vasodilatation, resulting in cerebral hypoperfusion which could favour the occurrence of ischaemic stroke. To date and to to our knowledge, only two studies have investigated the risk of early ischemic stroke associated with antipsychotic drugs in relation to these two receptors, but they are inconsistent and have several limitations. We hypothesise that antipsychotic drugs with 5-HT1A antagonism and strong α1-adrenergic antagonism are associated with a greater risk of hospitalisation for cerebral ischaemic events. The primary objective of our study is to evaluate whether prescribing antipsychotic drugs with strong α1-blocking affinity and 5-HT1A antagonist activity is associated with an increased risk of hospitalisation for ischaemic stroke or TIA within one year of initiation, compared with prescribing antipsychotic drugs with low α1-adrenergic affinity and no 5-HT1A antagonism (reference group). The secondary objective of our study is to assess the possible risk factors for ischaemic stroke or TIA hospitalisations associated with incident prescribing of these two groups of antipsychotics.
• Study status:
  Ongoing

Research institutions and networks

Institutions

Toulouse University Hospital

Pharmacologie En Population cohorteS et biobanqueS - Centre d’Investigation Clinique 1436

Study timelines

Date when funding contract was signed

Actual: 13/01/2021

Study start date

Actual: 08/02/2021

Data analysis start date

Planned: 03/05/2021

Date of final study report

Planned: 30/07/2021

Sources of funding

Other

More details on funding

Congrès Français de Psychiatrie

Study protocol

Initial protocol

Antipsychotics and ischaemic cerebral events - Role of a1-adrenergic antagonist activity and 5-HT1A antagonism - Cohort study in the French EGB

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable