To treat some psychiatric diseases, we use drugs called antipsychotics. One of these drugs, named aripiprazole, is widely used because it has fewer side effects such as weight gain compared to other antipsychotics. However, there is some concern that aripiprazole may rarely provoke a worsening of the psychiatric disease in some patients. To study this possibility further we will study patients who start using aripiprazole and compare them with otherwise similar people who start using another antipsychotic drug to treat psychiatric disease. We will follow these patients for one year to see whether or not patients starting aripiprazole are more likely to have a worsening of their disease compare with patients starting another antipsychotic drug. We will also assess whether the risk of worsening is influenced by the numbers of prescriptions and the dose of other antipsychotics drugs used before starting aripiprazole. The findings of our study are expected to help ascertain whether or not psychiatric worsening is a side-effect of aripiprazole and, if so, to determine potential risk factors, thereby aiding the development of preventive measures.
Since the introduction in 2005 of aripiprazole, a D2 dopamine partial agonist prescribed to manage schizophrenia or bipolar disorder, several cases of abrupt psychotic worsening have been reported. These psychiatric decompensations seem to occur in two clinical situations: in patients previously treated with an antipsychotic who switched to aripiprazole, or in whom aripiprazole is added to another antipsychotic. Therefore, the primary objective of this study will be to compare the incidence rate of psychiatric treatment failure (defined as a composite of hospitalization for a psychiatric event, non-fatal self-harm, or suicide) among a base cohort of antipsychotic users who switch to or add aripiprazole (new users of aripiprazole) relative to those who switch to or add another antipsychotic. This study will be conducted by linking the CPRD, the HES inpatient database, and the ONS (Office for National Statistics) mortality database between January 1, 2000 and March 31, 2016. For each patient who initiates aripiprazole, we will have one high dimensional propensity score (hdPS)-matched patient starting another antipsychotic at the time the patient start aripiprazole, using a prevalent new-user design. Patients will be followed for 1 year for the occurrence of psychiatric treatment failure.
First psychiatric treatment failure defined as a composite of hospitalisation for a psychiatric event, non-fatal self-harm, or suicide within 365 days after antipsychotic treatment switching or add-on; Psychiatric admission using the following ICD-10 codes: organic disorders (F05-F07, F09), substance misuse (F10-F19), schizophrenia and related psychoses (F20-F29), mood disorders (F30-F39), anxiety disorders (F40-F48), eating disorders (F50), behavioral syndromes (F51-F59), disorders of adult personality (F60-F69) and unspecified diagnosis (F99). Fatal and non-fatal self-harm will be measured by death from suicide using ONS mortality database and by hospitalisation for self-harm in the HES database; The following ICD10-codes: intentional self-harm (X60-X84 and event of undetermined intent (Y10-Y34); Psychiatric treatment failure on the basis of Read codes in the CPRD to measure fatal and non-fatal self-harm.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Christel Renoux - Corresponding Applicant - McGill University
Francois Montastruc - Collaborator - University Of Toulouse
Joelle MICALLEF - Collaborator - Service Hospitalo-Universitaire de Pharmacologie Clinique
Rui Nie - Collaborator - McGill University
Sophie Dell'Aniello - Collaborator - McGill University
HES Admitted Patient Care