Evaluation of the Incidence of Psychiatric Disorders As a Function of First-line Antiepileptic Drug Prescribing Practices: Use of Assurance Maladie Databases (PRADOV)

An estimated 600,000 people suffer from epilepsy in France, with a prevalence of around 0.6%. The disease and its associated co-morbidities, particularly psychiatric, have a detrimental effect on the patient's quality of life. Recommendations for the management of epilepsy are based primarily on antiepileptic drug treatment. Therapeutic recommendations for this management have a limited level of evidence (usually grade C or expert agreement), with very few high-level evidence recommendations (grade A or B). In the first instance, monotherapy with progressive doses is recommended to avoid adverse effects at the start of treatment, notably sedation and dizziness.

Levetiracetam is one of the most widely prescribed antiepileptic drugs, thanks to its broad spectrum of antiepileptic activity and its reputedly favorable safety profile. In practice, however, this drug is associated with sometimes severe psychobehavioral side effects, including irritability and insomnia, as well as psychiatric side effects such as manic episodes, depressive episodes and suicidal crises. These psycho-behavioral and psychiatric episodes are described in the literature in cohorts of patients monitored in expert centers. In contrast, there are few published data on a population scale in primary care. Moreover, the risk factors for psychobehavioral and psychiatric episodes on levotetracetam are insufficiently known, and there are few data in terms of impact on the safety of the care pathway. In addition to the development of psychiatric comorbidities, potential negative impacts on the patient's care pathway include interruptions in anti-epileptic treatment with the risk of therapeutic failure, increased healthcare consumption and, ultimately, a deterioration in the patient's quality of life.

As these psychiatric side-effects are not well known to the majority of general practitioners, who are the main primary prescribers of antiepileptic drugs, we can hypothesize that there are many patients for whom these psychiatric disorders are not attributed to the antiepileptic treatment, and that the latter is not modified, negatively impacting the safety of the care pathway. It is for this reason that the latest HAS report of March 23, 2023 recommends that the initiation of the first treatment be carried out on the recommendation of a neurologist. The main objective is to estimate, among patients with no psychiatric history, the risk of developing psychiatric disorders in the year following initiation of 1st-line antiepileptic treatment, as a function of (i) the treatment prescribed in 1st line and (ii) the sequence of treatments, i.e. the sequence of different antiepileptic treatments. It is a retrospective cohort on medico-administrative databases. The inclusion period is January 1, 2016 - December 31, 2023 and all adult patients (age ≥ 18 years), affiliated to the social security system with a first reimbursement of antiepileptic treatment is included.

Study Overview

• Status: Not yet recruiting
• Conditions: Epilepsy; Side Effects of Drugs

• Study Type: Observational
• Enrollment (Estimated): 355000

Contacts and Locations

• Study Contact: Name: Célia Chatignoux; Phone Number: 33156092000; Email: celia.chatignoux@aphp.fr
• Study Contact Backup: Name: Brigitte Sabatier, PharmD, PHD; Phone Number: 33156092000; Email: brigitte.sabatier@aphp.fr

Study Locations

• France
  • Paris, France, 75015
    • European Georges Pompidou Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients benefiting from reimbursement by French health insurance for long-term antiepileptic treatment, and appearing in the health insurance reimbursement database.

Description

Inclusion Criteria:

• All adult patients (age ≥ 18 years), affiliated to the social security system with a first reimbursement of antiepileptic treatment

Exclusion Criteria:

• Patients with a psychiatric comorbidity, treated or not in the year preceding the index date of first prescription of the antiepileptic drug

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
risk of developing psychiatric disorders in the year following initiation of 1st-line antiepileptic treatment	Incidence of psychiatric disorders 1 year after initiation of antiepileptic treatment, defined as : Any hospitalization in MCO or RIM-P for psychiatric causes: ICD-10 codes F00 to F99 in DP or DR, except codes F70 to F79 (mental retardation) and F90 to F98 (behavioral and emotional disorders appearing during childhood and adolescence),; Any consultation with a city psychiatrist or hospital psychiatrist (as part of an outpatient procedure),; Any first prescription of a psychotropic drug: anxiolytics (ATC N05B*) - hypnotics (ATC N05C*) - antidepressants (ATC N06A*) - antipsychotics (ATC N05A*).	12 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Ministry of Health, France; GHU Paris Psychiatry & Neurosciences

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 24, 2025
• First Submitted That Met QC Criteria: February 13, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 13, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: epilepsie; snds; bases de données médico-administratives
• Additional Relevant MeSH Terms: Behavioral Symptoms; Chemically-Induced Disorders; Problem Behavior; Mental Disorders; Drug-Related Side Effects and Adverse Reactions
• Other Study ID Numbers: APHP240983; PREPS 2024 - 983 (Other Grant/Funding Number: Ministry of health, France)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: French law does not allow the sharing of data from the French insurance database.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No