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

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.