Methylphenidate and manic relapse in bipolar disorders: A replication study in a nationwide claims database

Abstract

Background:

Methylphenidate can treat attention-deficit/hyperactivity disorders, which are frequently comorbid with bipolar disorders (BDs). Viktorin and collaborators (2017) reported that prescribing methylphenidate alone in adults with BD is associated with higher risk of manic relapse, whereas prescribing it in combination with mood-stabilizing medications is associated with lower risk.

Aims:

We aimed to replicate these findings.

Methods:

We identified adults with BD included in the French national healthcare claims database (SNDS) between 2008 and 2024. We compared the rate of manic relapse within 6 months before and after a new methylphenidate dispensation using self-controlled survival analysis.

Results/outcomes:

Among 2745 patients not receiving mood-stabilizing treatment, the rate of inpatient mania diagnoses was significantly higher within 3 months of methylphenidate dispensation compared to the pre-exposure period. This significance disappeared in self-controlled case-crossover analyses. Among 3526 patients receiving continuous mood-stabilizing treatment, there were no significant changes in the risk of an inpatient mania diagnosis after methylphenidate dispensation, except when administering >30 mg of methylphenidate. Treating the start of new antimanic therapy as an outcome event produced outlier results.

Conclusions/interpretation:

In patients with treated BD, methylphenidate is only associated with manic relapse at high dose. The strong significant risk of manic relapse we observed in untreated BD may be explained by natural progression of mania. This study highlights intrinsic limitations associated with self-controlled survival analysis.