Drug‐induced tics: An observational postmarketing study

Abstract

While drug-induced tics have been described, in particular with neuroleptics, psychostimulants, or anti-epileptics, the strength and the direction of these associations are still debated. The aim of this study was to investigate the association between tics and drug exposure through a two-step analysis in two pharmacovigilance databases. We first performed a descriptive clinical analysis of cases registered in the French pharmacovigilance database (FPVD) from January 1985 to December 2018. We then performed a disproportionality analysis in VigiBase®, the WHO pharmacovigilance database, from January 1967 to June 2019, through the calculation of reporting odds ratio (ROR). The drugs most frequently associated with tics in the FPVD were methylphenidate, lamotrigine, montelukast, tramadol, mirtazapine, venlafaxine, aripiprazole, and risperidone. In VigiBase®, we found a significant ROR with methylphenidate (ROR 37.54, 95% confidence interval [CI] 34.81-40.48), montelukast (ROR 12.18, 95% CI 10.29-14.41), aripiprazole (ROR 7.40, 95% CI 6.35-8.62), risperidone (ROR 4.40, 95% CI 3.72-5.21), and venlafaxine (ROR 1.52, 95% CI 1.14-2.03). This postmarketing study confirmed a potential harmful association with methylphenidate (the highest association, as expected), aripiprazole, risperidone, lamotrigine, and venlafaxine and, interestingly, found a strong signal with montelukast, which, to our knowledge, had never been published before.