Safety Comparison of Atomextine and Lisdexamfetamine: Using Pharmacovigilance Database and Tools

Background Our study is the first to utilize the OpenVigil 2.1, a universal novel web-based pharmacovigilance analysis tool to analyze real-life safety of ADHD medications with special emphasis on newer medications and psychiatric adverse events. Thorough knowledge of adverse events for each medication reveals safety signals and support treatment guidelines and clinical management of the events. Methods we analyzed adverse event cases documented in the OpenVigil 2.1 from mid-2003 until February 2020. The medical dictionary for regulatory activities (MedDRA browser English version 20.0) was used to group lower level terms with a common preferred term to be searched for in the database. The proportional reporting ratio (PRR) and the reporting odd ratio (ROR) were used to quantitate the strength of the association between reported adverse events for atomoxetine, lisdexamfetamine, amphetamine, methylphenidate (instant release, intermediate acting, long acting). Results During the period we evaluated a total of 38,412 cases reported for methylphenidate, atomoxetine, lisdexamfetamine, amphetamine. We found a significantly lower risk for depressed mood (ROR 0.026, 95%CI 0.016-0.042) and tics (ROR 0.48, 95%CI 0.30-0.76) reported for atomoxetine compared with methylphenidate. Lisdexamphetamine did not seem to decrease the risk of psychiatric events. On the contrary, lisdexamfetamine carried a six fold risk for suicidal adverse events compared with other drugs in the data and a twofold risk of suicidal adverse events and tics compared with methylphenidate. Conclusions we conclude that Atomoxetine is a good choice for patients with comorbid tics or depression or for patients who develop depressed mood on stimulants. There is a great overlap between ADHD symptoms and stimulant/non stimulant adverse events, therefore prior to medication switch, therapeutic response should be evaluated carefully. Data in the literature on lisdexamfetamine remains scarce. Owing to signals on tic disorders and suicidal adverse events, we highly recommend studying these issues further with RCT and Cohort studies.