Mechanisms Underlying Aggressive Behavior Induced by Antiepileptic Drugs: Focus on Topiramate, Levetiracetam, and Perampanel

Table 4

Studies reporting psychiatric and behavioral adverse reactions to topiramate.

Study	Study design	Study population	Main findings
Chen et al. 2017 [18]	Case-control, years	adults (mean age: 41 years) with epilepsy on ≥1 AED, of which TPM: 639	PBAR in 17.2%, leading to dose reduction or discontinuation in 13.8% (all patients) and 6.3% (TPM users).
Chung et al. 2007 [50]	Case-control, years	adults (mean age 38.5 years) on different AEDs (LEV: 196, LTG: 251, OXC: 97, TPM: 156, ZNS: 128)	TPM with the highest rate of discontinuation (55.8%), but only few due to PBAR (5 of 156 patients).
Endoh et al. 2012 [54]	Case-control, months	children with epileptic spasms, of which 33 used TPM	5 of 33 patients (15.2%) developed irritability.
Grosso et al. 2005 [81]	Cohort study, months	children < 2 years (mean age: 13 months) on TPM	Irritability is one of the most common adverse reactions.
Kanner et al. 2003 [82]	Cohort study, months	patients (mean age: 36.1 years) with epilepsy using TPM as monotherapy or add-on	PBAR in 12.6%, incl. aggression (10.7%), irritability (5.7%), and depression (5%). TPM discontinued in 27% with these adverse reactions.
Lee et al. 2011 [55]	Cohort study, weeks	children (2-18 months) with infantile spasms using TPM	Irritability in 4 patients (14.3%; most common adverse reaction).
Mula et al. 2003 [38]	Cohort study, months	patients (mean age 35.8 years) with epilepsy using TPM	PBAR in 24% (aggression: 5.6%).
Mula and Trimble 2003 [56]	Cohort study, months	patients on TPM	Mood symptoms in almost half of patients. Aggression is the second most common (23%), resolved after dose reduction or discontinuation of TPM.
Mula et al. 2007 [67]	Case-control, years	patients with epilepsy, treated with LEV and TPM (consecutively)	PBAR in 30%
Reith et al. 2003 [83]	Case-control, days	< 18 years (mean age: 8.1 years) with epilepsy using TPM; follow-up of of these	Aggression or psychosis treatment-limiting in 10 of 127 patients (7.9%).
Weintraub et al. 2007 [27]	Case-control, months	of which 112 patients (mean age: 41 years) used TPM	PBAR in 6.3% on TPM, which was lower than the mean frequency of all AEDs (8.4%)

RCT: randomized controlled trial, t: observation time; PBAR: psychiatric and/or behavioral adverse reactions; LEV: levetiracetam; LTG: lamotrigine; OXC: oxcarbazepine; TPM: topiramate, ZNS: zonisamide.