Summary of aggression-related behavior incidence and warnings, from AED labels
AEDs are listed in alphabetical order.
| AED | Aggression-Related AEs (and Incidence) | Other Related Text, Warnings, or Precautions | Epilepsy Specific? | Source |
|---|---|---|---|---|
| Carbamazepine | Aggression, agitation (rare: 0.01%–0.1%) | “The possibility of activation of a latent psychosis and, in elderly patients, of confusion and agitation should be borne in mind” | No | Tegretol (2014a,b) |
| Clobazam | “Aggressive behaviour towards self and others may be precipitated” | No | Frisium (2014), Onfi (2014) | |
| Irritability (7% with clobazam versus 5% with placebo) | Yes (LGS) | Onfi (2014) | ||
| Aggression (8% with clobazam versus 5%) | ||||
| Aggression (1 of the 6 AEs leading to clobazam discontinuation) | ||||
| Clonazepam | No incidence reported for aggression-related AEs | “Clonazepam generally has a beneficial effect on behaviour disturbances in epileptic patients. In certain cases, paradoxical effects such as aggressiveness, excitability, nervousness, hostility, anxiety, sleep disturbances, nightmares, vivid dreams, irritability, agitation, psychotic disorders and activation of new types of seizures may be precipitated” | Yes | Clonazepam (2014) |
| No incidence reported for aggression-related AEs | “Behaviour problems have been noted in approximately 25% of patients” | Yes | Klonopin (2013) | |
| Eslicarbazepine | Agitation, irritability (uncommon: 0.1%–1%) | Yes | Zebinix (2014) | |
| Ethosuximide | Aggression, irritability (uncommon: 0.1%–1%), psychiatric AEs are seen “particularly in patients who have previously exhibited psychological abnormalities” | Yes | Zarontin (2012, 2014) | |
| Felbamate | Aggressive behavior, agitation (common: ≥1%) | Yes | Felbatol (2012) | |
| Gabapentin | Hostility (common: 1%–10%) | Yes | Neurontin (2013a,b) | |
| In children, aggressive behavior is also common (1%–10%) | ||||
| Lacosamide | Irritability (common: 1%–10%) | Yes | Vimpat (2014a,b) | |
| Aggression, agitation (uncommon: 0.1%–1%) | ||||
| Lamotrigine | Aggression, irritability (common: 1%–10%) | No | Lamictal (2014a) | |
| Irritability (3% versus 2% with placebo, adjunctive use) | Yes | Lamictal (2014b) | ||
| Irritability (2%–5%, monotherapy) | ||||
| Levetiracetam | Hostility/aggression, nervousness/irritability (common: 1%–10%) | Yes | Keppra (2010) | |
| Anger, agitation (uncommon: 0.1%–1%) | ||||
| Behavioral AEs were more common in children/adolescents than adults: agitation (3.4%), aggression (8.2%), irritability (11.7%, children aged <4 yr) | ||||
| Nonpsychotic behavioral symptoms (levetiracetam versus placebo): | Warnings and precautions: “Behavioral abnormalities including psychotic symptoms, suicidal ideation, irritability, and aggressive behavior have been observed. Monitor patients for psychiatric signs and symptoms” | Yes | Keppra (2014) | |
| Adults (13.3% versus 6.2%) | ||||
| Pediatric (37.6% versus 18.6%) | ||||
| Oxcarbazepine | Agitation (1%–2% versus 1% with placebo) | Yes | Trileptal (2013, 2014) | |
| Perampanel | Adjunctive perampanel, occurrence in epilepsy clinical trials: aggression, anger, irritability (common: 1%–10%) | “Aggressive and hostile behaviour has been reported in patients receiving perampanel therapy. In perampanel-treated patients in clinical trials, aggression, anger and irritability were reported more frequently at higher doses. Most of the reported events were either mild or moderate and patients recovered either spontaneously or with dose adjustment. However, thoughts of harming others, physical assault or threatening behaviour were observed in some patients (<1% in perampanel clinical studies)” | Yes | Fycompa (2015) |
| Adjunctive perampanel, occurrence with 12 mg versus placebo in epilepsy clinical trials: | “Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking FYCOMPA. These reactions occurred in patients with and without prior psychiatric history, prior aggressive behaviour, or concomitant use of medications associated with hostility and aggression” | Yes | Fycompa (2014) | |
| Irritability: 12% versus 3% | ||||
| Aggression: 3% versus 1% | ||||
| Anger: 3% versus <1% | ||||
| Total incidence of hostility- and aggression-related adverse reactions: 20% with 12 mg, 12% with 8 mg, 6% with placebo | ||||
| Phenobarbital | AE rates are not given. The listing of undesirable effects includes: “paradoxical reaction (unusual excitement)” and “behavioural disturbances in children” | Yes | Phenobarbital (2013) | |
| Phenytoin | No mention of aggression-related behavior in the SPC or USPI | |||
| Pregabalin | Irritability (common: 1%–10%) | No | Lyrica (2014, 2015) | |
| Agitation, aggression, hostility (uncommon: 0.1%–1%) | ||||
| Retigabine | Aggression-related behaviors reported only in overdose | Yes | Potiga (2013), Trobalt (2014) | |
| Rufinamide | No aggression-related behaviors or adverse reactions are listed in the SPC | Yes | Inovelon (2013) | |
| Aggression (3% versus 2% with placebo) | Yes | Banzel (2015) | ||
| Stiripentol | Aggressiveness, irritability (common: 1%–10%) | Yes (children) | Diacomit (2014) | |
| Tiagabine | Hostility (2%–5% versus 1%–2% with placebo) | Yes | Gabitril (2010, 2014) | |
| Agitation (1% versus 0%) | ||||
| Topiramate | Irritability (>5%) | Aggression was more common in children than in adults | Mostlya | Topamax (2013) |
| Aggression, agitation, anger, abnormal behavior, irritability (common: 1%–10%) | ||||
| Aggression, agitation (3% versus 2% with placebo, clinical study in adults) | Yes (individual epilepsy clinical trial data) | Topamax (2014) | ||
| Aggression (2% versus 0% with placebo, clinical study in adults) | ||||
| Aggression (9% versus 4%, pediatric trials) | ||||
| Valproic acid | Aggression, agitation (common: 1%–10%), predominantly in children | Yes | Epilim (2013) | |
| No terms of interest are listed in the epilepsy clinical study tables in the USPI | Yes | Depakene (2015) | ||
| Aggression, hostility, and irritability are listed as adverse reactions reported in postmarketing experience (no incidence given) | ||||
| Vigabatrin | Pediatric: Agitation (very common: ≥10%) | “Vigabatrin should be used with caution in patients with a history of psychosis, depression or behavioural problems. Psychiatric events (e.g., agitation, depression, abnormal thinking, paranoid reactions) have been reported during vigabatrin treatment. These events occurred in patients with and without a psychiatric history, and were usually reversible when vigabatrin doses were reduced or gradually discontinued” | Yes | (Sabril, 2014) |
| Adults: aggression, agitation, and irritability (common: 1%–10%) | ||||
| Adults: irritability (23% with 6000 mg versus 7% with placebo) | Yes | Sabril (2013) | ||
| Adolescents: aggression (5% versus 0% with placebo) | ||||
| Infantile spasm: irritability (16%–23%) | ||||
| Zonisamide | Adjunctive use: | Yes | Zonegran (2014) | |
| Agitation, irritability (very common: >10%) | ||||
| Anger, aggression (uncommon, 0.1%–1%) | ||||
| Monotherapy: | ||||
| Agitation (common: 1%–10%); aggression (uncommon) | ||||
| Adjunctive use: | Yes | Zonegran (2012) | ||
| Agitation/irritability (9% versus 4% with placebo) |
LGS, Lennox–Gastaut syndrome; SPC, summary of product characteristics; USPI, US prescribing information.
↵a Predominantly epilepsy studies, but a minority of studies in migraine prophylaxis.