Antiepileptic medication side-effects

- Patients with previous psychiatric history are more likely to discontinue AEDs due to psychiatric side-effects (Stephen, Wishart, and Brodie, 2017)

- Patients with low socioeconomic status and recreational drug use also were more likely to develop psychiatric side-effects from levetiracetam (Josephson et al, 2019)

- In general, sodium channel blockers are less likely to cause neuropsychiatric side-effects (Stephen, Wishart, and Brodie, 2017)

- Temporal correlation to adverse side-effects is most important, though one must consider additional variables beyond drug titration. If aggressive behaviors develop or worsen in the setting of AED initiation or uptitration, often the aggressive behavior can only be stopped by discontinuing the AED (though one may consider downtitrating first and observing) (Brodie et al, 2016)

Specific antiseizure medication effects:

• Carbamazepine – lower likelihood of psychiatric side-effects
• Clobazam – can be disinhibiting or agitating
• Eslicarbazepine – lower likelihood of psychiatric and cognitive side-effects
• Felbamate
• Gabapentin – lower likelihood of psychiatric and cognitive side-effects
• Lacosamide – lower likelihood of cognitive side-effects
• Lamotrigine – lower likelihood of psychiatric and cognitive side-effects
• Levetiracetam – higher likelihood of psychiatric (depression, aggression, irritability, anxiety, insomnia; less common – psychosis, mania, suicidal ideation) and cognitive side-effects (Josephson et al, 2019; Brodie et al, 2016; Hansen et al, 2018)
• Oxcarbazepine – lower likelihood of psychiatric side-effects
• Perampanel – higher likelihood of psychiatric side-effects (aggression, anger, anxiety), dizziness (most common), and somnolence, fatigue, confusion (Brodie et al, 2016; Hansen et al 2018; Krauss et al, 2012)
• Phenobarbital – higher likelihood of psychiatric and cognitive side-effects
• Pregabalin – lower likelihood of psychiatric side-effects
• Primidone – higher likelihood of cognitive side-effects
• Rufinamide – lower likelihood of cognitive side-effects
• Tiagabine – lower likelihood of cognitive side-effects
• Topiramate – higher likelihood of psychiatric (depression, irritability, aggressive behavior, anxiety) and cognitive side-effects (bradyphrenia, expressive language disorder, confusion, disorientation) (Hansen et al, 2018; Kruass et al 2012)
• Valproic acid – lower likelihood of psychiatric side-effects
• Vigabatrin – higher likelihood of psychiatric side-effects
• Zonisamide – higher likelihood of psychiatric and cognitive side-effects

References

Brodie, M. J. et al. Epilepsy, Antiepileptic Drugs, and Aggression: An Evidence-Based Review. Pharmacol. Rev. 68, 563–602 (2016). https://pubmed.ncbi.nlm.nih.gov/27255267/

Krauss, G. L. et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology 78, 1408–1415 (2012). https://pubmed.ncbi.nlm.nih.gov/22517103/

Hansen, C. C., Ljung, H., Brodtkorb, E. & Reimers, A. Mechanisms Underlying Aggressive Behavior Induced by Antiepileptic Drugs: Focus on Topiramate, Levetiracetam, and Perampanel. Behav. Neurol. 2018, 2064027 (2018). https://pubmed.ncbi.nlm.nih.gov/30581496/

Josephson, C. B. et al. Prediction Tools for Psychiatric Adverse Effects After Levetiracetam Prescription. JAMA Neurol. 76, 440–446 (2019). https://pubmed.ncbi.nlm.nih.gov/30688969/

Stephen, L. J., Wishart, A. & Brodie, M. J. Psychiatric side effects and antiepileptic drugs: Observations from prospective audits. Epilepsy Behav. 71, 73–78 (2017) https://pubmed.ncbi.nlm.nih.gov/28551500/