Can carbamazepine or levetiracetam cause mood changes in children?

Mood Changes with Carbamazepine and Levetiracetam in Children

Both carbamazepine and levetiracetam can cause mood changes in children, but the nature and severity differ significantly between these medications. Carbamazepine primarily causes sedation, drowsiness, and dizziness, while levetiracetam is associated with more concerning psychiatric effects including irritability, aggression, and even acute psychosis in pediatric patients.

Carbamazepine-Associated Mood and Behavioral Effects

Carbamazepine causes arousal-related adverse effects rather than primary mood disturbances in children. The medication significantly impairs arousal and sensory-perceptual functions, manifesting as drowsiness, somnolence, and dizziness 1. These effects can indirectly impact mood by causing fatigue and cognitive slowing 1.

Common Side Effects in Pediatric Populations:

• Drowsiness and sedation are among the most frequently reported adverse effects 1
• Dizziness occurs commonly and may disturb daily activities, though taking medication at bedtime can minimize this effect 1
• Cognitive impairment has been documented, including attention and concentration difficulties 2

Important Clinical Context:

The sedative effects of carbamazepine are most pronounced during initial administration but may diminish with continued use due to cytochrome P450 enzyme induction, which decreases blood levels over days of administration 1. This pharmacokinetic property means acute effects may be more problematic than chronic effects.

Levetiracetam-Associated Mood and Behavioral Effects

Levetiracetam carries a significant risk of psychiatric adverse effects in children, including irritability, aggression, and acute psychosis. While generally well-tolerated with a favorable cognitive profile, behavioral side effects are a major concern in pediatric populations 3, 4.

Documented Psychiatric Adverse Effects:

Aggression and irritability are the most commonly reported mood-related side effects:

• Aggression was noted as a significant adverse event in clinical trials of children with autism spectrum disorder 1
• In one study, 70% of children on carbamazepine versus 45% on levetiracetam experienced at least one adverse event, though this difference was not statistically significant (p=0.07) 4

Acute psychosis represents the most severe psychiatric complication:

• Four pediatric cases (ages 5-17 years) developed acute psychosis within days to months of starting levetiracetam 3
• Manifestations included visual hallucinations, auditory hallucinations, insomnia, screaming behavior, acute agitation, hyperreligiosity, and persecutory delusions 3
• All four patients showed dramatic improvement within days of discontinuing or decreasing levetiracetam 3
• Three of the four adolescents had pre-existing mild behavioral problems, and all had prior cognitive deficits, suggesting potential risk factors 3

Positive Behavioral Effects in Specific Populations:

Paradoxically, levetiracetam may improve certain behavioral symptoms in children with autism:

• Statistically significant improvements in hyperactivity, impulsivity, and mood instability were observed in autistic children 5
• Emotional lability improved significantly on standardized scales 5
• Aggressive behavior showed improvement, particularly in children not recently weaned from other aggression-reducing medications 5

Comparative Safety Profile

Levetiracetam and carbamazepine demonstrate similar overall efficacy for seizure control but differ in their adverse effect profiles 4, 6:

• Neuropsychological function: Neither medication adversely affected overall neuropsychological function in a head-to-head comparison 6
• Depression scores: Levetiracetam showed improvement in depression scores (Children's Depression Inventory: LVT -1.97 vs CBZ +1.43, p=0.027), while carbamazepine showed worsening 6
• Internalizing behavioral problems: Levetiracetam-treated patients showed improvement (p=0.004) on standardized behavioral checklists 6

Clinical Algorithm for Monitoring

For Carbamazepine:

• Monitor for sedation, drowsiness, and dizziness at initiation and with dose increases 1
• Screen for HLA-B*15:02 before initiating in Han Chinese populations to reduce risk of Stevens-Johnson syndrome 1
• Expect potential improvement in sedative effects after several days due to enzyme induction 1

For Levetiracetam:

• Screen for pre-existing behavioral problems and cognitive deficits, as these may increase risk of psychiatric adverse effects 3
• Monitor closely for irritability, aggression, mood instability, and psychotic symptoms within the first 3 months of treatment 3, 5
• Assess behavioral changes at each visit using standardized scales when possible 5
• If acute psychosis or severe behavioral deterioration occurs, discontinue or reduce dose immediately, as symptoms typically resolve within days 3

Critical Pitfalls to Avoid

• Do not dismiss early behavioral changes with levetiracetam as unrelated to the medication—acute psychosis can develop rapidly and requires immediate intervention 3
• Avoid rapid titration of levetiracetam in children with pre-existing behavioral problems, as this may increase risk of psychiatric adverse effects 3
• Do not overlook the sedative effects of carbamazepine when prescribing to children who need to maintain alertness for school or other activities 1
• Consider timing of carbamazepine administration (bedtime dosing) to minimize impact of drowsiness on daily functioning 1