What are the manic side effects of Levetiracetam (Keppra)?

From the Guidelines

Keppra (levetiracetam) can cause manic side effects in some patients, though this is not among its most common adverse reactions, and patients with a history of mood disorders or psychiatric conditions are more likely to experience these effects. These manic symptoms may include increased energy, decreased need for sleep, racing thoughts, rapid speech, irritability, agitation, and impulsive behavior. According to the study published in the Annals of Emergency Medicine 1, the adverse effects of Levetiracetam include fatigue, dizziness, and rarely pain at the infusion site, but it does not specifically mention manic side effects. However, another study published in the Journal of the American Academy of Child and Adolescent Psychiatry 1 discusses the assessment and treatment of children and adolescents with bipolar disorder, which may be relevant to understanding the potential manic side effects of Keppra. If you experience these symptoms while taking Keppra, contact your healthcare provider immediately rather than stopping the medication abruptly, as sudden discontinuation of antiepileptic drugs can trigger seizures. Your doctor may need to adjust your dosage, switch you to a different medication, or add a mood stabilizer to your regimen. The mechanism behind Keppra-induced mania is not fully understood but may relate to its effects on neurotransmitters in the brain, particularly its impact on GABA and glutamate systems which regulate mood and behavior. Patients and caregivers should be vigilant for mood changes, especially during the initial weeks of treatment or after dosage adjustments.

Some key points to consider when taking Keppra include:

• Monitoring for mood changes, especially in patients with a history of mood disorders or psychiatric conditions
• Being aware of the potential for manic side effects, including increased energy, decreased need for sleep, racing thoughts, rapid speech, irritability, agitation, and impulsive behavior
• Contacting your healthcare provider immediately if you experience any of these symptoms
• Avoiding sudden discontinuation of Keppra, as this can trigger seizures
• Working with your healthcare provider to adjust your dosage or switch to a different medication if necessary.

From the FDA Drug Label

In controlled trials of adult patients with epilepsy experiencing partial onset seizures, 13.3% of levetiracetam patients experienced other behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.) compared to 6.2% of placebo patients. A total of 37.6% of the levetiracetam-treated patients experienced behavioral symptoms (reported as agitation, anxiety, apathy, depersonalization, depression, emotional lability, hostility, hyperkinesia, nervousness, neurosis, and personality disorder), compared to 18.6% of placebo patients. Hostility was reported in 11.9% of levetiracetam-treated patients, compared to 6.2% of placebo patients. Nervousness was reported in 9.9% of levetiracetam-treated patients, compared to 2.1% of placebo patients. Depression was reported in 3.0% of levetiracetam-treated patients, compared to 1.0% of placebo patients.

The manic side effects of Levetiracetam (Keppra) include:

• Agitation: reported in levetiracetam-treated patients
• Aggression: reported in levetiracetam-treated patients
• Hostility: reported in 11.9% of levetiracetam-treated patients
• Irritability: reported in levetiracetam-treated patients
• Emotional lability: reported in levetiracetam-treated patients These side effects are part of the broader category of behavioral abnormalities associated with levetiracetam use, as reported in 2 and 2.

From the Research

Manic Side Effects of Levetiracetam (Keppra)

• Levetiracetam is generally well-tolerated, but mild mood-related side effects such as anxiety, agitation, and depression have been observed in a minority of patients 3.
• There is preliminary evidence about the efficacy of levetiracetam in the treatment of different psychiatric disorders, including anxiety, panic, stress, mood and bipolar, autism, and Tourette's syndrome 4.
• The most serious adverse effects associated with levetiracetam use are behavioral in nature and might be more common in patients with a history of psychiatric and neurobehavioral problems 4.
• A case report described a teenage male patient with a history of seizure disorder who developed sudden, severe behavioral abnormalities and aggression following increases in his levetiracetam dosing, which resolved rapidly after return of his medication dosing to baseline 3.
• Another case report described a patient who experienced adverse events in succession to antiepileptic medications being used for both antiepileptic and mood-stabilization benefit, but was stabilized physically and psychiatrically on levetiracetam without any noted adverse events 5.
• Levetiracetam may provide mood-stabilizing qualities through a mechanism that is unique from that of other antiepileptic agents used for their mood-stabilizing properties 5.
• In overdose, levetiracetam is sedating and causes respiratory depression, however, recovery is rapid with supportive care 6.
• Common adverse events associated with levetiracetam use include somnolence and asthenia, which increased with increasing doses of levetiracetam 7.