Levetiracetam, a second-generation antiseizure medication (ASM) sold under brand names like Keppra®, is a widely used drug for managing various seizure types in both adults and children. While valued for its broad spectrum of action and favorable pharmacokinetic profile, it is also associated with a range of neuropsychiatric side effects. For some, these psychological effects are mild and transient, but for others, they can be severe enough to require a change in medication. Understanding the nature and risk factors of these effects is crucial for effective treatment planning and patient care.
The Spectrum of Psychological Effects
The psychological effects of levetiracetam are varied and can impact a patient's mood, behavior, and cognition. These effects are not experienced by everyone, but they are a known and important aspect of the drug's profile.
Common Mood and Behavioral Changes
Several mood and behavioral changes are frequently reported in patients taking levetiracetam. These can occur during the initial weeks of therapy or after a dose increase.
- Irritability and Anger: This is one of the most recognized behavioral side effects, with some studies indicating that levetiracetam can potentially worsen anger compared to other treatments. For some, this presents as increased sensitivity to triggers and more pronounced angry outbursts.
- Agitation and Aggression: Reports indicate that patients may experience agitation and aggression, which in rare, severe cases can lead to hostile or violent behavior.
- Depression and Anxiety: Some patients report experiencing depression, anxiety, or emotional lability. This can include new-onset depressive symptoms or worsening of pre-existing anxiety.
- Mood Swings and Lability: Emotional lability, or rapid and disproportionate mood changes, has also been noted as a potential side effect, impacting both adults and pediatric populations.
Severe Psychological Reactions
Although less common, more severe psychiatric reactions have been linked to levetiracetam. These are serious side effects that require immediate medical attention.
- Psychosis: While rare, with a prevalence estimated around 1–1.4%, levetiracetam can induce psychotic symptoms such as hallucinations and delusions. Case reports document patients developing severe paranoia and aggressive behavior that resolved after discontinuing the medication.
- Suicidal and Self-Harm Behavior: The activation of suicidal ideation and behaviors is a rare but significant risk associated with levetiracetam. This risk, though present with many antiseizure drugs, is an important consideration for prescribing physicians.
Cognitive Effects
Compared to older AEDs, levetiracetam is often considered to have a more favorable cognitive profile, but it is not without potential effects.
- Cognitive Impairment: At high doses or in combination with other medications (polytherapy), levetiracetam has been associated with cognitive impairment, affecting domains like language, attention, and memory recall.
- Improved Function: Interestingly, in certain populations, levetiracetam has shown potential positive cognitive effects. For instance, studies have shown it can improve executive function in some patients with Alzheimer's disease who also have epileptiform activity.
Managing Levetiracetam's Psychological Impact
For patients experiencing adverse psychological effects, several management strategies are available. The approach depends on the severity and nature of the symptoms.
The Role of Vitamin B6
Some anecdotal reports, primarily in pediatric populations and case studies in veterans, suggest that supplementation with pyridoxine (vitamin B6) may help mitigate irritability associated with levetiracetam. While the exact mechanism is not fully understood, vitamin B6 is a cofactor in the synthesis of neurotransmitters that regulate mood. It is important to note that the efficacy is not universal, and further research is needed.
Dose Adjustment and Discontinuation
If psychological side effects are intolerable, the most direct management approach is to adjust the dose or discontinue the medication. Severe symptoms like psychosis or self-harming behavior usually necessitate prompt withdrawal, with symptoms often improving rapidly once the drug is stopped.
Other Adjunctive Therapies
In cases where psychiatric symptoms persist or the drug cannot be discontinued, a physician may add other medications to the treatment regimen. For example, antipsychotic drugs can be used to manage severe psychiatric symptoms induced by levetiracetam.
Levetiracetam vs. Other Antiepileptic Drugs (AEDs)
Different AEDs have varying psychological side effect profiles. Here is a general comparison of levetiracetam with other common AEDs regarding their potential psychological impact.
| Feature | Levetiracetam | Lamotrigine | Valproic Acid | Carbamazepine |
|---|---|---|---|---|
| Common Side Effects | Irritability, aggression, anxiety, depression, emotional lability | Agitation, anxiety, insomnia, irritability, mood swings. Potential antidepressant effect | Sedation, fatigue, cognitive slowing, depression. Potential anxiolytic and antimanic effects | Cognitive impairment, sedation, confusion, mood effects. Psychomotor slowing |
| Severe Side Effects | Rarely psychosis and suicidality | Rarely suicidal ideation, psychosis. Stevens-Johnson syndrome risk | Rarely suicidal ideation. Sedation, encephalopathy | Rarely psychosis, mood disturbances |
| Cognitive Profile | Generally favorable, but potential for impairment at high doses or in polytherapy | Relatively neutral, some reports of attention enhancement | More significant cognitive slowing and sedation | Cognitive slowing and fatigue |
| Key Differences | Higher incidence of behavioral effects like irritability, aggression compared to some other AEDs. | May have a positive effect on mood in some cases. | Associated with sedation and weight gain. | Associated with sedation and cognitive slowing. |
Conclusion
What are the psychological effects of levetiracetam is a question with a complex answer. While it is often a highly effective and generally well-tolerated antiseizure medication, its use is associated with a distinct profile of psychological and behavioral side effects, including irritability, aggression, depression, anxiety, and, less commonly, psychosis and suicidality. Factors like prior psychiatric history and rapid dose titration can increase susceptibility. Fortunately, many of these effects are manageable through dose adjustments or adjuncts like vitamin B6, while more severe reactions typically resolve upon discontinuation. Open communication between patients and their healthcare providers is essential for prompt identification and management of these side effects, ensuring the best possible outcome for both seizure control and mental well-being. For more detailed information on antiepileptic drug-related adverse effects, consult NCBI PMC.
It is important for both patients and clinicians to be vigilant for these psychological changes, especially during the initial phase of treatment. By proactively monitoring for symptoms and considering individual risk factors, the risk of significant neuropsychiatric complications can be minimized while maximizing the therapeutic benefits of levetiracetam for patients with epilepsy.
