Why would an adult patient with schizophrenia, major depressive disorder, and anxiety be prescribed Keppra (levetiracetam) without a seizure disorder?

Off-Label Use of Keppra (Levetiracetam) in Psychiatric Patients

Levetiracetam (Keppra) is likely being used off-label for mood stabilization in this patient with schizophrenia, major depressive disorder, and anxiety, as it may help manage behavioral symptoms and emotional lability without a seizure disorder diagnosis.

Potential Reasons for Keppra Use in Psychiatric Patients

• Levetiracetam has been investigated for its mood-stabilizing properties in patients with psychiatric disorders, even without seizures 1
• It may help manage behavioral symptoms that are common in schizophrenia, including aggression, agitation, emotional lability, and irritability 2
• Some patients with psychiatric disorders who experience adverse effects with traditional mood stabilizers (like carbamazepine, valproate, or lithium) may tolerate levetiracetam better 3
• Levetiracetam has shown potential benefits for anxiety and depression symptoms in some studies, which could address the patient's comorbid conditions 4

Mechanism of Action in Psychiatric Conditions

• Unlike other antiepileptic drugs, levetiracetam has unique mechanisms of action that may benefit mood regulation 5:
  • Binding to synaptic vesicle protein 2A
  • Inhibiting calcium release from intraneuronal stores
  • Opposing negative modulators of GABA and glycine-gated currents
  • Inhibiting excessive synchronized neuronal activity

Behavioral Effects in Clinical Studies

• In clinical trials, 13.3% of levetiracetam-treated patients experienced behavioral symptoms (reported as aggression, agitation, anger, anxiety, apathy, depression, emotional lability, etc.) 2
• Levetiracetam has demonstrated improvement in depression and anxiety symptoms in some epileptic patients, suggesting potential benefit for these symptoms in non-epileptic psychiatric patients 4

Important Considerations and Risks

• Antiepileptic drugs, including levetiracetam, increase the risk of suicidal thoughts or behavior, requiring careful monitoring in psychiatric patients 2
• The risk of suicidal thoughts or behavior was higher in clinical trials for epilepsy than in trials for psychiatric conditions, but absolute risk differences were similar 2
• Behavioral abnormalities are common side effects, with 5% of levetiracetam-treated patients experiencing psychotic symptoms in controlled trials 2
• Patients with schizophrenia often have a lower seizure threshold than the general population, so levetiracetam might be addressing subclinical seizure activity 6

Monitoring Recommendations

• Regular assessment for emergence or worsening of depression, suicidal thoughts or behavior, and unusual changes in mood or behavior 2
• Monitoring for common side effects including sedation, dizziness, and coordination difficulties, which typically occur within the first 4 weeks of treatment 2
• Evaluation of therapeutic response in terms of behavioral symptoms, emotional stability, and overall psychiatric condition 6

Alternative Considerations

• If the patient is not responding well or experiencing adverse effects, other mood stabilizers might be considered 6
• For patients with schizophrenia and comorbid conditions, antipsychotic monotherapy is generally the first-line approach, with adjunctive medications added based on specific symptoms 6
• Clozapine may be considered for treatment-resistant cases of schizophrenia, though it carries its own risk profile including seizures 6

While levetiracetam is not FDA-approved for psychiatric indications, its use in this patient likely represents an off-label attempt to manage behavioral symptoms and mood instability associated with the patient's complex psychiatric presentation.