Does lithium lower the seizure threshold?

From the Guidelines

Lithium can lower the seizure threshold, and this risk should be carefully considered in patients with a history of seizures or those taking other medications that may also lower the seizure threshold. This effect is particularly relevant in patients with 22q11.2 deletion syndrome, who may already have a lowered seizure threshold 1. The "start low, go slow" approach to medication dosing, as well as consideration of prophylactic use of anticonvulsant medication, may be necessary to manage this risk 1. Key factors to consider when prescribing lithium include:

• Monitoring serum lithium levels to maintain them within the therapeutic range of 0.6-1.2 mEq/L
• Carefully evaluating the patient's medical history, including any history of seizures or epilepsy
• Considering alternative mood stabilizers if the seizure risk is significant
• Regularly monitoring patients for signs of seizures or changes in seizure frequency, particularly in those with a history of seizure disorders. The influence of lithium on neurotransmitter systems, particularly its impact on sodium channels and glutamate activity in the brain, is thought to contribute to its effects on the seizure threshold 1. By carefully managing lithium therapy and monitoring patients for potential side effects, healthcare providers can help minimize the risk of seizures and ensure effective treatment of bipolar disorder or other conditions.

From the FDA Drug Label

Central Nervous System: Blackout spells, epileptiform seizures, slurred speech, dizziness, vertigo, incontinence of urine or feces, somnolence, psychomotor retardation, restlessness, confusion, stupor, coma, acute dystonia, downbeat nystagmus

• The FDA drug label mentions epileptiform seizures as a possible adverse reaction, but it does not directly state that lithium lowers the seizure threshold.
• However, the presence of epileptiform seizures in the list of adverse reactions suggests that lithium may have some effect on seizure activity.
• It is essential to note that the label does not provide a clear answer to the question of whether lithium lowers the seizure threshold.
• Based on the available information, it is not possible to draw a definitive conclusion about the effect of lithium on the seizure threshold 2.

From the Research

Lithium and Seizure Threshold

• The relationship between lithium and seizure threshold is complex, with some studies suggesting that lithium may lower the seizure threshold, while others indicate that it may have anticonvulsant properties 3.
• A study published in 2015 found that lithium chloride increased the seizure threshold in a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice, suggesting that lithium may have anticonvulsant effects 4.
• Another study published in 2018 found that chronic lithium administration increased the seizure threshold significantly, while acute lithium administration showed pro-convulsive properties in a PTZ-induced seizure model 5.
• In contrast, a study published in 2002 noted that psychotropic drugs, including lithium, may lower the seizure threshold, although the magnitude of this effect is not well established 3.
• A case study published in 1988 found that lithium was effective in preventing the recurrence of affective episodes in bipolar patients with seizure disorders, without worsening seizure frequency, and may have an anticonvulsant effect in some patients 6.

Mechanisms of Lithium's Effects on Seizure Threshold

• The mechanisms by which lithium affects the seizure threshold are not fully understood, but may involve the α2-adrenergic system 4 and the NMDA receptor/nitric oxide pathway 5.
• Lithium's anticonvulsant effects may be mediated by its ability to reduce the level of nitric oxide and inhibit the ERK signaling pathway 5.

Clinical Implications

• The use of lithium in patients with seizure disorders requires careful evaluation and monitoring, as the risk of seizures may be increased in some individuals 3.
• However, lithium may be a safe and effective treatment option for bipolar patients with seizure disorders, and may even have anticonvulsant effects in some cases 6.