When do you use seizure prophylaxis in patients on clozapine?

The topic of the use of anticonvulsants for primary prophylaxis of clozapine-induced seizures continues to be debated. The idea of prescribing anticonvulsants prophylactically for patients taking >600 mg/day of clozapine was suggested by Devinksy et al., PMID 2006003 in 1991. Clozapine-induced seizures can occur at any dose, with the risk appearing to be dose (or more accurately, serum concentration level) related and can occur at any time during treatment though are more common in the initiation phase or during more rapid titration. The incidence in the literature is reported anywhere from 1-6%, with the risk thought to be ~4% at doses of ≥600 mg/day and to be most significant at serum concentrations of ≥1300 ng/ml. Several concerns have b...

I follow Stahl's recommendation in his Clozapine Handbook. From the book, the first large data set covering 1,481 clozapine-treated patients showed a seizure rate of 2.8% with a dose-dependent relationship. A subsequent 1994 analysis cited by the same authors of 5,629 patients found only 71 cases of tonic-clonic seizures, a rate of 1.3%. The seizures tended to occur in two patterns; at low doses (<300 mg) during titration and at high doses (>600 mg) at maintenance. The distribution was 1.6% <300 mg, 0.9% 300-599 mg and 1.9% >600 mg (Pacia and Devinsky, PMID 7991106). In the absence of a dose-dependent relationship in this large group of 5,629 patients, I prefer not to use prophylactic antiseizure medications in the absence of other variable...

Congruent with Dr. @Dr. First Last and as recommended by Caetano, PMID 23996793, I based my decisions more on the clozapine level than on the dose per se. When prescribing an anticonvulsant, I tend to prescribe Lamotrigine (anticonvulsant doses 400-600 mg/day divided into two doses) due to favorable side effect profile, i.e., less weight gain, when compared to valproate sodium.

As long as it is tolerated with careful monitoring of adverse effects and drug-drug interactions.

As soon as it is clear that clozapine is the actual culprit for the seizures and when the dose is 600 mg a day or more, clozapine plasma level above 500 μg/l.

I would not prescribe any anticonvulsant after the first seizure. I will be mindful of dose-dependent relationships (<300 mg and >600 mg daily).

Following the second clozapine-induced seizure, I would consult with the neurologist, if possible, or add Lamotrigine, while tapering clozapine off.

Get concentration levels, and review the medication list for seizure-inducers, but do not treat after the first seizure. If a second seizure occurs, repeat the above but treat the seizure with lamotrigine and re-evaluate anti-psychotic choices given the patient's history.