PMC5556608_01
Dose escalation and key events in the course of the patient's clozapine therapy. On Day 334 of clozapine therapy: dose = 400 mg per day, level = 541 ng/ml (pharmacokinetic study results included in the clozapine package insert report peak concentrations of 102-771 ng/ml and minimum steady state concentrations of 41-343 ng/ml). The patient was also on concurrent lithium 300 mg PO BID on Day 1 of clozapine therapy which was subsequently increased to 450 mg PO BID on Day 24 of clozapine therapy. The patient did not demonstrate any symptoms of lithium toxicity.
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fig1
The patient's dose of clozapine was gradually escalated on an outpatient basis and the progress of the dose escalation is summarized in Figure 1.
Electroencephalogram (EEG) demonstrating microseizures. The EEG was obtained on Day 134 of clozapine therapy [Day 88: clozapine dose escalation to 400 mg per day (with concurrent lithium 450 mg PO BID), Day 109: development of stutter].
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fig2
The study showed an abnormal waking and sleep EEG (Figure 2).