Dosage
Due to risk of serious side effects, clozapine treatment is commenced at a very low dose usually 12.5 mg once or twice on the first day and increased slowly until a therapeutic dose is reached. In severely ill and/or younger patients higher doses may be needed, while in the elderly much lower doses may be sufficient. Once the patient is stabilized and the maintenance dose has been determined, the greater part or all of the daily dose may be given at bedtime. This will ameliorate daytime sedation and orthostatic problems; most people benefit from the sedation to get to sleep anyway. Furthermore, compliance on medication taken more frequently than once daily drops off dramatically.
Norclozapine, the primary metabolite of clozapine, accumulates to, on average, 70% or so of the clozapine concentration in plasma at steady-state (their sample, i.e., pre-dose, ideally in the morning). However, there is substantial variation in the clozapine:norclozapine concentration ratio between individuals.
A steady-state plasma clozapine concentration of 0.35 to 0.6 mg/L (N.B.: quoted values may vary slightly) should produce a clinical response in most patients.
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