It is important that clinicians do everything possible to optimize the use of clozapine in individuals with treatment-resistant schizophrenia. To our knowledge, there are no published studies evaluating whether twice daily administration of clozapine is better than once daily administration in terms of effectiveness and tolerability. Although this may seem trivial at first, when we consider that clozapine has a relatively short half-life and dissociates quickly from the dopamine D2 receptor, it justifies further consideration. It takes on even more significance knowing that the established threshold clozapine plasma concentration for therapeutic response (i.e., 350-420 ng/ml) was determined using steady-state trough plasma samples (i.e., approximately 12 hours after the evening dose) in patients administered clozapine twice rather than once daily.
