Clozapine dosage

Lu, M. L. et al. (2000). Fluvoxamine reduces the clozapine dosage needed in refractory schizophrenic patients. /. Clin. Psychiatry, 61, 594—9. 

Matsuda, K.T. et al. (1996). Clozapine dosage, serum levels, efficacy, and side-effect profiles a comparison of Korean-American and Caucasian patients. Psychopharmacol. Bull, 32, 253-7. 

Ng, C. H. et al. (2005). An inter-ethnic comparison study of clozapine dosage, clinical response and plasma levels. Int. Clin. Psychopharmacol., 20, 163-8. 

Clinical Improvement exhibited a consistent linear relationship with plasma clozapine concentrations but not with clozapine dosage. No other data available. 

Case Example Because of a patient s partial response to 5 months of clozapine therapy at 600 mg/day, risperidone was added for augmentation (started with 0.5 mg b.i.d. and increased to 1 mg b.i.d. after 1 week). Before this addition, the clozapine plasma level was 344 ng/mL, but after 2 weeks of risperidone augmentation, the level was elevated to 598 ng/mL with no adverse effects and substantial clinical benefit. In another report, there was an increase in the steady-state plasma levels of clozapine (675 mg/day) and its active metabolite norclozapine after the addition of risperidone 2 mg/day in a patient treated for 2 years. Before the addition of risperidone, her clozapine and norclozapine levels were 829 and 1,384 ng/mL, respectively. Two days after risperidone was added, these levels rose to 980 and 1,800 ng/mL. Clozapine dosage was reduced to 500 mg/day, and after 5 days of combined treatment with 4 mg/day of risperidone, the clozapine and norclozapine levels were 110 and 760 ng/mL, respectively. Aside from some mild oculogyric crises, she had no symptoms of clozapine toxicity or clinical changes during the period of cross-tapering. In another case, risperidone was added to clozapine because the patient had relapsed after discontinuation of fluphenazine and had not responded to clozapine. The addition of risperidone resulted in an acute remission of psychosis ( 100). 

An increase in white blood cell count of at least 15% above previous counts is a sensitive, although not specific, predictor for the development of agranulocytosis within 75 days (149). Clozapine dosage and baseline white cell count do not appear to predict agranulocytosis. 

In a retrospective study, 27 of 61 Chinese patients who took clozapine for more than 3 months developed urinary incontinence, persistent in 15 cases (193). The reaction could not be related to age, sex, clozapine dosage, duration of clozapine use, duration of hospitalization, duration of illness, age at onset of schizophrenia, or concurrent treatment with other psychiatric drugs. 

The interaction between clozapine and carbamazepine is much more firmly established than that between clozapine and phenobarbital or phenytoin, but they appear to be clinically important. Monitor symptoms and be alert for the need to increase the clozapine dosage if any of these drugs are giv-... 

These interactions are established. Concurrent use need not be avoided, but it would be prudent to monitor the outcome closely when any is used with clozapine because of the rises in serum clozapine and norclozapine levels that can occur, and because of the rare potential for deterioration in clinical status. Adjust the clozapine dosage as necessary. The authors of one study suggest particularly close monitoring if the daily clozapine dosage exceeds 300 mg or 3.5 mg/kg. The interaction is greatest with fluvoxamine, so other SSRIs may be a more prudent choice, although close monitoring is still required. 

Staff providing smoking cessation advice must understand the inplications for clozapine dosage. 

It can be difficult to dispute clozapine toxicity as the cause of death at an inquest, with the associated implication that clozapine dosage was inappropriate. This is because blood clozapine and norclozapine often rise after death, e.g. clozapine x5 norclozapine x4. If you have regularly (e.g. yearly in apparently successful therapy) measured plasma clozapine in life, this places you in a much stronger position to answer questions about the possible role of clozapine in a death. 

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