The Clinical Use of Plasma Clozapine Levels

Abstract

The data reviewed present a case for increasing the dose of clozapine in non-responsive patients to achieve a plasma level of at least 350-420 ng mL-1. Non-response at these levels, however, should not preclude a further upward titration of dose. This should occur unless (i) clinical response is obtained at a lower dose, (ii) intolerable side effects occur, or (iii) a daily dose of 900 mg is reached.

Involvement of histamine receptors in the atypical antipsychotic profile of clozapine: a reassessment in vitro and in vivo

“…We, and others (Bell et al 1998), failed to find a clear correlation between clozapine plasma levels and occurrence of sedation or weight gain, indicating that these side effects were not dose dependent. This was rather expected considering that the therapeutic doses are much higher than those fully occupying H 1 Rs and that a plateau was therefore probably reached at all the doses tested.…”

“…This was rather expected considering that the therapeutic doses are much higher than those fully occupying H 1 Rs and that a plateau was therefore probably reached at all the doses tested. Possibly due to the same pharmacological background, it is worth noting that most of the other side effects of clozapine, such as sialorrhoea, tachycardia, nausea, enuresis, or constipation, that are related to blockade or activation of other receptors are also not dose dependent (Bell et al 1998).…”

Clozapine and its Major Stable Metabolites, N-desmethylclozapine and Clozapine N-oxide do not Affect Human Bone Marrow Stromal Cells in vitro

“…Whilst 350 to 420 ng mL 1 drug is considered the threshold for clinical response [15] , the upper limit for clozapine efficacy has yet to be defined with concentrations as high as 2000 ng mL 1 observed [16,17] . Hence a wide drug concentration range covering therapeutic and supratherapeutic plasma levels was used in this study.…”

“…Plasma levels of clozapine and its metabolites can vary widely between individuals with results dependent on pharmacokinetics, metabolism, compliance and study design [14,15] . Whilst 350 to 420 ng mL 1 drug is considered the threshold for clinical response [15] , the upper limit for clozapine efficacy has yet to be defined with concentrations as high as 2000 ng mL 1 observed [16,17] .…”

Recommendations for the Monitoring of Serum Concentrations of Antipsychotic Drugs in the Treatment of Schizophrenia

“…The AGNP again grants its strongest level of recommendation to the monitoring of clozapine, with a recommended therapeutic range of 350-600 ng/mL. Indeed, a threshold for response of approximately 350 ng/ mL is one of the more reliable findings in the literature on TDM in psychopharmacology, 9 and levels above at least 600 ng/mL (and certainly 1,000 ng/mL) are routinely associated with an increased risk of seizure. 10 Additionally, as smoking is well known to lower serum clozapine levels through induction of CYP1A2, levels are likely to vary considerably in individual patients at different points in the course of treatment, particularly during the transition to the outpatient setting from inpatient hospitalization.…”