How long does chlorpromazine last?

Abstract

How long does chlorpromazine last? This question regarding the persistence of chlorpromazine (CPZ) in chronically medicated schizophrenic patients after drug discontinuation led to wide ranging preliminary answers. These varied from a few to several days for blood studies up to many months for urinary and clinical studies. At least two implications of the question need to be considered: a) the pharmacological persistence of active drug and/or metabolites after drug discontinuation; and b) the persistence of the therapeutic effects regardless of whether or not active drug and/or metabolites are pharmacologically present. For example, a patient's behavior may improve while on CPZ and this improvement may persist after the active drug and/or metabolites cease to be present in the patient's body. These two areas of inquiry were examined by looking at blood, urinary, and clinical data. Although blood studies undoubtedly give the most definitive data, they are greatly complicated by the lack of definitive information regarding the active moiety (moieties) and crucial sites of action, the large number of metabolites (up to 150 or so), the minute quantities involved (ng/ml), the wide inter- and intrapatient variations, and the newness and lack of complete comparability of the quantitative methodologies. Within these limitations, there are a number of studies that are fairly consistent in showing a half-life of disappearance from the plasma of CPZ and/or metabolites in the range of a few to several hours. This would usually mean that most of the drug and metabolites are cleared from the plasma in a few days after drug discontinuation. Urinary studies are related less directly than blood studies to desired clinical effects. Under steady-state conditions in various studies, 43 to 63 per cent of a daily therapeutic dose of CPZ can be recovered in the urine in 24 hours. After drug discontinuation, urinary drug and/or metabolites in most studies last from about 3 to 18 days, with sometimes minimal or trace amounts after this. The clinical studies show a continuation of therapeutic benefits for up to 6 months and longer in some studies, but there are a number of studies showing placebo (withdrawn) groups deteriorating significantly more than continued drug groups much before this, even as early as 1 to 2 weeks off drug. This examination of the literature tends toward a duration of substantial pharmacological (therapeutic) action of CPZ of no more than a few days after drug discontinuation. For a small number of patients, clinical deterioration begins about the same time, whereas in many others, clinical improvement lasts weeks or months. Some of this latter continuation of improvement is likely not due to CPZ and/or metabolites currently active. There do remain many unanswered questions regarding the persistence of minute amounts of CPZ and/or metabolites in storage and possibly at active sites, and whether or not in some patients this makes a significant contribution.