Serum levels and clinical response in long-term pharmacotherapy with zuclopenthixol decanoate

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Abstract
Twenty-six patients diagnosed as chronic schizophrenics were given injections of zuclopenthixol decanoate (cis(Z)-clopenthixol decanoate) 200 mg every 3 weeks for at least 6 months. Before treatment and on each day of injection the patients' mental state was assessed by Brief Psychiatric Rating Scale (BPRS), 18 items. A registration of side effects and basal laboratory data was also performed. Blood samples were drawn on each day of injection before injection and 3–7 days after injection (time of maximum concentration). Neuroleptic activity, which was considered equivalent to the concentration of zuclopenthixol, was determined in serum by radio-receptor assay (RRA). Based on amelioration scores ≥50% on the BPRS, 15 patients were characterized as responders and 11 as non-responders. The responder group showed a statistically significant reduction in BPRS score, whereas this was not the case for the non-responders. Apart from a few patients, the serum concentrations showed a low intra-individual variation, but a relatively high inter-individual variation. The responder group had a significantly higher mean preinjection concentration than the non-responder group, whereas no significant difference was found in day 3–7 concentrations. The fluctuation of the serum concentration expressed as the ratio between maximum (days 3–7) and minimum (pre-inj.) was found to be significantly lower for responders than for non-responders. Thus although the present study did not demonstrate a clear relationship between serum level and clinical effect, it indicates that the best antipsychotic effect is obtained with a serum concentration which fluctuates only slightly (the ratio max/min concentration not exceeding 2.1).