Outcomes in treatment-resistant schizophrenia: symptoms, function and clozapine plasma concentrations. (October 2021)

• Record Type: Journal Article
• Authors: Krivoy, Amir; Whiskey, Eromona; Webb-Wilson, Henrietta; Joyce, Dan; Tracy, Derek K.; Gaughran, Fiona; MacCabe, James H.; Shergill, Sukhwinder S.
• Is Part Of: Therapeutic advances in psychopharmacology. Volume 11(2021)
• Publication Date: 2021-10
• Subjects: psychosis -- clozapine -- norclozapine; Psychopharmacology -- Periodicals; Psychotherapy -- Periodicals; 615.7805
• DOI: 10.1177/20451253211037179
• Languages: English
• ISSNs: 2045-1253

Abstract

Background: Clozapine is the only medication licenced for treating patients with treatment-refractory schizophrenia. However, there are no evidence-based guidelines as to the optimal plasma level of clozapine to aim for, and their association with clinical and functional outcome. Objective: We assessed the relationship between clinical and functional outcome measures and blood concentrations of clozapine among patients with treatment-refractory psychosis. Methods: Data were reviewed in 82 patients with treatment-refractory psychosis admitted to a specialised tertiary-level service and treated with clozapine. Analysis focussed on the relationship between clozapine and norclozapine plasma concentrations and the patient's clinical symptoms and functional status. Results: Clinical symptom improvement was positively correlated with norclozapine plasma concentrations and inversely correlated with clozapine to norclozapine plasma concentrations ratio. Clozapine concentrations showed a bimodal association with clinical improvement (peaks around 350 and 660 ng/ml). Clinical symptom improvement correlated with functional outcomes, although there was no significant correlation between the latter and clozapine or norclozapine plasma concentrations. Conclusion: Clozapine treatment was associated with optimal clinical improvement at two different peak plasma concentrations around 350 and 650 ng/ml. Clinical improvement was associated with functional outcome; however, functionality was not directly associated with clozapine concentrations. A subset of patients may require higher clozapine plasma concentrations to achieve clinical improvement.