Petru Ifteni1, Christoph U Correll2, Jimmi Nielsen3, Victoria Burtea1, John M Kane2, Peter Manu4. 1. Faculty of Medicine, Transilvania University, Brasov, Romania. 2. Zucker Hillside Hospital, Glen Oaks, NY, USA; Hofstra North Shore - LIJ School of Medicine, Hempstead, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA. 3. Aalborg University Hospital, Psychiatry, Aalborg, Denmark; Clinical Department of Medicine, Aalborg University, Aalborg, Denmark. 4. Zucker Hillside Hospital, Glen Oaks, NY, USA; Hofstra North Shore - LIJ School of Medicine, Hempstead, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: pmanu@nshs.edu.
Abstract
BACKGROUND: Clozapine is effective in treatment-refractory bipolar disorder (BD). Guidelines recommend slow titration to prevent seizures, hypotension and myocarditis, but this stance is not supported by comparative data. OBJECTIVE: To evaluate the safety and effectiveness of rapid clozapine titration in BD. METHODS: Analysis of a consecutive cohort of treatment-refractory BD patients with mixed/manic episode admitted on alternate days to one of two units of a psychiatric hospital. On one unit, clozapine was started at 25mg followed by 25-50mg as needed every 6h (maximum=100mg/day) on day 1, followed by increases of 25-100mg/day. On the other unit, clozapine was initiated with 25mg in day 1, followed by increases of 25-50mg/day. The primary outcome was the number of days from starting clozapine until readiness for discharge, adjusted in logistic regression for the number of antipsychotics tried during the hospitalization, psychotropic co-treatments and presence of psychotic features. RESULTS: Patients subject to rapid (N=44) and standard (N=23) titration were similar in age, gender, smoking status, body mass index, illness severity at baseline and discharge, and highest clozapine dose. Clozapine was discontinued due to hypotension (N=1) and pneumonia (N=1) during rapid titration, and for excessive sedation (N=1) in each titration group. The number of hospital days from starting clozapine until readiness for discharge was 3.8 days shorter in the rapid titration group (12.7±6.3 vs. 16.5±5.8, p=0.0077). CONCLUSION: Rapid clozapine titration appeared safe and effective for treatment-refractory BD. The potential for shorter hospital stays justifies prospective trials of this method.
BACKGROUND:Clozapine is effective in treatment-refractory bipolar disorder (BD). Guidelines recommend slow titration to prevent seizures, hypotension and myocarditis, but this stance is not supported by comparative data. OBJECTIVE: To evaluate the safety and effectiveness of rapid clozapine titration in BD. METHODS: Analysis of a consecutive cohort of treatment-refractory BD patients with mixed/manic episode admitted on alternate days to one of two units of a psychiatric hospital. On one unit, clozapine was started at 25mg followed by 25-50mg as needed every 6h (maximum=100mg/day) on day 1, followed by increases of 25-100mg/day. On the other unit, clozapine was initiated with 25mg in day 1, followed by increases of 25-50mg/day. The primary outcome was the number of days from starting clozapine until readiness for discharge, adjusted in logistic regression for the number of antipsychotics tried during the hospitalization, psychotropic co-treatments and presence of psychotic features. RESULTS:Patients subject to rapid (N=44) and standard (N=23) titration were similar in age, gender, smoking status, body mass index, illness severity at baseline and discharge, and highest clozapine dose. Clozapine was discontinued due to hypotension (N=1) and pneumonia (N=1) during rapid titration, and for excessive sedation (N=1) in each titration group. The number of hospital days from starting clozapine until readiness for discharge was 3.8 days shorter in the rapid titration group (12.7±6.3 vs. 16.5±5.8, p=0.0077). CONCLUSION: Rapid clozapine titration appeared safe and effective for treatment-refractory BD. The potential for shorter hospital stays justifies prospective trials of this method.
Authors: Jimmi Nielsen; Corina Young; Petru Ifteni; Taishiro Kishimoto; Yu-Tao Xiang; Peter F J Schulte; Christoph U Correll; David Taylor Journal: CNS Drugs Date: 2016-02 Impact factor: 5.749
Authors: Sarah E Fitzpatrick; Laura Srivorakiat; Logan K Wink; Ernest V Pedapati; Craig A Erickson Journal: Neuropsychiatr Dis Treat Date: 2016-06-23 Impact factor: 2.570
Authors: S M Yasir Arafat; S M Atikur Rahman; Md Maruful Haque; Mohsin Ali Shah; Sultana Algin; Jhunu Shamsun Nahar Journal: Case Rep Psychiatry Date: 2016-07-25