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Antipsychotic Polypharmacy in a Treatment-Refractory Schizophrenia Population Receiving Adjunctive Treatment With Electroconvulsive Therapy

Kristensen, Diana MD*; Hageman, Ida MD*; Bauer, Jeanett MD*; Jørgensen, Martin Balslev MD*; Correll, Christoph U. MD†‡§∥

doi: 10.1097/YCT.0b013e31828b34f6
Original Studies

Background Antipsychotic polypharmacy (APP) is frequent, but its pattern is unknown in treatment-refractory schizophrenia-spectrum patients receiving electroconvulsive therapy (ECT).

Methods We performed a retrospective chart review of ECT-treated inpatients hospitalized at 2 Danish University hospitals from 2003 to 2008, focusing on APP patterns in patients with schizophrenia-spectrum disorders (n = 79, 13.2%). In addition to univariate analyses, a multivariate logistic regression analysis was performed to identify independent predictors of APP.

Results Of 79 antipsychotic-treated patients (aged 48.6 ± 14.2 years; illness duration, 18.3 ± 10.6 years) ultimately treated with ECT, 86.1% received 2 or more psychotropic medications, including mood stabilizers (19.0%), antidepressants (32.9%), and APP (72.2%; 2 antipsychotics = 41.8%, 3 = 21.5%, 4–5 = 7.6%). Most patients received first-generation antipsychotic (FGA) + second-generation antipsychotic (SGA) (48.1%), followed by SGA + SGA (24.1%), SGA monotherapy (22.8%), and FGA monotherapy (5.1%). Individual antipsychotics included olanzapine (44.3%), risperidone (26.6%), clozapine (26.6%), quetiapine (22.1%), ziprasidone (13.9%), aripiprazole (10.1%), and sertindole (3.8%). Antipsychotic polypharmacy was associated with a greater number of FGAs (0.8 ± 0.7 vs 0.1 ± 0.4, P < 0.0001) and SGAs (1.7 ± 0.8 vs 0.8 ± 0.4, P < 0.0001), zuclopenthixol use (31.6% vs 0%, P = 0.0019), olanzapine use (52.6% vs 22.7%, P = 0.017), less serotonin-noradrenaline reuptake inhibitor use (3.5% vs 18.2%, P = 0.027), and a trend toward more good to excellent ECT response (86.0% vs 68.2%, P = 0.071). In the logistic regression analysis, APP was independently associated with a higher number of FGAs (P = 0.0002) and olanzapine use (P = 0.0098) (r 2 = 0.314, P < 0.0001).

Discussion Only 22.6% of this treatment-refractory population received clozapine, yet 72.4% received APP. Following the results from our study as well as the general level of evidence, patients with refractory schizophrenia-spectrum disorder should receive clozapine or ECT before being tried on APP.

From *Psychiatric Centre Copenhagen, Copenhagen, Denmark; and †The Zucker Hillside Hospital, Psychiatry Research, North Shore–Long Island Jewish Health System, Glen Oaks; ‡Albert Einstein College of Medicine, Bronx; §The Feinstein Institute for Medical Research, Manhasset; and ∥Hofstra North Shore LIJ School of Medicine, Hempstead, NY.

Received for publication August 26, 2012; accepted February 1, 2013.

Reprints: Diana Kristensen, MD, Bispebjerg Bakke 25 Dept. 13.2, 2400 København NV, Denmark (e-mail:

This study has no sources of funding.

Dr Kristensen has been a consultant to AstraZeneca. Dr Jørgensen has been a consultant and/or advisor to or has received honoraria from Eli Lilly and Bristol-Myers Squibb and has received grants from The Lundbeck Foundation. Dr Correll has been a consultant and/or advisor to or has received honoraria from Actelion, Alexza, American Academy of Child and Adolescent Psychiatry, AstraZeneca, Biotis, Bristol-Myers Squibb, Cephalon, Desitin, Eli Lilly, Gerson Lehrman Group, GSK, IntraCellular Therapies, Lundbeck, Medavante, Medscape, Merck, Novartis, Ortho-McNeill/Janssen/J&J, Otsuka, Pfizer, ProPhase, Sunovion, Takeda, and Teva. He has received grant support from BMS, Feinstein Institute for Medical Research, Janssen/J&J, National Institute of Mental Health, National Alliance for Research in Schizophrenia and Depression, and Otsuka.

The authors have no conflicts of interest or financial disclosures to report.

© 2013 by Lippincott Williams & Wilkins