title: Augmentation of clozapine with ziprasidone in refractory schizophrenia: a double-blind, placebo-controlled study.
abstract: The present 16-week double-blind, randomized, placebo-controlled trial was aimed to explore the efficacy of ziprasidone add-on pharmacotherapy on clinical symptoms and cognitive functioning in 40 schizophrenic patients (active group, n = 20; placebo group, n = 20) with residual symptoms (Brief Psychiatric Rating Scale mean [SD] baseline total score in active group vs placebo, 40.4 [5.9] vs 37.9 [6.8]) despite receiving clozapine monotherapy at the highest tolerated dosage. The results obtained evidenced that ziprasidone augmentation of clozapine significantly reduced Positive and Negative Syndrome Scale "Negative" (P = 0.006, mean change [SD] in active group vs placebo, -2.7 [2.3] vs 1.1 [2.1], Cohen d = 1.7) and "General Psychopathology" (P = 0.009, mean change [SD] in active group vs placebo, -5.3 [3.8] vs -0.7 [2.0], Cohen d = 1.5). Regarding cognitive domains, ziprasidone was more effective than placebo in improving semantic fluency (P < 0.0001, mean change [SD] in active group vs placebo, 4.4 [3.5] vs -0.1 [4.1], Cohen d = 1.2). Ziprasidone had only a small effect on prolongation of heart-rate corrected QT interval (QTc) of the electrocardiogram, not significantly different from placebo (QTc milliseconds, mean [SD], week 16 in active group vs placebo, 408.17 [20.85] vs 405.45 [17.11], P = 0.321); within-group comparison revealed that QTc prolongation induced by ziprasidone was statistically significant (baseline vs week 16, P = 0.002). Ziprasidone added to clozapine was effective on negative and cognitive symptoms, although it may be proposed as a helpful treatment in schizophrenia, mainly for those patients who partially respond to clozapine monotherapy.
authors.affiliation: From the *Section of Psychiatry, Department of Neurosciences, University of Messina, Messina; and †Istituto Clinico "Prof. Dr. R. De Blasi," Reggio Calabria; and ‡Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy.
authors.forename: Maria Rosaria A
authors.initials: MR
authors.lastname: Muscatello
authors.forename: Gianluca
authors.initials: G
authors.lastname: Pandolfo
authors.forename: Umberto
authors.initials: U
authors.lastname: Micò
authors.forename: Eduardo
authors.initials: E
authors.lastname: Lamberti Castronuovo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Abenavoli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Scimeca
authors.forename: Edoardo
authors.initials: E
authors.lastname: Spina
authors.forename: Rocco
authors.initials: R
authors.lastname: Zoccali
authors.forename: Antonio
authors.initials: A
authors.lastname: Bruno
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone; D003024:Clozapine