Abstract
In this double-blind study, patients with an acute exacerbation of schizophrenia or schizoaffective disorder were randomized to receive either ziprasidone 80 mg/day (n = 106) or 160 mg/day (n = 104) or placebo (n = 92), for 6 weeks. Both doses of ziprasidone were statistically significantly more effective than placebo in improving the PANSS total, BPRS total, BPRS core items, CGI-S, and PANSS negative subscale scores (p < .05). Ziprasidone 160 mg/day significantly improved depressive symptoms in patients with clinically significant depression at baseline (MADRS ≥ 14, over-all mean 23.5) (p < .05) as compared with placebo. The percentage of patients experiencing adverse events was similar in each treatment group, and resultant discontinuation was rare. The most frequent adverse events associated with ziprasidone were generally mild dyspepsia, nausea, dizziness, and transient somnolence. Ziprasidone was shown to have a very low liability for inducing movement disorders and weight gain. The results indicate that ziprasidone is effective and well tolerated in the treatment of the positive, negative, and depressive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder.
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References
American Psychiatric Association. (1987): Diagnostic and statistical manual of mental disorders, 3rd edition, revised, APA, Washington, DC
Barnes TRE . (1989): A rating scale for drug-induced akathisia. Br J Psych 154: 672–682
Barnes TRE, Curson DA, Liddle PF, Patel M . (1989): The nature and prevalence of depression in chronic schizophrenic inpatients. Br J Psychiatry 154: 486–491
Bartels SJ, Drake RE . (1988): Depressive symptoms in schizophrenia: Comprehensive differential diagnosis. Compr Psychiatry 29: 467–483
Beasley CM, Satterlee W, Sanger T, Tollefson G, Tran P, Hamilton S . (1996): Olanzapine versus placebo: Results of a double-blind, fixed-dose olanzapine trial. Psychopharmacology 124: 159–167
Bench CJ, Lammertsma AA, Dolan RJ, Grasby PM, Warrington SJ, Gunn K, Cuddigan M, Turton DJ, Osman S, Frackowiak RS . (1993): Dose-dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: A study using positron emission tomography and 11C-raclopride. Psychopharmacology 112: 308–314
Bench CJ, Lammertsma AA, Grasby PM, Dolan RJ, Warrington SJ, Boyce M, Gunn KP, Brannick LY, Frackowiak RSJ . (1996): The time course of binding to striatal dopamine D2 receptors by the neuroleptic ziprasidone (CP-88,059-01) determined by positron emission tomography. Psychopharmacology 124: 141–147
Briley M, Moret C . (1993): Neurobiological mechanisms involved in antidepressant therapies. Clin Neuropharmacol 16: 387–400
Brooks EW, Mansbach RS . (1997): Effects of the combined 5-HT2/D2 antagonist ziprasidone on drug-disrupted prepulse inhibition in the rat. Soc Neurosci Abstr 23: 1953
Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman PW . (1996): Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology 14: 87–96
Casey DE . (1996): Side-effect profiles of new antipsychotic agents. J Clin Psychiatry 57: 40–45
Casey DE, Keepers GA . (1988): Neuroleptic side effects: Acute extrapyramidal syndromes and tardive dyskinesia. In Psychopharmacology: Current Trends. Berlin: Springer, pp 74–93
Deutch AY, Moghaddam B, Innis RB, Krystal JH, Aghajanian GK, Bunney BS, Charney DS . (1991): Mechanisms of action of atypical antipsychotic drugs. Implications for novel therapeutic strategies for schizophrenia. Schiz Res 4: 124–156
Drake RE, Gates C, Whitaker A, Cotton PG . (1985): Suicide among schizophrenics. Compr Psychiat 26: 90–100
Fischman A, Williams SA, Drury C, Etienne P, Rubin R . (1996): Sustained 5HT2 receptor occupancy of ziprasidone using PET ligand [18F]setoperone in healthy volunteers. Eur Neuropsychopharmacol 6: 177
Goff DC, Posever T, Herz L, Simmons J, Kletti N, Lapierre K, Wilner KD, Law GC, Ko GN . (1998): An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder. J Clin Psychopharmacol 18 (4): 296–304
Janiszewski JS, Fouda HG, Cole RO . (1995): Development and validation of a high-sensitivity assay for an antipsychotic agent, CP-88,059, with solid-phase extraction and narrow-bore high-performance liquid chromatography. J Chromatog 668: 133–139
Johnson DAW . (1981): Studies of depressive symptoms in schizophrenia. Br J Psychiat 139: 89–101
Kay SR, Opler LA, Lindenmeyer JP . (1989): The positive and negative syndrome scale (PANSS): Rationale and standardization. Br J Psychiat 155: 59–65
Keck P, Buffenstein A, Ferguson J, Feighner J, Jaffe W, Harrigan EP, Ziprasidone Study Group. (1998): Ziprasidone 40 mg/day and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: A 4-week placebo-controlled trial. Psychopharmacology 140 (2): 173–184
Keepers GA, Clappison VJ, Casey DE . (1983): Initial anticholinergic prophylaxis for neuroleptic-induced extrapyramidal syndromes. Arch Gen Psychiat 40: 1113–1117
Knights A, Hirsch SR . (1981): Revealed depression and drug treatment for schizophrenia. Arch Gen Psychiat 38: 806–811
Koreen AR, Siris SG, Chakos M, Alvir J, Mayerhoff D, Lieberman J . (1993): Depression in first-episode schizophrenia. Am J Psychiat 160: 1643–1648
Kramer MS, Vogel WH, DiJohnson C, Dewey DA, Sheves P, Cavicchia S, Little P, Schmidt R, Kimes I . (1989): Antidepressants in “depressed” schizophrenic inpatients. A controlled trial. Arch Gen Psychiat 46: 922–928
Lindenmeyer J-P, Grochowski S, Kay SR . (1991): Schizophrenic patients with depression: Psychopathological profiles and relationship with negative symptoms. Compr Psychiat 32: 528–533
Lu Y, Zorn SH, Rollema H . (1997): Comparison of the novel antipsychotic ziprasidone with clozapine: Effects on dopamine release in rat prefrontal cortex and dorsolateral striatum. Soc Neurosci Abstr 23: 1931
Marder SR, Meibach RC . (1994): Risperidone in the treatment of schizophrenia. Am J Psychiat 151: 825–835
Martin RL, Cloninger CR, Guze SB, Clayton PJ . (1985): Frequency and differential diagnosis of depressive syndromes in schizophrenia. J Clin Psychiat 46: 9–13
Matsubara S, Matsubara R, Kusumi I, Koyama T, Yamashita I . (1993): Dopamine D1, D2 and serotonin2 receptor occupation by typical and atypical antipsychotic drugs in vivo. J Pharmacol Exp Ther 265: 498–508
Mauri MC, Bravin S, Fabiano L, Vanni S, Boscati L, Invernizzi G . (1995): Depressive symptoms and schizophrenia: A psychopharmacological approach. L'Encéphale 21: 555–558
McGlashan TH, Carpenter WT . (1976): Postpsychotic depression in schizophrenia. Arch Gen Psychiat 33: 231–239
Meltzer HY . (1995): Role of serotonin in the action of atypical antipsychotic drugs. Clin Neurosci 3: 64–75
Meltzer HY, Shigero M, Lee JC . (1989): The ratios of serotonin 2 and dopamine 2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacol Bull 25: 390–392
Metropolitan Life Insurance Company. (1993): Height and Weight Standards
Meyer MC, Baldessarini RJ, Goff DC, Centorrino F . (1996): Clinically significant interactions of psychotropic agents. Drug Saf 15: 333–346
Möller HJ . (1993): Neuroleptic treatment of negative symptoms in schizophrenic patients. Efficacy problems and methodological difficulties. Eur Neuropsychopharmacol 3: 1–11
Möller HJ, Van Praag H, Aufdembrinke B, Working Group on Negative Symptoms in Schizophrenia. (1994): Negative symptoms in schizophrenia: Considerations for clinical trials: Working Group on Negative Symptoms in Schizophrenia. Psychopharmacology 115: 221–228
Montgomery S, Åsberg M . (1979): A new depression scale designed to be sensitive to change. Br J Psychiat 134: 382–389
Moore NA, Calligaro DO, Wong DT, Bymaster F, Tye NC . (1993): The pharmacology of olanzapine and other new antipsychotic agents. Curr Opin Investiga Drugs 24: 281–293
National Institutes of Mental Health. (1976a): Clinical Global Impression Improvement Scale. In Guy W (ed), ECDEU Assessment Manual for Psychopharmacology
National Institutes of Mental Health. (1976b): Clinical Global Impression Severity Scale. In Guy W (ed), ECDEU Assessment Manual for Psychopharmacology
National Institutes of Mental Health. (1976c): Abnormal Movement Scale. In Guy W (ed), ECDEU Assessment Manual for Psychopharmacology
Neal-Beliveau BS, Joyce JN, Lucki I . (1993): Serotonergic involvement in haloperidol-induced catalepsy. J Pharmacol Exp Ther 265: 201–217
Newman-Tancredi A, Chaput C, Verriele L, Millan MJ . (1996): Clozapine is a partial agonist at cloned, human serotonin 5-HT1A receptors. Neuropharmacology 35: 119–121
Niemegeers CJE, Janssen PAJ . (1979): A systematic study of the pharmacological activities of dopamine antagonists. Life Sci 24: 2201–2215
Ortiz A, Gershon S . (1986): The future of neuroleptic psychopharmacology. J Clin Psychiat 47: 3–11
Pfeiffer W, Kockott G, Fischl B, Schleuning G . (1991): Adverse effects of long-term psychopharmacologic therapy on sexual functions. Psychiatrische Praxis 18: 92–98
Reynolds LS, Braselton JP, Sprouse JS . (1997): Ziprasidone, unlike olanzapine, inhibits 5-HT neuronal activity by a 5-HT1A mechanism. Soc Neurosci Abstr 23: 1931
Rickels K, Schweizer E . (1993): The treatment of generalized anxiety disorder in patients with depressive symptomology. J Clin Psychiat 54: 20–22
Schotte A, Janssen PFM, Gommeren W, Luyten WHML, Van Gompel P, Lesage AS, De Loore K, Leysen JE . (1996): Risperidone compared with new and reference antipsychotic drugs: In vitro and in vivo receptor binding. Psychopharmacology 124: 57–73
Seeger TF, Seymour PA, Schmidt AW, Zorn SH, Schulz DW, Lebel LA, McLean S, Guanowsky V, Howard HR, Lowe JA, Heym J . (1995): Ziprasidone (CP-88,059): A new antipsychotic with combined dopamine and serotonin receptor antagonist activity. J Pharmacol Exp Ther 275: 101–113
Seeman P, van Tol HHM . (1993): Dopamine receptor pharmacology. Curr Opin Neurol Neurosurg 6: 602–608
Sharma RP, Shapiro LE . (1996): The 5-HT1A receptor system: Possible implications for schizophrenic negative symptomatology. Psychiat Anns 26: 88–92
Silverstone T, Smith G, Goodall E . (1988): Prevalence of obesity in patients receiving depot antipsychotics. Br J Psychiat 153: 214–217
Simpson GM, Angus JWS . (1970): A rating scale for extrapyramidal side effects. Acta Psychiat Scand 212: 11–19
Stockmeier CA, DiCarlo JJ, Zhang Y, Thompson P, Meltzer HY . (1993): Characterization of typical and atypical antipsychotic drugs based on in vivo occupancy of 5HT2 and D2 receptors. J Pharmacol Exp Ther 266: 1375–1384
Tandon R, Harrington E, Zorn SH . (1997): Ziprasidone: a novel antipsychotic with unique pharmacology and therapeutic potential. J Serotonin Research 4: 159–177
Van Putten T . (1974): Why do schizophrenic patients refuse to take their drugs? Arch Gen Psychiat 31: 67–72
Young JL, Zonana HV, Shepler L . (1986): Medication noncompliance in schizophrenia: Codification and update. Bull Am Acad Psychiat Law 14: 105–122
Acknowledgements
This study was sponsored by Central Research Division, Pfizer Inc, Groton, CT, U.S.A. The authors and the study sponsor thank all the investigators in the Ziprasidone Study Group, and the patients, and their families, who participated in this study. The following investigators comprise the Ziprasidone Study Group: Rajiv Tandon, University of Michigan Medical Center Department of Psychiatry Ann Arbor, MI, USA; Cecilia Peabody, Veterans Administration Medical Center, Menlo Park, CA, USA; Alan Buffenstein, The Queens Medical Center, Honolulu, HI, USA; Harold Harsch, John L Doyne Hospital, Milwaukee, WI, USA and Mental Health Center, Milwaukee, WI, USA; James Ferguson and Robert Nash, United States Veterans Administration Hospital, Salt Lake City, UT, USA and CPC Olympus View, Salt Lake City, UT, USA and Wyoming State, Evanston, WY, USA; Sheldon Preskorn, Psychiatric Research Institute, Wichita, KS, USA; Richard Borison, Neuropsychopharmacology Unit, Medical Center, Augusta, GA, USA and Georgia Regional Hospital Oak Unit, Augusta, GA, USA; Mauricio Tohen, McLean Hospital, Belmont, MA, USA; James Claghorn and Michael Lesem, Claghorn-Lesem Research Clinic Inc, Bellaire, TX, USA and HCA Medical Center Hospital, Houston, TX, USA and Charter Hospital of Sugar Land, Sugar Land, TX, USA and West Oaks Hospital, Houston, TX, USA; George Jaskiw, Brecksville Veterans Administration Medical Center, Brecksville, OH, USA; Charles Merideth, Alvarado Parkway Institute, Le Mesa, CA, USA and Charter Behavioral Health Systems of San Diego, Alvarado Parkway Institute, La Mesa, CA, USA and Bayview Hospital, Chula Vista, CA, USA and Harbor View Medical Center, San Diego, CA, USA and Affiliated Research Institute, San Diego, CA, USA; S Craig Risch, Institute of Psychiatry-3N, Medical University of South Carolina, Charleston, SC, USA and Charleston Memorial Hospital, Charleston, SC, USA; Michael Sernyak, Connecticut Mental Health Center, New Haven, CT, USA; James Lohr, San Diego Veterans Affairs Medical Center, Psychiatry Service 116A, San Diego, CA, USA; Louis Fabre, Fabre Research Clinics Incorporated, Houston, TX, USA; William Burke, University of Psychiatric Services, University of Nebraska Medical Center, Omaha, NE, USA and Veterans Administration Medical Center, Omaha, NE, USA; Carl Houck, University of Alabama at Birmingham, Department of Psychiatry, Birmingham, AL, USA and University of Alabama at Birmingham, Clinical Research, Birmingham, AL, USA; John Carman, Carman Research, 4000 Cumberland Parkway, Building 100, Suite A, Atlanta, GA, USA; Donald Addington, Calgary General Hospital, Calgary Alberta, Canada and Foothills Hospital, Calgary Alberta, Canada; Matthew Byerly, Psychiatric Specialty Clinic, University of Florida Shands Clinic, Shands Hospital, Gainesville, FL, USA and Psychotic Disorders Program, Gainesville Veterans Affairs Medical Center, Gainesville, FL, USA; Louis Kirby, Thunderbird Samaritan Behavioral Health Center, Glendale, AZ, USA; Mary Ann Knesevich, Terrell State Hospital, Terrell, TX, USA and Charter Grapevine Behavioral Health System, Grapevine, TX, USA and St Paul Medical Center at Southwestern Medical Center, Dallas, TX, USA; Herbert Meltzer, University Hospitals of Cleveland, Case Western Reserve, University School of Medicine, 2040 Abington Road, Cleveland, OH, USA and University Hospitals of Cleveland, Case Western Reserve, University School of Medicine, 11100 Euclid Avenue, Cleveland, OH, USA; Jorg Pahl, Board of Regents of the University of Oklahoma, Health Sciences Center, Department of Psychiatry, Oklahoma City, OK, USA and Pahl Brain Associates PC, 13301 North Meridian, Suite 101, Oklahoma City, OK, USA and Deaconess Hospital, Oklahoma City, OK, USA and Bethany Pavilion, 76000 Northwest 23rd Street, Bethany, OK, USA; David Garver and Jay Griffith, Dallas Veterans Affairs Medical Center, 4500 South Lancaster Road, Dallas, TX, USA and Veteran Affairs Medical Center, 4500 South Lancaster Road 116A, Dallas, TX, USA; Alan Gelenberg, University of Arizona Health Sciences Center, Tucson, AZ, USA; Roger Hammond, University of New Mexico, School of Medicine, Department of Psychiatry, Albuquerque, MN, USA; Uriel Halbreich, State University of New York at Buffalo, Clinical Center BB 170, Buffalo, NY, USA and Buffalo General Hospital, Buffalo, NY, USA and Erie County Medical Center, Buffalo, NY, USA; Kevin McKenna, Caritas Health Group, Grey Nuns Hospital, Edmonton Alberta, Canada; Jambur Ananth, Harbor-University of California, Los Angeles Medical Center, Torrance, CA, USA; G Michael Shehi, Mountain View Hospital, Gadsden, AL, USA. We also thank Dr. Stevin H. Zorn for assistance in compiling data for the receptor binding table.
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Daniel, D., Zimbroff, D., Potkin, S. et al. Ziprasidone 80 mg/day and 160 mg/day in the Acute Exacerbation of Schizophrenia and Schizoaffective Disorder: A 6-Week Placebo-Controlled Trial. Neuropsychopharmacol 20, 491–505 (1999). https://doi.org/10.1016/S0893-133X(98)00090-6
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DOI: https://doi.org/10.1016/S0893-133X(98)00090-6
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