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`haloperidol, IM ziprasidone was consistently associated with a
`lower movement disorder burden leg, akathisia, dystonia, EPS.
`hypertonia} at all doses investigated. in all studies. clinically signifi-
`cant changes in blood pressure and heart rate associated with
`IM ziprasidone were isolated and transient; treatment-emergent
`postural hypotension was observed in one ziprasidone-treated
`patient in one study. There were no QTC values 2500 msec with
`IM ziprasidone.
`Conclusion: In clinical trials. IM ziprasidone in divided doses up
`to 80 mglday was well tolerated. with low incidences of AE-related
`discontinuations and movement disorder AEs.
`
`Flesults: Aripiprazole produced statistically significant improve-
`ments in Y-MFIS Total score {-8.15 vs. ~3.35. p£0.01] compared
`to placebo. The response rate was significantly higher in the aripi-
`prazole group than the placebo group (40% vs. 19%, p$0.01}. For
`all efficacy variables, aripiprazole separated from placebo by day
`4. Discontinuations due to adverse events did not differ between
`the aripiprazole and placebo groups. and there were no significant
`changes in weight versus placebo.
`Conclusion: Aripiprazole was effective and well tolerated in the
`treatment of acute mania in patients with bipolar disorder in this
`randomized. placebo-controlled trial.
`
`H3313
`
`Wednesday, May 22, 12:00 p.m.-2:00 p.m.
`
`nears
`
`Wednesday, May 22, 12:00 p.m.-2:00 p.m.
`
`Olanzapine Improves Tardive Dysklnesla in Patients
`with Schizophrenia
`Bruce J. Kinon, M.D.. Lilly Fiesearch Lab, Eli Lilly And
`Company. Lilly Corporate Center, indianapolis. IN 46285;
`Virginia L. Stautfer. Pharm.D.. Lynn Wang. M.S., Khanhn T. Thi
`
`Summary:
`
`Objective: We report preliminary findings of the effects of clan-
`zapine (OLZ) treatment upon tardive dyskinesia TD.
`Methods: Eligible schizophrenic subjects met restricted Fle-
`search Diagnosis Tardive Dyskinesia criteria (restricted FiD-TD}
`that specified for abnormal involuntary movements to be of at
`least moderate severity. Subjects received OLZ, 5-20 mgiday
`for 8 months within a double-blind design that included up to 2
`medication reduction (75%) periods of 2 weeks duration. TD was
`assessed with the Abnormal Involuntary Movement Scale {AIMS}
`and psychopathology with the Positive and Negative Syndrome
`Scale {PANSSL
`Flesulls: A significant reduction in mean AlMS Total score was
`demonstrated (N=95; BL=11.9; EP=7.5; p<.001; LOCF}. Nearly
`?0% of subjects no longer met the restricted FID-TD criteria after
`up to 8 months of treatment, with greater than 50% improving as
`early as 8 weeks. No statistically significant rebound worsening
`of TD was found during the blinded drug reduction periods. A
`significant improvement in the PANSS occurred (BL=66.2; EP=
`59.7; p<.001. LOCF}.
`Conclusion: These data, suggesting an ameliorative, rather than
`masking effect. and the concurrent further improvement in clinical
`status suggests that OLZ may offer a potential treatment alterna
`live for managing the schizophrenic patient with pre-existing TD.
`
`NFI314
`
`Wednesday, May 22, 12:00 p.m.-2:00 p.m.
`
`Aripiprazole Versus Placebo in Acute Mania
`
`Paul E. Keck. Jr.. M.D.. Biological Psychiatry Department. Univ.
`of Cincinnatti College of Medicine, 231 Albert Sabin Way.
`ML559, Cincinnati, OH 45267-0559; Anutosh Fl. Saha, Ph.D.,
`Taro lwamoto, Ph.D., Darlene Jody, M.D.. Stavros
`Tourkodimitris, Ph.D.. Donald G. Archibald, M.Phil., Flonald N.
`Marcus, MD.
`
`Summary:
`
`Objective: To compare the efficacy and safety of aripiprazole.
`thefirst next-generation atypical antipsychotic with a unique mech-
`anism of action (dopamine-serotonin system stabilizer} to placebo
`in patients with acute bipolar mania.
`Methods: This Phase III. multicenter. double-blind. placebo-
`controlled study randomized 262 patients with acute mania to
`aripiprazole 30 mg (reduced to 15 mg if unable to tolerate) or
`placebo for 3 weeks. Patients remained hospitalized for a mini-
`mum of two weeks of the treatment phase. The primary measure
`ct efficacy was the change in Y-MRS Total score. Flesponse was
`delined as a decrease of 250% in Y-MRS Total score.
`
`ziprasidone Versus Olanzapine in Schizophrenia:
`Six-Month Continuation Study
`George M. Simpson. M.D.. Department of Psychiatry. l.AC/
`USMC Medical Center, 2020 Zonal Avenue, lFlD Floom 20. Los
`Angeles, CA 90033, Peter J. Weiden, M.D.. Teresa A. Pigctt.
`M.D.. Steven J. Ftomano. M.D., Cynthia Siu, Ph.D.
`
`Summary:
`
`Objective: To compare long-term efficacy and tolerability of zi-
`prasidone and olanzapine in schizophrenia or schizoalfective dis-
`order.
`Methods: This 6-month. blinded continuation study followed
`hospitalized patients who had completed a 6-week randomized
`trial with satisfactory clinical response (CG!-I 52 or 220% reduction
`in symptom severity by PANSS Total} and were discharged on
`olanzapine 5-15 mg OD {n=71) or ziprasidone 40-80 mg BID {n=
`62}. Primary efficacy measures were BPFIS and CG]-S; secondary
`variables included PANSS Total and Positive and Negative Sub-
`scale scores. Toierablllty assessments included tasting lipids. in-
`sulin. glucose, and weight.
`Results: Ziprasidone- and olanzapine-treated patients demon-
`strated comparable changes in BPRS, CGI-S. and PANSS Total
`and Subscale scores from baseline of 6-week study to endpoint
`of 6-month continuation. Changes during continuation phase did
`not differ significantly between groups. Olanzapine-treated pa-
`tients exhibited signiflcant mean increases versus ziprasidone in
`endpoint weight (P<0.001} and BM] (P=0.001}. and significant
`median increases versus baseline in LDL-C {P<0.01),
`insulin
`(P<0.05). glucose {P=0.D5}, and fasting liver enzymes (P<0.05).
`Both agents displayed low incidence of movement disorders. No
`patients had QTc 2500 msec.
`Conclusions: ziprasidone and olanzapine demonstrated com-
`parable antipsychotic efficacy in long-term treatment. Olanzapine
`patients alone exhibited sustained weight gain and deleterious
`metabolic changes.
`
`H3316
`
`Wednesday, May 22, 12:00 p.m.-2:00 p.m.
`
`Antlpsychotlc llitonotherapy Versus Combination
`Treatment with Valporate in Hospitalized Patients
`with Acute Schizophrenia: A Double-Blind, Multi-
`Center Study
`Leslie L. Citrome. M.D.. Clinical Research/CHEF. Nathan Kline
`institute, I40 Old Orangeburg Road. Building 37, Orangeburg,
`NY 10962-2210, David G. Daniel. M.D.. Adel A. Wassef. M.D..
`Katherine A. Tracy, M.D.. Patricia Wozniak. Ph.D.. Daniel E.
`Casey. M.D.
`
`Summary:
`
`Obiective: This study compared the efficacy and safety of atypi-
`cal antipsychotic monotherapy (olanzapine or risperidone} versus
`combination treatment with valproate (divalproex sodium) in pa-
`tients with an acute episode of schizophrenia.
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