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P.2.151 Olanzapine versus placebo in the treatment of psychosis with or without associated behavioral disturbances in patients with Alzheimer's dementia
I?2. Psychotic
disorders
Methods: In this 21-day, double-blind trial, iupatieuts =18 years old with Bipolar I Disorder, most recent episode manic or mixed, aud MRS =14 with scores =2 ou =4 items at baseline were randomized to ziprasidoue (40 mg BID at day 1, 80 mg BID at day 2, aud SO-160 mgiday thereafter) or placebo. Lithium dosage was adjusted after Day 1 to maiutaiu serum levels of 0.8 to 1.2 mEq/L. Primary efficacy variables were MRS aud Clinical Global Impression-Severity (CGI-S). S ecoudary variables included MRS Manic Syndrome aud Behavior aud Ideation scales, Hamilton Depression scale, CGI-improvement (CGI-I), aud Total, Positive aud Negative subscales of the Positive aud Negative Syudrome Scale (PANSS). Assessments were performed at Visit Days 2, 4, 7, 14 aud 21 (or early termination). Between-group differences in rates of chauge (Days 4 aud 14) aud in least squares meau chauge (all visits) were compared using ANCOVA. Results: A total of 102 patients were treated with ziprasidoue aud 103 patients were treated with placebo. At Day 4, rates of chauge (mixed effects ANCOVA, all patieuts, OC) were significantly greater with ziprasidoue thau with placebo for MRS (PiO.O5), CGI-S (PiO.Ol), CGI-I (PiO.Ol), Behavior aud Ideation (PiO.Ol), aud extracted Hamilton Depression (PiO.05) (observed cases). Least squares meau chauges were siguificautly greater for MRS (PiO.O5), CGI-S (PiO.O5), CGI-I (PiO.O5), aud Manic Syndrome (PPO.01) (all patieuts, LOCF). At Day 14, rates of chauge in primary aud secondary variables were comparable betweeu groups, with uo statistically significant differences; however, ziprasidoue-treated patients demonstrated siguificautly greater least squares meau chauges in PANSS Total (PiO.Ol), PANSS Positive (PiO.05) aud PANSS Negative (PiO.05) at Day 14, aud in PANSS Total (PiO.01) aud PANSS Positive (PiO.05) aud Negative (PiO.005) subscales at Day 21 or early discoutiuuatiou (all patieuts, LOCF). Ziprasidoue administered with lithium was geuerally well tolerated; rates of discoutiuuatiou for adverse eveuts attributed to study treatment were ~5% in both groups. Conclusions: In treatment of acute mama in patients with Bipolar Disorder who were receiving lithium, ziprasidoue exhibited significantly greater rates of chauge in mama aud related psychopathology at Day 4 thau did placebo, suggesting that adjuuctive therapy with ziprasidoue plus lithium may effect au earlier ouset of clinical improvement thau lithium alone. Ziprasidoue was geuerally well tolerated. References [l]
Keck PE, Versiani M, Potkin S, West S, Giller E, Ice K, and the Ziprasidone in Mania Study Group (2003). Ziprasidone in the Treatment of Acute Bipolar Mania: A Three-Week, Placebo-Controlled, DoubleBlind, Randomized Trial. Am J Psychiatry 160, 741-748
m P2
151
Olanzapine of psychosis beiaiioral Alzheimer’s
versus placebo in the treatment with or without associated disturbances in patients with dementia
P.P. De Deyu’, M.M. Carrasco2, W. Deberdt3, C. Jeaude14, D.P. Hay3, P.D. Feldmau3, C.A. Youug3, D.L. Lehmau3, A. Breier3. ‘University of Antwerp, Department of Neurology, Antwerp, Belgium; 2Clinica Psiquiatrica Padre Menni, Pamplona, Spain; 3Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, US.A.; 4CHU H6pital La ColomDidre, Internal Medicine & Geriatric Service, Montpellier, France Introduction:
Psychotic
symptoms
aud
behavioral
disturbances
and
antipsychotics
s345
are a major couceru in the care of elderly patients with Alzheimer’ s dementia (AD). Methods: Followiug a placebo lead-in period (~14 days), iupatients in long-term or coutiuuiug-care (uursiug home, hospital) settiugs aud diagnosed with AD aud delusions or halluciuatious were randomly assigned to receive placebo (N=129) or olauzapiue at a daily fixed dose of 1.0 mg (N=129), 2.5 mg (N=135), 5.0 mg (N=127), or 7.5 mg (N=132) for up to 10 weeks of double-blind treatmeiit. Results: Patieuts’ meau age was 76.6 years, aud 75.0% were female. Meau Mini-Meutal State Examination (MMSE) score was 13.715.1. Relative to placebo (19.4%), significantly fewer patients who received 2.5~mg (8.2%, p=.Ol l), 5.0~mg (8X%, p=.O19), or 7.5~mg (6.1%, p=.OOl) olauzapiue discoutiuued due to lack of efficacy. At eudpoiut, significant decreases from baseline in the NPINH Psychosis Total @elusious+Halluciuatious) were seeu in all five treatment groups (pi.00 1). Repeated-measures analysis showed uo significant differences among treatment groups at the 1 O-week eudpoiut, but last-observation-carried-forward decreases in the 7.5~mg olauzapiue group were significantly greater thau placebo (p=.OOS), aud mediau time to response (~30% improvemeut in Psychosis Total) was significantly shorter (15.0 versus 29.0 days, p=.O20). Chauges in extrapyramidal measures aud coguitiou were uot significant in auy treatment group. No treatmeutemergeut adverse eveuts occurred with a significantly higher iucideuce in auy olauzapiue group relative to placebo. Meau chauges from baseline in glucose, triglyceride, aud cholesterol levels were uot significantly differeut across treatment groups, aud uo clinically relevant significant chauges were seeu across groups in auy other vital sign or laboratory measure. Conclusions: These data indicate that olauzapiue at 7.5 “g/day is well tolerated aud effective for treatment of psychotic symptoms associated with AD.
mP2
152
Ziprasidone double-blind,
in mania: placebo
A 21-day controlled
randomized, trial
S. Segal’ , R.A. Rieseuberg2, K. Ice3, P Euglish4. ‘Segal Institute for Clinical Research North Miami, N/A, North Miami, US.A.; 2Atlanta Center for Medical Research Inc., N/A, Atlanta, US.A.; 3Pfizer Inc., Medical, New York, US.A.; 4Pfizer Global Research and Development, CNS Clinical Development, New London, US.A. Purpose: To compare the efficacy aud tolerability of ziprasidoue versus placebo in patients with mama. Methods: In a 21-day, double-blind, parallel-group trial, patieuts with Bipolar I Disorder, curreut episode manic or mixed aud with or without psychotic features, were randomly assigned to ziprasidoue (40 to 80 mg BID) or placebo in a 2: 1 ratio. Assessmeuts were performed at Baseline aud Days 2, 7, 14, aud 21 or early discoutiuuation The primary efficacy measure was the meau chauge from baseline to eudpoiut (last observatiou carried forward [LOCF]) in the Mama Rating Scale @IRS); secondary measures included meau chauges in Clinical Global Impression-Severity (CGI-S) aud CGI-Improvement (CGI-I). Least-squares meaus were used to compute significance, with pair-wise comparisons against placebo based ou au ANCOVA model for post-baseline time points. Results: A total of 139 patients were treated with ziprasidoue aud 66 with placebo; 137 aud 65 patieuts, respectively, were evaluable for efficacy. Patients in the ziprasidoue group had a
disorders
Methods: In this 21-day, double-blind trial, iupatieuts =18 years old with Bipolar I Disorder, most recent episode manic or mixed, aud MRS =14 with scores =2 ou =4 items at baseline were randomized to ziprasidoue (40 mg BID at day 1, 80 mg BID at day 2, aud SO-160 mgiday thereafter) or placebo. Lithium dosage was adjusted after Day 1 to maiutaiu serum levels of 0.8 to 1.2 mEq/L. Primary efficacy variables were MRS aud Clinical Global Impression-Severity (CGI-S). S ecoudary variables included MRS Manic Syndrome aud Behavior aud Ideation scales, Hamilton Depression scale, CGI-improvement (CGI-I), aud Total, Positive aud Negative subscales of the Positive aud Negative Syudrome Scale (PANSS). Assessments were performed at Visit Days 2, 4, 7, 14 aud 21 (or early termination). Between-group differences in rates of chauge (Days 4 aud 14) aud in least squares meau chauge (all visits) were compared using ANCOVA. Results: A total of 102 patients were treated with ziprasidoue aud 103 patients were treated with placebo. At Day 4, rates of chauge (mixed effects ANCOVA, all patieuts, OC) were significantly greater with ziprasidoue thau with placebo for MRS (PiO.O5), CGI-S (PiO.Ol), CGI-I (PiO.Ol), Behavior aud Ideation (PiO.Ol), aud extracted Hamilton Depression (PiO.05) (observed cases). Least squares meau chauges were siguificautly greater for MRS (PiO.O5), CGI-S (PiO.O5), CGI-I (PiO.O5), aud Manic Syndrome (PPO.01) (all patieuts, LOCF). At Day 14, rates of chauge in primary aud secondary variables were comparable betweeu groups, with uo statistically significant differences; however, ziprasidoue-treated patients demonstrated siguificautly greater least squares meau chauges in PANSS Total (PiO.Ol), PANSS Positive (PiO.05) aud PANSS Negative (PiO.05) at Day 14, aud in PANSS Total (PiO.01) aud PANSS Positive (PiO.05) aud Negative (PiO.005) subscales at Day 21 or early discoutiuuatiou (all patieuts, LOCF). Ziprasidoue administered with lithium was geuerally well tolerated; rates of discoutiuuatiou for adverse eveuts attributed to study treatment were ~5% in both groups. Conclusions: In treatment of acute mama in patients with Bipolar Disorder who were receiving lithium, ziprasidoue exhibited significantly greater rates of chauge in mama aud related psychopathology at Day 4 thau did placebo, suggesting that adjuuctive therapy with ziprasidoue plus lithium may effect au earlier ouset of clinical improvement thau lithium alone. Ziprasidoue was geuerally well tolerated. References [l]
Keck PE, Versiani M, Potkin S, West S, Giller E, Ice K, and the Ziprasidone in Mania Study Group (2003). Ziprasidone in the Treatment of Acute Bipolar Mania: A Three-Week, Placebo-Controlled, DoubleBlind, Randomized Trial. Am J Psychiatry 160, 741-748
m P2
151
Olanzapine of psychosis beiaiioral Alzheimer’s
versus placebo in the treatment with or without associated disturbances in patients with dementia
P.P. De Deyu’, M.M. Carrasco2, W. Deberdt3, C. Jeaude14, D.P. Hay3, P.D. Feldmau3, C.A. Youug3, D.L. Lehmau3, A. Breier3. ‘University of Antwerp, Department of Neurology, Antwerp, Belgium; 2Clinica Psiquiatrica Padre Menni, Pamplona, Spain; 3Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, US.A.; 4CHU H6pital La ColomDidre, Internal Medicine & Geriatric Service, Montpellier, France Introduction:
Psychotic
symptoms
aud
behavioral
disturbances
and
antipsychotics
s345
are a major couceru in the care of elderly patients with Alzheimer’ s dementia (AD). Methods: Followiug a placebo lead-in period (~14 days), iupatients in long-term or coutiuuiug-care (uursiug home, hospital) settiugs aud diagnosed with AD aud delusions or halluciuatious were randomly assigned to receive placebo (N=129) or olauzapiue at a daily fixed dose of 1.0 mg (N=129), 2.5 mg (N=135), 5.0 mg (N=127), or 7.5 mg (N=132) for up to 10 weeks of double-blind treatmeiit. Results: Patieuts’ meau age was 76.6 years, aud 75.0% were female. Meau Mini-Meutal State Examination (MMSE) score was 13.715.1. Relative to placebo (19.4%), significantly fewer patients who received 2.5~mg (8.2%, p=.Ol l), 5.0~mg (8X%, p=.O19), or 7.5~mg (6.1%, p=.OOl) olauzapiue discoutiuued due to lack of efficacy. At eudpoiut, significant decreases from baseline in the NPINH Psychosis Total @elusious+Halluciuatious) were seeu in all five treatment groups (pi.00 1). Repeated-measures analysis showed uo significant differences among treatment groups at the 1 O-week eudpoiut, but last-observation-carried-forward decreases in the 7.5~mg olauzapiue group were significantly greater thau placebo (p=.OOS), aud mediau time to response (~30% improvemeut in Psychosis Total) was significantly shorter (15.0 versus 29.0 days, p=.O20). Chauges in extrapyramidal measures aud coguitiou were uot significant in auy treatment group. No treatmeutemergeut adverse eveuts occurred with a significantly higher iucideuce in auy olauzapiue group relative to placebo. Meau chauges from baseline in glucose, triglyceride, aud cholesterol levels were uot significantly differeut across treatment groups, aud uo clinically relevant significant chauges were seeu across groups in auy other vital sign or laboratory measure. Conclusions: These data indicate that olauzapiue at 7.5 “g/day is well tolerated aud effective for treatment of psychotic symptoms associated with AD.
mP2
152
Ziprasidone double-blind,
in mania: placebo
A 21-day controlled
randomized, trial
S. Segal’ , R.A. Rieseuberg2, K. Ice3, P Euglish4. ‘Segal Institute for Clinical Research North Miami, N/A, North Miami, US.A.; 2Atlanta Center for Medical Research Inc., N/A, Atlanta, US.A.; 3Pfizer Inc., Medical, New York, US.A.; 4Pfizer Global Research and Development, CNS Clinical Development, New London, US.A. Purpose: To compare the efficacy aud tolerability of ziprasidoue versus placebo in patients with mama. Methods: In a 21-day, double-blind, parallel-group trial, patieuts with Bipolar I Disorder, curreut episode manic or mixed aud with or without psychotic features, were randomly assigned to ziprasidoue (40 to 80 mg BID) or placebo in a 2: 1 ratio. Assessmeuts were performed at Baseline aud Days 2, 7, 14, aud 21 or early discoutiuuation The primary efficacy measure was the meau chauge from baseline to eudpoiut (last observatiou carried forward [LOCF]) in the Mama Rating Scale @IRS); secondary measures included meau chauges in Clinical Global Impression-Severity (CGI-S) aud CGI-Improvement (CGI-I). Least-squares meaus were used to compute significance, with pair-wise comparisons against placebo based ou au ANCOVA model for post-baseline time points. Results: A total of 139 patients were treated with ziprasidoue aud 66 with placebo; 137 aud 65 patieuts, respectively, were evaluable for efficacy. Patients in the ziprasidoue group had a