1 of2
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`Alkermes, Ex. 1008
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`1 of 2
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`Alkermes, Ex. 1008
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`

`
`Methods: A total of 249 inpatients with schizophrenia were ran-
`domly assigned to receive olanzapine plus placebo, olanzapine
`plus divalproex. risperidone plus placebo, or risperidone plus dival-
`proex in a double-blind 28-day multi-center trial. Target daily dose
`was 15 mg for olanzapine. 6 mg for risperidone, and up to 30 mgl
`kg (minim um 15 mglkg) for divalproex. The Positive and Negative
`Syndrome Scale (PANSS} was the principal efficacy measure.
`Flesults: The PANSS Total and the PANSS Positive subscale
`scores of patients receiving combination therapy with divatproex
`indicated significantly greater improvement than those of patients
`receiving antipsychotic monotherapy. This was evident as early
`as Day 3 (ANOVA, p<0.05} and was present throughout the 28
`days as demonstrated using repeated measures ANOVA (PANSS
`Total Score p=0.020; PANSS Positive Subscale p=0.0020). Ad-
`verse events and rates of discontinuation were similar between
`the treatments.
`
`Conclusion: Divalproex significantly enhances antipsychotic el-
`ficacy in patients with schizophrenia. Combination therapy with
`divalproex was as well tolerated as monotherapy with olanzapine
`or risperidone.
`
`NR317
`
`Wednesday, May 22, 12:00 p.m.-2:00 p.m.
`
`Pharmacokinetics and Safety of Aripiprazole and
`Concomitant Mood Stabilizers
`
`Leslie L. Citrome. M.D., Clinical Research/CHEF, Nathan Kline
`institute, 140 Old Orangeburg Fioad, Building 3?. Orangeburg,
`NY 10962-2210. Flichard Josiassen, Ph.D., Nigel M. Bark,
`M.D., Karen S. Brown, M.S., Suresh Mallikaarjun, Ph.D., Daniel
`F. Salazar, Ph.D.
`
`Summary:
`
`Objective: To assess the salety profile and phannacokinetics
`oi aripiprazole. an antipsychotic with a unique pharmacologic pro-
`file of dopamine D2 partial agonism, serotonin 5HT1,t partial ago-
`nism and 5HT2,t antagonism, when coadminislered with lithium
`or divalproex sodium.
`Methods: Two open-label, sequential treatment design studies
`were conducted in chronically institutionalized patients with
`schizophrenia or schizoaflective disorder requiring treatment with
`lithium (n=7) or divalproex sodium {n=6). Patients received aripi-
`prazole 30 mglday on Days 1-14 and aripiprazole with concomi-
`tant therapy on Days 15-36. Lithium was titrated from 900 mg
`until serum concentrations reached 1.0-1.4 mEqiL for 25 days.
`Divalproex sodium was titrated to 50-125 rnglL.
`Flesults: Coadministration with lithium increased mean Cma, and
`AUC values of aripiprazole by about 19% and 15%, respectively.
`while the apparent oral clearance decreased by 15%. There was
`no effect on the steady state phannacokinetics of the active metab-
`olite ot aripiprazole. Coadministration with dtvalproex sodium de-
`creased the AUC, Cm, and Cm.-n of aripiprazole by 24%, 26%, and
`22%, respectively, with minimal effects on the active metabolite.
`Conclusion: Aripiprazole can be administered safely with thera-
`peutic doses of Iith ium or divaiproex sodium in patients with schizo-
`phrenia or schizoalfective disorder.
`
`NR318
`
`Wednesday, May 22, 12:00 p.m.-2:00 p.m.
`
`The Intersept Scale for Suicidal Thinking: Reliability
`and validity
`Jean-Pierre Lindenmayer, M.D., N. Kline institute for
`Psychiatric Ftesearch, New York University, Manhattan
`Psychiatric Center, Wards island, New York, NY 10035; Pal
`Czobor, Larry Alphs, M.D., Ann-Marie Nathan, M.A., Ravi
`Anand. M.D., Zahur Islam, Ph.D., James C. Chou, M.D.
`
`87
`
`Summary:
`
`Background: The lnterSePT Scale for Suicidal Thinking {ISST]
`is a 12-item instrument for the assessment of current suicidal
`ideation in patients with schizophrenia or schizoaflective disorder.
`We report the psychometric characteristics of this new scale based
`on two studies.
`
`Method: In Study 1 , 22 inpatients with schizophrenia or schizoat-
`tective disorder who had recently attempted suicide or engaged
`in suicidal ideation were rated by 3 trained independent raters to
`calculate interrater reliability. In Study 2, 980 patients with schizo-
`phrenia or schizoaffective disorder with a history of suicidal ide-
`ation in the past 36 months were enrolled in a 2-year industry-
`sponsored suicide prevention study. At baseline, these patients
`were administered the ISST by the Principal Investigator (PI) and
`by a blind rater (BFI), the Positive and Negative Symptom Scale
`(PANSS), the Calgary Depression Scale (CD3), and the Clinical
`Global Impression Scale for Severity of Suicidality {CGI-SS}. Indi-
`oes of internal reliability, construct and discriminant validity were
`examined.
`
`Results: The interrater agreement (ICC) for the total ISST score
`for in Study 1 was 0.90 and mean weighted item kappa coefficients
`ranged from 0.66-0.92. In Study 2 internal reliability (Cronbach
`alpha} for all items was 0.88. The ISST (Pl) total score was highly
`correlated with the CGI-Severity of Suicidality by the blind rater
`(r=0.El6, p-:0.0001). ISST total scores significantly differentiated
`the different levels of CGI-SS {F=519.3; df=4,955: p<0.0001 }. Fle-
`sults ot construct and discriminant validity analyses are also pre-
`sented.
`
`NI-I319
`
`Wednesday, May 22, 12:00 p.m.-2:00 p.m.
`
`Do Atypicals change the syndrome! Profile in
`Treatment-Resistant Schizophrenia?
`
`Jean-Pierre Lindenmayer, M.D., N. Kline institute for
`Psychiatric Flesearch, New York University, Manhattan
`Psychiatric Center, Wards island. New York, NY 10035; Jan
`Volavka, M.D., Jeffrey A. Lieberman, M.D., Leslie L. Citrorne,
`M.D., Brian Sheitman, M.D., Joseph P. McEvoy, M.D., Thomas
`Cooper, M.A.
`
`Summary:
`
`There has been considerable support for the observation that
`atypicals have a different pattern of clinical effects than traditional
`antipsychotics. We are exploring whether this difference can also
`be seen in treatment-resistant schizophrenia. We are presenting
`data from two PANSS-based factor analyses (baseline and end-
`point} from a prospective. double-blind, randomized 14-week trial
`in which 157 inpatients with DSM-IV treatment-resistant schizo-
`phrenia or schizoaffective disorder were assigned to either clozap—
`ine. olanzapine. risperidone, or haloperidol. We found both at
`baseline and endpoint a five-factor solution based on principal
`component analysis of the 30 PANSS items and after orthogonal
`factor rotation. While treatment was associated with an overall
`
`modest change, there was a change in the amount of variance
`explained by the excitement, cognitive, positive and depressionl
`anxiety factors explaining 60% of the variance. At endpoint, the
`largest variance was explained by the cognitive factor followed by
`the excitement, positive, negative and depressionlanxiety factors
`explaining 59% of the total variance. This change meant that
`negative symptoms contributed less to total psychopathology.
`while cognitive symptoms were more predominant after treatment
`with atypicals. The implications of these findings in comparison
`with results from studies with treatment responsive patients are
`discussed.
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`2 of 2
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`Alkermes, Ex. 1008