ziprasidone shows advantages in schizophrenia

Inpharma 1358 - 5 Oct 2002

Ziprasidone shows advantages in schizophrenia– Raewyn Poole –

The atypical antipsychotic ziprasidone [‘Geodon’] is an effective and well tolerated therapy for schizophrenia,according to studies presented at the XII World Congress of Psychiatry [Yokohama, Japan; August 2002]. In onestudy, ziprasidone and olanzapine [‘Zyprexa’] provided comparable improvements in psychopathology, globalillness severity, and cognitive function in patients with schizophrenia. A second study showed that ziprasidonewas as effective as the conventional antipsychotic haloperidol [‘Haldol’] in the treatment of acute schizophrenia,although IM ziprasidone provided more rapid improvement in some measures. Ziprasidone demonstratedfavourable tolerability profiles in these studies; ziprasidone was less likely than olanzapine to adversely affectbodyweight or metabolic parameters, and the incidence of movement disorders was significantly lower inziprasidone, compared with haloperidol, recipients. Switching to ziprasidone was shown to provide furtherimprovement of symptoms in patients previously treated with conventional antipsychotics, olanzapine orrisperidone [‘Risperdal’], according to an analysis of data from three studies.

withstood correction for the overall number of testsZiprasidone vs olanzapineperformed’. Neither treatment group experiencedZiprasidone and olanzapine were compared in asignificant mean improvements in the Digit Span Test or6-week randomised, double-blind, multicentre studythe Letter Fluency Test, relative to baseline.involving 269 inpatients with acute schizophrenia or

‘The improvements seen with ziprasidone acrossschizoaffective disorder.1;2* Patients receivedseveral important domains of cognitive functionziprasidone 40–80mg twice daily (n = 136) orcorroborate findings from earlier, open-label studies, andolanzapine 5–15mg once daily.suggest that ziprasidone can potentially ameliorateThe Brief Psychiatric Rating Scale (BPRS), Clinicaldeficits that contribute to poor functional outcome inGlobal Improvement Severity (CGI-S) and CGIschizophrenia’, commented the researchers.Improvement (CGI-I) scales were used to assess

symptoms at baseline and at weekly intervals Tolerability advantages?throughout the study, Positive and Negative Symptom Ziprasidone and olanzapine were generally wellScale (PANSS) measurements were taken at screening, tolerated, with similar proportions of patientsbaseline, and at the end of weeks 1, 3 and 6. Mood- discontinuing the study as a result of treatment-relatedrelated symptoms were assessed using the Calgary adverse events (2.2% vs 1.5%). However, ziprasidoneDepression Scale for Schizophrenia (CDSS) at baseline, demonstrated a more favourable tolerability profile withand at the end of weeks 3 and 6. Cognitive function was respect to metabolic parameters [see table 2].assessed at baseline and at the study endpoint. Significantly smaller increases in bodyweight and total

Treatment was completed by 51.5% of ziprasidone cholesterol, triglyceride and LDL-cholesterol levels wererecipients, compared with 63.2% of patients receiving observed in ziprasidone recipients, compared witholanzapine; however, similar proportions of patients in patients treated with olanzapine. Furthermore, patientseach group discontinued treatment for reasons related treated with olanzapine experienced significantto the study drug (11.8% vs 9.8%). increases in median fasting plasma insulin levels, and

fasting HOMA IR (log), relative to baseline (3.3 µU/mlComparable efficacy overalland 0.26; p < 0.0001 for both); these parameters wereRapid improvements in BPRS scores, relative tonot significantly affected in ziprasidone recipients.baseline, were observed in ziprasidone and olanzapine‘These differences in important metabolic parametersrecipients, with no significant difference between themay influence long-term health outcomes in patientstwo groups at the study endpoint. Furthermore, therewith schizophrenia’, said the researchers.were no significant differences in PANSS total scores or

CGI-S (LOCF) scores. Improvements in CDSS scores, Ziprasidone vs haloperidolrelative to baseline, were observed in the majority of Ziprasidone was at least as effective as haloperidol inpatients in both treatment groups; there no significant controlling symptoms in a multicentre study involvingdifferences between the proportions of ziprasidone and 567 inpatients with acute schizophrenia andolanzapine recipients who experienced improvements schizoaffective disorders.3* Patients were randomised toof 20, 30 or 40% in CDSS scores. receive sequential therapy with ziprasidone ≤ 40mg IM

followed by twice daily oral doses of 40–80mg (n =Similar effects on cognition429), or haloperidol ≤ 10 mg/day IM then oral doses ofPatients in both the ziprasidone and olanzapine5–20mg twice daily for 6 weeks. The median duration ofgroups experienced significant improvement in mostIM treatment was 2 days for both groups; the majority ofindicators of cognitive function, compared with baselineziprasidone and haloperidol recipients were given two[see table 1]. Although only the olanzapine groupIM doses per day.experienced a significant mean improvement in

The efficacy of ziprasidone was equivalent to that ofWisconsin Card Sorting Test score, compared withhaloperidol for most of the study endpoints in thebaseline, this was not significantly greater than theoverall study population, and in a subset of patients whoimprovement in ziprasidone recipients. Olanzapine, butwere seriously ill [see table 3]. However, significantlynot ziprasidone recipients achieved a significant meangreater improvements in BPRS total scores and Coviimprovement in verbal fluency scores, relative toanxiety scale scores were observed in ziprasidone,baseline (p < 0.05). Although the difference in the meancompared with haloperidol, recipients at the end of thescore change was statistically significant between theIM phase (p < 0.01 for both). The reduction in BPRStwo groups for the overall patient population, thetotal scores was also significantly greater at the end ofresearchers commented that ‘it would not have

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Inpharma 5 Oct 2002 No. 13581173-8324/10/1358-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved

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Ziprasidone shows advantages in schizophrenia – continuedthe IM phase in seriously ill patients treated with levels were observed in patients switching fromziprasidone, compared with those given haloperidol. conventional antipsychotics and risperidone. ‘The

differential long-term effects of novel agents on riskLower incidence of movement disordersfactors associated with physical health warrantBoth ziprasidone and haloperidol were generally well prospective study’, commented the researchers.tolerated, with mostly mild-to-moderate adverse events

reported. However, the incidence of movementTable 1. Improvement in cognitive function indisorders, indicated by mean changes in extrapyramidalstudy completers according to therapysymptom rating scale (ESRS) and Barnes Akathisia Scale

(BAS) scores, relative to baseline, was significantly lower Ziprasidone Olanzapinein ziprasidone, compared with haloperidol recipients (p Mean change in cognitive function parameters, relative to baseline:< 0.0001). Furthermore, ziprasidone recipients

attention/vigilance + 0.262* + 0.328**experienced a mean reduction in prolactin levels of 8 ng/ (Total Signalml, compared with a mean increase of 4 mg/ml in Detection Score)patients treated with haloperidol. The incidences of visuomotor speed – 16.709* – 6.942†

(seconds taken toother adverse events were similar between the twocompletegroups. A higher proportion of haloperidol, comparedTrailmaking testwith ziprasidone, recipients discontinued treatment as a part A)

result of adverse events (9.4% vs 4.2%). executive function – 17.345† – 28.623‡(seconds toSwitch to ziprasidone beneficialcompleteThe results from the two comparative studies Trailmaking test

presented at the meeting demonstrated that ziprasidone part B)has comparable efficacy to both olanzapine and executive – 0.038 + 0.435†

function(Wisconsinhaloperidol, but may have advantages with respect tocard sorting test -tolerability. Thus, ziprasidone may be an attractivenumber ofalternative to these agents for patients with categories attained)

schizophrenia; the effects of switching to ziprasidone learning/ + 4.919† + 6.494‡from other antipsychotic agents are therefore of interest. secondary memory

An analysis of data from three identical 6-week open- (serial VerbalLearning Test sumlabel, multicentre studies indicated that switching toof trial 1–5ziprasidone from conventional antipsychotics (n = 108),performance)olanzapine (104) or risperidone (58) provided

* p < 0.01 vsbaselinesymptomatic improvement in symptoms of** p < 0.001 vsbaselineschizophrenia.4;5* Significant improvements in PANSS† p < 0.05 vsbaselinetotal and negative scores, and BPRSD scores were‡ p < 0.0001 vsbaselineobserved in patients switching to ziprasidone in all three

groups. Those switching from conventionalantipsychotics and olanzapine also had significantimprovements in PANSS positive scores. Furthermore, Table 2. Mean changes in bodyweight and lipidimprovements in CGI-S scores were observed following parameters in patients with schizophreniathe change to ziprasidone; patients switching from according to therapyconventional antipsychotics or risperidone also

Ziprasidone Olanzapineexperienced improvements in Simpson-Angus RatingMean change from baseline to week 6:Scale scores.

bodyweight (kg) + 0.93 + 3.57*‘Patients can be switched to ziprasidone fromBody Mass Index + 0.24 + 1.17**conventional and novel antipsychotics successfully and

(kg/m2)in a relatively short time frame, using a variety offasting total – 1 + 20*†strategies commonly employed in clinical practice,

cholesterol (mg/dl)including abrupt discontinuation or cross tapering offasting LDL- – 1 + 13†**previous treatment’, concluded the researchers. ‘The cholesterol (mg/dl)

data indicate that clinicians may choose a strategy based fasting – 2 + 26†‡on each patient’s clinical status’. triglycerides (mg/

dl)Some adverse events ameliorated* p < 0.0001 vsziprasidoneZiprasidone also appeared to offer benefits with** p < 0.001 vsziprasidonerespect to tolerability; patients switching from† p < 0.0001 vsbaselineolanzapine and risperidone experienced significant‡ p < 0.01 vsziprasidonereductions in bodyweight, body mass index and total

cholesterol levels. Significant reductions in prolactin

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Ziprasidone shows advantages in schizophrenia – continued

Table 3. Effects of sequential IM/oral antipsychotics * This study was supported by Pfizer.in patients with schizophrenia according to therapy 1. Simpson G, et al. Ziprasidone vs. olanzapine in schizophrenia. 12th World

Congress of Psychiatry 2: 326-327 (plus poster), 24 Aug 2002.Ziprasidone Haloperidol2. Harvey PD, et al. Ziprasidone vs olanzapine: effects on cognition. 12th World

Congress of Psychiatry 2: 327-328 (plus poster), 24 Aug 2002.Overall patient n = 429 n = 1383. Brook S, et al. Sequential IM/oral therapy: ziprasidone vs. haloperidol. 12thpopulation

World Congress of Psychiatry 2: 328 (plus poster), 24 Aug 2002.Mean change in BPRS total score, relative to baseline: 4. Weiden PJ, et al. Therapeutic response in patients switched to ziprasidone. 12th

World Congress of Psychiatry 2: 327 (plus poster), 24 Aug 2002.end of IM phase – 6.147* (n = 426) – 4.1345. Weiden PJ, et al. Health status in stable patients switched to ziprasidone. 12th

end of oral phase – 14.989 – 15.79 World Congress of Psychiatry 2: 327 (plus poster), 24 Aug 2002.800888554Mean change in CGI-S score, relative to baseline:

end of IM phase – 0.448 – 0.358end of oral phase – 1.347 – 1.537

Severely ill patients n = 359 n = 118(CGI-S ≥ 5 atbaseline)

Mean change in BPRS total score, relative to baseline:end of IM phase – 6.51** – 4.9end of oral phase – 15.78 – 17.69

* p < 0.01 vshaloperidol** p < 0.05 vshaloperidol

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Inpharma 5 Oct 2002 No. 13581173-8324/10/1358-0003/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved