Inpharma 1254 - 9 Sep 2000

In another study, researchers from Eli Lilly & Co.,Olanzapine making a mark inWindlesham, UK, and colleagues, found thatschizophrenia intramuscularly administered olanzapine is effective inthe treatment of acutely agitated patients withThe move of atypical antipsychotics such asschizophrenia, schizophreniform or schizoaffectiveolanzapine to supplant conventional antipsychotics indisorder.2the treatment of schizophrenia was clearly seen at the

In this study, 311 such patients were randomised to22nd Collegium Internationale Neuro-receive up to 3 IM injections of olanzapine 10mg (n =Psychopharmacologium Congress [Brussels, Belgium;131), haloperidol 7.5mg (126) or placebo, over aJuly 2000], where these agents featured in a number of24-hour period, followed by a 4-day oral therapy period.sessions on the treatment of schizophrenia. At one of

the symposia, dedicated to the subject of whether ‘Non-inferior’ to haloperidolatypical antipsychotics should be used as first-line Analysis showed that olanzapine was ‘non-inferior’ totherapy for schizophrenia, Dr John Kane from Hillside haloperidol in terms of the reduction from baseline inHospital, Glen Oaks, New York, US, explained that ‘we scores on the Positive and Negative Syndrome Scaletend to divide the treatment of this condition into (PANSS) excited component.† Both olanzapine anddifferent phases – acute, resolving, residual and remitted. haloperidol recipients experienced reductions fromPatients may not achieve a state of full remission, but baseline in PANSS excited component scores over thethey may continue to experience psychotic symptoms’.* 2-hour period following the first IM dose; however, theHe added that ‘clearly the long-term course is very varied reductions were significantly greater in olanzapine,and we’d like to do what we can to try to produce the compared with haloperidol, recipients at 15, 30 and 45best outcome we can in the largest proportion of minutes.patients’. Studies presented at poster sessions showed There was no significant difference between thethat olanzapine has efficacy in several phases of olanzapine and haloperidol groups in the proportion ofschizophrenia, schizophreniform disorder and patients who experienced a reduction from baseline inschizoaffective disorder. PANSS excited component scores of ≥ 40% at 2 hours

In a study conducted by researchers from Lilly after the first IM dose.Research Laboratories, Indianapolis, Indiana, US,

Lower incidence of EPSolanzapine was shown to be superior to haloperidol inA significantly smaller proportion of olanzapine,the treatment of behavioural agitation and positive

compared with haloperidol, recipients experiencedpsychotic symptoms associated with schizophrenictreatment-emergent dystonia and extrapyramidaldecompensation.1

symptoms (EPS) and required anticholinergicThe researchers retrospectively analysed data from amedication during the 24-hour IM treatment period.study in which 1996 patients with schizophrenia,

The researchers conclude that ‘IM olanzapineschizophreniform or schizoaffective disorder wereprovides the advantages of treatment with an atypicalrandomised to receive 6 weeks of acute therapy withantipsychotic to patients who require rapidolanzapine 5–20 mg/day (n = 1336) or haloperidol 5–20tranquilization or who refuse oral antipsychotic therapy’.mg/day; data were evaluable from 1313 and 635

An open-label, observational study conducted bypatients, respectively. 257 and 131 patients in theresearchers from Eli Lilly and Company, Madrid, Spain,respective treatment groups had predominantly positiveand colleagues, demonstrated that olanzapine showspsychotic symptoms at baseline; of these, 252 and 130efficacy in the treatment of inpatients withpatients, respectively, were evaluable.schizophrenia who are hospitalised due to an acute

Greater improvement in agitation psychotic episode.3

Last observation carried forward (LOCF) analysis In this study, data were analysed from 904 suchshowed that in the overall study population, the mean patients who received treatment with olanzapine alonereduction from baseline in Brief Psychiatric Rating Scale or in combination with other drugs (n = 483) or(BPRS) agitation subscores was significantly greater in conventional antipsychotics (the most commonly usedolanzapine, compared with haloperidol, recipients being haloperidol).(–2.59 vs –1.7); reductions in scores indicated

Higher response ratesimprovement in symptoms.** These reductions wereThe proportion of patients who experienced asignificantly greater in olanzapine, compared with

response to treatment was significantly higher in thehaloperidol, recipients at weeks 4, 5 and 6.olanzapine, compared with the conventionalAmong the patients with predominantly positiveantipsychotic, group (71.9 vs 58.7% of patients).‡ Thesymptoms at baseline, significantly greater meanmean reductions in clinical scale scores, adjusted forreductions from baseline in BPRS positive symptombaseline values, were significantly greater in olanzapine,subscores were seen in olanzapine, compared withcompared with conventional antipsychotic, recipientshaloperidol, recipients (–4.04 vs –2.9); again, significant[see table].between-group differences favouring olanzapine

A significantly greater proportion of conventionalrecipients were seen at weeks 4, 5 and 6.antipsychotic, compared with olanzapine, recipients

First-line therapy for acute episodes? experienced adverse events (55.8 vs 27.3% of patients).The researchers concluded that their results support The incidence of any treatment-emergent EPS was

‘the beneficial effects of olanzapine in rapidly controlling significantly lower in the olanzapine, compared with thebehavioral agitation and positive psychotic symptoms conventional antipsychotic, group (16.4 vs 44.5%); aassociated with schizophrenic decompensation’. They between-group difference in favour of olanzapine wasadd that the data ‘indicate that olanzapine may be seen for dystonia, hypertonia, hypokinesia,considered as a first-line treatment of an acute episode of Parkinsonism, akathisia and dyskinesia.schizophrenia’. The fourth study, conducted by researchers from Eli

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Inpharma 9 Sep 2000 No. 12541173-8324/10/1254-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved

Single Article

1. Kinon BJ, et al. Effective resolution of acute presentation of behavioral agitationLilly and Company, Indianapolis, US, found olanzapineand positive psychotic symptoms in schizophrenia with olanzapine. Internationalto be superior to placebo in the prevention of relapse in Journal of Neuropsychopharmacology 3 (Suppl. 1): 154 (plus poster), Jul 2000.

2. Wright P, et al. A double-blind study of intramuscular olanzapine, haloperidolclinically stable patients with schizophrenia orand placebo in acutely agitated schizophrenic patients. International Journal ofschizoaffective disorder.4Neuropsychopharmacology 3 (Suppl. 1): 139 (plus poster), Jul 2000.

The study involved patients who had experienced no 3. Gomez JC, et al. Safety and effectiveness of olanzapine versus typicalantipsychotic drugs in the treatment of inpatients with schizophrenia (EUROPAor few symptoms for at least 6 weeks. Patients werestudy). International Journal of Neuropsychopharmacology 3 (Suppl. 1): 140initially converted from their existing antipsychotic (plus poster), Jul 2000.

therapy to open-label olanzapine for the stabilisation 4. Beasley CM, et al. Olanzapine long-term therapy and relapse prevention ofschizophrenia and schizoaffective disorder. International Journal ofphase, then were randomised to receive olanzapine (n =Neuropsychopharmacology 3 (Suppl. 1): 139-140 (plus poster), Jul 2000.224) or placebo (102) during the double-blind 800840031

maintenance phase. The mean durations of therapy inthe respective treatment groups were 98 and 65 days.

Significantly lower relapse ratesThe time to relapse was significantly longer in

olanzapine, compared with placebo, recipients. Relapserates were significantly lower in olanzapine, comparedwith placebo, recipients, regardless of whether theanalysis included all patients and classified patients whodiscontinued the study early without relapsing asnonrelapsers (4 vs 27.5% of patients) or as relapsers(13.4 vs 53.9%), or was restricted to patients who eitherrelapsed or completed the study (4.4 vs 37.3%).

Among the observed cases at each timepoint, therewere significant between-group differences in favour ofolanzapine, compared with placebo, in the mean changefrom baseline in PANSS total scores at weeks 2, 3, 4, 8,12 and 16. Furthermore, LOCF analysis showedimprovement from baseline in measures of quality of lifein olanzapine recipients, while patients in the placebogroup experienced worsening of these measures.

Table. Adjusted mean decreases in clinical scalescores according to therapy

Olanzapine (n = Conventional483) antipsychotics (n =

421)

Clinical GlobalImpression Scale:

–1.8 –1.6*Brief PsychiatricRating Scale:

total –27.6 –24.8**positive –9.1 –8.4†negative –3.4 –2.6‡agitation –10.3 –9.3**

* p = 0.0031 compared with olanzapine recipients** p < 0.001 compared with olanzapine recipients† p = 0.017 compared with olanzapine recipients‡ p = 0.0014 compared with olanzapine recipients

* The symposium was supported by an unrestricted educational grantfrom Janssen-Cilag and Organon.** The BPRS agitation subscore assessed anxiety, tension, hostility,uncooperativeness and excitement.† The PANSS excited component assessed poor impulse control,tension, hostility, uncooperativeness and excitement.‡ A response to treatment was defined as a decrease from baseline inBPRS scores of ≥ 40% plus a Clinical Global Impression Scale score of ≤3 or a final BPRS score of < 18.

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