| Study name | Beasley 1996 |
|---|---|
| Study design | RCT CCT |
| Blinding | Double-blind |
| Absolute number of participants | 152 |
| Country of origin | USA |
| Health condition |
Acute Exacerbation Chronic Disease Normals Residual Schizophrenia Schizoaffective Disorder Schizophrenia Schizophrenia, Catatonic Schizophrenia, Disorganized Schizophrenia, Paranoid Schizophreniform Disorders Subchronic Illness Undifferentiated Schizophrenia |
| Age | Adults Unspecified age group |
| Interventions | Dosage of Drug Haloperidol Olanzapine Placebos |
| Outcomes |
Abnormal Involuntary Movement Scale (AIMS) Adverse effects Akathisia Barnes Akathisia Scale (BAS) Brief Psychiatric Rating Scale (BPRS) Clinical Global Impression (CGI) Coding Symbol and Thesaurus for Adverse Reaction Terms (COSART) Dopamine receptor blockade Dyskinesia Dystonia Extrapyramidal symptoms Global improvement / deterioration Kaplan-Meier Survival Curve Mental State Movement disorders Negative symptoms / indifference to environment / emotional withdrawal Parkinsonism Patient Global Impression (PGI) Physical tests Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Positive symptoms Prolactine level Research Diagnostic Criteria for Tardive Dyskinesia Schooler-Kane Research Diagnostic Criteria for Tardive Dyskinesia Simpson & Angus Neurological Rating Scale for Extrapyramidal Effects / Simpson-Angus Scale (SAS) Tardive dyskinesia |
| Link to Cochrane review | Olanzapine for schizophrenia |
| Collaborative Review Group | Cochrane Schizophrenia Group |
| Title | The acute and long-term effect of olanzapine compared with placebo and haloperidol on serum prolactin concentration |
| Authors | B. JONES et al. |
| Source | Schizophrenia Research |
| Date of publication | 1998 |
| Volume | 29 |
| Issue | 1,2 |
| Pages | 204 |
| Abstract | Prolaction elevation is both a common and persistent event with the currently marketed antipsychotic, excluding clozapine. Elevations have been associated with both acute (galactorrhea, amenorrhea) and chronic (predisposition to osteoporosis) treatment-emergent adverse events. One of the defining criteria for an atypical antipsychoitc is the relative lack of persistent prolactinemia. |
| Language | English |
| Title | What is the differential risk of tardive dyskinesia with the atypical antipsychotic olanzapine? |
| Authors | R. N. TAMURA et al. |
| Source | Schizophrenia Research |
| Date of publication | 1998 |
| Volume | 29 |
| Issue | 1 |
| Pages | 176 |
| Abstract | The incidene of tardive dyskinesia (TD) was evaluated in 1714 patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder treated with olanzapine or haloperidol for a period of up to 2.6 years in three randomized, double-blin, multicentre studies. It was hypothesized that olanzapine would be associated with a lower incidence of TD than haloperidol. |
| Language | English |
| Title | Extrapyramidal symptoms and tolerability of olanzapine versus haloperidol in the acute treatment of schizophrenia |
| Authors | P. V. TRAN et al. |
| Source | Journal of Clinical Psychiatry |
| Date of publication | 1997 |
| Volume | 58 |
| Issue | 5 |
| Pages | 205-11 |
| Abstract | BACKGROUND: A relative lack of extrapyramidal symptoms (EPS, i.e., the syndromes of dystonia, parkinsonism, akathisia, dyskinesia) is one criterion used to determine whether an antipsychotic is atypical. The extrapyramidal symptom profiles of the novel antipsychotic olanzapine and the conventional antipsychotic haloperidol were compared in a population of 2606 patients from three well-controlled prospective clinical trials. METHOD: Extrapyramidal symptom data were analyzed for 1796 patients treated with olanzapine (5 to 20 mg/day) and 810 patients treated with haloperidol (5 to 20 mg/day) for up to 6 weeks of therapy. Patients were monitored weekly by three methods of extrapyramidal symptom assessment: (1) detection of extrapyramidal adverse events (signs and symptoms) by casual observation, nonprobing inquiry, and spontaneous report; (2) objective rating scale scores: and (3) use of concomitant anticholinergic medications. Emergence of EPS was assessed by (1) analysis of the incidence of extrapyramidal syndrome categories based on adverse events, (2) the incidence of extrapyramidal syndromes based on categorical analysis of rating scale scores, (3) analysis of mean maximum change in rating scale scores, and (4) categorical analysis of anticholinergic medication use. Outcome of EPS was assessed by (1) analysis of mean change in rating scale scores at endpoint and (2) mean anticholinergic use at endpoint. RESULTS: Olanzapine was statistically significantly (p = .014, p < .001) superior to haloperidol in all four analyses related to emergence of EPS and in the two analyses related to outcome. Furthermore, during acute treatment, statistically significantly fewer patients treated with olanzapine (0.3%) discontinued the study because of any extrapyramidal adverse event than patients treated with haloperidol (2.7%, p < .001). CONCLUSION: Olanzapine exhibited a statistically significantly lower extrapyramidal symptom profile than the conventional antipsychotic haloperidol at comparably effective antipsychotic doses. The lower extrapyramidal symptom profile with olanzapine was evident despite statistically significantly more frequent use of anticholinergic drugs among haloperidol-treated patients. Fewer olanzapine-treated than haloperidol-treated patients discontinued because of EPS, suggesting that olanzapine should contribute to better compliance with longer term maintenance treatment, with minimal anticholinergic-associated events. |
| Language | English |
| MEDLINE Accession Number | 97328056 |
| Available Links | Link to the PubMed abstract on the National Library of Medicine website |
| Keywords | Adult-; Antipsychotic-Agents-Adverse-Effects; Basal-Ganglia-Diseases-Epidemiology; Double-Blind-Method; Drug-Administration-Schedule; Drug-Tolerance; Haloperidol-Adverse-Effects; Incidence-; Patient-Compliance; Patient-Dropouts; Pirenzepine-Adverse-Effects; Pirenzepine-Therapeutic-Use; Treatment-Outcome. *Antipsychotic-Agents-Therapeutic-Use; *Basal-Ganglia-Diseases-Chemically-Induced; *Haloperidol-Therapeutic-Use; *Pirenzepine-Analogs-and-Derivatives; *Schizophrenia-Drug-Therapy; ; Adult; Antipsychotic Agents/ae [Adverse Effects]; *Antipsychotic Agents/tu [Therapeutic Use]; *Basal Ganglia Diseases/ci [Chemically Induced]; Basal Ganglia Diseases/ep [Epidemiology]; Comparative Study; Double-Blind Method; Drug Administration Schedule; Drug To |
| Title | Olanzapine versus placebo, results of the United-States double-blind olanzapine trial |
| Authors | C. BEASLEY et al. |
| Source | 20th Congress of the Collegium Internationale Neuro-psychopharmacologicum; 1996 Jun 23-27; Melbourne, Australia |
| Date of publication | 1996 |
| Abstract | Study HGAP (n = 152) was a multicenter, double-blind, parallel trial comparing 2 fixed doses of olanzapine (Olz10.0, 10 mg/day and Olz1.0, 1 mg/day) to placebo with schizophrenic patients. The patients had an initial BPRS Total score of at least 24 (items scored 0). Efficacy analyses indicated that the Olz10.0 treatment group experienced statistically significantly greater mean improvement in BPRS Total, BPRS Positive, PANSS Total, PANSS Positive, PANSS Negative and PANSS General Psychopathology scores than the placebo treatment group. No statiscally significant differences were found between Olz1.0 and placebo in any of the efficacy scales. There were no adverse events reported at a statistically significantly greater rate among Olz10.0 treated patients compared to placebo treated patients. Very few treatment emergent events resulted in patient discontinuation from the olanzapine treatment arms (9.6% Olz1.0; 4% Olz10.0). A negligible number of treatment emergent extrapyramidal symptoms occured in patients on olanzapine. The results of this study indicates that olanzapine was effective in treating both the positive and negative symptoms of schizophrenia and was well tolerated. |
| Language | English |
| Title | The acute and long-term effect of olanzapine compared with placebo and haloperidol on serum prolactin concentrations |
| Authors | A. M. CRAWFORD et al. |
| Source | Schizophrenia Research |
| Date of publication | 1997 |
| Volume | 26 |
| Issue | 1 |
| Pages | 41-54 |
| Abstract | Prolactin elevation is both a common and a persistent event with the currently marketed antipsychotics, excluding clozapine. Elevations have been associated with both acute (galactorrhea, amenorrhea) and chronic (predisposition to osteoporosis) treatment-emergent adverse events. One of the defining criteria for an atypical antipsychotic is the relative lack of persistent prolactinemia. A double-blind, placebo- (N = 68) and haloperidol- (Hal: 15 +/- 5 mg/day, N = 69) controlled trial of three dose ranges of olanzapine (Olz-L: 5 +/- 2.5 mg/day, N = 65; Olz-M: 10 +/- 2.5 mg/day, N = 64; Olz-H: 15 +/- 2.5 mg/day, N = 69) in the treatment of schizophrenia afforded the opportunity to assess the temporal course of the influence of olanzapine and haloperidol on serum prolactin concentration. Consistent with its potent D2 antagonism, haloperidol was associated with a statistically significantly higher incidence of treatment-emergent prolactin elevation (72%) than seen with placebo (8%; p < 0.001) at week 2 of therapy. Expectedly, this elevation was also persistent at weeks 4 and 6. In contrast, olanzapine-associated treatment- emergent prolactin elevations were both lower in magnitude and transient. At week 2, 38% of the Olz-H, 24% of the Olz-M, and 13% of the Olz- L treatment groups exhibited a treatment-emergent prolactin elevation, with a mean increase of 0.35, 0.52, and 0.61 nmol/l, respectively; for haloperidol the mean increase was 1.23 nmol/l. For only the Olz-M and the Olz-H treatment groups did the week 2 incidence of treatment- emergent prolactin elevations differ statistically significantly from placebo. Both the incidence of elevations and the mean increase, in prolactin concentration were less than that seen with haloperidol. Furthermore, by treatment week 6, all three olanzapine groups exhibited incidences of treatment-emergent prolactin elevation that were comparable to placebo and were statistically significantly less than observed with haloperidol. Rapid adaptation was observed in the temporal course of prolactin elevations associated with olanzapine based on both the categorical analysis of treatment-emergent high values and the analyses of temporal change in mean concentrations. In contrast to haloperidol, the magnitudes of the treatment-emergent elevations associated with olanzapine were minimal. The rates of elevation were approximately one-half to one-third those observed with haloperidol and were significantly more transient. Olanzapine, even at the highest doses (15 +/- 2.5 mg/day) used, was not associated with persistent elevations of prolactin, consistent with an 'atypical' pharmacologic profile. |
| Language | English |
| MEDLINE Accession Number | 98017425 |
| Available Links | Link to the PubMed abstract on the National Library of Medicine website |
| Keywords | ; Adult; *Antipsychotic Agents/ae [Adverse Effects]; Antipsychotic Agents, Butyrophenone/ae [Adverse Effects]; Chi-Square Distribution; Cross-Sectional Studies; Dopamine Antagonists/ae [Adverse Effects]; Double-Blind Method; Female; *Haloperidol/ae [Adverse Effect; Adult-; Antipsychotic-Agents,-Butyrophenone-Adverse-Effects; Chi-Square-Distribution; Cross-Sectional-Studies; Dopamine- |
| Title | Randomised double-blind comparison of the incidence of tardive dyskinesia in patients with schizophrenia during long-term treatment with olanzapine or haloperidol |
| Authors | C. M. BEASLEY et al. |
| Source | British Journal of Psychiatry |
| Date of publication | 1999 |
| Volume | 174 |
| Pages | 23-30 |
| Abstract | BACKGROUND: Tardive dyskinesia is important in the side-effect profile of antipsychotic medication. AIMS: The development of tardive dyskinesia was evaluated in patients treated with double-blind, randomly assigned olanzapine or haloperidol for up to 2.6 years. METHODS: Tardive dyskinesia was assessed by the Abnormal Involuntary Movement Scale (AIMS) and Research Diagnostic Criteria for Tardive Dyskinesia (RD-TD), it was defined as meeting RD-TD criteria at two consecutive assessments. The risk of tardive dyskinesia, the relative risk, incidence rate, and incidence rate ratio were estimated. RESULTS: The relative risk of tardive dyskinesia for the overall follow up period for haloperidol (n = 522) v. olanzapine (n = 1192) was 2.66 (95% CI = 1.50-4.70). Based on data following the initial six weeks of observation (during which patients underwent medication change and AIMS assessments as frequently as every three days), the one-year risk was 0.52% with olanzapine (n = 513) and 7.45% with haloperidol (n = 114). The relative risk throughout this follow-up period was 11.37 (95% CI = 2.21-58.60). CONCLUSION: Our results indicated a significantly lower risk of tardive dyskinesia with olanzapine than with haloperidol. |
| Language | English |
| MEDLINE Accession Number | 99227593 |
| Available Links | Link to the PubMed abstract on the National Library of Medicine website |
| Keywords | ; *Antipsychotic Agents/ae [Adverse Effects]; Double-Blind Method; *Dyskinesia, Drug-Induced/et [Etiology]; *Haloperidol/ae [Adverse Effects]; Human; Pirenzepine/ae [Adverse Effects]; *Pirenzepine/aa [Analogs & Derivatives]; Risk Factors; *Schizophrenia/dt [Drug T; Double-Blind-Method; Pirenzepine-Adverse-Effects; Risk-Factors; Survival-Analysis. *Antipsychotic-Agents-Adverse-Effects; *Dyskinesia,-Drug-Induced-Etiology; *Haloperidol-Adverse-Effects; *Pirenzepine-Analogs-And-Derivatives; *Schizophrenia-Drug-Therapy. Antipsychotic-Agents; olanzapine; Pirenzepine; Haloperidol |
| Title | Additional clinical experience with olanzapine, an atypical antipsychotic |
| Authors | W. SATTERLEE et al. |
| Source | Schizophrenia Research |
| Date of publication | 1995 |
| Volume | 15 |
| Issue | 1,2 |
| Pages | 163 |
| Abstract | Olanzapine, structurally a thienobenzodiazepine, has demonstrated in vitro affinity for serotonin (5-HT)2a, 5-HT2c, dopamine (D)2, D4, D1, muscarine (particularly M1), x1-adrenergic, and H1 receptors. This broad receptor profile includes greater activity at 5-HT2a than at D2 receptors. In a randomized DOUBLE blind mulicentre clinical trial desinged to test the efficacy and safety of olanzapine, 152 schizophrenic patients were randomly assinged to 1 or 10 mg/d of olanzapine or placebo (Pbo). When baseline and endpoint scores were compared, the 10 mg dose olanzapine (-7.7) was statistically significantly superior to bo (-0.4) relative to mean change in BPRS positive, PANSS total, PANSS positive, and PANSS negative scores were compared olanzapine (10 mg) was statistically significally superior to Pbo and few treatment emergent extrapyramidal symptoms occurred in patients on olanzapine. Olanzapine (1mg does) was not significantly different than Pbo in terms of efficacy. Olanzapine's receptor profile, efficacy and its safety profile strongly suggest that olanzapine is a very promising atypical antipsychotic agent. |
| Language | English |
| Title | Olanzapine versus placebo - results of a double-blind, fixed dose olanzapine trial |
| Authors | J. r. BEASLEY CM et al. |
| Source | Psychopharmacology |
| Date of publication | 1996 |
| Volume | 124 |
| Issue | 1-2 |
| Pages | 159-67 |
| Abstract | Olanzapine is a potential new 'atypical' anTI:psychotic agent. This double-blind, acute phase study compared two doses of olanzapine [1 mg/day (Olz1.0); 10 mg/day (Olz10.0)] with placebo in the treatment of 152 patients who met the DSM-III-R criteria for SCHIZophrenia and had a Brief Psychiatric Rating Scale (BPRS)-total score (items scored 0-6)>=24. In overall symptomatology improvement [BPRS-total score and Positive and Negative Syndrome Scale (PANSS)-total score], Olz10.0 was statistically significantly superior to placebo. In positive symptom improvement (PANSS-positive score, BPRS-positive score), Olz10.0 was statistically significantly superior to placebo. In negative symptom improvement (PANSS-negative score), Olz10.0 was statistically superior to placebo. Olz 1.0 was clinically comparable to placebo in all efficacy comparisons. The only adverse event to show an overall statistically significant incidence difference was anorexia (reported for 10% of placebo- treated and 0% of Olz10.0- treated patients). The Olz10.0-treated patients improved over baseline with respect to parkinsonian and akathisia symptoms, and these changes were comparable with those observed with placebo. There were no dystonias associated with Olz10.0 treatment. At endpoint, the incidence of patients with elevated prolactin values did not differ statistically significantly between placebo-treated and Olz10.0- treated patients. Olanzapine appears to be not only safe and effective, but a promising atypical antipsychotic candidate. |
| Language | English |
| Keywords | neuroleptic agent/adverse drug reaction, olanzapine/adverse drug reaction, neuroleptic agent/clinical trial, olanzapine/clinical trial, |