- Email: [email protected]
Olanzapine for those with schizophrenia: A cochrane systematic review
187
HVA/5HIAA, and treatment response to clozapine in SA patients.
University Department, Psychiatric Hospital Vrapce, Bolnicka cesta 32, HR-IO000 Zagreb, Croatia
B. Olanzapine
Sample includes 47 schizophrenic patients, diagnosed according to DSM-IV, in a stable phase of illness, treated with clozapine ( N = 2 2 ) or olanzapine (N=25). Method: UKU Side Effect Rating Scale and ESRS were used in first six months of treatment. The patients self-evaluated the distress caused by each specific side effect at the time observed. Results: The most often side effects were: in olanzapine group - - weight gain (76% patients); in clozapine group salivation (45% patients) and sedation (36% patients). There is no significant difference in frequency of side effects in both groups. Significant difference was found in weight gain, salivation and sedation between two groups. Conclusion: The new antipsychotic drugs seem to produce fewer of less troublesome side effects; nevertheless, the substantial frequency of side effects could occur during the treatment. In order to enhance compliance and prevent relapse, the patients' distress should be brought to the psychiatrist's attention.
B.29. IS O L A N Z A P I N E A SUBSTITUTE CLOZAPINE? THE EFFECTS ON PSYCHOMOTOR PERFORMANCE
FOR
E.A.P. Oliemeulen 1, J.J.M. v a n H o o f 1, B.J.M. JogemsK o s t e r m a n 1, W. Hulstijn 1, H.G. T u y n m a n - Q u a 2 llnstitute for Mental Health Care, Oost-Brabant, PO Box 1, 5240 BA Rosmalen, The Netherlands, 2Eli Lilly Netherlands Olanzapine is a new atypical antipsychotic drug, which probably does have the advantages of clozapine, such as a positive effect on negative and cognitive symptoms and less (extrapyramidal) motor side effects, but not the disadvantages, like the incidence of agranulocytosis. This study aims at comparing the cognitive and motor effects of the two drugs. To this end a new method was used consisting of the computerized recording and analysis of writing and drawing movements on a digitizing tablet. Tasks were a figure copying task, a simple motor aiming task and a key-pressing task. In addition were administered three standard neuropsychological tests, the Digit Symbol Test (DST), the Trailmaking Test and a maze test, while pen movements were recorded. Subjects were therapy-resistant patients who met DSM-IV criteria for schizophrenia or other psychotic disorders. Patients were randomly assigned to receive olanzapine (n =21 ) or clozapine (n = 15). Our first analyses indicate that, after a treatment period of 8 weeks, the patients treated with clozapine showed a greater clinical improvement (PANSS) than the olanzapine treated patients. However, this was only significant (p<0.01) for the positive symptoms. Where the PANSS only showed a trend, psychomotor tests showed significant improvements in both the clozapine and olanzapine group and these improvements were about similar. Significant differences between the medication groups were found for the 'matching time' of the computerised SDS (in favour of clozapine) and the 'reaction time' of the Fitt's Aiming task (in favour of olanzapine). These first results show that our instrument seems to be more sensitive than classical scales and show differences in frontal lobe functioning of the two medication groups.
B.30. O L A N Z A P I N E VS. C L O Z A P I N E : SIDE EFFECTS AND DISTRESS IN SCHIZOPHRENIC PATIENTS M. Bajs-Bjegovic, P. Jelacic, S. Ivezic, S. U z u n , V. Folnegovic Smalc
References 1. Schausberger B., Folnegovic Smalc V., et al. Impact of Olanzapine vs. Fluphenazine on Patient's Drug Acceptance During Acute Treatment of Schizophrenia. 11tla World Congress of Psychiatry, Hamburg, August 6 11, 1999. Abstracts Vol. 2: 169. 2. Collaborative Working Group on Clinical Trial Evaluations: Measuring outcome in schizophrenia: differences among the atypical antipsychotics. J Clin Psychiatry, 1998; 59, Suppl 12: 3-9. 3. Kozaric Kovacic D., Folnegovic Smalc V., Mimica N., et al. Incidence of neuroleptic malignant syndrome during a 10-year follow-up at a psychiatric department. Neurologia Croatia, 43(2): 65 140, 1994.
B.31. O L A N Z A P I N E FOR THOSE WITH SCHIZOPHRENIA: A COCHRANE SYSTEMATIC REVIEW L. Duggan*, M. Fenton, R.M. Dardennes, A. E1-Dosoky, S. I n d r a n * Corresponding author: Dr Lorna Duggan, Consultant Forensic Psychiatrist in Development Disabilities, St Andrews Hospital, Billing Road, Northampton, NN1 5DG. Tel." (+44) 1604 616314; e-mail. 106650 3245@compuserve. corn Background: The search for antipsychotic agents to manage both 'positive' and 'negative' symptoms has produced a class of drug now called the 'atypical' antipsychotics. These compounds, including olanzapine, are said to have addressed the limitations of traditional antipsychotics in that they have promised better efficacy and/or side effect profiles. We present a systematic review assessing the efficacy of olanzapine in comparison with other treatments. Methods: A search was undertaken to identify all randomised
188
trials comparing olanzapine to placebo or other antipsychotic treatments for those with schizophrenia. All data were quality assessed, and included, if possible, into the review. Results: Eight trials were found. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (NNT 8). When olanzapine was compared to typical antipsychotics the greatest effect was seen in the outcome of 'no important clinical response' with 15mg olanzapine/day. Those given olanzapine had significantly fewer movement disorders than those receiving typical antipsychotics. Comparing olanzapine to other atypical antipsychotic drugs favour olanzapine in the long term for the outcome of 'no important clinical response'. Study attrition was high. By 52 weeks 83% of those taking olanzapine had left compared to 91% of those allocated to the comparitor drugs. Conclusions: Global impression suggests that 10-15 mg/day of olanzapine is antipsychotic, being better than placebo. If the illness is more severe then there is little to choose between olanzapine and typical and atypical antipsychotics.
B.32. T H E U S E O F O L A N Z A P I N E NHS TRUST
IN A UK
S.A. Osborne, J.C. Munro, R.W. Kerwin
Section of Clinical Neuropharmacology, Department of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK Objectives: To elucidate local olanzapine prescribing practices and treatment outcomes, for all inpatients in a psychiatric hospital who were prescribed olanzapine over a period of six months. Method: Prescription charts for adult inpatients within the Bethlem and Maudsley NHS Trust were screened weekly. Patients prescribed olanzapine were identified, and DSM-IV diagnosis as recorded by the Responsible Medical Officer was noted. Treatment endpoints were categorized as discharge on olanzapine, or discontinuation of olanzapine. Where olanzapine was discontinued, subsequent treatment was recorded. Results: Within six months, one hundred and twenty one patients reached an endpoint. Eighty-nine (73.5%) had a diagnosis of either schizophrenia or schizoaffective disorder, of these: fifty-two (58.4%) were discharged on olanzapine and thirty-seven (41.6%) discontinued olanzapine. Subsequent treatment for the thirty-seven who discontinued olanzapine: fifteen (40.5%) depot antipsychotic, nine (24.3%) clozapine, three (8.1%) haloperidol, two (5.4%) risperidone, one (2.7°/,) each for amisulpride, droperidol, quetiapine, sulpiride and trifluoperazine, three (8.1%) refused further medication. Conclusions: Currently in the UK, olanzapine is indicated only for the treatment of schizophrenia, but within this hospital trust, olanzapine was also being prescribed for patients with other diagnoses (e.g. bipolar disorder, personality disorder, organic psychosis). Less than one quarter of patients discontinuing olanzapine were subsequently treated with clozapine (the likely progression if treatment resistant). More than half the
patients switched from olanzapine to typical antipsychotics, the majority of those, receiving a depot preparation, suggesting that treatment adherence may have been a problem. B.33. C O M P A R A T I V E E F F I C A C Y O F OLANZAPINE AND HALOPERIDOL FOR PATIENTS WITH TREATMENT-RESISTANT SCHIZOPHRENIA A. Breier, M D , S.H. Hamilton, MS
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana Background: There is relatively little information regarding the efficacy of newer atypical antipsychotic drugs for patients with schizophrenia who are treatment-resistant to neuroleptic agents. Several lines of evidence suggest that a clinical trial of olanzapine in this population is warranted. Methods: A sub-population of patients (N=526) meeting treatment-resistant criteria selected from a large, prospective, double-blind, six-week study assessing the effÉcacy and safety of olanzapine and haloperidol was examined. Both last-observation-carried-forward (LOCF) and completers (observed cases) analyses were conducted. Results: Olanzapine demonstrated significantly greater mean improvement from baseline in Positive and Negative Syndrome Scale (PANSS) negative symptoms, co-morbid depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale, akathisia as measured by Barnes Akathisia Scale and extrapyramidal symptoms as measured by Simpson-Angus Extrapyramidal Rating Scale with both LOCF and completers analyses. In addition, olanzapine was significantly superior to haloperidol for Brief Psychiatric Rating Scale (BPRS) total (p=0.006), PANSS total (p=0.005), and PANSS positive symptoms (p=0.017) in completers of the six-week study. Significantly greater response rates were observed in olanzapine-treated (47%) than haloperidol-treated (35%) patients in the LOCF analysis (p = 0.008), but significance was not reached in the completers analysis (p=0.093). Mean doses (_+SD) of olanzapine and haloperidol were 11.1 _+3.4 mg/day and 10.0 + 3.6 mg/day, respectively. Conclusions: Olanzapine was superior to haloperidol for key symptom domains and parkinsonian adverse events. Implications of these data for the therapeutics of this severely ill subgroup are discussed.
B.34. D O S E S O F O L A N Z A P I N E , RISPERIDONE, AND HALOPERIDOL IN CLINICAL PRACTICE: RESULTS OF A PROSPECTIVE PHARMACOEPIDEMIOLOGICAL STUDY (EFESO) J.A. Sacristan, J.C. G6mez, K.J. Gregor, A.L. Montejo, E. Vieta, and the E F E S O Study G r o u p
HVA/5HIAA, and treatment response to clozapine in SA patients.
University Department, Psychiatric Hospital Vrapce, Bolnicka cesta 32, HR-IO000 Zagreb, Croatia
B. Olanzapine
Sample includes 47 schizophrenic patients, diagnosed according to DSM-IV, in a stable phase of illness, treated with clozapine ( N = 2 2 ) or olanzapine (N=25). Method: UKU Side Effect Rating Scale and ESRS were used in first six months of treatment. The patients self-evaluated the distress caused by each specific side effect at the time observed. Results: The most often side effects were: in olanzapine group - - weight gain (76% patients); in clozapine group salivation (45% patients) and sedation (36% patients). There is no significant difference in frequency of side effects in both groups. Significant difference was found in weight gain, salivation and sedation between two groups. Conclusion: The new antipsychotic drugs seem to produce fewer of less troublesome side effects; nevertheless, the substantial frequency of side effects could occur during the treatment. In order to enhance compliance and prevent relapse, the patients' distress should be brought to the psychiatrist's attention.
B.29. IS O L A N Z A P I N E A SUBSTITUTE CLOZAPINE? THE EFFECTS ON PSYCHOMOTOR PERFORMANCE
FOR
E.A.P. Oliemeulen 1, J.J.M. v a n H o o f 1, B.J.M. JogemsK o s t e r m a n 1, W. Hulstijn 1, H.G. T u y n m a n - Q u a 2 llnstitute for Mental Health Care, Oost-Brabant, PO Box 1, 5240 BA Rosmalen, The Netherlands, 2Eli Lilly Netherlands Olanzapine is a new atypical antipsychotic drug, which probably does have the advantages of clozapine, such as a positive effect on negative and cognitive symptoms and less (extrapyramidal) motor side effects, but not the disadvantages, like the incidence of agranulocytosis. This study aims at comparing the cognitive and motor effects of the two drugs. To this end a new method was used consisting of the computerized recording and analysis of writing and drawing movements on a digitizing tablet. Tasks were a figure copying task, a simple motor aiming task and a key-pressing task. In addition were administered three standard neuropsychological tests, the Digit Symbol Test (DST), the Trailmaking Test and a maze test, while pen movements were recorded. Subjects were therapy-resistant patients who met DSM-IV criteria for schizophrenia or other psychotic disorders. Patients were randomly assigned to receive olanzapine (n =21 ) or clozapine (n = 15). Our first analyses indicate that, after a treatment period of 8 weeks, the patients treated with clozapine showed a greater clinical improvement (PANSS) than the olanzapine treated patients. However, this was only significant (p<0.01) for the positive symptoms. Where the PANSS only showed a trend, psychomotor tests showed significant improvements in both the clozapine and olanzapine group and these improvements were about similar. Significant differences between the medication groups were found for the 'matching time' of the computerised SDS (in favour of clozapine) and the 'reaction time' of the Fitt's Aiming task (in favour of olanzapine). These first results show that our instrument seems to be more sensitive than classical scales and show differences in frontal lobe functioning of the two medication groups.
B.30. O L A N Z A P I N E VS. C L O Z A P I N E : SIDE EFFECTS AND DISTRESS IN SCHIZOPHRENIC PATIENTS M. Bajs-Bjegovic, P. Jelacic, S. Ivezic, S. U z u n , V. Folnegovic Smalc
References 1. Schausberger B., Folnegovic Smalc V., et al. Impact of Olanzapine vs. Fluphenazine on Patient's Drug Acceptance During Acute Treatment of Schizophrenia. 11tla World Congress of Psychiatry, Hamburg, August 6 11, 1999. Abstracts Vol. 2: 169. 2. Collaborative Working Group on Clinical Trial Evaluations: Measuring outcome in schizophrenia: differences among the atypical antipsychotics. J Clin Psychiatry, 1998; 59, Suppl 12: 3-9. 3. Kozaric Kovacic D., Folnegovic Smalc V., Mimica N., et al. Incidence of neuroleptic malignant syndrome during a 10-year follow-up at a psychiatric department. Neurologia Croatia, 43(2): 65 140, 1994.
B.31. O L A N Z A P I N E FOR THOSE WITH SCHIZOPHRENIA: A COCHRANE SYSTEMATIC REVIEW L. Duggan*, M. Fenton, R.M. Dardennes, A. E1-Dosoky, S. I n d r a n * Corresponding author: Dr Lorna Duggan, Consultant Forensic Psychiatrist in Development Disabilities, St Andrews Hospital, Billing Road, Northampton, NN1 5DG. Tel." (+44) 1604 616314; e-mail. 106650 3245@compuserve. corn Background: The search for antipsychotic agents to manage both 'positive' and 'negative' symptoms has produced a class of drug now called the 'atypical' antipsychotics. These compounds, including olanzapine, are said to have addressed the limitations of traditional antipsychotics in that they have promised better efficacy and/or side effect profiles. We present a systematic review assessing the efficacy of olanzapine in comparison with other treatments. Methods: A search was undertaken to identify all randomised
188
trials comparing olanzapine to placebo or other antipsychotic treatments for those with schizophrenia. All data were quality assessed, and included, if possible, into the review. Results: Eight trials were found. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (NNT 8). When olanzapine was compared to typical antipsychotics the greatest effect was seen in the outcome of 'no important clinical response' with 15mg olanzapine/day. Those given olanzapine had significantly fewer movement disorders than those receiving typical antipsychotics. Comparing olanzapine to other atypical antipsychotic drugs favour olanzapine in the long term for the outcome of 'no important clinical response'. Study attrition was high. By 52 weeks 83% of those taking olanzapine had left compared to 91% of those allocated to the comparitor drugs. Conclusions: Global impression suggests that 10-15 mg/day of olanzapine is antipsychotic, being better than placebo. If the illness is more severe then there is little to choose between olanzapine and typical and atypical antipsychotics.
B.32. T H E U S E O F O L A N Z A P I N E NHS TRUST
IN A UK
S.A. Osborne, J.C. Munro, R.W. Kerwin
Section of Clinical Neuropharmacology, Department of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK Objectives: To elucidate local olanzapine prescribing practices and treatment outcomes, for all inpatients in a psychiatric hospital who were prescribed olanzapine over a period of six months. Method: Prescription charts for adult inpatients within the Bethlem and Maudsley NHS Trust were screened weekly. Patients prescribed olanzapine were identified, and DSM-IV diagnosis as recorded by the Responsible Medical Officer was noted. Treatment endpoints were categorized as discharge on olanzapine, or discontinuation of olanzapine. Where olanzapine was discontinued, subsequent treatment was recorded. Results: Within six months, one hundred and twenty one patients reached an endpoint. Eighty-nine (73.5%) had a diagnosis of either schizophrenia or schizoaffective disorder, of these: fifty-two (58.4%) were discharged on olanzapine and thirty-seven (41.6%) discontinued olanzapine. Subsequent treatment for the thirty-seven who discontinued olanzapine: fifteen (40.5%) depot antipsychotic, nine (24.3%) clozapine, three (8.1%) haloperidol, two (5.4%) risperidone, one (2.7°/,) each for amisulpride, droperidol, quetiapine, sulpiride and trifluoperazine, three (8.1%) refused further medication. Conclusions: Currently in the UK, olanzapine is indicated only for the treatment of schizophrenia, but within this hospital trust, olanzapine was also being prescribed for patients with other diagnoses (e.g. bipolar disorder, personality disorder, organic psychosis). Less than one quarter of patients discontinuing olanzapine were subsequently treated with clozapine (the likely progression if treatment resistant). More than half the
patients switched from olanzapine to typical antipsychotics, the majority of those, receiving a depot preparation, suggesting that treatment adherence may have been a problem. B.33. C O M P A R A T I V E E F F I C A C Y O F OLANZAPINE AND HALOPERIDOL FOR PATIENTS WITH TREATMENT-RESISTANT SCHIZOPHRENIA A. Breier, M D , S.H. Hamilton, MS
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana Background: There is relatively little information regarding the efficacy of newer atypical antipsychotic drugs for patients with schizophrenia who are treatment-resistant to neuroleptic agents. Several lines of evidence suggest that a clinical trial of olanzapine in this population is warranted. Methods: A sub-population of patients (N=526) meeting treatment-resistant criteria selected from a large, prospective, double-blind, six-week study assessing the effÉcacy and safety of olanzapine and haloperidol was examined. Both last-observation-carried-forward (LOCF) and completers (observed cases) analyses were conducted. Results: Olanzapine demonstrated significantly greater mean improvement from baseline in Positive and Negative Syndrome Scale (PANSS) negative symptoms, co-morbid depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale, akathisia as measured by Barnes Akathisia Scale and extrapyramidal symptoms as measured by Simpson-Angus Extrapyramidal Rating Scale with both LOCF and completers analyses. In addition, olanzapine was significantly superior to haloperidol for Brief Psychiatric Rating Scale (BPRS) total (p=0.006), PANSS total (p=0.005), and PANSS positive symptoms (p=0.017) in completers of the six-week study. Significantly greater response rates were observed in olanzapine-treated (47%) than haloperidol-treated (35%) patients in the LOCF analysis (p = 0.008), but significance was not reached in the completers analysis (p=0.093). Mean doses (_+SD) of olanzapine and haloperidol were 11.1 _+3.4 mg/day and 10.0 + 3.6 mg/day, respectively. Conclusions: Olanzapine was superior to haloperidol for key symptom domains and parkinsonian adverse events. Implications of these data for the therapeutics of this severely ill subgroup are discussed.
B.34. D O S E S O F O L A N Z A P I N E , RISPERIDONE, AND HALOPERIDOL IN CLINICAL PRACTICE: RESULTS OF A PROSPECTIVE PHARMACOEPIDEMIOLOGICAL STUDY (EFESO) J.A. Sacristan, J.C. G6mez, K.J. Gregor, A.L. Montejo, E. Vieta, and the E F E S O Study G r o u p