Quality of life in schizophrenia: a multicenter, randomized, naturalistic, controlled trial comparing olanzapine to first-generation antipsychotics

OBJECTIVE: To assess the effectiveness of olanzapine for treating schizophrenia and to assess if olanzapine promotes a better quality of life than first-generation antipsychotics (FGAs). METHOD: Multicenter, naturalistic, randomized controlled study, comparing olanzapine with FGAs, at hospitalization and during a 9-month follow-up. Outcome assessors were blind to the allocated drug. The dose of antipsychotic was determined by doctors according to their clinical practice routines. Data collection was performed from April 1999 to August 2001. RESULTS: 197 patients with DSM-IV-diagnosed schizophrenia were allocated to olanzapine (N = 104) and FGA (N = 93). Patients taking olanzapine showed greater improvements in Positive and Negative Syndrome Scale (PANSS) negative symptoms (mean difference = 2.3, 95% CI = 0.6 to 4.1) and general psychopathology (mean difference = 4.0, 95% CI = 0.8 to 7.2) sub-scales and fewer incidences of tardive dyskinesia (RR = 2.4, 95% CI = 1.4 to 4.2, p < .0001). Olanzapine was also associated with greater improvement in a number of health-related quality-of-life outcomes on the Medical Outcomes Study 36-item Short-Form Health Survey, including physical functioning (mean difference = 6.6, 95% CI = 1.2 to 11.9), physical role limitations (mean difference = 13.7, 95% CI = 3.0 to 24.3), and emotional role limitations (mean difference = 12.1, 95% CI = 0.7 to 23.5). Patients taking olanzapine gained significantly more weight during the trial than patients taking FGAs, with a correspondent endpoint increase in the body mass index (BMI) of 28.7 versus 25.3 (p < .001). CONCLUSION: Compared with FGAs, olanzapine has advantages in terms of improvements of negative symptoms and quality of life. It is also associated with fewer incidences of tardive dyskinesia and greater increases in weight and BMI. These findings are highlighted by the naturalistic approach adopted in this trial.     

Weight decline in patients switching from olanzapine to quetiapine

This open-label study investigated the strategy of switching patients who had gained excessive weight on olanzapine to quetiapine, with assessments of safety and continued efficacy as well as weight change. Patients who were psychiatrically stable on olanzapine but had gained >20% in weight and had body mass index >25 mg/kg(2) were switched to quetiapine over a 4-week period and followed for 6 weeks, the total study duration being 10 weeks. Assessments included weight change, antipsychotic efficacy using the Positive and Negative Symptom Syndrome Scale (PANSS), extrapyramidal adverse events using the Simpson-Angus Scale (SAS), and laboratory studies for metabolic measures. Of 16 enrolled patients, 12 completed the study. Mean weight loss was 2.25 kg (Cohen's d = 0.12; P = 0.03). There were no significant changes in PANSS total scores, SAS scores, or metabolic parameters. Switching patients to quetiapine, appears to be a viable strategy for managing olanzapine-induced weight gain as indicated by this 10-week open-label study. Prospective controlled trials of longer duration and larger number of subjects are needed.     

Effectiveness and safety of olanzapine in the treatment of schizophrenia among Asian patients switching from conventional antipsychotics

OBJECTIVES: The objectives of this study were: (1) to investigate, in a clinical practice setting, the effectiveness of olanzapine in the treatment of schizophrenia among partially-responding, symptomatic Asian patients who switch from conventional antipsychotic treatment, (2) to assess the safety of olanzapine and (3) to assess the change in quality of life in Asian patients with schizophrenia who switch to olanzapine. METHODS: Effectiveness, safety and quality of life were assessed in outpatients with schizophrenia (n=1267) who lacked symptomatic control with conventional antipsychotics and were switched to olanzapine therapy. Data for this prospective, observational study were collected for 12 months from Asian patients in China, Hong Kong, the Philippines, South Korea and Taiwan. RESULTS: Significant clinical improvements (P<0.05) were observed following 12 months of olanzapine treatment and 87.3% of the subjects responded to treatment at endpoint (i.e. Brief Psychiatric Rating Scale Total score reduced by > or =30% relative to baseline; last observation carried forward). Abnormal involuntary movements (mean change in Abnormal Involuntary Movement Scale: -3.20, P<0.001) and quality of life were significantly improved in patients treated with olanzapine. However, some patients experienced significant weight gain (3.60+/-4.50 kg, P<0.001) with olanzapine treatment, relative to baseline. CONCLUSIONS: This study shows that switching to olanzapine may be effective in improving symptoms, may be well-tolerated and may improve the quality of life in Asian patients who are only partially responsive to treatment with conventional antipsychotics. The pragmatic design and naturalistic setting of this large study make the findings relevant for treating patients from some Asian countries in routine clinical practice.     

Switching to risperidone after unsuccessful treatment of olanzapine in the first-episode schizophrenia: an open trial

The purpose of this study was to assess the effect of switching to risperidone in the treatment of first-episode schizophrenia who had failed to respond to an initial-prescribed antipsychotic, olanzapine. Fifty-one patients with first-episode schizophrenia after unsuccessful treatment of olanzapine (the mean (S.D.) dosage: 16.4 (4.4) mg/day) were included in this switching study. Of the 51 patients, 43 (84.3%) completed the full 12-week trial and 8 (15.7%) dropped out. The mean dosage of risperidone at the endpoint (last observation) was 3.1 (2.0) mg/day. The total scores of Brief Psychiatric Rating Scales (BPRS) were significantly reduced from baseline to endpoint, especially in the positive and excitement factors (p<0.001). Responder rate (at least 20% decrease in BPRS total score plus final Clinical Global Impression score of 3 or less) was 35.3%. These findings indicate that the switching to risperidone could be one of the useful treatment options in this population.     

奥氮平换用齐拉西酮治疗精神分裂症的安全性和有效性研究

目的 观察不能耐受奥氮平治疗或经奥氮平治疗无效的精神分裂症患者换用齐拉西酮治疗12周的安全性和有效性.方法 100例不能耐受奥氮平治疗或治疗无效、符合美国精神疾病诊断与统计手册第4版(DSM-IV)精神分裂症诊断标准、首次发作或非难治性复发精神分裂症患者,换用可变剂量的齐拉西酮治疗12周.分别于基线和治疗第2、4、8、12周末进行疗效评估,包括阳性和阴性综合征量表(PANSS)、卡尔加里抑郁量表(CDSS)、临床总体印象量表(CGI)、生活质量量表(SF-12).分别于基线和治疗第4、8周末进行安全性评估,包括锥体外系不良反应量表(SAS)、实验室检查和心电图检查.采用重复测量方差分析进行统计学分析.结果 86例患者完成实验.PANSS总分随观察时点变化有显著性降低(P ＜0.001),多项抑郁症状(CDSS评估)、临床总体印象(CGI评分)及社会功能(SF-12评估)随观察时点变化有显著改善(P ＜0.001).有完整的不良反应记录共61例,常见的锥体外系不良反应22例(36.07％),相对少见的不良反应10例(16.39％),包括激越2例(3.28％)、恶心1例(1.64％)、便秘1例(1.64％)、失眠1例(1.64％)、头晕1例(1.64％)、头痛1例(1.64％)、焦虑1例(1.64％)、口干1例(1.64％)、心动过速1例(1.64％).空腹血糖、糖化血红蛋白、甘油三酯、总胆固醇和催乳素以及心电图QTc间期和心率随观察时点的变化无统计学意义(P＞0.05).结论 不能耐受奥氮平治疗或经奥氮平治疗无效的患者换用齐拉西酮治疗后,临床症状显著改善,不良反应较少,对代谢指标的影响小.     

Switching from depot antipsychotic drugs to olanzapine in patients with chronic schizophrenia

BACKGROUND: Patients with chronic schizophrenia (DSM-IV criteria) often receive depot antipsychotic medications to assure longer administration and better compliance with their treatment regimen. This study evaluated whether patients stabilized on depot antipsychotic medication could be successfully transitioned to oral olanzapine. METHOD: In a 3-month open-label study, 26 clinically stable patients with schizophrenia taking depot antipsychotics for over 3 years were randomly assigned to continue on their current depot dose or to switch to oral olanzapine. Clinical ratings (Positive and Negative Syndrome Scale [PANSS], Global Assessment of Functioning [GAF] scale, and Clinical Global Impressions [CGI] scale) and side effect parameters (Abnormal Involuntary Movement Scale [AIMS], Barnes Akathisia Scale, AMDP-5 scale, vital signs, and weight) were obtained monthly. RESULTS: Oral olanzapine patients (N = 13) demonstrated significant clinical improvement over the depot control group (N = 13) from baseline to 3-month endpoint (PANSS total, p =.012; PANSS general, p =.068; PANSS negative, p =.098; CGI-Improvement, p =.007; CGI-Severity, p =.026; GAF, p =.015). Side effect rating scales showed no statistical differences between the 2 groups (AIMS, Barnes Akathisia Scale, AMDP-5, vital signs). The depot control group showed no statistical superiority in any measure except weight change (p =.0005). After 3 months, all olanzapine patients preferred olanzapine to their previous depot medications and chose to continue on olanzapine treatment. CONCLUSION: Clinicians may expect clinical improvement when switching chronically psychotic patients from traditional depot antipsychotic drugs to oral olanzapine. Switching may be completed within a 4-week period with relative compliance being maintained and patients preferring oral olanzapine to their previous depot medications.     

Atypical antipsychotics in the treatment of fibromyalgia: a case series with olanzapine

Fibromyalgia is a common and disabling chronic pain syndrome. Although a wide array of symptomatic pharmacological treatments has been used to treat this condition, only modest results have been obtained. Olanzapine has been proven effective in some chronic pain conditions. The authors present a case series of patients suffering from fibromyalgia who received olanzapine as add-on therapy during a 3-month period. Olanzapine (2.5-20.0 mg/day) was administered to 25 consecutive patients (24 females, 1 male) meeting the American College of Rheumatology diagnostic criteria for fibromyalgia, and who were receiving nonsteroidal anti-inflammatory drugs (NSAIDs; 68%), benzodiazepines/zolpidem (48%), antidepressants (32%), and cyclobenzaprine (4%), either alone or in combination. Overall, 6 of the 14 patients (43%) who completed the 12-week trial reported to be much or very much improved ('responders'), according to the Clinical Global Impression (CGI) scale and 7 of them (50%) reported a good or very good sense of well-being. Olanzapine's modal dose among responders was 10.0 mg/day. It was discontinued in 11 patients (44%) due to adverse reactions, most commonly weight gain (n=5, 20%). Our preliminary findings suggest a possible role for olanzapine in treating fibromyalgia. Unfortunately, the beneficial outcome of olanzapine was largely obscured by its poor tolerability, which could be explained by the greater propensity of patients with fibromyalgia to adverse drug reactions, and the greater risk of antipsychotic-induced weight gain among women. Whether other atypical antipsychotics will provide similar symptomatic relief, while showing a better tolerability profile than olanzapine in patients with fibromyalgia, should be further investigated.     

Insight in persons with schizophrenia: effects of switching from conventional neuroleptics to atypical antipsychotics

The primary aim of our study is to evaluate the level of insight during the switch from a classical antipsychotic drug to a atypical neuroleptic. Twenty-two schizophrenic patients were admitted to the study, 9 were male and 13 were female. Standardized questionnaire were: Scale for Assessment of Negative Symptoms (SANS), Scale for Assessment of Positive Symptoms (SAPS), Brief Psychiatric Rating Scale (BPRS) and Schedule for Assessing the three components of Insight (SAI). All patients were receiving haloperidol at time of recruitment. Eight patients were switched to clozapine, 3 to risperidone and 11 to olanzapine. The global function, measured with BPRS, increased after administration of atypical antipsychotics. The positive and negative symptoms were reduced. The level of insight was increased after the administration of the atypical antipsychotics. The cognitive effect of the atypical antipsychotics changed the level of insight and augmented the compliance.     

An unblinded comparison of the clinical and cognitive effects of switching from first-generation antipsychotics to aripiprazole, perospirone or olanzapine in patients with chronic schizophrenia

The objective of this study, the effect of aripiprazole on clinical symptoms and cognitive function in patients with chronic schizophrenia was compared to that of perospirone and olanzapine. The subjects were 31 patients, they were diagnosed with schizophrenia on the basis of the criteria of the DSM-IV. Clinical symptoms were assessed using Brief Psychiatric Rating Scale (BPRS), and cognitive function was assessed using the Wisconsin Card Sorting Test (Keio Version: KWCST) and the St. Marianna University School of Medicine's Computerized Memory Test (STM-COMET) as executive function and memory/attention function tests at baseline and 8 weeks after switching. As a result, comparison of the BPRS mean total score revealed no significant difference between aripiprazole and the other medications. Aripiprazole resulted in significant changes in the number of categories achieved (CA) and difficulty maintaining set (DMS) compared to olanzapine at the second level of the KWCST. Comparison thus revealed no difference in clinical effect between aripiprazole and the other medications, but might suggest possible differences between aripiprazole and olanzapine in the profiles of the improvement effects on executive function, memory, and attention function.     

Defining and assessing adherence to oral antipsychotics: a review of the literature

The definition and assessment of adherence vary considerably across studies. Increasing consensus regarding these issues is necessary to improve our understanding of adherence and the development of more effective treatments. We review the adherence literature over the past 3 decades to explore the definitions and assessment of adherence to oral antipsychotics in schizophrenia patients. A total of 161 articles were identified through MEDLINE and PsycINFO searches. The most common method used to assess adherence was the report of the patient. Subjective and indirect methods including self-report, provider report, significant other report, and chart review were the only methods used to assess adherence in over 77% (124/161) of studies reviewed. Direct or objective measures including pill count, blood or urine analysis, electronic monitoring, and electronic refill records were used in less than 23% (37/161) of studies. Even in studies utilizing the same methodology to assess adherence, definitions of an adherent subject varied broadly from agreeing to take any medication to taking at least 90% of medication as prescribed. We make suggestions for consensus development, including the use of recommended terminology for different subject samples, the increased use of objective or direct measures, and the inclusion in all studies of an estimate of the percentage of medication taken as prescribed in an effort to increase comparability among studies. The suggestions are designed to advance the field with respect to both understanding predictors of adherence and developing interventions to improve adherence to oral antipsychotic medications.     

Efficacy and tolerability of aripiprazole: a 26-week switching study from oral antipsychotics

Objective

To determine if the maintenance effectiveness and tolerability of aripiprazole demonstrated in a 12-week study were maintained in an extension phase (up to 26 weeks).

Methods

This study was the extension of our switching study from other antipsychotics to aripiprazole in symptomatically stable patients with schizophrenia or schizoaffective disorder. All the patients were randomly assigned to the aripiprazole group or the non-aripiprazole group. The effectiveness analysis consisted of the comparison of the upper bound of the 95% confidence interval (CI) of the mean Clinical Global Impression-Improvement (CGI-I) score to 4 (no change) at the end of the study.

Results

At the baseline, the aripiprazole group (n=135) and the non-aripiprazole group (n=31) were comparable with respect to their mean ages, gender distribution, baseline Positive and Negative Syndrome Scale scores, and Clinical Global Impression-Severity (CGI-S) scores. The study showed that the mean CGI-I score was 2.92 (95% CI: 2.72-3.12) in the aripiprazole group and 2.81 (95% CI: 2.35-3.26) in the non-aripiprazole group at 26 weeks. In the aripiprazole group, the remission rates at 12 and 26 weeks were 74.8% and 72.6%, respectively, and 80.2% of the patients with remission at 12 weeks maintained their remission state until the end of the study. About one-fourth of the patients in the aripiprazole group reported one or more spontaneous treatment-emergent adverse events, such as insomnia, headache, and nausea.

Conclusion

This study suggested that most clinically stable outpatients with schizophrenia maintain their remission states after being switched to aripiprazole, without serious symptom aggravation and adverse events over a course of 26 weeks.     

Switching from conventional antipsychotics to ziprasidone: A randomized,open-label comparison of regimen strategies

In clinical psychopharmacology, the optimal method of switching from treatment A to treatment B with regard to efficacy and tolerability is an important area of study. We investigated the effects on efficacy and tolerability of switching patients from conventional antipsychotics to ziprasidone. This was a 6-week open-label, randomized study of 54 patients with persistent schizophrenia or schizoaffective disorder. Patients received ziprasidone 40 mg BID for 2 days, with titration up to 80 mg BID thereafter. The switch from conventional antipsychotics to ziprasidone was achieved using one of three discrete schedules: (1) abrupt discontinuation of conventional antipsychotics on day 1; (2) fast taper—50% of conventional antipsychotic dosage on days 1 through 7, followed by discontinuation and (3) slow taper—100% of conventional antipsychotic dosage on days 1 and 2, followed by 50% on days 3 through 7, then discontinuation. We found some evidence that the slow-taper strategy was associated with greater reductions in BPRS total scores early in the study compared to the other two strategies. However, these differences did not remain significant at endpoint, suggesting that there was no overall difference between the strategies.     

Effects of switching from conventional antipsychotics to risperidone in Japanese patients with chronic schizophrenia

Atypical antipsychotics are rapidly evolving to become the standard pharmacotherapy in schizophrenia; however, the trend of switching to such drugs is not necessarily progressing quickly in East Asia. This might be due to the scarcity of evidence for the efficacy of switching from conventional to atypical antipsychotics, which prompted the authors to examine effects of switching from conventional antipsychotics to an atypical drug, risperidone, in Japanese patients. Fifty patients with chronic schizophrenia completed the study in which combination therapy with other antipsychotics was allowed if monotherapy with risperidone was not tolerated. Symptoms were assessed with the brief psychiatric rating scale (BPRS). Switching to monotherapy was achieved in 34 patients (68%). The number of antipsychotics prescribed to each patient was reduced (from 2.1 to 1.4 drugs; P < 0.001) and the use of antiparkinsonian drugs decreased (P < 0.001). The mean BPRS score was also reduced 6 months after initiation of the switch (P < 0.001). Failure in switching to monotherapy was associated with higher dosage of antipsychotics at baseline. Switching from conventional antipsychotics to risperidone reduced schizophrenia symptoms, antiparkinsonian medication, and polypharmacy. However, a portion of patients, particularly those who receive an excessive dosage of antipsychotics, might not tolerate such switching.     

Eight-year follow-up of olanzapine therapy in a previous treatment-refractory schizophrenic patient: a case report

The introduction of atypical antipsychotic drugs during the 1990s represented a great step forward in the treatment of schizophrenia and other psychoses. These drugs might more effectively prevent relapse because of their effectiveness against a wider range of schizophrenic symptoms, as well as their improved tolerability, which leads to improved medication compliance. Olanzapine, a thienobenzodiazapine, is an antipsychotic drug with high affinity for the serotonergic receptors 5-HT 2 and 5-HT 6 and high affinity for dopaminergic receptors, mainly D2, D3 and D4, and with a lower propensity to cause extrapyramidal symptoms or increasing prolactin levels. The long-term efficacy and safety of olanzapine for treating treatment-refractory schizophrenia is still being investigated. The authors present a case of a 43-year-old man suffering from chronic treatment-resistant schizophrenia with both positive and negative symptoms, who was successfully treated with olanzapine for 8 years. (Int J Psych Clin Pract 2002; 6: 211-214 )     

Atypical antipsychotics and weight gain in Chinese patients: a comparison of olanzapine and risperidone

OBJECTIVE: To compare the effect of olanzapine with that of risperidone on weight change among Chinese patients in Hong Kong. METHOD: The body weight of subjects maintained on olanzapine or risperidone treatment was recorded at the outpatient clinic of a teaching hospital. Pretreatment weight of the subjects was retrieved from case records. Subjects on olanzapine treatment were matched in sex, age, and diagnosis with those on risperidone treatment, and demographic and clinical data were analyzed. The study was conducted in May and June 2002. RESULTS: Twenty-eight olanzapine-risperidone matched pairs were studied. All were diagnosed with DSM-IV schizophrenia. In patients treated with olanzapine and risperidone, respectively, mean +/- SD duration of treatment with atypical neuroleptics was 103.5 +/- 47.4 weeks and 93.2 +/- 50.6 weeks (range, 21-255 weeks), and mean doses were 12.4 +/- 6.7 mg/day and 4.5 +/- 2.8 mg/day. The mean +/- SD weight gain of subjects on treatment with olanzapine and risperidone, respectively, was 8.34 +/- 5.97 kg (18.53 +/- 13.27 lb) and 2.74 +/- 8.09 kg (6.09 +/- 17.98 lb) with a statistically significant difference at p < .005. Lower baseline body weight and body mass index were associated with greater weight gain in both olanzapine- and risperidone-treated subjects. Gender, age, mean daily dose, and duration of treatment had no effect on weight change. CONCLUSION: Treatment with olanzapine was associated with significantly greater weight gain than treatment with risperidone in Chinese schizophrenia patients in Hong Kong. The effect of adjunctive anticonvulsant treatment on weight gain requires further study.     

Improvement in cognitive function following a switch to ziprasidone from conventional antipsychotics, olanzapine, or risperidone in outpatients with schizophrenia

OBJECTIVE: To assess changes in cognitive function in stable outpatients with schizophrenia switched to ziprasidone from conventional antipsychotics (n = 108), olanzapine (n = 104), or risperidone (n = 58) because of suboptimal efficacy or poor tolerability. METHODS: In three separate 6-week trials, patients received ziprasidone 40 mg b.i.d. for 2 days, followed by 20-80 mg b.i.d. for the next 40 days. Before switching, and at endpoint, patients were evaluated with tests of working and secondary verbal memory, vigilance, visuomotor speed, verbal fluency, and executive functioning. Principal components factor analysis was performed to test for clustering of cognitive variables. RESULTS: Significant improvements were seen at endpoint in secondary verbal memory (in all three groups), vigilance (in patients switched from conventional antipsychotics or risperidone), executive function (in patients switched from conventional antipsychotics or risperidone), and verbal fluency. Factor analysis on baseline scores suggested reduction of the cognitive variables to three factors: verbal skills, attention and short-term memory, and executive functioning. Analysis of z-transformed mean change in factor scores showed significant improvement in verbal skills and global score following the switch from conventional antipsychotics, olanzapine, or risperidone. CONCLUSIONS: Patients requiring a change in antipsychotic therapy may exhibit cognitive improvement following a switch to ziprasidone.