Effect of olanzapine orally disintegrating tablet versus oral standard tablet on body weight in patients with schizophrenia: a randomized open-label trial

Olanzapine has frequently been reported to induce substantial weight gain, which is associated with an increased prevalence of dyslipidemia and type 2 diabetes. Several reports have described that olanzapine orally disintegrating tablets (ODT) induce less weight gain than oral standard tablets (OST) do, although both forms have equal bioavailability. We tried to clarify whether or not body weight change differed between olanzapine ODT and OST treatments in olanzapine-naïve schizophrenia patients. An open-label, 12-month, multicenter, randomized, flexible-dose study was conducted for direct comparison of the effects of OST (mean dosage, 15.7 mg; N = 57) and ODT (mean dosage, 15.2 mg; N = 61) on body weight and metabolic measures such as blood glucose, hemoglobin_A1c, total cholesterol and HDL-cholesterol, and triglycerides in olanzapine-naïve patients with schizophrenia. Outcome measures included Positive and Negative Syndrome Scale (PANSS), Global Assessment of Function (GAF), The World Health Organization Quality of Life 26 (WHO-QOL26), Drug Attitude Inventory (DAI)-10, and tolerability assessed by the UKU side-effect rating scale. This study was conducted between June 2007 and April 2010. No significant difference was found in the weight gain between the two forms of olanzapine. No significant difference was found between the two groups in any metabolic measure, efficacy, tolerability, WHO-QOL26, or DAI-10 score. Previous reports describing that olanzapine ODT induced less weight gain than OST were not supported by results of this randomized study.     

Olanzapine orally disintegrating tablet vs. risperidone oral solution in the treatment of acutely agitated psychotic patients

OBJECTIVE: Efficacy and tolerability of risperidone oral solution (RIS-OS) and olanzapine orally disintegrating tablet (OLZ-ODT) were compared for the treatment of acute psychotic agitation. METHOD: During a 2-month period, patients scoring > or =15 on the Excited Component for Positive and Negative Syndrome Scale (PANSS-EC) were assigned to treatment with OLZ-ODT (n=34) or RIS-OS (n=53) on psychiatric emergency situations, and assessed every 15 min. RESULTS: Two (OLZ-ODT and RIS-OS) by five (0-, 15-, 30-, 45- and 60-min time points) repeated-measures analysis of variance revealed only a significant main effect of time course on PANSS-EC (F=82.2, P<.0001). No differences in the number of patients receiving additional injection due to worsening were found (OLZ-ODT, 11.8%; RIS-OS, 9.4%). No differences in rate of extrapyramidal symptoms and patient satisfaction with assigned treatment were found. However, patients in the OLZ-ODT group recovered significantly more from tachycardia than those in the RIS-OS group (t=2.17, P=.03). CONCLUSION: OLZ-ODT and RIS-OS treatments yielded similar improvements in acutely agitated patients who accepted oral medication. However, on one physiological parameter (i.e., tachycardia) OLZ-ODT might be superior to RIS-OS. Physiological indicators may also be useful for measuring levels of agitation.     

Dissolution profile, tolerability, and acceptability of the orally disintegrating olanzapine tablet in patients with schizophrenia.

OBJECTIVE: This pilot study investigates the dissolution profile, tolerability, and acceptability of an orally disintegrating olanzapine tablet in patients with schizophrenia. METHOD: Eleven patients with schizophrenia stabilized on oral olanzapine (mean dosage 12.7 mg daily [SD5.2]) were given an orally disintegrating olanzapine tablet, rather than their usual tablet, daily for 7 days. At each visit, visual assessments were made for elapsed time to initial disintegration (every 15 seconds) and complete disintegration (every 1 minute). At the end of the study, patients completed a drug-acceptance questionnaire. RESULTS: The mean time to initial disintegration was 15.78 seconds, and mean time to complete disintegration was 0.97 minutes. All patients found the orally disintegrating tablet acceptable and expressed positive comments. Nonserious clinically significant adverse events, asthenia, purpuric rash, headache, depression, and insomnia (preexisting, except for asthenia and insomnia) were reported in 3 patients. CONCLUSION: The orally disintegrating olanzapine tablet disintegrates rapidly and is a well-tolerated and acceptable alternative to standard olanzapine tablets in patients with schizophrenia.     

Olanzapine orally disintegrating tablet: a review of efficacy and compliance

Medication nonadherence, especially in psychiatric disorders, has been associated with treatment failure and other negative outcomes. Orally disintegrating formulations have been developed as an alternative to improve medication adherence. This report reviews the properties, efficacy, and safety profile of olanzapine as an orally disintegrating tablet, and explores their association with medication compliance compared with standard oral formulation. Medical literature, published on orally disintegrating formulation of olanzapine identified using Pubmed and EMBASE, was used. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug. Studies evaluating the biostability, biodisposability, pharmacokinetics, efficacy, and safety of orally disintegrating olanzapine as treatment of patients with psychiatric disorders were reviewed. Measurement tools included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale, and Nursing Assessment of Medication Acceptance (NAMA). Orally disintegrating olanzapine, an effective atypical antipsychotic with an acceptable safety profile, can facilitate the burden of treatment on patients and caregivers due to its ease of administration. This is especially important in diseases such as schizophrenia and bipolar disorder, which can be chronic and require long-term treatment.     

Neurocognitive disorders in psychiatry: a case example of diagnostic and treatment dilemmas

We present a case example that illustrates the diagnostic and treatment difficulties engendered by adult psychiatric patients with primary behavioral problems and neurocognitive disorders. In the case cited, the neuropsychological evaluation plays a significant role in reconceptualizing a patient who had accrued multiple psychiatric diagnoses including schizophrenia, borderline personality, and impulse control disorder. Formal examination revealed deficits in language, executive, and attentional functions that were far greater than had been expected and led to a major change in treatment strategy, including successful trial of imipramine and nadolol and more structured milieu therapy. The cognitive deficit and intrapsychic conflict models are used to demonstrate the critical aspects of our diagnostic reclassification of the patient to Neurodevelopmental Disorder of Unknown Etiology and Auditory Attention Deficit Disorder.     

Orally disintegrating olanzapine for the treatment of a manic patient with esophageal stricture plus chronic pharyngitis

An orally disintegrating tablet formulation of olanzapine (ODT olanzapine) is designed to dissolve rapidly upon contact with saliva. We describe a manic patient who has an esophageal stricture and chronic pharyngitis, two conditions that impede the swallowing of medications. She was successfully treated for her mania with this orally disintegrating formulation. This case report shows that ODT olanzapine may be useful in the psychiatric management of manic and other patients for whom olanzapine is appropriate, and who have an underlying medical condition that impedes swallowing oral medications.     

Factors associated with adherence to treatment with olanzapine and other atypical antipsychotic medications in patients with schizophrenia

ObjectivesPoor treatment response is an important factor contributing to lack of treatment adherence. The goals of this research were to determine whether improvements in Positive and Negative Syndrome Scale (PANSS) symptom domains predict the likelihood of staying on treatment and whether differential responses to treatment with various atypical antipsychotics in specific symptom domains account for differences in discontinuation rates or treatment adherence.MethodsWe conducted a post-hoc analysis of pooled data from 5 randomized, double-blind, 24- to 28-week clinical trials in 1103 olanzapine-treated and 1090 risperidone-, quetiapine-, ziprasidone-, or aripiprazole-treated adult patients with schizophrenia. The 5 PANSS factors were tested as potential predictors of treatment adherence for all treatment groups combined. Treatment differences in the 5 PANSS factors and individual items were assessed between olanzapine and the other atypical antipsychotics combined. Secondary analyses repeated for the 21 Heinrichs Quality of Life Scale (QLS) items.ResultsImprovement in PANSS positive factor was the strongest predictor of treatment adherence, irrespective of medication (based on standardized scores, hazard ratio [HR], 1.58; 95% confidence interval [CI], +1.40 to +1.79; P < .001). Improvement in PANSS hostility (HR, 1.23; 95% CI, +1.11 to +1.37; P < .001) and depressive (HR, 1.15; 95% CI, +1.05 to +1.27; P = .002) factors was also a significant predictor; negative and disorganized thoughts factors were not. All QLS items had significant predictive effects. Olanzapine-treated patients showed significantly greater improvements than all other groups at week 24 on all 5 PANSS factors (P = .028 for negative; P < .001 for all others) and on 3 QLS items.ConclusionSignificant improvement in positive symptoms, regardless of treatment, followed by significant improvement in hostility and depressive symptoms, may best predict treatment adherence. Olanzapine-treated patients experienced significantly greater improvements in these specific symptoms than patients treated with the other atypical antipsychotics examined. These findings may further explain why olanzapine-treated patients continue treatment more often.     

Assessing the infrequent oral supplementation of olanzapine long-acting injection in the treatment of schizophrenia

Objective

Adding another antipsychotic to a treatment regimen was previously used in evaluating the medication's efficacy. Supplementation of depot antipsychotics with oral antipsychotics is particularly meaningful because depot formulations are typically chosen for patients struggling with adherence to oral antipsychotics. This post-hoc analysis assessed supplementation of olanzapine long-acting injection (olanzapine-LAI) with oral olanzapine.

Subjects and methods

We used 12 months of data from an open-label, single-arm extension study of patients with schizophrenia or schizoaffective disorder (N = 931) treated with olanzapine-LAI. The prevalence, duration, time to first supplementation, and best predictors of oral supplementation were assessed.

Results

Oral supplementation occurred in 21% of patients for a median of 31 days with mean modal dose of 10.8 mg/day. Mean time to first supplementation was shorter for patients who were at least moderately ill at baseline compared to less ill patients (47 vs. 97 days, p < 0.001). Best predictors of oral supplementation included a more severe illness profile at baseline, lower olanzapine-LAI dose prior to oral supplementation, supervised living arrangements, and being African-American.

Conclusion

Supplementation of olanzapine-LAI appears to be infrequent, of relatively short duration, and reserved for more severely ill patients who may require a targeted rescue medication due to signs of impending relapse.     

The relevance of pharmacological studies to sleep research in psychiatry

The involvement of central serotonergic mechanisms in the organisation of human sleep has been confirmed in several single and multiple-dose clinico-pharmacological studies with the specific serotonin-S2-antagonist ritanserin. The pronounced thymosthenic effect observed with this compound in patients suffering from dysthymia, generalized anxiety disorder and negative symptoms of schizophrenia can possibly be attributed to a restoration of the energetic function during the night as a consequence of a dramatic increase in slow wave sleep during treatment with ritanserin.     

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.     

奥氮平合并碳酸锂治疗女性急性躁狂发作的疗效及依从性

目的探讨使用奥氮平、利培酮、氯氮平3种非典型抗精神病药分别合并碳酸锂治疗女性躁狂发作疗效和院外服药依从性。方法按照随机的原则将84例女性患者分为3组,分别使用奥氮平、氯氮平、利培酮合并碳酸锂治疗,在急性期不少于4周的住院期间使用Bech—Rafaelsen躁狂量表（BRMS）、临床总体印象量表（CGI）评估疗效;院外治疗期8周内,应用在Morisky问卷基础上改进的自编依从性问卷对患者及其家属进行调查。结果住院期间奥氮平组起效时间中位数为3d,明显早于利培酮组的（7d）（Z=4．75,P〈0．01）;奥氮平组与氯氮平组（3d）的起效时间差异无统计学意义;治疗2周、4周后奥氮平组BMRS减分值与氯氮平组相当（Z=0．54、0．67,P=0．40、0．49）,而大于利培酮组（Z=3．04、1．98,P〈0．01、P=0．04）。随访期间奥氮平组服药依从性评分高于其他两组。结论奥氮平应用于女性急性躁狂发作患者起效迅速,维持治疗时服药依从性良好,其常见不良反应为过度镇静、头晕和体质量增加。     

Depression and anxiety: from clinic to pharmacological treatment

Either as a symptom or as a trait of an axis I disorder, anxiety is frequently associated with depressive episodes. Its treatment depends mainly of the syndrome in which it is included. While the selective serotonin reuptake inhibitors seem to be indicated in depression with comorbid anxiety disorders and in anxious depression, in agitated depression may be preferable to indicate mood stabilizers or sedative antipsychotics. Benzodiazepines may be useful at the beginning of the treatment of these special forms of depression, but it is advisable to tapper them off once the affective and/or the anxiety disorders improve.     

奥氮平治疗抑郁症的增效作用

目的：探讨小剂量奥氮平对艾司西酞普兰治疗无精神病性症状抑郁症的增效作用及安全性。方法：将60例无精神病性症状抑郁症患者随机分为艾司西酞普兰组及艾司西酞普兰合并奥氮平组,治疗6周。于治疗前、治疗1、2、6周末分别应用Hamilton抑郁量表（HAMD）及治疗中出现的症状量表（TESS）评定疗效及不良反应。结果：合用小剂量奥氮平组疗效显著好于单用艾司西酞普兰组,合用组治疗各周HAMD评分下降比单用组更为显著。两组TESS评分无显著差异。结论：合用小剂量奥氮平治疗抑郁症可提高疗效,且起效快。