olanzapine and Dyskinesia--Drug-Induced

The aim of this paper is to present a case of paliperidone-induced Pisa syndrome and provide treatment experience.. The case report is combined with a review of the literature.. A 37-year-old man had been diagnosed with paranoid-type schizophrenia for about 10 years. He received three-month treatment of paliperidone extended release (ER) at 6 mg per day, but showed a progressively Pisa-like physical position. We initially added an anticholinergic drug, but saw no improvement. The paliperidone ER was replaced by olanzapine at 10 mg per day, and the Pisa-like symptom improved after 1 month of the drug replacement.. We propose olanzapine as a possible replacement choice for patients with paliperidone-related Pisa syndrome.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Dystonia; Humans; Male; Olanzapine; Paliperidone Palmitate; Psychiatric Status Rating Scales; Schizophrenia, Paranoid; Syndrome

The purpose of this project was to provide evidence-based guidance concerning when and how it is appropriate to undertake elective changes in antipsychotic medications in order to reduce adverse effects, with a focus on those adverse effects associated with increased long-term health risks. This project extends the results of the National Institute of Mental Health-funded 2009 Schizophrenia Patient Outcomes Research Team (PORT) psychopharmacologic treatment recommendations. The authors reviewed the literature on switching antipsychotics, focusing on randomized controlled trials published since the 2009 Schizophrenia PORT. The studies reviewed support a recommendation that an elective switch from higher to lower metabolic risk antipsychotics can produce weight and lipid benefits without significant risk of clinical deterioration. Evidence also suggests that certain antipsychotic switches may improve other adverse effects, including extrapyramidal symptoms and prolactin elevation. In deciding to make an elective change of antipsychotic medication, it is important to conduct a careful risk/benefit assessment with the patient. Before initiating a switch, patients should be educated about what to expect during the process. Studies also support gradual discontinuation of the current medication in order to minimize problems early in the switching process.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Weight; Drug Substitution; Dyskinesia, Drug-Induced; Evidence-Based Medicine; Humans; Lipids; Olanzapine; Patient Outcome Assessment; Piperazines; Psychiatric Status Rating Scales; Quinolones; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study was funded by the National Institute of Mental Health to compare the effectiveness of drugs for schizophrenia. The focus here is not on its conclusions but on the knotty issues of design and methods, in order to support appropriate clinical interpretation of the conclusions, and on using the CATIE experience to indicate directions for improvement of future clinical trials. While many of the CATIE design and implementation decisions are excellent and serve as models for future research, other decisions resulted in a study with a large study group but inadequate power. Multiple treatment interventions, unbalanced randomization within and across clinical sites, and multiple secondary outcomes are among the issues that require even more serious consideration in future large multisite clinical trials. Moreover, it is crucial to clarify whether the intent of a study is to establish superiority of some treatments or to establish equivalence, for the appropriate designs and analyses differ in these situations. If the study is designed, as was CATIE, to demonstrate some treatments' superiority, statistically nonsignificant results should not be misinterpreted as evidence of "equivalence." For establishing either superiority or equivalence, future treatment comparisons might better be designed with fewer sites, more subjects per site, fewer treatments, and fewer outcomes, in order to have the power for definitively establishing superiority or equivalence at a lower cost.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Olanzapine; Outcome Assessment, Health Care; Perphenazine; Randomized Controlled Trials as Topic; Research Design; Schizophrenia; United States

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Brain; Cardiomyopathies; Child; Clozapine; Dyskinesia, Drug-Induced; Energy Metabolism; Feeding Behavior; Female; Gene Expression; Genetic Association Studies; Humans; Male; Myocarditis; Olanzapine; Pericarditis; Risperidone; Tourette Syndrome; Twin Studies as Topic; Weight Gain

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Cognition Disorders; Drug Tolerance; Dyskinesia, Drug-Induced; Haloperidol; Humans; Olanzapine; Piperazines; Quinolones; Risperidone; Schizophrenia; Sulpiride; Time Factors

Tardive dyskinesia (TD), the principal adverse effect of long-term conventional antipsychotic treatment, can be debilitating and, in many cases, persistent. We sought to explore the incidence and management of TD in the era of atypical antipsychotics because it remains an important iatrogenic adverse effect.. We conducted a review of TD incidence and management literature from January 1, 1965, to January 31, 2004, using the terms tardive dyskinesia, management, therapy, neuroleptics, antipsychotics, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole. Additional articles were obtained by searching the bibliographies of relevant references. We considered articles that contributed to the current understanding of both the incidence of TD with atypical antipsychotics and management strategies for TD.. The incidence of TD is significantly lower with atypical, compared with typical, antipsychotics, but cases of de novo TD have been identified. Evidence suggests that atypical antipsychotic therapy ameliorates long-standing TD. This paper outlines management strategies for TD in patients with schizophrenia.. The literature supports the recommendation that atypical antipsychotics should be the first antipsychotics used in patients who have experienced TD as a result of treatment with conventional antipsychotic agents. The other management strategies discussed may prove useful in certain patients.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Incidence; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles

Based on lower rates of acute extrapyramidal side effects associated with second-generation antipsychotics, compared to first-generation antipsychotics, and based on preliminary data, second-generation antipsychotics are expected to cause less tardive dyskinesia than first-generation antipsychotics. This hypothesis was examined in a systematic review of studies involving open or controlled treatment with any second-generation antipsychotic.. Studies of treatment with second-generation antipsychotics lasting > or =1 year and reporting on new cases of tardive dyskinesia or dyskinesia were systematically reviewed.. In 11 studies, 2,769 patients received treatment with risperidone (five studies, N=1,235), olanzapine (two studies, N=610), quetiapine (two studies, N=386), amisulpride (one study, N=331), or ziprasidone (one study, N=207) for a weighted mean and median duration of 263 and 306 days, respectively. Study designs were double blind and randomized (N=3); open-label extensions of double-blind, randomized trials (N=4); and open label (N=4). Of the four trials that had a comparator (all involving adults with schizophrenia spectrum disorders), three used haloperidol (N=408) and one used placebo (N=71). Studied populations included children (N=77), adults (N=1,419), adults and elderly persons (N=794), and exclusively patients age 54 years or older (N=479). The weighted mean annual incidence of tardive dyskinesia for second-generation antipsychotics was 0% in the children, 0.8% (range=0.0%-1.5%) in the adults, 6.8% in the mixed adult and elderly population, and 5.3% (range=0.0%-13.4%) in the patients age 54 years and older, compared to 5.4% (range=4.1%-7.4%) in adults treated with haloperidol.. Results from 11 long-term studies support the idea that second-generation antipsychotics have a reduced risk for tardive dyskinesia, compared to first-generation antipsychotics, although the doses of haloperidol used in the comparator studies were relatively high. More carefully designed studies, ideally lasting beyond 1 year and comparing the effects of different second-generation antipsychotics in patients who have never taken first-generation antipsychotics, are needed to estimate the true risk. It would not appear premature for clinicians to consider these findings in making long-term treatment decisions.

Topics: Adolescent; Adult; Aged; Amisulpride; Antipsychotic Agents; Benzodiazepines; Child; Dibenzothiazepines; Double-Blind Method; Dyskinesia, Drug-Induced; Haloperidol; Humans; Middle Aged; Neurologic Examination; Olanzapine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risk; Sulpiride; Thiazoles

We report the case of a 17-year-old-boy with schizophrenia who developed tardive dystonia after 9 months of treatment with olanzapine. This case and the relevant literature show that when neuroleptic treatment is indicated, switching to another atypical neuroleptic might be helpful for both tardive dystonia and schizophrenia. In such a case, clozapine appears to be the first-line therapeutic option.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Male; Olanzapine

Tardive dyskinesia is a chronic drug-induced movement disorder that tends to be persistent in older adults who are treated with antipsychotics. Tardive dyskinesia can affect older patients both physically and psychologically, leading to frequent falls, difficulty eating, and depression. While atypical antipsychotics may cause tardive dyskinesia, the percentage is usually significantly lower than with conventional antipsychotics. Using atypical antipsychotics, particularly at lower doses, may aid in preventing symptoms of tardive dyskinesia in older adults.

Topics: Adult; Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Humans; Incidence; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Data from clinical trials reviewed in this article fulfill predictions based on preclinical findings that atypical antipsychotic drugs are associated with a reduced potential for inducing extrapyramidal symptoms (EPS) and other movement disorders. Atypical drugs have been shown to reduce all subtypes of acute EPS, the frequency of EPS-related patient dropouts, and the need for concomitant antiparkinsonian drug use. Clozapine remains superior to other atypicals in treating psychosis without worsening motor symptoms in patients with Parkinson's disease. Atypicals may be selectively advantageous in treating schizophrenic patients with a predisposition to catatonia. Although the risk of developing lethal neuroleptic malignant syndrome may be diminished with atypical drugs, clinicians must remain alert to the signs of this disorder. Atypicals have reduced liability for inducing tardive dyskinesia (TD) and show antidyskinetic properties in patients with preexisting TD. Passive resolution of TD may be facilitated in some patients by the use of these agents. Thus, the risk of movement disorders has become only one of several considerations in choosing among antipsychotic drugs.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Humans; Neuroleptic Malignant Syndrome; Neurotoxicity Syndromes; Olanzapine; Pirenzepine; Risperidone

Currently, tardive dyskinesia (TD) remains an important clinical problem. The average prevalence is estimated at 30%. The appearance of antipsychotics has opened new paths. The extrapyramidal profile of these molecules is more favorable than that of conventional neuroleptics. In order to assess their prophylactic as well as curative potential, we reviewed the literature concerning four of these atypical antipsychotics: clozapine, risperidone olanzapine and amisulpride. Clozapine seems to induce fewer cases of TD than the conventional neuroleptics, and has a specific therapeutic effect. However, the risk of agranulocytosis reduces the possibility of utilisation. Risperidone appears to be an effective therapy, but several authors report cases of TD during treatment. Furthermore, larger studies and longer follow-ups are necessary to confirm the efficiency of olanzapine and amisulpride. Further studies and observations are still necessary before drawing any conclusion for these new atypical antipsychotic actions. They are doubtlessly promising, but we cannot ignore the notion of risk-benefit; regular monitoring and listening to the subjective experience of the patients must remain uppermost in the choice of therapy.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Humans; Olanzapine; Pirenzepine; Prevalence; Psychotic Disorders; Risperidone; Sulpiride

Four new antipsychotic medications--clozapine, risperidone, olanzapine, and quetiapine--have been introduced in the United States during the past decade. These new medications now account for the majority of antipsychotic prescriptions. The author reviews specific issues related to the use of traditional antipsychotic medications and then highlights the emerging clinical research data regarding the new medications, which have all been shown to be efficacious in the treatment of schizophrenia. Clinical research data indicate that they are also more useful for a broader array of symptoms associated with schizophrenia than traditional compounds. Furthermore, movement disorder side effects are substantially decreased--a property that leads to higher acceptability. Surprisingly, there has been little relationship between the pivotal trials designed for FDA approval and current dosing strategies in broader clinical settings. These dosing issues are described. New uses, including treatment of mood disorders and conduct disorder, are also discussed. These medicines offer substantial hope for improved treatment of schizophrenia.

Topics: Agranulocytosis; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Humans; Olanzapine; Pirenzepine; Prolactin; Quetiapine Fumarate; Risperidone; Schizophrenia

Rapid improvement of tardive dyskinesia was identified following initiation of olanzapine in an elderly male patient formally treated with chlorpromazine.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chlorpromazine; Chronic Disease; Dyskinesia, Drug-Induced; Humans; Male; Olanzapine; Pirenzepine; Selective Serotonin Reuptake Inhibitors

Given the problematic nature of tardive dyskinesia in persons taking conventional antipsychotics, evaluation of newer atypical antipsychotic agents should include a systematic assessment of tardive dyskinesia liability. Results of a prospective double-blind, randomized study of schizophrenic patients who participated in 3 preclinical olanzapine studies and were treated with 5 to 20 mg/day of olanzapine (N = 1192) or haloperidol (N = 522) recently indicated a significantly lower risk of development of tardive dyskinesia with olanzapine treatment than haloperidol treatment. This article discusses the known effects of atypical antipsychotic medications on tardive dyskinesia movements (both withdrawal and persistent) and the incidence rate of tardive dyskinesia among schizophrenic patients undergoing long-term treatment with olanzapine or haloperidol.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Double-Blind Method; Drug Administration Schedule; Dyskinesia, Drug-Induced; Haloperidol; Humans; Incidence; Molindone; Olanzapine; Pirenzepine; Prospective Studies; Risk Factors; Risperidone; Schizophrenia; Substance Withdrawal Syndrome; Survival Analysis

The enthusiasm produced by the introduction of antipsychotic medication in the 1950s gave way to a certain frustration in the 1970s and 1980s. Despite the development of a large number of new drugs, little progress was made in treatment because these new agents were, in essence, therapeutically equivalent. This lack of progress was perhaps also related to an emphasis on tardive dyskinesia in the 1970s, i.e., the preoccupation with a negative effect of treatment. The reverse is taking place today. Clozapine and the other atypical antipsychotics are associated in people's minds with fewer or absent extrapyramidal symptoms and less tardive dyskinesia than the older typical agents. As a result, a certain amount of complacency exists. Tardive dyskinesia not only may be painful and disfiguring, but it also predicts poor outcome in patients with schizophrenia. Although many treatments have been tried, none have proven completely efficacious. The best treatment for tardive dyskinesia and dystonia is prevention, which is a function of medication choice. Pharmacologic interventions for tardive dyskinesia include clozapine and the other atypical antipsychotics. If typical antipsychotics must be used, they should be started at the lowest possible levels. Studies of risperidone suggest that it, too, should be used at very low doses to minimize the risk of tardive dyskinesia. It is also possible that schizophrenic patients taking atypical antipsychotics may experience fewer spontaneous dyskinesias, although further study is warranted.

Topics: Adult; Akathisia, Drug-Induced; Algorithms; Antipsychotic Agents; Benzodiazepines; Clozapine; Decision Trees; Drug Administration Schedule; Dyskinesia, Drug-Induced; Dystonia; Female; Humans; Male; Olanzapine; Pirenzepine; Probability; Reserpine; Risperidone; Schizophrenia; Substance Withdrawal Syndrome; Tetrabenazine; Treatment Outcome; Vitamin E

The results of controlled studies of the efficacy of the new atypical neuroleptics in treating negative symptoms show that these antipsychotics have a more pronounced effect on negative symptoms in acute schizophrenic patients than the classical neuroleptics. Supplementary complex statistical analyses substantiate that the increased efficacy of the atypical neuroleptics in treating negative symptoms can only partially be explained by indirect effects of better extrapyramidal tolerability, better effects on productive psychotic symptoms, etc. Instead, it is due largely to the stronger direct effect of these atypical neuroleptics. Clinical studies to evaluate their efficacy in chronic schizophrenic patients with stable, predominantly negative symptoms are still mostly lacking. First results support the presumption that atypical neuroleptics have a direct effect. Parallel to the evaluation of the new atypical neuroleptics, important progress has been made in the methodology of clinical studies in this area.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dibenzothiepins; Double-Blind Method; Dyskinesia, Drug-Induced; Humans; Imidazoles; Indoles; Neurotransmitter Agents; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Schizophrenic Psychology; Sulpiride; Thiazoles

Elderly patients with schizophrenia and dementia patients with agitation are frequently candidates for antipsychotic treatment. Conventional neuroleptics have relatively little effect on negative symptoms and may cause considerable side effects, especially in elderly patients. The authors have found a 29% cumulative annual incidence of tardive dyskinesia (TD) in middle-aged and elderly outpatients treated with relatively low doses of conventional neuroleptics Newer antipsychotics are less likely to cause extrapyramidal symptoms and may be associated with a lower risk of TD. They are generally effective for both positive and negative symptoms and may also improve some aspects of cognition, but these drugs have their own side effects. Dosing requirements for elderly patients tend to be much lower than those for younger adults.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Typical antipsychotic agents produce central nervous system effects, especially extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). Nearly every patient who receives neuroleptic therapy has one or more identifiable risk factors for TD, among the most significant of which are older age, female gender, presence of EPS, diabetes mellitus, affective disorders, and certain parameters of neuroleptic exposure (i.e. dose and duration of therapy). The typical course of TD is a gradual onset after several years of drug therapy, followed by slow improvement or remission, but a large number of patients have persistent TD with irreversible symptoms. In the management of TD, the patient's mental status is of primary concern. Currently, no uniformly safe and effective therapies for TD exist, though a variety of therapeutic agents, including some of the atypical neuroleptics, have been reported to treat TD successfully in some patients. Because TD liability is so much lower with novel antipsychotic therapy, all patients who have TD or are at risk for TD, as well as EPS, should be considered candidates for switching to these new drugs.

Topics: Adult; Age Factors; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Risperidone; Schizophrenia; Sex Factors

Soon after the introduction of antipsychotic drugs into clinical practice, these agents were observed to be capable of producing not only acute extrapyramidal ("parkinsonian") side effects, but also later occurring abnormal involuntary movements that came to be called tardive dyskinesia. Since antipsychotic drugs are used in a variety of conditions that include psychotic features, studies have attempted to determine whether specific diagnostic subgroups may experience different degrees of vulnerability to drug-induced movement disorders. This issue is important not only to inform clinical practice, but also to provide clues to pathophysiology. A number of studies suggest that patients with affective disorders are at greater risk for developing tardive dyskinesia (controlling, to the extent possible, for other relevant variables such as age, sex, length of treatment). Encouraging preliminary data with new antipsychotic drugs such as olanzapine suggest that the risk of tardive dyskinesia associated with long-term antipsychotic drug use may be substantially reduced. This would go a long way toward improving the benefit-to-risk ratio of antipsychotic drug treatment, particularly in patients with affective disorders.

Topics: Adult; Affective Disorders, Psychotic; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Imidazoles; Indoles; Male; Olanzapine; Piperazines; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risk Assessment; Risk Factors; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

The primary aim of the long-term treatment of patients with schizophrenia is to prevent relapse, which is costly both in psychological and economic terms. Although with conventional antipsychotic drugs relapse may occur despite compliance with maintenance regimens, the rate of relapse is reduced in compliant patients. However, this benefit is achieved at the cost of side-effects and the risk of developing tardive dyskinesia, even among patients who have taken these drugs for only a year or two. To provide the therapeutic benefits of maintenance medication without its drawbacks, intermittent dosing and long-term therapy with reduced doses of conventional medications have been explored. The atypical antipsychotic agent, olanzapine, has been shown to be effective maintenance medication and has an improved safety profile.

Topics: Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Humans; Long-Term Care; Olanzapine; Patient Compliance; Pirenzepine; Recurrence; Schizophrenia

Olanzapine is an atypical antipsychotic agent which is at least as effective as the conventional agent haloperidol and the atypical agent risperidone. Olanzapine may be superior to haloperidol in some respects, including treatment of negative symptoms. A major advantage of olanzapine over haloperidol is its lower risk of extrapyramidal symptoms. Olanzapine improves quality of life and other aspects of functioning to a greater extent than haloperidol, and improves quality of life to at least the same extent as risperidone. However, olanzapine has a high acquisition cost compared with conventional antipsychotics. Despite this, most pharmacoeconomic analyses indicate that treatment with olanzapine does not significantly increase, and may even decrease, the overall direct treatment costs of schizophrenia, compared with haloperidol. Total direct medical costs calculated from prospective resource utilisation data were lower with olanzapine than with haloperidol by $US388 (1995 values) per patient over 6 weeks and by $US55 per patient per month during 46 weeks extended treatment. In a mixed effects linear model of the same data, total costs over 1 year were $US10,301 (1996 values) per patient lower with olanzapine than haloperidol, and olanzapine was associated with 18.3 more symptom-free days per patient. Compared with risperidone, mean total direct medical costs over 28 weeks were $US493 (1995 values) per patient lower with olanzapine. In a Markov model of 5 years' treatment, olanzapine was associated with more time in a disability-free state than haloperidol at a total cost per patient that was lower by $US1539 (1995 values), 816 Pounds (1995/1996 values), 977 Dutch guilders (NLG; 1995 values) and 2296 Deutschmarks in US, UK, Dutch and German analyses, respectively. In a similar Spanish analysis, the overall total cost was higher with olanzapine, giving an incremental cost effectiveness for olanzapine of 32,516 pesetas (1995 values) per month of disability-free time gained. When risperidone was a comparator, the total cost per patient was $US1875 and NLG202 lower with olanzapine in US and Dutch analyses, respectively.. The high acquisition cost of olanzapine is offset by reductions in other treatment costs in patients with schizophrenia. Compared with haloperidol, the drug improved patient outcome and quality of life, while overall direct treatment costs were generally not increased, or even decreased. Olanzapine has also been reported to decrease overall treatment costs compared with risperidone, but confirmation is required. Olanzapine is a cost-effective alternative to conventional agents for the treatment of moderately to severely ill patients with longstanding schizophrenia.

Topics: Antipsychotic Agents; Benzodiazepines; Costs and Cost Analysis; Dyskinesia, Drug-Induced; Humans; Olanzapine; Pirenzepine; Quality of Life; Schizophrenia

Antipsychotic medications are the mainstay of treatment for schizophrenia. The recent advent of atypical antipsychotics has provided new clinical options and set higher expectations for the treatment of schizophrenia. It is not yet clear how each different drug will fit within the therapeutic armamentarium and this lack is most evident with considering patients with treatment refractory schizophrenia. On the other hand, the expectation of superior efficacy, more benign side effect profile and potential to impact the longitudinal course of schizophrenia provide a rationale for the use of novel antipsychotics as a first-line treatment of schizophrenia.

Topics: Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Clozapine; Dibenzothiazepines; Dopamine Antagonists; Drug Resistance; Dyskinesia, Drug-Induced; Humans; Neurobehavioral Manifestations; Olanzapine; Pirenzepine; Psychopharmacology; Quetiapine Fumarate; Schizophrenia; Serotonin Antagonists

To review the existing literature on the efficacy and tolerability of antipsychotics for adolescent psychosis. The review focuses in particular on literature regarding adverse effects that are thought to have an increased incidence in young patients and on the possible neurobiological bases for such differential sensitivity.. Pertinent studies were sought using Medline searches, supplemented by selected bibliographies, and reviewed.. There is a relative paucity of research in this area; in particular, well-controlled trails are lacking. The existing literature suggests fairly good efficacy of both typical and atypical antipsychotics in the treatment of psychotic disorders in children and adolescents. However, the incidence of certain side effects, particularly extrapyramidal symptoms (EPS). is found to be higher in younger patients compared with adults. Positron emission tomography (PET) receptor studies in adults have demonstrated that the incidence of EPS is related to dose-dependent dopamine type-2 (D2) receptor occupancy and that there is a significant relationship between the number of these receptors and age.. Improved tolerability is leading to the increasing us of atypical antipsychotics for adolescent patients, though these new drugs to have specific adverse effects of their own. There is a need for more controlled studies of atypical antipsychotics in children and adolescents. In particular, dose-finding studies are needed to determine the optimal dose range to produce the greatest improvement with the least side effects for each of these drugs.

Topics: Adolescent; Adolescent Psychiatry; Age Factors; Antipsychotic Agents; Benzodiazepines; Cholinergic Fibers; Clozapine; Controlled Clinical Trials as Topic; Corpus Striatum; Disease Susceptibility; Dyskinesia, Drug-Induced; Humans; Olanzapine; Pirenzepine; Receptors, Dopamine D2; Risperidone; Schizophrenia; Tomography, Emission-Computed

Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.

Topics: Agranulocytosis; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Central Nervous System Diseases; Clozapine; Dibenzothiazepines; Drug Interactions; Dyskinesia, Drug-Induced; Health Status; Humans; Hypotension, Orthostatic; Olanzapine; Pirenzepine; Quality of Life; Quetiapine Fumarate; Receptors, Cholinergic; Risperidone; Schizophrenia; Sexual Dysfunctions, Psychological; Sleep Wake Disorders; Treatment Refusal; Weight Gain

The incidence of acute extrapyramidal symptoms (EPS)--akathisia, dystonia, and parkinsonism--associated with traditional antipsychotics varies, but most researchers agree that neuroleptic-induced EPS occur in 50% to 75% of patients who take conventional antipsychotics. Atypical antipsychotics were developed to widen the therapeutic index and to reduce EPS. Although the mechanisms are unclear, the risk of EPS is less with the novel antipsychotics than with conventional drugs, and agents that produce low levels of acute EPS are likely to produce less tardive dyskinesia. Nevertheless, clinicians should exercise caution when comparing data from investigations of the novel antipsychotics and, until long-term data become available, should administer the new drugs at doses below the EPS-producing level.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Dystonia; Humans; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Substance Withdrawal Syndrome

Placebo-controlled maintenance studies of conventional antipsychotic agents demonstrate a significant reduction in the risk of schizophrenic relapse in neuroleptic-treated patients. Neuroleptic discontinuation even in patients who remained in remission for as long as 5 years results in a relapse rate comparable to that seen for patients initially assigned to placebo. Yet, patients maintained on conventional neuroleptics are exposed to the risk of tardive dyskinesia (approximately 5% per year for patients with up to 10 years of neuroleptic exposure). Attempts have been made to reduce neuroleptic exposure. A lower maintenance dose was associated with higher relapse rates, as was intermittent, targeted therapy. Psychoeducational treatment studies reaffirmed that the major influence on the rate of rehospitalization was the dose of conventional maintenance medication. Although data are scarce for maintenance treatment with atypical antipsychotic drugs, findings suggest that atypical agents are at least as efficacious and may be better tolerated. Olanzapine has demonstrated efficacy in maintenance treatment as well as a reduced risk of tardive dyskinesia compared with haloperidol.

Topics: Antipsychotic Agents; Benzodiazepines; Caregivers; Dyskinesia, Drug-Induced; Humans; Olanzapine; Pirenzepine; Risk Assessment; Risperidone; Schizophrenia

Most traditional neuroleptics have a narrow therapeutic-to-toxic index, and thus, the novel antipsychotics are the result of a search to substantially widen the distance between the dose that treats psychosis and the one that produces adverse effects. In vitro binding profiles have been created for the atypical antipsychotics that have been approved by the U.S. Food and Drug Administration (FDA)-clozapine, olanzapine, and risperidone and those that are under FDA review-quetiapine and sertindole. These profiles, which were compared with that of the typical neuroleptic haloperidol, provide guidance for predicting the adverse effects produced by these drugs. Most conventional antipsychotics have central nervous system effects, particularly extrapyramidal symptoms (EPS) and tardive dyskinesia, sedation, and dulling of cognition. Other adverse effects of the typical antipsychotics include the neuroleptic malignant syndrome, orthostatic hypotension, changes in liver function, anticholinergic and antiadrenergic side effects, sexual dysfunction, and weight gain. The newer agents have a lower incidence of EPS and tardive dyskinesia, while weight gain and changes in blood pressure and liver function tests are adverse effects that have been associated with the use of the newer agents. The favorable side effect profile of these new antipsychotics is likely to make patients more willing to continue treatment, and thus these agents represent a step forward in the treatment of patients with severe, chronic mental illness.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Haloperidol; Humans; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Receptors, Neurotransmitter; Seizures; Sleep; Weight Gain

Topics: Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Olanzapine; Pirenzepine; Psychotic Disorders

Although neuroleptic drugs have become the mainstay of treating acute and chronic psychosis, they are substantially limited by troublesome side effects. The traditional neuroleptic drugs have a wide array of central nervous system and peripheral system side effects that often lead to problems in management or patient noncompliance. Of particular difficulty are the extrapyramidal symptoms and tardive dyskinesia. However, other side effects of seizures, sedation, neuroleptic malignant syndrome and cardiovascular, hematologic, endocrinological, and weight gain problems remain as clinical management challenges posed by existing antipsychotic drug therapy. Considerable progress has been made in improving the motor side effect profile with the advent of clozapine and risperidone. However, each of these drugs has its own dose-limiting side effect profile. Two new drugs, olanzapine and sertindole, are now added to the pharmacopeia for treating psychosis. They further improve the benefit/ risk ratio because they have even fewer EPS and other side effects. Overall, these new antipsychotic agents greatly improve the treatment of psychosis by reducing drug-induced morbidity and improving the quality of life for patients.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Humans; Imidazoles; Indoles; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Schizophrenia; Seizures; Sleep; Weight Gain

Biomarkers are now widely used in many fields of medicine, and the identification of biomarkers that predict antipsychotic efficacy and adverse reactions is a growing area of psychiatric research. Monoamine molecules of the peripheral bloodstream are possible prospective biomarkers based on a growing body of evidence indicating that they may reflect specific changes in neurotransmitters in the brain. The aim of this study was to detect peripheral biogenic amine indicators of patients with acute psychosis and to test the correlations between the biological measures studied and the psychopathological status of the patients.. This research included 60 patients with acute psychosis treated with olanzapine (n = 30) or haloperidol (n = 30). Here, we measured biogenic amine indicators, including mRNA levels of dopamine receptor D4 (DRD4) and the serotonin 2A receptor (5HTR2A), in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction and serum dopamine concentrations by enzyme linked immunosorbent assay (ELISA). Psychopathological status was evaluated using psychometric scales. The assessments were conducted prior to and after 14 and 28 days of treatment.. The administration of haloperidol, but not olanzapine, up-regulated 5HTR2A mRNA in a linear manner, albeit without statistical significance (p = 0.052). Both drugs had non-significant effects on DRD4 mRNA levels. Nevertheless, a positive correlation was found between DRD4 and 5HTR2A mRNA levels over a longitudinal trajectory, suggesting co-expression of the two genes. A significant positive correlation was observed between 5HTR2A mRNA levels and total Positive and Negative Syndrome Scale (PANSS) scores in both groups of patients before treatment. A significant correlation between baseline 5HTR2A mRNA levels and PANSS scores on days 14 and 28 of treatment remained for patients treated with olanzapine only. Moreover, a significant positive correlation was observed between blood serum dopamine levels and scores on extrapyramidal symptom scales in the olanzapine group.. The DRD4 and 5HTR2A genes are co-expressed in PBMCs during antipsychotic administration. Despite a correlation between the studied biogenic amine indicators and the psychopathological status of patients, reliable biomarkers of treatment response could not be determined.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Biomarkers; Dopamine; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D4; Treatment Outcome; Young Adult

Ziprasidone (ZIP) is often used with olanzapine (OLZ) in 'switch' and combination therapy but empirical evidence to support these strategies is limited.. This study was therefore designed to compare the efficacy and tolerability of switching from OLZ to ZIP, the combination of both medications, and OLZ and ZIP monotherapy, in patients with schizophrenia spectrum disorders (SSD).. In this 12 week open-label, assessor-blinded randomized trial, 148 patients with SSD who had not used antipsychotics for at least 3 months were assigned to ZIP (n = 49) or OLZ monotherapy (n = 31); OLZ for 4 weeks then a switch to ZIP (OLZ/ZIP, n = 35); or combination therapy (OLZ + ZIP, n = 33). The severity of psychosis and abnormal involuntary movements was evaluated at baseline, 1, 2, 4, 8, and 12 weeks using standard instruments. Baseline-to-endpoint changes in weight gain and metabolic measures were compared.. The efficacy of both OLZ/ZIP and OLZ + ZIP was comparable OLZ monotherapy and better than ZIP monotherapy in reducing overall psychotic and negative symptoms at most 8 and 12 week measurement points. Changes in weight gain, glucose, and lipid measures did not differ between OLZ/ZIP and OLZ + ZIP, but were markedly higher following OLZ monotherapy. The OLZ + ZIP group had the lowest overall incidence of adverse events and extrapyramidal symptoms of all the treatment regimens.. We conclude that combining ZIP and OLZ at the outset of treatment is superior to switching from OLZ to ZIP in terms of improving psychotic symptoms and limiting movement side effects without increasing the risk of metabolic syndrome.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Drug Substitution; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Male; Metabolic Syndrome; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Single-Blind Method; Thiazoles; Treatment Outcome; Weight Gain

Tardive dyskinesia (TD) is a debilitating adverse effect associated with antipsychotic treatment. Older age and the presence of mood disorder have been identified as risk factors for the development of TD. Thus, we assessed the incidence of TD in younger and older patients with major depressive disorder with psychotic features who participated in a 12-week clinical trial comparing olanzapine plus sertraline versus olanzapine plus placebo. All subjects (n = 259) were assessed with the Abnormal Involuntary Movement Scale at baseline and after 4, 8, and 12 weeks of treatment (or at termination). We used 7 different published criteria to estimate the prevalence of TD at baseline and the incidence over the duration of the trial. We compared the incidence of TD in subjects 60 years or older and those younger than 60 years. The overall prevalence and incidence of TD varied almost 10-fold, depending on the criteria (prevalence range, 1.2%-8.9%; incidence range, 0.0%-5.9%). Tardive dyskinesia was observed as a clinical adverse event in only 1 subject (0.4%). Whereas older subjects had a higher prevalence of TD at baseline, the incidence in younger and older subjects did not differ significantly. The incidence of TD was relatively low in both younger and older patients with major depressive disorder with psychotic features treated acutely with olanzapine. However, the estimate of the risk of TD varies widely, depending on the criteria used to define TD.

Topics: Age Factors; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Humans; Incidence; Middle Aged; Olanzapine; Prevalence; Psychotic Disorders; Risk Factors; Sertraline; Time Factors

The aim of this study was to investigate the long-term effectiveness and efficacy of haloperidol, risperidone and olanzapine in first-episode schizophrenia-spectrum disorders. This was a prospective, randomized, open-label study. Data for the present investigation were obtained from a large epidemiological and 3-year longitudinal intervention programme of first-episode psychosis conducted at the University Hospital Marques de Valdecilla, Santander, Spain. One hundred and seventy-four patients were randomly assigned to haloperidol (N = 56), olanzapine (N = 55), or risperidone (N = 63) and followed up for 1 year. The primary effectiveness measure was all causes of treatment discontinuation. Effectiveness analyses were based on intend-to-treat populations. In addition, an analysis based on per protocol populations was conducted in the analysis for clinical efficacy. The treatment discontinuation rate for any cause was higher with haloperidol than with risperidone and olanzapine (χ(2) = 8.517; p = 0.014). The difference in discontinuation rate between risperidone and olanzapine was not significant (χ(2) = 0.063; p = 0.802). There were no significant advantages of any of the three treatments in reducing the severity of psychopathology. Risperidone and olanzapine demonstrated higher effectiveness relative to haloperidol, but the three antipsychotics were equally effective in reducing the severity of psychopathology. Specific clinical programmes and the use of second-generation antipsychotics may enhance the effectiveness of antipsychotic treatments.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Severity of Illness Index; Treatment Failure

No clear recommendations exist regarding which antipsychotic drug should be prescribed first for a patient suffering from psychosis. The primary aims of this naturalistic study were to assess the head-to-head effectiveness of first-line second-generation antipsychotics with regards to time until drug discontinuation, duration of index admission, time until readmission, change of psychopathology scores and tolerability outcomes.. Patients >or= 18 years of age admitted to the emergency ward for symptoms of psychosis were consecutively randomized to risperidone (n = 53), olanzapine (n = 52), quetiapine (n = 50), or ziprasidone (n = 58), and followed for up to 2 years.. A total of 213 patients were included, of which 68% were males. The sample represented a diverse population suffering from psychosis. At admittance the mean Positive and Negative Syndrome Scale (PANSS) total score was 74 points and 44% were antipsychotic drug naïve. The primary intention-to-treat analyses revealed no substantial differences between the drugs regarding the times until discontinuation of initial drug, until discharge from index admission, or until readmission. Quetiapine was superior to risperidone and olanzapine in reducing the PANSS total score and the positive subscore. Quetiapine was superior to the other drugs in decreasing the PANSS general psychopathology subscore; in decreasing the Clinical Global Impression - Severity of Illness scale score (CGI-S); and in increasing the Global Assessment of Functioning - Split version, Functions scale score (GAF-F). Ziprasidone was superior to risperidone in decreasing the PANSS positive symptoms subscore and the CGI-S score, and in increasing the GAF-F score. The drugs performed equally with regards to most tolerability outcomes except a higher increase of hip-circumference per day for olanzapine compared to risperidone, and more galactorrhoea for risperidone compared to the other groups.. Quetiapine appears to be a good starting drug candidate in this sample of patients admitted to hospital for symptoms of psychosis.. ClinicalTrials.gov ID; URL: http://www.clinicaltrials.gov/: NCT00932529.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Galactorrhea; Hospitalization; Humans; Length of Stay; Male; Olanzapine; Patient Readmission; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Thiazoles; Treatment Outcome

To compare the efficacy of risperidone and olanzapine in schizophrenic patients with tardive dyskinesia on treatment with first-generation antipsychotics.. We conducted a 24-week, rater-blinded, flexible-dose study. Sixty patients with DSM-IV schizophrenia (n = 58) or schizoaffective disorder (n = 2) met the DSM-IV research criteria for neuroleptic-induced tardive dyskinesia and were randomly assigned to a risperidone or olanzapine group. The primary outcome was a comparison of the change in the total scores on the Abnormal Involuntary Movement Scale (AIMS) from baseline to study end point between the groups. The study was conducted from July 2000 to June 2004.. The mean ± SD doses of risperidone and olanzapine from baseline to study end point were 1.9 ± 0.7 to 4.1 ± 1.4 mg/d and 8.1 ± 2.0 to 12.6 ± 5.4 mg/d, respectively. There were no statistically significant differences in demographic data, severity of tardive dyskinesia, or psychotic symptoms between risperidone and olanzapine groups at baseline assessment. Both groups showed significant improvement in mean ± SD AIMS total scores (risperidone: −7.4 ± 6.9, P < .0001; olanzapine: −6.2 ± 8.0, P = .0002). However, there was a more statistically significant change in the slope of AIMS total scores in the risperidone group than in the olanzapine group (P = .0001).. Our findings demonstrated that olanzapine may not have better potential for tardive dyskinesia improvement than risperidone did. Double-blinded, fixed dose studies with a larger sample size on schizophrenic patients with tardive dyskinesia from different ethnic groups are needed to confirm the results of our study.. clinicaltrials.gov Identifier NCT00621998

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neurologic Examination; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Taiwan

The concepts of partial recovery and remission have become increasingly important for the evaluation of the effectiveness of schizophrenia therapeutics. The relationship of baseline symptoms and changes in symptoms to remission of psychosis was evaluated. Fifty-six outpatients with residual schizophrenia completed a double-blind trial of olanzapine versus haloperidol and were then enrolled into a one-year open-label trial of olanzapine. Out of these 56 subjects, 13 (23%) met remission criteria at the beginning of the open-label treatment and were excluded. During the one-year study, 7/43 (16%) subjects met remission criteria. These subjects had significantly lower baseline ratings for tardive dyskinesia (TD) than subjects who did not achieve remission (1.8 +/- 1.5 vs. 4.2 +/- 4.6, P = 0.03). As expected, remitted subjects had significantly greater improvements in Brief Psychiatric Rating Scale total scores, positive subscale scores and scale for the Assessment of Negative Symptoms total scores. Remitted subjects also experienced a significantly greater improvement in depressive symptoms (P = 0.001), activation (P = 0.005), and Clinical Global Impressions scores (P < 0.001), as well as greater improvements in extrapyramidal symptoms (P = 0.007) and TD (P < 0.001). These results suggest that the relationship of depressive symptoms and improved side effects to the construct of remission in schizophrenia may deserve special attention. Future studies should aim to relate remission criteria to functional outcomes, cognition, and other important symptom domains.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Depression; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Quality of Life; Remission Induction; Schizophrenia; Severity of Illness Index

The authors provide an overview of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) sponsored by the National Institute of Mental Health. CATIE was designed to compare a proxy first-generation antipsychotic, perphenazine, to several newer drugs. In phase 1 of the trial, consenting patients were randomly assigned to receive olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone for up to 18 months on a double-blind basis. Patients with tardive dyskinesia were excluded from being randomly assigned to perphenazine and were assigned to one of the four second-generation antipsychotics in phase 1A. Clozapine was included in phase 2 of the study. Overall, olanzapine had the longest time to discontinuation in phase 1, but it was associated with significant weight and metabolic concerns. Perphenazine was not significantly different in overall effectiveness, compared with quetiapine, risperidone, and ziprasidone. Also, perphenazine was found to be the most cost-effective drug. Clozapine was confirmed as the most effective drug for individuals with a poor symptom response to previous antipsychotic drug trials, although clozapine was also associated with troublesome adverse effects. There were no differences in neurocognitive or psychosocial functioning in response to medications. Subsequent randomizations suggest that a poor response to an initial medication may mean that a different medication will be more effective or better tolerated. Although the CATIE results are controversial, they are broadly consistent with most previous antipsychotic drug trials and meta-analyses; however, the results may not generalize well to patients at high risk of tardive dyskinesia. Patient characteristics and clinical circumstances affected drug effectiveness; these patient factors are important in making treatment choices.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cost-Benefit Analysis; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Perphenazine; Piperazines; Psychology; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles

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.. 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.. 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.. 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.

Topics: Adult; Antipsychotic Agents; Asian People; Benzodiazepines; Dyskinesia, Drug-Induced; Female; Humans; Male; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Quality of Life; Sample Size; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Several studies have demonstrated the effective use of dehydroepiandrosterone (DHEA) in the management of mood, however studies of its use in psychosis remain limited. The aim of this study was to investigate for the first time efficacy of DHEA augmentation with standardized antipsychotic medication (olanzapine) and to explore effects of DHEA augmentation on side-effect profiles including weight gain, glucose tolerance, aggression, quality of life and neurocognitive function. Finally, we aimed to analyze any relationship between plasma levels and clinical response to DHEA administration. Forty patients with chronic schizophrenia stabilized on olanzapine were randomized in double-blind fashion to receive either DHEA (titrated up to 150mg) or placebo augmentation for a period of 12-weeks. Blood samples were collected at baseline, mid-study and study completion. Results indicated improvement of negative symptoms (SANS scale) even when baseline scores were controlled as a covariate. Some improvement in Parkinsonism and akathisia compared to baseline was seen in patients receiving DHEA. No change in psychosis as reflected by the PANSS was noted. Patients receiving DHEA appeared to demonstrate relatively stable glucose levels compared to controls at the end of the study. An improvement in cognitive performance (most notably memory), which did not reach significance due to low sample number, was observed following DHEA administration. Results further suggest preliminary evidence of involvement of the neurosteroid system in schizophrenia pathophysiology, and confirm initial "cautious" findings identifying an agent capable of improving negative symptoms and certain features of extrapyramidal side effects.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Cognition; Dehydroepiandrosterone; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Glucose Tolerance Test; Hormones; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Quality of Life; Schizophrenia; Schizophrenic Psychology; Weight Gain

This pooled analysis of four 6-week, randomized, open-label, parallel trials of patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) compared the efficacy and tolerability of olanzapine (5-20 mg/d) with those of chlorpromazine (200-800 mg/d). Of the 123 patients randomly allocated to olanzapine (n = 83) or chlorpromazine (n = 40), 109 completed the study (olanzapine, n = 77; chlorpromazine, n = 32). Olanzapine-treated patients showed significantly greater baseline-to-end point mean improvements in the primary efficacy measure, Brief Psychiatric Rating Scale total, compared with chlorpromazine-treated patients (least-squares means: olanzapine, -21.1; chlorpromazine, -10.4; P < 0.001). Response rate was significantly higher in the olanzapine group (66.3% vs. 32.4%; P = 0.001). Baseline-to-maximum changes in the UKU scores for akathisia were significantly different between the groups (P = 0.018). A decrease (improvement) in these scores was observed in 6/74 (8.1%) of olanzapine- and 1/36 (2.8%) chlorpromazine-treated patients. Weight gain was the only common (> or =10%) adverse event that occurred more frequently, although not significantly differently, in the olanzapine group (27.7%) than the chlorpromazine group (12.5%), whereas postural hypotension was the only common adverse event whose occurrence was significantly different between the groups (olanzapine, 0.0%; chlorpromazine, 10.0%; P = 0.010). Both the incidence of > or =7% weight gain from baseline (olanzapine, 26.3%; chlorpromazine, 24.3%) and baseline-to-end point changes in weight (mean +/- SD, kg: olanzapine, 3.41 +/- 3.14; chlorpromazine, 2.81 +/- 2.65) were not significantly different between the treatment groups. Baseline-to- end point changes in nonfasting glucose differed significantly between the groups (mean +/- SD, mmol/L: olanzapine, 0.09 +/- 1.11; chlorpromazine, 0.72 +/- 2.04; P = 0.042). This analysis suggests that, compared with chlorpromazine, olanzapine may be more efficacious and have a more favorable tolerability profile in treating patients with schizophrenia.

Topics: Adolescent; Adult; Africa, Northern; Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Dyskinesia, Drug-Induced; Electrocardiography; Endpoint Determination; Female; Humans; Male; Middle Aged; Middle East; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia

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).. 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.. 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).. 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.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brazil; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Quality of Life; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

The efficacy and tolerability of risperidone long-acting injectable were investigated in patients with schizophrenia or other psychotic disorders who had previously been symptomatically stable on olanzapine treatment. Patients received risperidone long-acting injectable, 25 mg, by intramuscular injection every 2 weeks; the dose could be increased to 37.5 or 50 mg if necessary. Patients were transferred directly from their previous medication to risperidone long-acting injectable without a run-in period of oral risperidone treatment. Of 192 patients recruited, 134 patients (70%) completed the study. The principal reasons for discontinuation were withdrawal of consent (8%), adverse events (6%), insufficient response (5%) and non-compliance (4%). Risperidone long-acting injectable produced a significant improvement (p = 0.0001) in Positive and Negative Syndrome Scale (PANSS) total scores, from 74.2+/-21.3 at baseline to 65.8+/-21.4 at endpoint. There were also significant reductions in PANSS subscales (positive symptoms, negative symptoms, general psycho-pharmacology) and Marder factor scores. The Clinical Global Impression increased significantly from baseline to endpoint (p = 0.0001), as reflected by the increase in the proportion of patients rated as 'not ill' or 'borderline ill' from 10% at baseline to 21% at endpoint. Risperidone long-acting injectable was also associated with significant improvements in Global Assessment of Function, patient satisfaction with treatment, and quality of life, measured on the SF-36 scale. Movement disorders, measured on the Extrapyramidal Symptom Rating Scale, were significantly reduced following the change to risperidone long-acting injectable. Treatment with risperidone long-acting injectable was well tolerated, and no significant weight gain occurred during the study. This open study suggests that risperidone long-acting injectable produces symptomatic improvement in schizophrenia patients previously considered symptomatically stable with olanzapine, along with improvement in movement disorders. The combination of improved efficacy and good tolerability may have important implications for patient adherence to therapy and subsequent long-term outcomes.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Delayed-Action Preparations; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Risperidone; Treatment Outcome

To assess the impact of olanzapine versus conventional neuroleptic therapy among subjects with schizophrenia on ratings of tardive dyskinesia (TD).. The naturalistic study was conducted in three psychiatric hospitals in Brazil. Patients had a diagnosis of schizophrenia and related disorders (DSMIV) and with a BPRS score>24. Patients were evaluated by means of the PANSS scale for symptomatology (Kay et al. 1986), the Clinical Global Impression, The UKU side effect rating scale (Lingjaerde et al. 1987), and the Tardive Dyskinesia AIMS scale (Guy et al. 1976). Patients were seen by the treating physician routinely while hospitalized and then monthly on an out-patient basis. All scale assessments were repeated after 9 months of discharge.. The sample was comprised of 190 patients (99 in the olanzapine and 91 in the standard treatment), with a completion rate of 88.2% for olanzapine and 84.9% for the conventional treatment (p=0.385, n. s.). The mean change from baseline in the PANSS total score favored olanzapine regarding negative symptoms (2.3, 95% C. I. 0.6-4.1, p<0.001); and general psychopathology (4.0, 95% C.I. 0.8-7.2, p<0.02) factors. TD was defined by applying Morgenstern & Glazer (1993) and Schooler & Kane (1982) criteria, on the basis of the AIMS scale. Both results favored olanzapine at the end of the follow-up (Morgenstern & Glazer: 25.6% versus 56.3%; Schooler & Kane: 16.3% versus 45.2%). At the end of the follow-up, by using the overall rating of the AIMS scale, the presence of TD was 2.3% for olanzapine (2/87), and 16.7% (12/72) for the conventional treatment.. The results of this open label naturalistic trial showed that olanzapine had an impact on negative symptoms, decreased general psychopathology and reduced the risk of tardive dyskinesia.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Demography; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Hospitalization; Humans; Male; Middle Aged; Movement Disorders; Olanzapine; Prevalence; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

Frequency of adverse reactions (ARs) related with antipsychotics usage is high. Along with clinical implications, economic impact might be important. The purpose of this study was to model the economic consequences of ARs related with ziprasidone, olanzapine, risperidone, and haloperidol in Spain, by means of a cost-effectiveness model developed using a Markov modeling approach. The model simulated treatment of a cohort of 1000 schizophrenics for 12 months, initiating treatment with one of four antipsychotic drugs; haloperidol, risperidone, olanzapine and ziprasidone. Conditional probabilities of developing any of four adverse events were calculated. Treatment was modified (decrease dose, switch medication) according to incidence of ARs and physician judgments, obtained from a local cross-sectional study and clinical trials previously published. The analysis was conducted in year 2002 from a third party payer perspective. Results are shown as annual cost per month with psychotic symptoms controlled and included univariate sensitivity analysis. The therapeutic strategy starting with ziprasidone showed the lower costs and the greater number of months with symptoms controlled in most scenarios evaluated versus the other options considered, although the differences were weak: 9.6, 9.3, 9.5 and 9.5 controlled months per patient in base scenario, with annual cost per patient per month with symptoms controlled of 1035 Euros, 1084 Euros, 1087 Euros and 1090 Euros for ziprasidone, haloperidol, risperidone and olanzapine, respectively. Results were robust to one-way sensitivity analysis. Despite the unlike drug prices of antipsychotics, a considerable economic impact due to adverse reactions was seen in our setting. These results should be taken into account by health decision makers and clinicians in the management of patients with schizophrenia.

Topics: Antipsychotic Agents; Benzodiazepines; Cost-Benefit Analysis; Dyskinesia, Drug-Induced; Follow-Up Studies; Haloperidol; Hospitalization; Humans; Mental Disorders; Models, Econometric; Olanzapine; Outpatients; Patient Compliance; Piperazines; Psychiatric Status Rating Scales; Retrospective Studies; Risperidone; Sensitivity and Specificity; Spain; Survival Analysis; Thiazoles; Treatment Outcome; Weight Gain

The role of simple reaction time in schizophrenia has been extensively reported to date in professional literature. However, most studies have examined basic reaction time under static conditions using a single measurement. The aim of the present study was to establish whether any changes occur in simple reaction time during treatment with risperidone or olanzapine in in-patients suffering a relapse of schizophrenia.. Seventeen in-patients suffering acute relapse of schizophrenia (DSM IV criteria) and twenty matched, healthy controls participated in an eight-week, double-blind pilot study. The patients were treated with conventional antipsychotics for seven days after admission and were then randomised to the treatment arms with risperidone (4 mg/day) or with olanzapine (10 mg/day) at a fixed dosage in the first week and thereafter in flexible dosages for the remaining seven weeks. Since no differences were found between reaction times of patients treated with risperidone or olanzapine, the two treatment groups were merged in the statistical analysis before being compared with the normal controls. Psychopathological symptoms were assessed using the Positive and Negative Symptom Scale (PANSS) and extrapyramidal symptoms with the Simpson Angus Scale and Abnormal Involuntary Movement Scale. Reaction time was measured with the Alpha apparatus, connected to a personal computer. All assessments and measurements were conducted four times during the treatment phase of the study.. The reaction time of patients was significantly longer than that of the healthy controls (t1 = 17.11; p1 < 0.05). After eight weeks of treatment the reaction time of patients significantly improved but did not reach that of the healthy controls (t4 = 28.18, p4 < 0.05). Furthermore, the improved reaction time in the patients did not correlate with improvement of psychopathological symptoms or with improved extrapyramidal symptoms.. The results of the study suggest that simple reaction time can improve during treatment with atypical antipsychotics.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Male; Neurologic Examination; Neuropsychological Tests; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Reaction Time; Recurrence; Risperidone; Schizophrenia; Schizophrenic Psychology; Slovenia

To evaluate and compare the drug response and side effects of adolescents with schizophrenia treated with olanzapine, risperidone, and haloperidol.. Forty-three patients were treated with olanzapine (n = 19), risperidone (n = 17) and haloperidol (n = 7) for 8 weeks in an open clinical trial. Clinical improvement was evaluated with the Positive and Negative Syndrome Scale (PANSS), and side effects with the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale.. Significant clinical improvement was observed by week 4 for all medications. Olanzapine and haloperidol induced fatigability more frequently than risperidone. Haloperidol was associated with a higher frequency of depression and more severe extrapyramidal symptoms.. To the best of our knowledge this is the first study in adolescents to compare the efficacy and side effects of three most commonly prescribed antipsychotic medications. Olanzapine, risperidone and haloperidol appear to be equally effective for the treatment of schizophrenia in adolescent inpatients but have different side effect profiles.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Depression; Dopamine Antagonists; Dyskinesia, Drug-Induced; Fatigue; Female; Haloperidol; Humans; Male; Olanzapine; Pirenzepine; Risperidone; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Treatment Outcome

Minimum doses of haloperidol might show similar efficacy and side-effects compared to atypical antipsychotics. The objectives of this study were to compare the efficacy of minimum doses of haloperidol with standard doses of risperidone and olanzapine on a 6-month open trial in first psychotic episode patients and to examine the effect of compliance on their outcome. Forty-two patients were recruited and started on flexible doses of these drugs. Olanzapine was given with no cost to the patients. Efficacy and side-effects were monitored every 3 months using standardized assessments. Thirty patients completed the study. All treatment groups showed improvement in positive, negative and depressive symptoms. There were no differences in side-effects among them. The haloperidol group required higher doses of anticholinergics. The rate of treatment discontinuation was higher in the risperidone group due to the direct cost. Minimum doses of haloperidol might prove to be a good choice of treatment for patients with a first episode of psychosis.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Cholinergic Antagonists; Dose-Response Relationship, Drug; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Male; Mexico; Neurologic Examination; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptic drugs is a major challenge. Clozapine has been one treatment option; however, it is not universally effective and is limited in its use by safety concerns. With the introduction of newer agents, their performance relative to clozapine is of great clinical interest.. The primary objective of this study was to evaluate the efficacy and safety of olanzapine versus clozapine among treatment resistant DSM-IV schizophrenic patients. The study was primarily designed to demonstrate the "noninferiority" of olanzapine compared to clozapine after 18 weeks of double-blind treatment. Conclusions were based on the one-sided lower 95% confidence limit about the treatment effect observed from the primary efficacy variable (Positive and Negative Syndrome Scale [PANSS] Total).. Mean changes from baseline to end point in PANSS Total score, using a last observation carried forward technique, showed that both agents were comparably effective in neuroleptic resistant patients, i.e., demonstrated the "noninferiority" of olanzapine when compared to clozapine. Overall, significantly fewer olanzapine-treated patients (4%) discontinued for an adverse event than their clozapine-treated (14%) counterparts (p =.022). Among spontaneously reported adverse events, increased salivation, constipation, dizziness, and nausea were reported significantly more often among clozapine-treated patients, whereas only dry mouth was reported more often among olanzapine-treated patients.. Olanzapine was demonstrated to be noninferior to clozapine and better tolerated among resistant schizophrenic patients clinically eligible for treatment with clozapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Pressure; Body Weight; Clozapine; Double-Blind Method; Drug Resistance; Dyskinesia, Drug-Induced; Female; Humans; Male; Olanzapine; Patient Compliance; Pirenzepine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Time Factors

Conventional antipsychotic agents can induce extrapyramidal symptoms (EPS) that may be alleviated by switching patients to novel agents such as olanzapine. Patients with schizophrenia and related disorders (ICD-10) who were taking haloperidol (N = 94; mean dose = 12.7 mg/day) and had EPS (Simpson-Angus Scale [SAS] > 3) were directly switched to 6 weeks of open-label olanzapine treatment (mean dose = 11.4 mg/day). There were significant mean improvements (p <0.001 for all measurements) from baseline to endpoint on the SAS (-9.69+/-5.33; percentage change, 87.2%), the Barnes Akathisia Scale (-1.00+/-1.19; percentage change, 82.5%), and the Abnormal Involuntary Movement Scale (-1.48+/-2.89; percentage change, 81.1%), and anticholinergic use decreased from 47.9% to 12.8% (mean baseline to endpoint change: -1.52+/-1.91-mg equivalents of benztropine; p < 0.001). Significant mean baseline to endpoint improvements (p < 0.001 for all measurements) were observed on the Positive and Negative Syndrome Scale (PANSS; -25.28+/-18.67; percentage change, 30.3%), the PANSS-extracted Brief Psychiatric Rating Scale (0-6 scale, -13.41+/-10.16; percentage change, 54.4%), and the Clinical Global Impressions Severity scale (-1.16+/-1.19; percentage change, 26.4%). Spontaneously reported treatment- emergent adverse events with a greater than 5% incidence were somnolence (16.0%), increased appetite (14.9%), weight gain (11.7%), headache (8.5%), anxiety (7.4%), dizziness (6.4%), and insomnia (5.3%). Criteria for a successful switch were met by 90.5% of patients. Psychotic symptom exacerbation was experienced by 30.9% of patients at any time during the study and by 11.7% of patients at endpoint. Results suggest that a direct switch to olanzapine is a therapeutic option when patients with haloperidol-induced EPS are unable to tolerate a more gradual switch.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Latin America; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Schizophrenia; Treatment Outcome

Neurocognitive deficits are an enduring characteristic of schizophrenia, and remain prominent in patients whose positive symptoms have decreased after treatment with typical neuroleptics. Recent research has reported that olanzapine improves cognitive functioning in relapsing schizophrenia followed in an outpatient setting. Whether olanzapine will have an effect on improving cognitive function in chronic schizophrenics who have been hospitalized for long periods of time, and have shown a poor response to other conventional and atypical neuroleptics, has not been established. This study investigated cognitive function in chronic medication refractory schizophrenics who were treated with olanzapine or haloperidol in a double-blind study for 8 wk, and followed in an open olanzapine study for several additional months. Patients were evaluated with psychopathology rating scales and a battery of neuropsychological tests at baseline, end of double-blind and end of open-label phases of the study. At the end of the double-blind phase there were no significant differences between olanzapine and haloperidol, except for a trend for improvement on the Wisconsin Card Sort Test on olanzapine, which was significant at traditional but not corrected significance levels. After an additional 3 months of treatment with olanzapine doses of 20-40 mg/d, our statistical analysis showed significant improvement on overall neuropsychological test performance and specific cognitive tasks assessing verbal memory. However, these open-label results are difficult to interpret definitively because of the lack of a comparison drug group and the olanzapine dose escalation over time. Neurocognitive changes were not correlated with changes in psychopathology as assessed by PANSS or SANS scores.

Topics: Antipsychotic Agents; Benzodiazepines; Chronic Disease; Cognition; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Male; Memory; Middle Aged; Neuropsychological Tests; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

Given the problematic nature of tardive dyskinesia in persons taking conventional antipsychotics, evaluation of newer atypical antipsychotic agents should include a systematic assessment of tardive dyskinesia liability. Results of a prospective double-blind, randomized study of schizophrenic patients who participated in 3 preclinical olanzapine studies and were treated with 5 to 20 mg/day of olanzapine (N = 1192) or haloperidol (N = 522) recently indicated a significantly lower risk of development of tardive dyskinesia with olanzapine treatment than haloperidol treatment. This article discusses the known effects of atypical antipsychotic medications on tardive dyskinesia movements (both withdrawal and persistent) and the incidence rate of tardive dyskinesia among schizophrenic patients undergoing long-term treatment with olanzapine or haloperidol.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Double-Blind Method; Drug Administration Schedule; Dyskinesia, Drug-Induced; Haloperidol; Humans; Incidence; Molindone; Olanzapine; Pirenzepine; Prospective Studies; Risk Factors; Risperidone; Schizophrenia; Substance Withdrawal Syndrome; Survival Analysis

Olanzapine is a novel antipsychotic effective in reducing positive and negative symptoms of schizophrenia and with a safe side-effect profile. Premarketing trials, however, included only a few elderly patients. Further data are needed regarding the effects of olanzapine in the elderly and those with comorbid medical illness. In this pilot study, 11 hospitalized patients (age range 60-85 years) who manifested symptoms of psychosis related to schizophrenia and schizoaffective disorders were treated with olanzapine (dose range, 5-20 mg/day). Efficacy and safety were assessed by the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale (CGI), Extrapyramidal Symptom Rating Scale (ESRS), Mini-Mental State Examination (MMSE), Calgary Depression Scale For Schizophrenia (CDSS), EKG, physical examination, and various laboratory tests. Seven patients responded to treatment and all of them showed improvement in both positive and negative symptoms, with greater reduction in positive symptoms. Treatment was discontinued in 2 patients whose symptoms showed no improvement or worsened. The CGI showed significant improvement in 9 patients, remained the same in 1, and worsened in 1 patient. ESRS showed significant reduction from baseline to final visit. Of the 10 patients who cooperated for MMSE, 9 had improved scores. The CDSS showed significant reduction in scores from baseline to final visit. No significant changes were noted in laboratory tests, prolactin levels, EKG, and physical examination. Concomitant administration of lorazepam, carbamazepine, divalproex sodium, and lithium carbonate caused no adverse consequences. The reduction of positive and negative symptoms, lack of significant extrapyramidal symptoms and other side effects, and lack of any significant drug interaction suggest that olanzapine may be a safe and effective antipsychotic medication in the elderly.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Drug Interactions; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Pilot Projects; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Treatment Outcome

To assess the usefulness of low-dose olanzapine (2.5 to 7. 5 mg/day) for Levodopa-induced-dyskinesias (LID) in patients with PD.. Ten patients with PD and LID took part in this randomized, placebo-controlled, double blind, crossover trial. Patients received a 2-week course of olanzapine or placebo in each treatment phase with 1-week washout in between. Dyskinesias were assessed at baseline and after each treatment period with an acute dopaminergic challenge and unified PD rating scale (UPDRS) questionnaires. Patients also kept on/off and dyskinesia diaries for the last 3 days prior to each assessment.. There was a 41% difference in dyskinesia reduction on olanzapine compared to placebo, as measured by objective dyskinesia rating scales (mean percentage reduction abnormal involuntary movement score: 30% versus -11.2%, p < 0.02). Similar differences were demonstrated by patient diaries (mean reduction: 46% versus -2%, p < 0.02) and UPDRS items 32 and 33. Compared with placebo, treatment with olanzapine resulted in significant increases in 'off' time as measured by patient diaries (30% versus 2%) and reported adverse events (1.7 versus 0.1) including increased parkinsonism (1.1 versus 0.1) and a nonsignificant reported increase in drowsiness.. Low-dose olanzapine is effective in reducing dyskinesias in PD, but even at very low doses can result in unacceptable increases in parkinsonism and 'off' time.

Topics: Aged; Benzodiazepines; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Levodopa; Male; Middle Aged; Olanzapine; Pirenzepine

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.. A subpopulation of patients (n = 526) meeting treatment-resistant criteria selected from a large, prospective, double-blind, 6-week study assessing the efficacy and safety of olanzapine and haloperidol were examined. Both last-observation-carried-forward (LOCF) and completers (observed cases) analyses were conducted.. Olanzapine demonstrated significantly greater mean improvement from baseline in Positive and Negative Syndrome Scale (PANSS) negative symptoms, comorbid 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 total (p = .006), PANSS total (p = .005), and PANSS positive symptoms (p = .017) in completers of the 6-week study. Significantly greater response rates were observed in olanzapine-treated (47%) than haloperidol-treated (35%) patients in the LOCF analysis (p = .008), but significance was not reached in the completers analysis (p = .093). Mean doses (+/- SD) of olanzapine and haloperidol were 11.1 +/- 3.4 mg/day and 10.0 +/- 3.6 mg/day, respectively.. Olanzapine was superior to haloperidol for key symptom domains and parkinsonian side effects. Implications of these data for the therapeutics of this severely ill subgroup are discussed.

Topics: Adult; Akathisia, Drug-Induced; Analysis of Variance; Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Chi-Square Distribution; Double-Blind Method; Drug Resistance; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Prospective Studies; Schizophrenia; Treatment Outcome

Tardive dyskinesia is important in the side-effect profile of antipsychotic medication.. The development of tardive dyskinesia was evaluated in patients treated with double-blind, randomly assigned olanzapine or haloperidol for up to 2.6 years.. 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.. 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).. Our results indicated a significantly lower risk of tardive dyskinesia with olanzapine than with haloperidol.

Topics: Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Dyskinesia, Drug-Induced; Haloperidol; Humans; Olanzapine; Pirenzepine; Risk Factors; Schizophrenia; Survival Analysis

Little controlled data exist on the treatment of substance induced psychotic disorders. In this study, 30 patients meeting DSM-IV criteria for cannabis induced psychotic disorder were randomly allocated to receive either olanzapine or haloperidol in a 4-week double-blind clinical trial. There were no significant outcome differences between the two groups on any of the primary outcome measures, the Brief Psychiatric Rating Scale (haloperidol 25.7; olanzapine 27.1; P = 0.70); Clinical Global Impression (CGI) severity scale (haloperidol 1.8, olanzapine 2.3; P = 0.21) or the CGI improvement scale (haloperidol 1.3, olanzapine 1.7; P = 0.16). The haloperidol group however, developed significantly more extrapyramidal side-effects as measured by the Simpson Angus Scale (haloperidol 11.4, olanzapine 2.5; P = 0.014). Significantly (P = 0.027) more biperidin was used for extrapyramidal side-effects in the haloperidol (7.143 mg) than in the olanzapine (0.357 mg) group. Olanzapine appears to be as effective as haloperidol in the treatment of cannabis induced psychotic disorder, but is associated with a lower rate of extrapyramidal side-effects.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cannabis; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychoses, Substance-Induced

Tardive dyskinesia is a serious and common complication of neuroleptic treatment. Olanzapine is a novel antipsychotic agent exhibiting regional mesolimbic dopaminergic selectivity and a broad-based pharmacology encompassing serotonin, dopamine, muscarinic, and adrenergic receptor binding affinities. The authors' goal was to compare the incidence of tardive dyskinesia among patients receiving olanzapine and those receiving the conventional dopamine 2 antagonist haloperidol.. Data were analyzed from three actively controlled and blind long-term responder studies of subjects meeting DSM-III-R criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder treated with olanzapine (N = 707, up to 20 mg/day, 237 median days of exposure) or haloperidol (N = 197, up to 20 mg/day, 203 median days of exposure) who did not have evidence of tardive dyskinesia at baseline. All of the subjects had a chronic disease course (mean greater than 10 years), and there were no significant between-treatment group differences in demographic or disease characteristics. The Abnormal Involuntary Movement Scale and research diagnostic criteria for tardive dyskinesia were used to define the comparative incidence rates of long-term treatment-emergent tardive dyskinesia.. The incidence of newly emergent tardive dyskinesia at any visit after baseline, at the final visit, and at the final two clinical assessments was statistically significantly lower among olanzapine-treated patients than among haloperidol-treated patients.. These findings support an atypical extrapyramidal symptom profile and the potential of a significantly lower risk of tardive dyskinesia with olanzapine than with haloperidol among patients requiring maintenance antipsychotic treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Incidence; Male; Olanzapine; Pirenzepine; Placebos; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Treatment Outcome

Olanzapine and risperidone, both second-generation antipsychotic agents, represent two different pharmacologic strategies. Although they share some in vitro properties, they differ by virtue of their chemical structure, spectrum of receptor binding affinities, animal neuropharmacology, pharmacokinetics, and in vivo neuroimaging profile. Based on such differences, it was hypothesized that the two compounds would show distinct safety and/or efficacy characteristics. To test this hypothesis, an international, multicenter, double-blind, parallel-group, 28-week prospective study was conducted with 339 patients who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms. However, olanzapine demonstrated significantly greater efficacy in negative symptoms (Scale for Assessment of Negative Symptoms summary score), as well as overall response rate (> or = 40% decrease in the Positive and Negative Syndrome Scale total score). Furthermore, a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves. The incidence of extrapyramidal side effects, hyperprolactinemia, and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients. In addition, statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts. Thus, the differential preclinical profiles of these two drugs were also evident in a controlled, clinical investigation. Olanzapine seemed to have a risk-versus-benefit advantage.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Neurologic Examination; Olanzapine; Pirenzepine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Risperidone; Schizophrenia; Treatment Outcome

Olanzapine is a potential new "atypical" antipsychotic agent. The double-blind acute phase of this study compared three dosage ranges of olanzapine (5 +/- 2.5 mg/day [Olz-L], 10 +/- 2.5 mg/day [Olz-M], 15 +/- 2.5 mg/day [Olz-H]) to a dosage range of haloperidol (15 +/- 5 mg/day [Hal]) and to placebo in the treatment of 335 patients who met the DSM-III-R criteria for schizophrenia. In overall symptomatology improvement (Brief Psychiatric Rating Scale [BPRS]-total), Olz-M, Olz-H, and Hal were significantly superior to placebo. In positive symptom improvement (BPRS-positive), Olz-M, Olz-H, and Hal were comparable and significantly superior to placebo. In negative symptom improvement (Scale for the Assessment of Negative Symptoms [SANS]-composite), Olz-L and Olz-H were significantly superior to placebo and Olz-H was also significantly superior to Hal. The most common treatment-emergent adverse events included somnolence, agitation, asthenia, and nervousness. No acute dystonia was observed with olanzapine. Treatment-emergent parkinsonism occurred with Olz-H at approximately one-third the rate of Hal, and akathisia occurred with Olz-H at approximately one-half the rate of Hal. Prolactin elevations associated with olanzapine were not significantly greater than those observed with placebo and were also significantly less than those seen with haloperidol.

Topics: Adolescent; Adult; Aged; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Schizophrenia

We report the patient of a 53-year-old woman who developed subacute-onset marked tonge protrusion and bite. She was diagnosed as dementia with Lewy bodies (DLB) from the clinical features including progressive cognitive decline, visual hallucinations, parkinsonism, and severe insomnia and depression, and the radiological finding of low dopamine transported uptake in basal ganglia by Dat SCAN and low blood circulation in occipital lobe of cerebrum. The patient received 600 mg doses of levodopa for over a year, followed by rotigotine and ropinirole with a rapid increase of dosage. It is believed that these treatments stimulated and sensitized dopamine D1 receptors, thereby inducing lingual dystonia. Furthermore, the patient demonstrated dyspnea and attacks of apnea caused by the closure of bilateral vocal cords due to laryngeal dyskinesia. After initiation of the neuroleptic, olanzapine, for a short duration, the high dose of levodopa overlapped with neuroleptic sensitivity, suggesting DOPA-induced dystonia and dyskinesia. This interaction can sometimes lead to lethal adverse events, and must be considered very important when treating patients with DLB.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bites and Stings; Drug Interactions; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Dystonia; Female; Humans; Indoles; Laryngeal Diseases; Levodopa; Lewy Body Disease; Middle Aged; Olanzapine; Receptors, Dopamine D1; Tetrahydronaphthalenes; Thiophenes; Tongue Diseases

Second-generation antipsychotic (SGA) effects in youth were monitored to quantify extrapyramidal side effects (EPS) and to identify risk profiles for treatment-emergent EPS.. Data were analyzed for the nonrandomized, prospective Second-generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) inception cohort study. EPS were assessed at baseline and 4, 8, and 12 weeks after naturalistic SGA initiation for schizophrenia, mood, disruptive behavior, and autism spectrum disorders using the Simpson-Angus Scale (SAS), Barnes Akathisia Scale, Abnormal Involuntary Movement Scale (AIMS), and Treatment Emergent Side Effect Scale. Drug-induced parkinsonism was defined by incident mean SAS score >0.33, anticholinergic initiation, or increasing total SAS score ≥2 in patients with baseline EPS.. In 342 youth aged 13.6 ± 3.5 years (male = 58.2%, antipsychotic-naive = 65.8%), 15.2% developed drug-induced parkinsonism. Raw SGA-grouped drug-induced parkinsonism rates were as follows: quetiapine = 1.5%, olanzapine = 13.8%, risperidone = 16.1%, ziprasidone = 20.0%, and aripiprazole = 27.3%. SGA type, dose, higher age, and lower baseline functioning were jointly associated with drug-induced parkinsonism (R(2) = 0.18; p < .0001). Controlling for these factors, drug-induced parkinsonism rates were significantly lower only for quetiapine and olanzapine. Subjectively reported EPS (5%), EPS-related treatment discontinuation (3.3%), and anticholinergic initiation (3%) were infrequent. Anticholinergic initiation was most frequent with risperidone (10.2%; p = .0004). Treatment-emergent dyskinesia ranged from 4.5% (aripiprazole) to 15.5% (olanzapine). SGA type, younger age, white race/ethnicity, and baseline AIMS were jointly associated with treatment-emergent dyskinesia (R(2) = 0.31; p < .0001). Controlling for these factors, treatment-emergent dyskinesia rates differed among SGA subgroups, with higher rates with olanzapine and ziprasidone. At baseline, psychostimulant use was associated with dyskinesia, and number of psychotropic comedications was associated with subjective EPS.. In youth, SGA-related EPS rates did not generally exceed those reported in adults, with particularly low rates with quetiapine and olanzapine.

Topics: Adolescent; Akathisia, Drug-Induced; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Male; Mental Disorders; Multivariate Analysis; New York; Olanzapine; Parkinson Disease, Secondary; Piperazines; Prospective Studies; Quetiapine Fumarate; Regression Analysis; Risperidone; Thiazoles

The aim of this study was to evaluate demographic, clinical, and treatment factors that may impact on neurological adverse effects in naive and quasi-naive children and adolescents treated with antipsychotics.. This was a 1-year, multicenter, observational study of a naive and quasi-naive pediatric population receiving antipsychotic treatment. Two subanalyses were run using the subsample of subjects taking the 3 most used antipsychotics and the subsample of antipsychotic-naive subjects. Total dyskinesia score (DyskinesiaS) and total Parkinson score (ParkinsonS) were calculated from the Maryland Psychiatric Research Center Involuntary Movement Scale, total UKU-Cognition score was calculated from the UKU Side Effect Rating Scale. Risk factors for tardive dyskinesias (TDs) defined after Schooler-Kaine criteria were studied using a logistic regression.. Two hundred sixty-five subjects (mean age, 14.4 [SD, 2.9] years) with different Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders were recruited. DyskinesiaS (P < 0.001) and ParkinsonS (P < 0.001) increased at 1-year follow-up. Risperidone was associated with higher increases in DyskinesiaS compared with quetiapine (P < 0.001). Higher increases in ParkinsonS were found with risperidone (P < 0.001) and olanzapine (P = 0.02) compared with quetiapine. Total UKU-Cognition Score decreased at follow-up. Findings were also significant when analyzing antipsychotic-naive subjects. Fifteen subjects (5.8%) fulfilled Schooler-Kane criteria for TD at follow-up. Younger age, history of psychotic symptoms, and higher cumulative exposure time were associated with TD at follow-up.. Antipsychotics increased neurological adverse effects in a naive and quasi-naive pediatric population and should be carefully monitored. Risperidone presented higher scores in symptoms of dyskinesia and parkinsonism. Quetiapine was the antipsychotic with less neurological adverse effects. Younger subjects, psychosis, and treatment factors predicted an increased risk of TD.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Male; Olanzapine; Parkinson Disease, Secondary; Quetiapine Fumarate; Risperidone

The incidence of extrapyramidal symptoms (EPS) has been shown to be generally low among patients with schizophrenia receiving oral olanzapine. A long-acting injection (LAI) of olanzapine has recently been approved for the treatment of schizophrenia in a number of countries. Accordingly, the objective of the current analyses was to compare the incidences of EPS during treatment with olanzapine LAI versus oral olanzapine.. The incidences of treatment-emergent EPS were examined in adults with schizophrenia receiving olanzapine LAI or oral olanzapine for up to 3 years. Short-term data were obtained from two double-blind studies of olanzapine LAI: one included a placebo comparator, and the other included oral olanzapine as an active comparator. Long-term data were obtained from an open-label extension study for olanzapine LAI and from an integrated database for oral olanzapine.. The short-term incidence of EPS was 5.6% during treatment with olanzapine LAI (45-405 mg every 2-4 weeks) and 5.0% with oral olanzapine (5-20 mg/day). Akathisia (2.6% LAI, 1.2% oral), and Parkinson-like symptoms (1.8% LAI, 3.7% oral) were similar between treatment groups. The incidence of EPS for long-term treatment was 9.2% for olanzapine LAI. Incidences of EPS events were not significantly different between patients receiving olanzapine LAI or oral olanzapine for up to 3 years.. These findings suggest that EPS profiles are similar for olanzapine LAI and oral olanzapine.

Topics: Administration, Oral; Adolescent; Adult; Aged; Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Delayed-Action Preparations; Dyskinesia, Drug-Induced; Dystonia; Humans; Incidence; Middle Aged; Olanzapine; Parkinsonian Disorders; Schizophrenia; Young Adult

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Drug Substitution; Dyskinesia, Drug-Induced; Humans; Isoxazoles; Male; Olanzapine; Paliperidone Palmitate; Pyrimidines; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Tardive dyskinesia (TD) rates with second-generation antipsychotics (SGAs) are considered to be low relative to first-generation antipsychotics (FGAs), even in the particularly vulnerable elderly population. However, risk estimates are unavailable for patients naïve to FGAs. Therefore, we aimed to determine the TD incidence in particularly vulnerable, antipsychotic-naïve elderly patients treated with the SGA risperidone or olanzapine. The present work describes a prospective inception cohort study of antipsychotic-naïve elderly patients aged 55 years identified at New York Metropolitan area in-patient and out-patient geriatric psychiatry facilities and nursing homes at the time of risperidone or olanzapine initiation. At baseline, 4 weeks, and at quarterly periods, patients underwent assessments of medical and medication history, abnormal involuntary movements, and extra-pyramidal signs. TD was classified using Schooler-Kane criteria. Included in the analyses were 207 subjects (age: 79.8 years, 70.0% female, 86.5% White), predominantly diagnosed with dementia (58.9%) or a major mood disorder (30.9%), although the principal treatment target was psychosis (78.7%), with (59.4%) or without (19.3%) agitation. With risperidone (n=159) the cumulative TD rate was 5.3% (95% confidence interval (CI): 0.7, 9.9%) after 1 year (mean dose: 1.0±0.76 mg/day) and 7.2% (CI: 1.4, 12.9%) after 2 years. With olanzapine (n=48) the cumulative TD rate was 6.7% (CI: 0, 15.6%) after 1 year (mean dose: 4.3±1.9 mg/day) and 11.1% (CI: 0, 23.1%) after 2 years. TD risk was higher in females, African Americans, and patients without past antidepressant treatment or with FGA co-treatment. The TD rates for geriatric patients treated with risperidone and olanzapine were comparable and substantially lower than previously reported for similar patients in direct observation studies using FGAs. This information is relevant for all patients receiving antipsychotics, not just the especially sensitive elderly.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Incidence; Male; Olanzapine; Prospective Studies; Risperidone

Topics: Antipsychotic Agents; Benzodiazepines; Brain; Drug Substitution; Dyskinesia, Drug-Induced; Humans; Olanzapine; Receptors, Dopamine; Risperidone; Schizophrenia; Treatment Outcome

Tardive dyskinesia (TD) is a devastating adverse effect of long-term antipsychotic drug treatment. Atypical antipsychotics produce less TD, and it has been shown that they may have a therapeutic effect on pre-existing TD. Here, we report a case of olanzapine-induced TD which did not improve after switching to risperidone but improved after the addition of quetiapine to risperidone regimen. We also provide a brief review of the reported cases on TD induced by atypical antipsychotics which improved after switching to another atypical agent. It is unclear whether some atypical antipsychotics are more effective than others in the treatment of TD. Differences in this property and the underlying mechanism require further study.

Topics: Adult; Anti-Dyskinesia Agents; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia, Paranoid

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Olanzapine; Schizophrenia; Sulpiride

This Schizophrenia Outcome Survey compared medical costs, psychopathology and adverse events in outpatients for 2 years following hospitalisation for an acute schizophrenic episode.. Adults stabilised with haloperidol, olanzapine or risperidone entered this observational study or=1 EPS; 69% (p<0.013), 40 and 44%, respectively, had >or=1 sexual problem (NS). Mean weight gain was 0.4 (NS), 2.6 (p<0.05) and 2.6 kg (p<0.05), respectively.. In this naturalistic study, treatment allocation might have introduced a bias in the interpretation of efficiency results, but olanzapine and risperidone caused less EPS than haloperidol during 2 years of outpatient follow-up.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Belgium; Benzodiazepines; Brief Psychiatric Rating Scale; Dyskinesia, Drug-Induced; Female; Haloperidol; Health Care Costs; Hospitalization; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Weight Gain

SOHO is a 3-year, prospective, observational study of schizophrenia patients who started a new antipsychotic in 10 European countries. Cohorts of patients were defined according to the antipsychotic started at baseline: olanzapine, risperidone, quetiapine, amisulpride, clozapine, oral typical and depot typical antipsychotics. Tolerability in terms of rates of extrapyramidal symptoms (EPS), tardive dyskinesia (TD), anticholinergic use, loss of libido/impotence, amenorrhoea/galactorrhoea/gynaecomastia, and weight change was assessed in 4939 patients who started monotherapy. Logistic regression models related medication initiated at study entry to adverse events over follow-up, adjusting by baseline differences among treatment cohorts. Patients taking typical antipsychotics or risperidone were more likely to experience EPS and TD during follow-up than patients taking olanzapine. Patients taking olanzapine were less likely to have loss of libido/impotence during follow-up than patients in the risperidone, amisulpride, clozapine, oral typical and depot typical cohorts. Weight gain occurred in all groups, but was greater with olanzapine. In conclusion, antipsychotics have different tolerability profiles in terms of the adverse events we monitored. Results should be interpreted conservatively due to the observational study design.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Body Weight; Cohort Studies; Delayed-Action Preparations; Dyskinesia, Drug-Induced; Erectile Dysfunction; Europe; Female; Humans; Libido; Male; Middle Aged; Odds Ratio; Olanzapine; Outpatients; Prolactin; Schizophrenia; Sexual Dysfunction, Physiological; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Chronic Disease; Dyskinesia, Drug-Induced; Humans; Olanzapine; Perphenazine; Piperazines; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome

Topics: Adjuvants, Anesthesia; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Olanzapine

Adjunctive treatment with the selective alpha2 adrenoceptor antagonist idazoxan augments the effect of conventional antipsychotics in treatment-resistant schizophrenics comparing favourably with clozapine. Clozapine has high affinity for alpha2 adrenoceptors. Previously, we found that adjunctive idazoxan treatment to the dopamine (DA) D2/3 antagonist raclopride enhanced raclopride-induced effects in an animal model of antipsychotic activity (conditioned avoidance response, CAR) and, similarly to clozapine, reversed the disruption of working memory induced by N-methyl-D-aspartate receptor blockade in rats with a concomitant increase in prefrontal DA efflux. To further investigate the significance of alpha2 adrenoceptor affinity for antipsychotic efficacy, we here investigated, in rats, the effects of adjunctive idazoxan treatment to low doses of a typical (haloperidol) and an atypical (olanzapine) antipsychotic drug, both lacking appreciable alpha2 adrenoceptor affinity, on (i) CAR; (ii) catalepsy; and (iii) DA output in the prefrontal cortex and the nucleus accumbens using microdialysis. Adjunctive treatment with idazoxan to haloperidol or olanzapine enhanced suppression of CAR to a level predicting sufficient antipsychotic activity, increased DA output preferentially in the prefrontal cortex, and reversed haloperidol-induced catalepsy. Our data confirm and extend our previous findings as well as clinical observations, and suggest that adjunctive alpha2 adrenoceptor blockade both typical and atypical antipsychotic drugs, lacking appreciable affinity for the alpha2 adrenoceptor, may contribute to a more advantageous therapeutical profile of these drugs in schizophrenia treatment, allowing for reduced DA D2 occupancy and reduction of unwanted side-effects.

Topics: Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Antagonists; Animals; Antipsychotic Agents; Avoidance Learning; Benzodiazepines; Catalepsy; Dopamine; Dose-Response Relationship, Drug; Drug Synergism; Dyskinesia, Drug-Induced; Haloperidol; Idazoxan; Male; Microdialysis; Motor Activity; Nucleus Accumbens; Olanzapine; Prefrontal Cortex; Rats; Rats, Wistar

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Olanzapine; Quetiapine Fumarate; Time Factors; Withholding Treatment

Atypical antipsychotics are often addressed as one class of drugs, although there are marked differences in their pharmacological profiles. It is unknown how this is seen by practitioners and to what extent they differentiate between the various atypical compounds. In a drug utilization study, 472 schizophrenic outpatients who were switched for individual reasons from either olanzapine or risperidone to amisulpride were monitored. Data on patients, illness and treatment as well as on reasons to switch were collected. The reasons to switch from olanzapine to amisulpride were preferably 'weight gain' (72.6% of the physicians), or the 'expectancy of less weight gain with amisulpride' (84.1%) and 'patient request' (60.2%). Specific reasons to switch from risperidone were 'extrapyramidal symptoms' (58.5%), or the 'expectancy of few extrapyramidal symptoms with amisulpride' (82.5%). In conclusion, this study confirms that physicians do not consider 'atypical antipsychotics' as one homogeneous class of drugs but make differences that reflect the specific pharmacological profiles of the respective drugs.

Topics: Adolescent; Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Drug Utilization; Dyskinesia, Drug-Induced; Female; Germany; Humans; Male; Middle Aged; Olanzapine; Risperidone; Schizophrenia; Schizophrenic Psychology; Structure-Activity Relationship; Sulpiride; Weight Gain

Although the positive symptoms of schizophrenia are more likely than the negative symptoms to result in a patient's hospitalization, positive symptoms tend to respond more completely to antipsychotic drugs.When positive symptoms are controlled, residual negative symptoms may remain. If these negative symptoms persist, they can have a considerable impact on a patient's ability to function in society. Current therapies have only a limited effect on negative symptoms. Consequently, broad-spectrum agents that effectively treat both positive and negative symptoms are needed. One obstacle to the regulatory approval of an agent for treating negative symptoms is the difficulty of designing a trial to demonstrate efficacy for these symptoms. Agreeing on a definition of negative symptoms, establishing patient inclusion criteria, and determining how to account for confounding factors represent only a few of the challenges to study design. How these challenges can be met is illustrated in the design of a series of clinical trials to assess the efficacy of asenapine, a psychopharmacologic agent being developed for the treatment of schizophrenia and, in particular, the treatment of negative symptoms associated with schizophrenia. These trials, the protocols for which are described in this paper, will not only determine the efficacy of asenapine but will add to our knowledge of patients with predominant, persistent negative symptoms, an understudied and inadequately treated patient population.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clinical Trials, Phase III as Topic; Depressive Disorder; Dibenzocycloheptenes; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Endpoint Determination; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Middle Aged; Multicenter Studies as Topic; Neurologic Examination; Olanzapine; Patient Selection; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Research Design; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Following ten years of continuous olanzapine therapy a 51 years old man developed a Gilles de la Tourette syndrome which disappeared after changing to amisulprid. The Tourette-syndrome will be attributed to a tardive dyskinesia induced by olanzapine.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Humans; Long-Term Care; Male; Middle Aged; Olanzapine; Promethazine; Sulpiride; Tourette Syndrome; Verbal Behavior

Topics: Anti-Dyskinesia Agents; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Male; Middle Aged; Olanzapine; Schizophrenia; Tetrabenazine

Reported herein is a case of methamphetamine psychosis in which tardive dystonia was treated successfully with clonazepam. The patient was a 69-year-old man who had taken methamphetamine habitually for approximately 40 years. Auditory hallucinations had developed 25 years previously, for which haloperidol had been prescribed. Tardive dystonia had developed in December 2005. Haloperidol was withdrawn and risperidone or olanzapine alone had been administered, but neither had improved the dystonic posture. However, when clonazepam was added, a gradual improvement in the dystonic posture became evident. Tardive dystonia is currently treated on a trial-and-error basis. Accumulation of further cases similar to the present one is very important for establishing an effective treatment.

Topics: Aged; Anti-Dyskinesia Agents; Antipsychotic Agents; Benzodiazepines; Biperiden; Central Nervous System Stimulants; Clonazepam; Dyskinesia, Drug-Induced; Hallucinations; Haloperidol; Humans; Male; Methamphetamine; Olanzapine; Posture; Psychoses, Substance-Induced; Risperidone

Topics: Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Magnetic Resonance Imaging; Middle Aged; Olanzapine; Schizophrenia; Schizophrenic Psychology; Tics

Topics: Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Olanzapine; Risk Factors

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Clinical Trials, Phase I as Topic; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Humans; Olanzapine; Patient Dropouts; Perphenazine; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Receptors, Dopamine D2; Schizophrenia; Up-Regulation

To report a case of olanzapine-induced Pisa syndrome that improved after treatment with clozapine.. A 22-year-old male with paranoid schizophrenia presented with insidious onset tonic truncal flexion with axial rotation and difficulty in walking after exposure to olanzapine in doses up to 15 mg/day for 9 months. An objective causality assessment suggested that Pisa syndrome was probably related to olanzapine. There was improvement in his symptoms after 6 weeks of treatment with clozapine in doses gradually titrated to 350 mg/day.. Pisa syndrome is a type of dystonia that has been associated with both typical and atypical antipsychotics. Both acute and insidious onset cases have been described in the literature, which have different course and treatment response. Clozapine was found to be effective in reducing the severity of olanzapine-induced Pisa syndrome.. Clozapine may be a useful treatment option for Pisa syndrome that has been caused by olanzapine.

Topics: Adult; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Dystonia; Humans; Male; Olanzapine; Schizophrenia, Paranoid; Syndrome

Continuous, but not intermittent, infusion with a conventional antipsychotic (haloperidol, HAL) can induce the vacuous chewing movement (VCM) syndrome in rats. The objective of this study was to determine whether continuous, versus intermittent, olanzapine (OLZ) infusion differently affects the development of VCMs.. Experiment 1: Animals were treated with 7.5 mg/kg/day of OLZ or vehicle (VEH) via either minipump (MP) or daily subcutaneous (SC) injections for 8 weeks. Experiment 2: A separate group of rats were treated with 15 mg/kg/day of OLZ, or 1 mg/kg/day of HAL or VEH via MP for 8 weeks. Dopamine D2 receptor occupancy levels were measured, ex vivo, with [3H]-raclopride.. Experiment 1: Rats receiving 7.5 mg/kg/day of OLZ via MP (51% D2 occupancy), but not those receiving the same dose via daily SC injections (94% peak D2 occupancy), showed significant VCM levels compared with control animals (p = .02). Experiment 2: Both OLZ (67% D2 occupancy) and HAL (79% D2 occupancy) led to similar increases in VCMs compared with VEH (p = .005).. This study provides strong evidence that even an atypical antipsychotic like OLZ, which rarely gives rise to tardive dyskinesia in the clinic, can lead to the VCM syndrome in rats if the antipsychotic is administered in a method (via MP) that leads to continuous presence of the drug in the brain.

Topics: Analysis of Variance; Animals; Behavior, Animal; Benzodiazepines; Disease Models, Animal; Dopamine Antagonists; Drug Administration Routes; Dyskinesia, Drug-Induced; Haloperidol; Infusion Pumps; Male; Mastication; Olanzapine; Raclopride; Radioligand Assay; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2; Selective Serotonin Reuptake Inhibitors; Time Factors; Tritium

Rabbit syndrome (RS) is a rare extrapyramidal side effect of antipsychotic treatment. It is characterized by involuntary, rhythmic dyskinesias of mouth and lips excluding the tongue, and is most common under typical neuroleptics. There are also several reports of the syndrome in patients with the atypical antipsychotics risperidone and aripiprazole. We report a 74 year-old patient suffering from a bipolar affective disorder, who developed a rabbit syndrome following the intake of 20 mg/d olanzapine. To our knowledge this is the first case report of a RS due to olanzapine.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Humans; Neurologic Examination; Olanzapine; Syndrome

Antipsychotics are the keystone in schizophrenia treatment. Although the benefits of the new generation of antipsychotics has been demonstrated over the last decade, the issues of patient compliance and higher purchasing price of atypical antipsychotics remain unresolved. Risperidone is the only atypical antipsychotic agent with long-acting formulation. Long-acting risperidone is a water-based injection and it has been associated with a low level of pain. The aim of the present study was to test whether an improvement in compliance with the use of a long-acting risperidone, compared with olanzapine and depot haloperidol, can increase the effectiveness and the cost-effectiveness indexes. An economic comparison model with decision tree, rather than a prospective design with real clinical drug trial, was applied. The unit cost for each medical procedure was obtained from the claimed-database of the Bureau of National Health Insurance in Taiwan. An executive committee simulated the incidence of extrapyramidal side-effects and proposed a therapeutic model for each strategy based on a literature review. The probabilities of treatment response of different agents and those of different mental health states were estimated by the executive committee and 10 senior psychiatrists who were randomly selected. Sensitivity analysis was performed for drug cost-effectiveness and compliance improvement for using long-acting risperidone. The results showed that long-acting risperidone is more cost-effective than either olanzapine or depot haloperidol for treating schizophrenia patients whose conditions are stable and whose illness duration ranges from 1 to 5 years. The comparison model with the Kaplan-Meier decision tree may serve as an alternative to prospectively designed studies for cost-effectiveness of atypical antipsychotics.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Cost Savings; Costs and Cost Analysis; Decision Trees; Delayed-Action Preparations; Dyskinesia, Drug-Induced; Female; Hospitalization; Humans; Long-Term Care; Male; Mental Health; Models, Economic; Olanzapine; Patient Compliance; Public Health; Risperidone; Schizophrenia; Schizophrenic Psychology; Taiwan; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; GABA Antagonists; Humans; Olanzapine; Patient Compliance; Schizophrenia

To compare the incidence and persistence of tardive dyskinesia between patients diagnosed with schizophrenia (ICD-10 and/or DSM-IV) who were treated with second-generation antipsychotics and first-generation antipsychotics in routine clinical practice.. The European Schizophrenia Outpatient Health Outcomes (SOHO) study is a 3-year, prospective, observational study. Each country had a start date for patient enrollment before October 2000. All enrollment was completed by June 30, 2001. A simple, global measure of tardive dyskinesia was rated by participating clinicians. For the current analysis, data at baseline, 3 months, and 6 months were analyzed using a generalized estimating equation model.. Second-generation antipsychotics conferred a lower risk for tardive dyskinesia at 6 months than first-generation antipsychotics (0.9% vs. 3.8%, odds ratio [OR] = 0.29, 95% confidence interval [CI] = 0.18 to 0.46). In addition, patients with tardive dyskinesia at baseline who were receiving second-generation antipsychotics were less likely than patients receiving first-generation antipsychotics to have tardive dyskinesia symptoms at 6 months (43.6% vs. 60.8%, OR = 0.50, 95% CI = 0.30 to 0.85). A sensitivity analysis suggested no bias related to pharmaceutical industry financial support.. The results suggest that the relative advantage of second-generation antipsychotics in terms of lower rates of incidence and persistence of tardive dyskinesia, observed in technical randomized controlled trials, generalizes to routine clinical care.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Dyskinesia, Drug-Induced; Europe; Female; Follow-Up Studies; Humans; Incidence; Male; Olanzapine; Outcome Assessment, Health Care; Prospective Studies; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Risk Factors; Schizophrenia; Treatment Outcome

The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study was designed to provide information regarding use and outcome of antipsychotic treatments in a large, diverse population in real practice settings.. Outpatients with schizophrenia (ICD-10 or DSM-IV) who initiated or changed to a new antipsychotic entered this 3-year, naturalistic, prospective observational study. Four monotherapy treatment groups were defined according to the antipsychotic prescribed at baseline, namely olanzapine, risperidone, quetiapine, and haloperidol. Efficacy was assessed using the Clinical Global Impressions-Severity of Illness rating scale (CGI-S), inclusive of subscales for positive, negative, depressive, and cognitive symptoms. Tolerability was assessed by adverse event questionnaires and weight measurements. Six-month findings are described.. At baseline, 5833 participants were prescribed monotherapy and the mean severity of illness was moderate to marked (CGI-S). At 6 months, olanzapine resulted in significantly greater improvements in overall, positive, negative, depressive, and cognitive symptoms compared with quetiapine, risperidone or haloperidol (p <.001). Improvements in overall, negative, and cognitive symptoms were significantly higher for risperidone compared with haloperidol (p <.001), whereas improvements across all symptoms were comparable for quetiapine and haloperidol. Extra-pyramidal symptoms and tardive dyskinesia decreased compared with baseline in the olanzapine, quetiapine, and risperidone groups but increased in the haloperidol group (p <.001, likelihood of extrapyramidal symptoms with haloperidol compared with olanzapine, quetiapine, or risperidone). Sexual function adverse events were most prominent in the haloperidol and risperidone treatment groups. Weight change was significantly greater for olanzapine compared with the other antipsychotics (p <.001).. Our results support the previously reported positive impact of atypical antipsychotics, particularly olanzapine, in patients with schizophrenia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Hyperprolactinemia; International Classification of Diseases; Male; Observation; Olanzapine; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index; Sexual Dysfunction, Physiological; Surveys and Questionnaires; Weight Gain

Evidence suggests atypical antipsychotic treatment is associated with a lower incidence of tardive dyskinesia (TD) than typical antipsychotic drugs, and is a potential antidyskinetic treatment. We present the case of a middle-aged woman never previously exposed to antipsychotic treatment who developed TD after 6 months of olanzapine monotherapy. Substitution of quetiapine for olanzapine alleviated her TD symptoms. The case demonstrates that atypical antipsychotic drugs have different effects in relation to TD. Potential psychopharmacological mechanisms explaining these differences are discussed, highlighting the importance of D2 receptor occupancy by atypical antipsychotic drugs for TD.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Olanzapine; Quetiapine Fumarate; Receptors, Dopamine D2; Risperidone; Schizophrenia; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Male; Olanzapine; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Olanzapine; Pirenzepine

There is no generally accepted treatment for tardive dyskinesia following intake of neuroleptics. Many compounds with effects on serotonine, GABA, cholinergic or dopamine receptors have been clinically useful. We report on a 71-year-old female patient suffering from orofacial tardive dyskinesia after treatment with haloperidol, which did not respond to monotherapy with antidyskinetic drugs. The syndrome disappeared almost completely within two weeks after a multidrug approach consisting of tetrabenazine, olanzapine and tiapride. A combination of antidyskinetic drugs should be considered in patients with severe tardive dyskinesia.

Topics: Aged; Anti-Dyskinesia Agents; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Olanzapine; Pirenzepine; Tetrabenazine; Tiapamil Hydrochloride; Treatment Outcome

The underlying pathophysiological basis of tardive dyskinesia (TD) remains speculative. Haloperidol (HP) inhibits neuronal nitric oxide (NO) synthase (NOS) activity in vitro, but has not to date been studied in an intact animal model. Recent animal studies have found that extrapyramidal dysfunction evoked by chronic HP is associated with suppression of striatal cyclic guanosine monophosphate (cGMP), as well as plasma nitrogen oxides. Striatal dopamine (DA) is central to motor control, while NO plays an important neuroregulatory role in striatal DA function. Recent case reports suggest that atypical antipsychotics, such as olanzapine (OLZ), may be effective in reversing TD. Here, rats treated with HP (1.5 mg/kg per day p.o.) for 28 days developed significant vacuous chewing movements (VCMs) together with significant suppression of striatal NOS activity. Acute challenge with OLZ (1 and 2 mg/kg i.p.) significantly reversed both HP-induced VCMs and suppression of striatal NOS activity. Therefore TD may involve attenuation of NO-mediated neuromodulation in the striatum. Reversal of VCMs and NOS suppression with OLZ suggests that disinhibition of striatal NOS activity may underlie the clinical benefit of OLZ in TD.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Corpus Striatum; Cyclic GMP; Dyskinesia, Drug-Induced; Haloperidol; Male; Mastication; Nitric Oxide; Nitric Oxide Synthase; Olanzapine; Pirenzepine; Rats; Rats, Sprague-Dawley

The behavioral and neurochemical effects of switching from typical to atypical medications have not been evaluated in the rodent models of tardive dyskinesia. Thus, we treated rats with haloperidol-decanoate for 12 weeks, and assessed the effects of additional treatment with olanzapine, haloperidol, clozapine, or vehicle on vacuous chewing movements and expression of transcripts for dopamine receptors, tyrosine hydroxylase, delta-opioid receptor, prodynorphin, preproenkephalin, glutamic acid decarboxylase-65 (glutamic acid decarboxylase (GAD)-65) and GAD-67 and N-methyl-D-aspartate (NMDA) receptor subunits in the striatum and its efferent pathways. Haloperidol-decanoate induced vacuous chewing movements extinguished following an additional 4 weeks of treatment with vehicle, olanzapine or haloperidol, but not clozapine. Post-treatment, vacuous chewing movements in the clozapine group were significantly higher than the vehicle, olanzapine and haloperidol groups. GAD-67 mRNA expression in the globus pallidus was decreased following additional treatment with olanzapine or haloperidol, but not clozapine. Changes in expression of other transcripts were not detected. These findings demonstrate important differences in the effects of typical and atypical antipsychotics on chronic vacuous chewing movements.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Brain; Clozapine; Dyskinesia, Drug-Induced; Gene Expression; Haloperidol; In Situ Hybridization; Injections, Intramuscular; Male; Mastication; Olanzapine; Rats; Rats, Sprague-Dawley; Receptors, Dopamine; Receptors, N-Methyl-D-Aspartate; RNA, Messenger

Our report of a patient with severe tardive dyskinesia (TD) who has been exposed to both typical antipsychotic and clozapine, olanzapine and quetiapine during a 124-week follow-up period supports the possible beneficial effect of atypical antipsychotics on pre-existing symptoms of TD. Persistently high AIMS scores during all the periods of treatment with typical antipsychotics contrast strongly with the drop in scores that occurs in strict chronological sequence after switching to both clozapine (45%), olanzapine (27.8%) and quetiapine (85%). Since the reversal to haloperidol from the three atypical agents was systemically associated with a return to high AIMS scores, it seems likely that the improvement noted with clozapine, olanzapine and quetiapine represents a temporary symptomatic effect rather than a sustained resolution of the disorder. The olanzapine-clozapine-quetiapine rank order of increasing effectiveness against TD symptoms suggests that this property, although shared by the atypical antipsychotics, is to some degree drug-specific. Patient- and/or drug-dependent mechanisms may be involved in this gradient of effect.

Topics: Amphetamine-Related Disorders; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Male; Olanzapine; Quetiapine Fumarate; Schizophrenia, Paranoid

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Female; Humans; Olanzapine; Pirenzepine; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Huntington Disease; Male; Middle Aged; Olanzapine; Pirenzepine

The authors report two cases of schizophrenia in which olanzapine proved to be an efficacious antipsychotic medication associated with the remission of movement disorder.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Male; Middle Aged; Olanzapine; Pirenzepine

Tardive dyskinesia is a severe complication of neuroleptic treatment. It may develop weeks, even years after starting a neuroleptic treatment and the symptoms may be irreversible. Neuroleptic compounds are not only used in cases of schizophrenia, but also in cases of severe depression with delusional symptoms. We want to present the case of a 67 year old female patient who developed haloperidol induced dyskinesea and stress unto the successful treatment of this complication with olanzapine in combination with paroxetine. Under this regime not only the improvement of the depression, but also of the tardive dyskinesea was impressive.

Topics: Affective Disorders, Psychotic; Aged; Benzodiazepines; Depressive Disorder, Major; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Neurologic Examination; Olanzapine; Paroxetine; Patient Admission; Pirenzepine

Atypical antipsychotic medications are increasingly prescribed for child and adolescent patients. Relatively little information on adverse events (AEs), specifically in children or adolescents taking atypical antipsychotics, is available.. The Food and Drug Administration spontaneous AE reporting postmarketing surveillance database was queried for olanzapine until March 31, 2000. Patient exposure estimates as of the same date were provided by the manufacturer. AE complaints and exposure estimates were divided by age: children (birth-9 years), adolescents (10-19), and adults (20+). AE complaint risks per 10,000 patients exposed were calculated along with risk ratios across age groups and their 95% confidence intervals.. Extrapyramidal syndrome complaint risks were similar across development, and tardive dyskinesia complaint risks were comparable in adolescents and adults. Overrepresented AE complaints in children included sedation, weight gain, liver function abnormalities, and tardive dyskinesia. Overrepresented AE complaints in adolescents included sedation, weight gain, liver function abnormalities, and prolactin increase.. Extrapyramidal syndromes may be no more common in children and adolescents with olanzapine than in adults. The frequency of some other AEs may differ across development. Caution is warranted because of the likelihood of reporting bias. Similar analyses should be conducted with other atypical antipsychotics.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Age Factors; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Child; Child, Preschool; Dyskinesia, Drug-Induced; Female; Humans; Infant; Infant, Newborn; Male; Olanzapine; Pirenzepine; Product Surveillance, Postmarketing; United States

In a retrospective chart review, efficacy and drug costs were compared in 91 consecutive outpatients receiving risperidone (n=70) or olanzapine (n=21) at the Veterans Affairs Medical Center in Syracuse, NY. Between-group differences in background characteristics, diagnoses (schizophrenia in more than half of each group) and antipsychotic efficacy [Clinical Global Impressions (CGI) scale scores] were not significant. The mean doses were 3.6+/-2.4 mg/day of risperidone and 10.7+/-7.6 mg/day of olanzapine. The VA costs of these mean doses were S3.32/day for risperidone and $6.67/day for olanzapine. Mean duration of treatment was significantly longer for risperidone (21 months) than for olanzapine (13 months). Incidence of parkinsonian symptoms (14% of both risperidone and olanzapine patients) and tardive dyskinesia (3% of risperidone patients and 5% of olanzapine patients) was similar in the two groups. Akathisia tended to occur more often in patients receiving olanzapine than risperidone (14% versus 3%, P=.08). The results of this retrospective survey indicate that, in comparable VA populations of patients with psychotic and other disorders, risperidone and olanzapine are equally efficacious but olanzapine may be more likely to produce akathisia and is twice as expensive as risperidone.

Topics: Antipsychotic Agents; Benzodiazepines; Drug Utilization; Dyskinesia, Drug-Induced; Female; Hospitals, Veterans; Humans; Male; Middle Aged; Olanzapine; Outpatients; Pirenzepine; Retrospective Studies; Risperidone; United States; United States Department of Veterans Affairs

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Treatment Outcome

This open-label pilot study explored the antiemetic activity of olanzapine, an atypical antipsychotic, in patients with advanced cancer requiring opioid analgesics for pain. Fifteen patients received 2 days of a washout and placebo "run-in" followed by two day periods on each of three doses of olanzapine (2.5 mgs, 5 mgs, and 10 mgs). Patients completed a daily food journal as well as the Mini Mental State Exam, Simpson Angus Scale, Barnes Akathisia Scale, and the Functional Assessment of Cancer Therapy-General across four time periods, with special attention being placed on the nausea item. Eleven women and 4 men with varied primary cancer sites participated. The average age of the sample was 58 years (SD = 16.8). All three dose levels were associated with significant reductions in nausea compared to baseline. Diary entries recorded by the subjects suggested substantial benefits to overall well being and the 5mg condition was associated with statistically significant improvement in overall quality of life over baseline (F = 12.0, p < 0.005). No extrapyramidal symptoms were noted and mental status exams were not changed over the course of the eight days. These results suggest an antiemetic effect for olanzapine and indicate the need for a controlled trial.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Benzodiazepines; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Pain; Palliative Care; Pilot Projects; Pirenzepine

Topics: Adult; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Dystonia; Female; Humans; Olanzapine; Pirenzepine; Tongue Diseases

Our previous work has shown that chronic haloperidol treatment decreases striatal symmetric synapses preferentially in rats which develop oral dyskinesias (vacuous chewing movements (VCMs)). The present experiment tests the hypothesis that olanzapine, which does not cause dyskinesia in humans or rats, would not cause the ultrastructural changes produced by haloperidol. After 6 months of treatment, VCM scores for the olanzapine group (5.1 +/- 4.5) were similar to those of controls (5.2 +/- 3.9), whereas rats in the haloperidol group were either nondyskinetic (4.3 +/- 2.2) or dyskinetic (16.9 +/- 6.7). The volume of the striatum (mm(3)), did not differ among the groups: control, 37.5 +/- 4.7; olanzapine, 36.4 +/- 4.3; haloperidol, nondyskinetic, 40.5 +/- 6.3; haloperidol, dyskinetic, 36.6 +/- 5.9. Synaptic density (per 1 microm(3)), obtained from the central region of the striatum, did not differ between the olanzapine (0.699 +/- 0.146) and control groups (0.652 +/- 0.108). The number of asymmetric synapses in the olanzapine group (0.624 +/- 0.136) was also similar to that of controls (0.550 +/- 0.090). The number of symmetric synapses in the olanzapine group (0.074 +/- 0.032) was not significantly different from that of controls (0.096 +/- 0.043). Thus, olanzapine, in contrast to haloperidol, did not produce dyskinesias or synapse loss. These results strengthen the correlation between the expression of VCMs and striatal synaptic changes and indicate that olanzapine has fewer behavioral and anatomical side effects than does haloperidol.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Haloperidol; Male; Neostriatum; Olanzapine; Pirenzepine; Presynaptic Terminals; Rats; Rats, Sprague-Dawley; Synapses

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Drug Interactions; Dyskinesia, Drug-Induced; Humans; Olanzapine; Ondansetron; Pirenzepine; Receptors, Serotonin; Serotonin Antagonists

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Male; Olanzapine; Pirenzepine; Risperidone; Treatment Outcome

Topics: Adult; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Male; Neurologic Examination; Olanzapine; Pirenzepine; Risperidone; Schizophrenia

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Hallucinations; Humans; Male; Olanzapine; Parkinson Disease; Pirenzepine

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Hepatolenticular Degeneration; Humans; Male; Muscle Rigidity; Olanzapine; Parkinsonian Disorders; Pirenzepine; Psychotic Disorders; Risperidone

A 21-year-old man with the diagnosis of paranoid schizophrenia was admitted to our clinic with cervical dystonia developing at the end of the first year of olanzapine therapy. The present case suggests that tardive dystonia in this patient is most likely associated with olanzapine administration as this is the main antipsychotic he received. Regarding the few case reports of olanzapine-associated tardive syndromes, patients taking olanzapine should be carefully screened for the appearance of tardive movements.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Male; Olanzapine; Pirenzepine; Schizophrenia, Paranoid

Converging evidence indicates that, in controlled drug trials, individuals receiving novel antipsychotic medications have fewer adverse effects than those receiving conventional antipsychotic medications. This in turn may lead to greater patient treatment satisfaction. This study examines patient satisfaction and burden of adverse effects in a county-wide epidemiologic study of first admission psychotic persons with psychosis who were receiving novel antipsychotic drugs (n = 42). Comparisons were made within this group, and between 25 of these persons and 25 others with the same diagnosis and sex, from the same epidemiologic study, who were receiving a comparable regimen of conventional antipsychotic drugs. Patients receiving novel antipsychotics were significantly more satisfied and were significantly less burdened by adverse effects than those receiving conventional antipsychotics. Among the group receiving novel antipsychotics, dosage was not related to satisfaction or burden of adverse effects. For those treated with risperidone (n = 27), there was a difference, approaching statistical significance, for greater satisfaction and less adverse effect burden among those persons with dosages less than 5 mg daily as compared to higher dosages.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Depressive Disorder, Major; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Neurologic Examination; Olanzapine; Patient Satisfaction; Pirenzepine; Risperidone; Schizophrenia; Schizophrenic Psychology

Neuroleptic-induced tardive dyskinesia, which often appears in middle-aged and older adults early in the course of treatment with low doses of conventional antipsychotics, is 5 to 6 times more prevalent in elderly than in younger patients. In addition to age, other risk factors for tardive dyskinesia include early extrapyramidal symptoms (EPS), cumulative amounts of neuroleptics, duration of neuroleptic treatment, and history of alcohol abuse and/or dependence. The atypical antipsychotics, which have a low liability for EPS, are likely to also have low potential for tardive dyskinesia, despite the paucity of controlled studies. Starting and maintenance doses of the atypical antipsychotics should generally be lower in older than in younger adults.

Topics: Adult; Age Factors; Aged; Alzheimer Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Incidence; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Female; Humans; Olanzapine; Pirenzepine; Schizophrenia; Selective Serotonin Reuptake Inhibitors

Topics: Acute Disease; Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Cost-Benefit Analysis; Dibenzothiazepines; Dibenzothiepins; Dyskinesia, Drug-Induced; Germany; Humans; Neurotransmitter Agents; Olanzapine; Patient Compliance; Pirenzepine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Sulpiride

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dopamine Antagonists; Dyskinesia, Drug-Induced; Flupenthixol; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Remission Induction; Selective Serotonin Reuptake Inhibitors

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blepharospasm; Dyskinesia, Drug-Induced; Humans; Male; Olanzapine; Pirenzepine; Risk Factors; Risperidone; Schizophrenia; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Neurologic Examination; Olanzapine; Pirenzepine

Topics: Acute Disease; Affect; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Drug Monitoring; Dyskinesia, Drug-Induced; Humans; Olanzapine; Pirenzepine

Topics: Aged; Alanine Transaminase; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Drug Interactions; Dyskinesia, Drug-Induced; Haloperidol; Humans; Liver; Middle Aged; Multicenter Studies as Topic; Olanzapine; Pirenzepine; Prolactin; Risk Factors; Safety; Schizophrenia

Topics: Adult; Alcoholism; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Treatment Outcome

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Female; Humans; Olanzapine; Pirenzepine; Schizophrenia

This case illustrates a marked improvement of tardive dyskinesia in a 59-year-old male patient with delusional disorder with a long history of neuroleptic exposure, following treatment with olanzapine.

Topics: Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dyskinesia, Drug-Induced; Dystonia; Female; Humans; Olanzapine; Pirenzepine

Topics: Alcoholism; Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus, Type 1; Dyskinesia, Drug-Induced; Hallucinations; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Risperidone

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Dystonia; Humans; Male; Olanzapine; Pirenzepine; Schizophrenia, Paranoid

Topics: Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Haloperidol; Humans; Olanzapine; Pirenzepine; Psychotic Disorders

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Male; Olanzapine; Physical Examination; Pirenzepine; Schizophrenia

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Hallucinations; Humans; Male; Olanzapine; Pirenzepine; Schizophrenia

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Biperiden; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Olanzapine; Pirenzepine; Schizophrenia; Substance Withdrawal Syndrome

Chronic haloperidol treatment typically produces late-onset, purposeless oral chewing movements in laboratory rats with a prevalence of 40 to 60%. Chronic clozapine does not produce these movements. Based on the phenomenologic and pharmacologic similarities between these rat chewing movements and human tardive dyskinesia (TD), the animal movements are often used as a model of tardive dyskinesia (TD). Here we report results of the association of oral chewing movements in rats with chronic administration of two new antipsychotic drugs, olanzapine and sertindole. Because each of these antipsychotic drugs has a very low incidence of acute Parkinsonism in human studies, they are candidates for showing a low tardive dyskinesia risk. Neither new drug produced a significant incidence of haloperidol-like chewing in rats, nor did movement ratings after their chronic administration differ from placebo; whereas, haloperidol produced a 60% prevalence of purposeless chewing and a prevalence significantly increased from placebo. This low rate of oral dyskinesias in rats is consistent with several of the preclinical characteristics of the drugs and correlates with their low acute motor side effects in clinical trials. We propose, although have not yet tested in humans, that these animal results will predict low TD liability of these drugs.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Haloperidol; Imidazoles; Indoles; Male; Mastication; Olanzapine; Pirenzepine; Rats; Rats, Sprague-Dawley

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Syndrome

Topics: Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Olanzapine; Pirenzepine