quetiapine-fumarate and Dyskinesia--Drug-Induced

We describe the case of a 12-year-old boy that developed invalidating motor symptoms after starting and gradually increasing the dose of quetiapine with extended release and phasing out aripiprazole. The symptoms met the definition of tardive dyskinesia given their duration and presentation. Symptoms decreased spontaneously after discontinuation of neuroleptic treatment. The literature and knowledge among clinicians concerning the occurrence of tardive dyskinesia in children and adolescents treated with atypical antipsychotics are limited. We give an overview of the available scientific findings with special attention to the presentation, the incidence and treatment possibilities.

Topics: Antipsychotic Agents; Aripiprazole; Child; Dyskinesia, Drug-Induced; Humans; Male; Quetiapine Fumarate; Tardive Dyskinesia

Atypical antipsychotics offer broader efficacy and improved tolerability compared with conventional agents. Many patients currently treated with conventional antipsychotics continue to experience persistent symptoms or troublesome side effects and may benefit from a change to one of the newer atypical agents. There are also significant differences in the side-effect profiles of the atypicals, such that a switch from one atypical agent to another could offer advantages to many patients. Unfortunately, many clinicians remain uncertain about the switching process and are reluctant to initiate change. The aim of this review is to identify the indications for a switch in antipsychotic therapy with a focus on recent switching data for the atypical antipsychotic, quetiapine. The clinical aspects of quetiapine's receptor binding characteristics are reviewed including the implications of the low D(2) antagonist properties that make quetiapine the treatment of choice when EPS persists with other atypical antipsychotics. Practical guidelines are given for managing the process of changeover, for avoiding pitfalls and for maximizing the chances of a successful switch. For example, when managing the antipsychotic crossover, it is important to consider the psychological effects of switching arising from symptom and side-effect changes. Finally, advice is provided on the assessments necessary when evaluating the success of a change in therapy, together with guidance on the optimal duration of treatment trials.

Topics: Animals; Antipsychotic Agents; Depressive Disorder; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Psychotic Disorders; Quetiapine Fumarate

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

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

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

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

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

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

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

Quetiapine is often prescribed at higher than approved doses. We investigated the safety, tolerability, and efficacy of quetiapine > 800 mg/d.. A trial was carried out from October 2003-September 2005 in 19 referral centers. Patients with DSM-IV schizophrenia or schizoaffective disorder were randomized on the basis of persistent symptoms of moderate severity (< 30% improvement in total Positive and Negative Syndrome Scale score after ≥ 4 weeks of quetiapine). The 8 week, double-blind study compared continuation of quetiapine 800 mg/d (n = 43) versus 1,200 mg/d (n = 88). The primary outcome measure was emergent or worsening parkinsonism (Simpson-Angus Scale). Secondary outcomes were adverse events, metabolic side effects, and symptom severity.. Mean doses obtained were 799 mg/d and 1,144 mg/d in the 800-mg/d and > 800-mg/d groups, respectively. Emergent or deteriorating parkinsonism in the high-dose group was 3.1% greater (95% CI, -7.8% to 14.0%; P = .76) than in the 800-mg/d group, a value that was within the a priori limit of 16% defined as noninferiority. Both doses of quetiapine were safe and well tolerated. Weight gain was greater in the high-dose group (1.7 kg over 12 weeks; ≥ 7% body weight, n = 11 [12.5%]) versus the 800-mg/d group (1.1 kg over 12 weeks; ≥ 7% body weight, n = 4 [9.3%]). The mean adjusted difference in weight gain (1.3 kg) was greater in the high-dose group (95% CI, 0.0-2.5; P = .044). Symptom severity declined, with no significant difference between groups.. The results did not demonstrate any advantage for use of quetiapine outside the approved dose range.. www.clinicaltrials.gov Identifier: NCT00328978.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Weight Gain

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

Persistent neuroleptic-induced movement disorders limit effective pharmacological management of psychotic disorders. Although antipsychotic switching is a common strategy for managing extrapyramidal side effects (EPSs), there is insufficient empirical support to guide the clinician. We designed the present study to examine whether patients with preexisting EPS switched to quetiapine would show greater reduction in EPS compared with control patients.. Twenty-two patients with schizophrenia meeting clinical criteria for tardive dyskinesia or coexisting parkinsonism were randomized either to switch from their current antipsychotic to quetiapine (n = 13) or to remain on their current treatment (n = 9). A battery of standard clinical assessments for EPS along with electromechanical instrumental measures was administered before randomization and again 1 and 3 months postrandomization.. We observed significant reduction in parkinsonism (P < 0.001) and akathisia (P = 0.02) based on clinical assessments and dyskinesia (P < 0.05) based on instrumental assessment for the quetiapine group. Subjects remaining on current treatment exhibited an increase in rigidity (P < 0.05) based on instrumental measures.. These findings support the switching to quetiapine in the management of preexisting neuroleptic-induced extrapyramidal side effects.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Male; Parkinson Disease, Secondary; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia

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

Patients with combat-related post-traumatic stress disorder (PTSD) with psychotic features frequently fail to respond to antidepressants. Previous research has shown that these patients improve significantly after monotherapy with two atypical antipsychotics, olanzapine and risperidone. This study investigated the clinical outcome of another atypical antipsychotic, quetiapine, in war veterans with combat-related PTSD with psychotic features. Male war veterans (n=53) with DSM-IV-diagnosed PTSD with psychotic symptoms completed 8 wk of in-patient treatment with quetiapine (25-400 mg/d). The reductions in the total and subscale scores on the Clinician-Administered PTSD Scale (CAPS), and the increase in the Clinical Global Impression - Improvement Scale (CGI-I) were the primary outcome measures, and reductions in the Positive and Negative Syndrome Scale (PANSS) were the secondary outcome measures. The CGI - Severity of Illness scale (CGI-S) was used to assess the global clinical improvement. Drug-Induced Extrapyramidal Symptoms scale recorded adverse effects. Two, 6 and 8 wk treatment with quetiapine significantly reduced total and the subscales scores on the CAPS, PANSS, and CGI-S scales, in patients with psychotic PTSD. The results indicate that 8 wk of monotherapy with quetiapine reduced the majority of the psychotic and PTSD symptoms in the patients. Our present and previous data suggest that treatment-resistant psychotic PTSD patients may improve after taking atypical antipsychotics.

Topics: Adolescent; Adult; Antipsychotic Agents; Combat Disorders; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Stress Disorders, Post-Traumatic

Atypical antipsychotics may be beneficial in treating the core psychopathology of anorexia nervosa (AN).. An 8 week open-label study of quetiapine was conducted in eight severely ill DSM-IV AN patients consecutively admitted to a specialist eating disorders unit. Participants were assessed by EDE-12, MADRS, YBOCS, SAPS-delusions and CDR neuropsychological battery at baseline, 4 weeks and 8 weeks, and by weekly body mass index (BMI), CGI and extrapyramidal scores. Quetiapine doses ranged from 50 mg to 800 mg per day, according to efficacy and tolerability.. Seven participants completed 4 weeks and five participants completed 8 weeks. All participants had clinically significant levels of specific eating disorders psychopathology, and mild to moderately severe depressive symptomatology. Apart from initial mild sedation, no subjects experienced any significant adverse events. Over 4 weeks there was no significant difference in BMI, but a significant difference in the EDE-12 restraint score. There were significant differences on BMI and EDE-12 restraint subscale scores over 8 weeks.. A double-blind placebo controlled study is required to further evaluate the therapeutic utility of quetiapine in severely ill AN patients beyond multidisciplinary specialist intervention.

Topics: Adult; Anorexia Nervosa; Antipsychotic Agents; Arousal; Body Mass Index; Delusions; Depression; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Male; Neuropsychological Tests; Obsessive Behavior; Psychiatric Status Rating Scales; Quetiapine Fumarate; Reaction Time; Weight Gain

Bipolar disorder (BD) is a disabling and often chronic condition. Patients with BD suffer from depression at least one-third of the time, but they do not always respond well to conventional mood stabilizers. Attempts to treat them with antidepressants can provoke a switch to mania or increased cycling. Our open-label trial aimed to assess the long-term response of patients with bipolar depression to the addition of quetiapine to their usual treatment. Our study also sought to assess the safety and tolerability of quetiapine in patients with BD.. To meet inclusion criteria for the study, patients had a DSM-IV diagnosis of type I or II BD, were aged 18 years and older, currently suffered from depression with a score of > 18 on the Hamilton Depression Rating Scale (HDRS), and had no change in antidepressant use for at least 3 weeks prior to the study. We added quetiapine to patients' medication and attempted to increase the dosage to at least 400 mg daily. Outcome was measured at baseline and once monthly for 12 months on the HDRS, the Young Mania Rating Scale, the Clinical Global Impression Scale (CGI), and the Abnormal Involuntary Movement Scale.. There were 19 patients enrolled in the study (6 men and 13 women), 2 of whom dropped out because they could not tolerate the drug. Seventeen completed at least 2 assessments, and 7 patients completed the full 12-month trial. Data for the 17 patients (that is, last observation carried forward) at 12 months shows HDRS scores reduced from 27.2 to 12.1 and CGI scores reduced from 4.7 to 2.6.. Quetiapine seems to be helpful to and relatively well tolerated by patients with bipolar depression when it is added to their usual treatment. There is, however, a need for controlled trials.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Chronic Disease; Depressive Disorder; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Periodicity; Prospective Studies; Quetiapine Fumarate; Surveys and Questionnaires; Treatment Outcome

Drug induced dyskinesias remain a challenging problem in the long term management of Parkinson's disease (PD). We have assessed the effect of quetiapine on dyskinesias in a double blind placebo controlled cross over study.. Nine patients with PD were enrolled and received 25 mg of quetiapine or placebo at night for two weeks in prerandomised order, with one week of wash out between treatment periods. Assessments were made using on-off diaries, self assessment of dyskinesias, and L-dopa challenges at baseline and after each treatment period. Videotapes were rated blindly by two raters using modified Abnormal Involuntary Movement Scale and Goetz scores. Patients subsequently went on open label quetiapine at 50 mg/day, for a mean duration of 30 days, and completed the same self assessment forms.. During the double blind phase, no significant change in dyskinesias was found on either 25 mg of quetiapine or placebo. Duration of off states and Unified PD Rating Scale motor scores also remained unchanged. Moderate tiredness and daytime sleepiness occurred in two patients on quetiapine. One patient dropped out early for unrelated reasons. Eight patients completed the open label phase. On 50 mg/day of quetiapine, a slight reduction in dyskinesias occurred on some scales. Reduction in dyskinesia severity on visual analogue scales was by 50.1%. Off time was not significantly increased. This improvement was not strongly reflected in patients' overall impression of treatment effect. Drowsiness and daytime sleep episodes led to discontinuation in four patients, after completion of the study, and two additional patients stopped treatment after the study because of lack of effect.. Our study failed to demonstrate an antidyskinetic effect of low dose (25 mg) quetiapine. The absence of an increase in parkinsonism combined with a possible antidyskinetic effect on higher doses warrants further investigation.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Cross-Over Studies; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Quetiapine Fumarate

While the atypical antipsychotics should ultimately reduce the prevalence of tardive dyskinesia, it is likely to remain a significant clinical problem for a long time to come. No strategy has clearly emerged as the treatment of choice for tardive dyskinesia. Atypical antipsychotics have reduced propensities for producing acute extrapyramidal symptoms (EPS) and possibly tardive dyskinesia and may be effective in treating patients with established tardive dyskinesia.. This 12-month, randomized, investigator-blinded study compared the efficacy of quetiapine (N = 22) and haloperidol (N = 23) in treating patients with DSM-IV schizophrenia or schizoaffective disorder and established tardive dyskinesia. Dyskinesia was assessed using the Extrapyramidal Symptom Rating Scale (ESRS) dyskinesia subscale scores and the Clinical Global Impression (CGI) dyskinesia scores. Other EPS, weight, serum prolactin level, and glycosylated hemoglobin level were also assessed. Subjects were enrolled in the study between April 2000 and March 2002.. Mean endpoint doses were 400 mg/day of quetiapine and 8.5 mg/day of haloperidol. Compared with the haloperidol group, the quetiapine group showed significantly greater improvements in ESRS dyskinesia (6 and 9 months [p or= 50% symptom reduction) was greater with quetiapine than haloperidol (64% [9/14] and 37% [6/16] at 6 months; 55% [6/11] and 28% [4/14] at 12 months). Other EPS decreased significantly with quetiapine at 3 (p =.01), 6 (p =.01), and 9 (p =.002) months. Serum prolactin levels decreased with quetiapine but increased with haloperidol, differing significantly between the groups at endpoint (p =.005). No significant changes in weight or glucose metabolism were recorded in either group.. Quetiapine effectively reduces the severity of tardive dyskinesia and is well tolerated in patients with established tardive dyskinesia.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Single-Blind Method; Treatment Outcome

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Dibenzothiazepines; Dopamine; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Quetiapine Fumarate

Psychoses are a common clinical problem in patients with Parkinson's disease. Treatment with typical neuroleptics or withdrawal of antiparkinsonian drugs may improve mental symptoms but will worsen the parkinsonism. Quetiapine (Seroquel), ICI 204,636, is a novel antipsychotic medication with a low potential for producing extrapyramidal side effects. In this open-label clinical study of 2 patients with Parkinson's disease, treatment with Seroquel successfully controlled psychotic symptoms without worsening of motor disability.

Topics: Aged; Antipsychotic Agents; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Male; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Serotonergic medications are used for the prevention and treatment of depression during pregnancy. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors (SNRIs) can cause poor neonatal adaptation, which has been attributed to withdrawal versus toxicity. Bupropion, a norepinephrine-dopamine reuptake inhibitor, is often used as an adjunctive agent to selective serotonin reuptake inhibitors or SNRIs for refractory depression. Quetiapine, an atypical antipsychotic, may also be used in more complex cases. When combined with serotonergic drugs, bupropion and quetiapine are associated with increased risk of serotonin syndrome in adults. We describe a neonate exposed to venlafaxine (an SNRI), bupropion, and quetiapine in utero who presented nearly immediately after birth with encephalopathy and abnormal movements. The severity and rapidity of symptoms may be attributable to potentiation of venlafaxine's serotonergic effects by bupropion and quetiapine. Neonatal providers should be aware of maternal medications and prepare for possible adverse effects, particularly from common psychotropic exposures.

Topics: Antidepressive Agents; Bipolar Disorder; Brain Diseases; Bupropion; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Infant, Newborn; Male; Neurotransmitter Uptake Inhibitors; Pregnancy; Pregnancy Complications; Quetiapine Fumarate; Stress Disorders, Post-Traumatic; Venlafaxine Hydrochloride

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

We report the case of a 35-year-old patient suffering from schizo-affective disorder since the age of 19 years, treated by a combination of first-generation antipsychotics, zuclopenthixol (100 mg/day) and lithium (1200 mg/day) (serum lithium=0.85 mEq/l). This patient had no associated personality disorder (particularly no antisocial disorder) and no substance abuse disorder. Within the 48 h following the gradual introduction of quetiapine (up to 600 mg/day), the patient presented severe agitation without an environmental explanation, contrasting with the absence of a history of aggressiveness or personality disorder. The diagnoses of manic shift and akathisia were dismissed. The withdrawal and the gradual reintroduction of quetiapine 2 weeks later, which led to another severe agitation, enabled us to attribute the agitation specifically to quetiapine.

Topics: Adult; Aggression; Antipsychotic Agents; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Male; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate

Although the benefits of antipsychotic pharmacotherapy can be pronounced, many patients develop unwanted adverse effects including a variety of movement disorders. Compared with the traditional antipsychotics, the atypical antipsychotics have a decreased risk for associated movement disorders. Drug-induced movement disorders can occur, however, and the risk of adverse events can increase significantly when medications are abused.. We describe the case of a 13-year-old male who presented to an emergency department with acute movement disorders after nasal insufflation of crushed quetiapine. The patient was admitted and successfully treated for neuroleptic toxicity with intravenous antihistamine pharmacotherapy. His primary care provider and psychiatrist were notified of the abuse, quetiapine was discontinued, and the patient was discharged and referred to a drug and alcohol awareness and abuse program.. The abuse of quetiapine has unfortunately become more common. This unique case report of acute movement disorders following nasal insufflation of quetiapine highlights the need for heightened vigilance when prescribing quetiapine and for increased awareness and education regarding medication-abuse.

Topics: Administration, Intranasal; Adolescent; Akathisia, Drug-Induced; Antipsychotic Agents; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Insufflation; Male; Myoclonus; Prescription Drug Misuse; Quetiapine Fumarate

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

The imaging of the dopamine transporter could demonstrate the implication of dopaminergic pathway in the appearance of tardive dyskinesia. We report a case with psychotic and tardive dyskinesia symptoms. A DAT scan showed decreased dopamine transporter uptake in the area of brain's basal gaglia. A trial with quetiapine improved both psychotic and TD symptoms while a second DAT scan showed improvement status. We conclude that increased dopamine transporter uptake seemed to associate with the improvement of TD.

Topics: Aged; Antipsychotic Agents; Corpus Striatum; Dibenzothiazepines; Dopamine Plasma Membrane Transport Proteins; Dyskinesia, Drug-Induced; Female; Humans; Quetiapine Fumarate; Schizophrenia; Tomography, Emission-Computed, Single-Photon

We report a case of quetiapine-induced dysphagia in a geriatric patient which improved with discontinuation of the antipsychotic. The patient had developed dysphagia while being treated with antipsychotics for bipolar disorder. The patient's dysphagia showed significant improvement when she was taken off quetiapine. We review the available literature on antipsychotic-related dysphagia and suggest that clinicians need to be aware of the potential for this syndrome even with lower potency antipsychotics.

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Deglutition Disorders; Diagnosis, Differential; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Quetiapine Fumarate

Second-generation antipsychotics (SGAs) are far more commonly used in the United States compared to first-generation antipsychotics (FGAs), but the relative safety of SGAs compared to FGAs following acute toxic ingestions has not been studied.. A retrospective cohort study was performed by chart review of the California Poison Control System electronic database of 1975 cases from the 10-year period 1997 to 2006 involving patients aged 18 to 65 years who ingested a single SGA or FGA. Cases were coded for overall severity of adverse outcome as defined by the American Association of Poison Control Centers criteria and for presence of specific symptoms and treatments. Odds ratios were calculated between SGAs and FGAs for various symptoms, treatments, and outcome severity.. Odds of a major adverse outcome or death were significantly higher for SGAs than FGAs (OR = 1.71, 95% CI = 1.09 to 2.71). Patients taking SGAs had higher odds of respiratory depression (OR = 2.39, 95% CI = 1.09 to 5.26), coma (OR = 2.18, 95% CI = 1.30 to 3.65), and hypotension (OR = 1.80, 95% CI = 1.23 to 2.63) compared to those taking FGAs but lower odds of dystonia (OR = 0.12, 95% CI = 0.08 to 0.19) or rigidity (OR = 0.30, 95% CI = 0.10 to 0.90).. SGAs appear no safer than FGAs in acute overdose. While neuromuscular symptoms appear less frequently with SGAs compared to FGAs, the relatively greater rates of central nervous system depression associated with SGA overdose may be more dangerous.

Topics: Antipsychotic Agents; Cause of Death; Cohort Studies; Coma; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Overdose; Dyskinesia, Drug-Induced; Follow-Up Studies; Humans; Hypotension; Long QT Syndrome; Neuroleptic Malignant Syndrome; Odds Ratio; Poison Control Centers; Quetiapine Fumarate; Respiratory Insufficiency; Retrospective Studies; Risk Factors; Schizophrenia; Survival Analysis

Topics: Antipsychotic Agents; Anxiety Disorders; Death, Sudden, Cardiac; Depressive Disorder, Major; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Metabolic Syndrome; Quetiapine Fumarate; Risk Factors; United States; United States Food and Drug Administration; Weight Gain

Quetiapine is an atypical antipsychotic that is believed to have a low D2 binding affinity in striatal and extrastriatal regions. We report the case of a female patient with the diagnosis of schizoaffective disorder (using DSM-IV-TR criteria) who initially received amisulpride for 3 months, discontinued gradually because of persistent and distressing extra-pyramidal symptoms, and who developed tardive dyskinesia 3 months later after the initiation of quetiapine. A trial with ziprasidone resulted in a further worsening of tardive dyskinesia symptoms. A further trial with aripiprazole, improved her tardive dyskinesia symptoms. Although, it is under consideration the possibility that the improvement could have been due to the discontinuation of quetiapine, we conclude that aripiprazole improved the TD symptoms.

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Sulpiride; Thiazoles

We performed a post marketing surveillance study (PMS study) to reveal the efficacy and tolerability of orally administered quetiapine in the treatment of acute psychosis over a period of up to three weeks. 398 respective inpatients were assessed in 88 psychiatric departments in Germany by use of the Clinical Global Impression Scale (CGI) and the Brief Psychiatric Rating Scale (BPRS) as well as the clinical impression of psychiatric raters. Safety and tolerability were assessed by vital parameters such as blood pressure, hearth rate and weight as well as the clinical impression of the psychiatric raters. In addition, dosing, concomitant and/or previous pharmacotherapies as well as certain aspects of psychiatric and medical history were documented. A significant reduction of psychopathology was found during three weeks of drug treatment. Daily dosages of quetiapine between 400 and 1200 mg were well tolerated with a limited number of adverse and no serious adverse events. Noteworthy, more than 35 % of all patients received and tolerated excellently more than 800 mg of quetiapine per day under naturalistic treatment conditions, well above the approved maximum daily dosage. This study reflects the clinical efficacy and good tolerability of quetiapine under real world treatment conditions and is in line with the results of the controlled clinical trials of phase II and III.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Body Mass Index; Child, Preschool; Dibenzothiazepines; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Humans; Inpatients; Male; Middle Aged; Product Surveillance, Postmarketing; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Clinical efficacy, safety and tolerability of quetiapine in the treatment of 23 hospitalized psychotic adolescents were evaluated retrospectively. Twelve patients were changed to quetiapine from another antipsychotic medication during their hospital stay. In these patients, CGI-S improved from 4.75+/-0.87 to 2.92+/-0.67 (observation period 3.7+/-1.6 months). The most common adverse events were transient tachycardia and sedation. Mild EPS occurred only in one patient under quetiapine monotherapy. Transaminase increases more than threefold above norm were observed in two patients. fT4 values were slightly below the norm in 67% of the cases. In 11 patients, quetiapine was initiated using a rapid titration schedule with high dosages in the acute phase. Receiving a mean maximum daily dose of 927+/-300 mg, CGI-S improved from 6.00+/-0.63 to 3.18+/-1.25 (observation period 2.9+/-1.8 months). Severe adverse events did not occur. Besides applying lorazepam temporarily in nine of the 11 patients, antipsychotic co-medication was not necessary in this group. In line with other studies, quetiapine may be considered as an effective treatment for adolescents with a severe psychotic disorder showing a favourable side-effect profile. Our preliminary data suggest that a rapid initiation with high doses could be a promising approach in acute psychotic adolescents.

Topics: Acute Disease; Adolescent; Antipsychotic Agents; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Hospitalization; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Schizophrenia

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

Haloperidol (HAL) is a typical antipsychotic drug and known to cause extrapyramidal symptoms (EPS) that may be associated with the blockade of dopamine D2-receptors in nigrostriatal pathway by the drug. In contrast, quetiapine (QTP) is an atypical antipsychotic drug that has the lowest incidence of producing EPS in patients with schizophrenia, while improving psychosis symptoms. In the present study, we investigated the possibility of reversing the HAL-induced changes in locomotor activity and in striatal tyrosine hydroxylase (TH) of rats. Rats were administered HAL (2mg/kg/day, p.o.) for 3 months, followed by vehicle (VEH), QTP (10mg/kg/day), HAL, or HAL+QTP for another 5 weeks. The locomotor activity and TH immunoreactivity of the rats were measured. Chronic administration of HAL caused significant increase in locomotor activity and lower levels of TH immunoreactivity in the caudate putamen of the striatum. When the long-term haloperidol treatment was removed, the change in TH immunoreactivity was normalized, while the HAL induced high level of locomotor activity was returned to normal level only in the rats that stopped HAL consumption and received QTP treatment. In the substantia nigra and ventral tegmental areas, all rats showed comparable numbers of TH-positive cell bodies, which had no shrinkage. These results support a previously proposed relationship between EPS and TH levels in the striatum and provide valuable preclinical information towards understanding why QTP produces a lowest incidence of EPS among antipsychotics and has been used to treat EPS caused by other antipsychotics, and eventually establish a principle of treating EPS.

Topics: Animals; Antipsychotic Agents; Caudate Nucleus; Dibenzothiazepines; Dyskinesia, Drug-Induced; Haloperidol; Male; Motor Activity; Neurons; Putamen; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Substantia Nigra; Tyrosine 3-Monooxygenase

Topics: Antipsychotic Agents; Aripiprazole; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Piperazines; Quetiapine Fumarate; Quinolones

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

A 75-year-old white female with schizoaffective disorder was admitted to an inpatient psychiatry unit for uncooperativeness in refusing to take scheduled medications. She complained of anticholinergic adverse effects and had abnormal involuntary movements in the oral/buccal region. The patient had been prescribed six psychotropic medications (i.e., thiothixene, lithium, divalproex sodium, amitriptyline, benztropine, and trazodone effects. The treatment team determined that the patient was noncompliant and experienced the effects of polypharmacy. She had been prescribed two mood stabilizers and suffered from anticholinergic adverse effects and the movement disorder tardive dyskinesia (TD). Four medications were discontinued: thiothixene, amitriptyline, lithium, and benztropine. Quetiapine, a second-generation antipsychotic, was recommended, with a daily titration schedule to reach a target dose of 600 mg per day in divided doses. This agent has less propensity to cause movement disorders compared with first-generation antipsychotics. All medications with additive anticholinergic properties also were discontinued. Lithium was stopped secondary to subtherapeutic levels and potential drug interactions. The pharmacist educated the inpatient team on the additive anticholinergic effects of each medication, reduced the total number of medications prescribed, and assisted in appropriate conversion to quetiapine to reduce TD symptoms.

Topics: Aged; Antipsychotic Agents; Cholinergic Antagonists; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Neuroleptic Malignant Syndrome; Polypharmacy; Psychotic Disorders; Quetiapine Fumarate; Treatment Refusal

Topics: Antipsychotic Agents; Depression; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Male; Middle Aged; Quetiapine Fumarate; Substance Withdrawal Syndrome

Topics: Antipsychotic Agents; Dibenzothiazepines; Dyskinesia, Drug-Induced; Dystonia; Female; Humans; Middle Aged; Quetiapine Fumarate; Treatment Outcome

Rabbit syndrome is characterized by rapid, fine, rhythmic movements of the perioral muscles along a vertical axis, mimicking the chewing actions of a rabbit. The present case demonstrates the possible usefulness of quetiapine as a mono-drug treatment strategy for dealing with rabbit syndrome and simultaneously treating psychotic symptoms.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Lip; Male; Periodicity; Quetiapine Fumarate; Schizophrenia; Syndrome

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; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Dystonia; Humans; Male; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

The purpose of this study was to examine the effectiveness and tolerability of quetiapine for aggression, hyperactivity, and self-injury in pervasive developmental disorders (PDDs).. The medical records of all patients with PDDs diagnosed according to DSM-IV criteria and treated with quetiapine were retrospectively reviewed. Patients who received quetiapine for at least 4 weeks and who were not concurrently treated with another antipsychotic or mood stabilizer were included. Improvement was measured with the Clinical Global Impressions-Improvement scale (CGI-I), with response determined by ratings of "much improved" or "very much improved." Data were collected from May 15, 2003 through November 30, 2003.. Of 857 records reviewed, 20 patients (16 male, 4 female) (mean +/- SD age = 12.1 +/- 6.7 years; range, 5-28 years) received a quetiapine trial (mean +/- SD dosage = 248.7 +/- 198.4 mg/day; range, 25-600 mg/day) over a mean duration of 59.8 +/- 55.1 weeks (range, 4-180 weeks). Eight (40%) of 20 patients were judged "responders" to quetiapine; the mean CGI-I score for the entire group was 3.0 +/- 1.1 (minimally improved). A statistically significant improvement (p = .002) was found between a mean pretrial CGI-Severity of Illness scale (CGI-S) score of 5.1 +/- 0.6 (markedly ill) and a posttrial CGI-S score of 4.2 +/- 1.1 (moderately ill). Adverse effects occurred in 50% (N = 10) of patients and led to drug discontinuation in 15% (N = 3) of patients.. Quetiapine was modestly effective for maladaptive behavior in patients with a PDD. Controlled studies are needed to further assess these preliminary findings.

Topics: Adolescent; Adult; Aggression; Antipsychotic Agents; Child; Child Development Disorders, Pervasive; Child, Preschool; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Hyperkinesis; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; Self-Injurious Behavior; Severity of Illness Index; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Weight Gain

Topics: Animals; Antipsychotic Agents; Callithrix; Clozapine; Dibenzothiazepines; Disease Models, Animal; Dyskinesia, Drug-Induced; Humans; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

To evaluate the long-term efficacy and tolerability of quetiapine for psychosis among parkinsonian patients, a retrospective analysis of all parkinsonian patients taking quetiapine for psychosis in a single movement disorders center was carried out. Demographic data, including type and severity of psychosis, presence of dementia, treatment response, before and after Unified Parkinson's Disease Rating Scale (UPDRS)-motor scores and Hoehn and Yahr (H&Y) scale were obtained. One hundred six parkinsonian patients with a mean age of 76.6 years were on an average levodopa (L-dopa) dose of 415 mg/d. Seventy-eight of 106 (74%) remained on quetiapine for a mean duration of 15 months at an average dose of 60 mg per day. Eighty-seven (82%) patients had partial or complete resolution of their psychosis whereas 19 (18%) patients had no improvement on quetiapine. Motor worsening was noted in 34 (32%) patients but was uncommonly sufficient to warrant quetiapine discontinuation. More quetiapine non-responders were noted to be demented, delusional, and experienced threatening psychosis but only the presence of dementia remained significant on multivariate analysis (OR = 11.6; 95% CI = 1.4-92.9). Also, patients who developed motor worsening while on quetiapine tended to be more demented (P = 0.07).

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Dibenzothiazepines; Drug Tolerance; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Levodopa; Male; Outcome Assessment, Health Care; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Severity of Illness Index

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Mood Disorders; Quetiapine Fumarate; Schizophrenia

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

There are very rare cases indicating the effectiveness of the atypical antipsychotics in the treatment of tardive dyskinesia except clozapine. We report three patients with schizophrenia who demonstrated improvement of tardive dyskinesia following treatment with quetiapine; two of them were unable to use clozapine because of intolerable side-effects.

Topics: Adult; Aged; Antipsychotic Agents; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

The contribution of serotoninergic mechanisms to motor dysfunction in Parkinson's disease (PD) has yet to be fully elucidated. Recent clinical observations increasingly suggest that drugs able to block serotonin 5HT2A/C receptors can benefit patients with certain extrapyramidal movement disorders. To further explore the roles of these and other neurotransmitter receptors in the pathogenesis of parkinsonian signs and levodopa-induced dyskinesias; we evaluated the effects of quetiapine, an atypical antipsychotic with 5HT2A/C and D2/3 antagonistic activity, on motor behavior in 6-hydroxydopamine-lesioned rats and MPTP-lesioned nonhuman primates. In hemiparkinsonian rats, quetiapine (5 mg/kg, po) reversed the shortened motor response to levodopa challenge produced by 3 weeks of twice-daily levodopa treatment (P < 0.01). Quetiapine (5 mg/kg po) also normalized the shortened response to the acute injection of either a dopamine D1 receptor agonist (SKF 38392) or a D2 agonist (quinpirole) in rats that had received chronic levodopa treatment. Quetiapine had no effect on parkinsonian dysfunction when given alone or with levodopa to parkinsonian rats and monkeys. Quetiapine (4 mg/kg, po) did, however, substantially reduce levodopa-induced dyskinesias when coadministered with levodopa (P < 0.05). These results suggest that quetiapine could confer therapeutic benefits to patients with levodopa-induced motor complications. Moreover, our findings may indicate that 5HT2A/C receptor-mediated mechanisms, alone or in combination with other mechanisms, contribute to the pathogenesis of the altered motor responses associated with the treatment of PD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Antipsychotic Agents; Behavior, Animal; Dibenzothiazepines; Disease Models, Animal; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Levodopa; Macaca fascicularis; Male; Motor Activity; Oxidopamine; Parkinsonian Disorders; Quetiapine Fumarate; Rats; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Serotonin; Serotonin Antagonists

Topics: Aged; Antipsychotic Agents; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Quetiapine Fumarate; Treatment Outcome

Two children with Tourette's syndrome and comorbid disorders were treated with quetiapine, an atypical antipsychotic successfully used in patients with psychoses and schizophrenia with low incidence of extrapyramidal side effects. Clinical observations and standardized rating scales suggested that this drug produced beneficial effects on tics and other symptoms. Adverse effects (at low doses) were minimal. Because it was suggested that tic efficacy of the newer antipsychotics was related to higher D2 occupancy (with the exception of quetiapine and clozapine, which have relatively low D2 activity), it is hypothesized that tic patients are D2 sensitive and need lower doses of medications. These children were treated naturalistically and were reported retrospectively because of their encouraging outcomes. However, these findings should be interpreted with caution, because no contrast groups, drug withdrawal, or placebo were utilized. Controlled studies are needed to determine the efficacy of quetiapine in the treatment of Tourette's syndrome.

Topics: Adolescent; Antipsychotic Agents; Anxiety Disorders; Attention Deficit Disorder with Hyperactivity; Basal Ganglia Diseases; Depressive Disorder; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Tourette Syndrome

A great need exists for antipsychotic drugs which will not induce extrapyramidal symptoms (EPS) and tardive dyskinesias (TDs). These side effects are deemed to be a consequence of nonselective blockade of nigrostriatal and mesolimbic dopamine D2 receptors. Nondyskinetic clozapine (1) is a low-potency D2 dopamine receptor antagonist which appears to act selectively in the mesolimbic area. In this work dopamine antagonism was assessed in two mouse behavioral assays: antagonism of apomorphine-induced climbing and antagonism of apomorphine-induced disruption of swimming. The potential for the liability of dyskinesias was determined in haloperidol-sensitized Cebus monkeys. Initial examination of a few close cogeners of 1 enhanced confidence in the Cebus model as a predictor of dyskinetic potential. Considering dibenzazepines, 2 was not dyskinetic whereas 2a was dyskinetic. Among dibenzodiazepines, 1 did not induce dyskinesias whereas its N-2-(2-hydroxyethoxy)ethyl analogue 3 was dyskinetic. The emergence of such distinctions presented an opportunity. Thus, aromatic and N-substituted analogues of 6-(piperazin-1-yl)-11H-dibenz[b,e]azepines and 11-(piperazin-1-yl)dibenzo[b,f][1,4]thiazepines and -oxazepines were prepared and evaluated. 11-(4-[2-(2-Hydroxyethoxy)ethyl]piperazin-1-yl)dibenzo[b,f][1,4]thiazepine (23) was found to be an apomorphine antagonist comparable to clozapine. It was essentially nondyskinetic in the Cebus model. With 23 as a platform, a number of N-substituted analogues were found to be good apomorphine antagonists but all were dyskinetic.

Topics: Animals; Antipsychotic Agents; Apomorphine; Behavior, Animal; Cebus; Dibenzothiazepines; Dopamine Antagonists; Dyskinesia, Drug-Induced; Female; Male; Mice; Quetiapine Fumarate; Receptors, Dopamine D2; Stereoisomerism; Structure-Activity Relationship

Topics: Acetates; Adult; Amines; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Cyclohexanecarboxylic Acids; Dibenzothiazepines; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lithium; Quetiapine Fumarate; Topiramate

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

In a single inpatient case study, a schizophrenic patient with tardive dyskinesia after prolonged treatment with typical neuroleptics was treated with the new atypical neuroleptic quetiapine, a dibenzothiazepin-derivative. Within 2 weeks of treatment with quetiapine, symptoms of tardive dyskinesia improved; 10 weeks after starting treatment tardive dyskinesia stopped completely. Over the same period, dopamine D2 receptor occupancy decreased substantially, as measured by IBZM-SPECT after 14 and 77 days of treatment.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Receptors, Dopamine D2; Schizophrenia; Schizophrenic Psychology; Tomography, Emission-Computed, Single-Photon

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: Adolescent; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Dibenzothiazepines; Dyskinesia, Drug-Induced; Humans; Male; Quetiapine Fumarate; Risperidone; Substance Withdrawal Syndrome; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Seroquel was compared to clozapine and several other antipsychotic agents in tests predictive of antipsychotic activity or extrapyramidal symptoms. In the conditioned avoidance test in squirrel monkeys as well as several paradigms using apomorphine or amphetamine-induced behavioral alterations, seroquel displayed the profile of a drug with potential antipsychotic activity. In these paradigms the potency of seroquel was somewhat less than clozapine in rodent tests, while the reverse was true in higher species, i.e. monkeys, cats. In tests designed to evaluate the propensity to induce EPS or tardive dyskinesia, for example, the production of dyskinetic reactions in haloperidol-sensitized cebus monkeys, seroquel displayed a profile similar to clozapine and disparate from typical antipsychotic drugs. In drug-naive cebus monkeys seroquel sensitized significantly fewer monkeys than haloperidol and the dyskinetic reactions were of significantly less intensity. It is anticipated that this novel antipsychotic agent will have a significantly reduced propensity to produce extrapyramidal symptoms and tardive dyskinesia than typical antipsychotics.

Topics: Amphetamine; Animals; Antipsychotic Agents; Apomorphine; Avoidance Learning; Basal Ganglia Diseases; Behavior, Animal; Catalepsy; Cats; Cebus; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Fixation, Ocular; Male; Mice; Motor Activity; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Saimiri; Stereotyped Behavior; Swimming