quetiapine-fumarate and Basal-Ganglia-Diseases

Behavioral and psychological symptoms of dementia pose management challenges for caregivers and clinicians. Firstline nonpharmacologic treatments include eliminating physical and emotional stressors, modifying the patient's environment, and establishing daily routines. Family members and caregivers benefit from education about dementia symptoms and reminders that the behaviors are normal and unintentional. Cognitive and emotion-oriented interventions, sensory stimulation interventions, behavior management techniques, and other psychosocial interventions are modestly effective. In refractory cases, physicians may choose to prescribe off-label antipsychotics. Aripiprazole has the most consistent evidence of symptom improvement; however, this improvement is small. Olanzapine, quetiapine, and risperidone have inconsistent evidence of benefit. Physicians should use the smallest effective dose for the shortest possible duration to minimize adverse effects, most notably an increased mortality risk. Other adverse effects include anticholinergic and antidopaminergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, postural hypotension, metabolic syndrome, cardiac arrhythmia, and sedation. Patients should be monitored for these effects while receiving treatment; however, laboratory monitoring may be limited to patients receiving long-term therapy.

Topics: Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Basal Ganglia Diseases; Behavior Therapy; Benzodiazepines; Cognitive Behavioral Therapy; Dementia; Emotions; Humans; Hypotension, Orthostatic; Metabolic Syndrome; Neuroleptic Malignant Syndrome; Olanzapine; Practice Guidelines as Topic; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Topics: Antidepressive Agents, Second-Generation; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials, Phase I as Topic; Cost-Benefit Analysis; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risk; Risperidone; Schizophrenia; Thiazoles

This analysis evaluated the tolerability profile of quetiapine using data from all comparative controlled studies in patients with schizophrenia or related disorders in the AstraZeneca clinical trials database, focusing on extrapyramidal symptoms (EPS).. Adverse event (AE) data from randomised, double-blind, controlled studies in the AstraZeneca clinical trials database were pooled, allowing comparison of quetiapine (mean daily doses 357-496 mg/day) with placebo, haloperidol (10.4 mg/day), risperidone (5.5 mg/day) or chlorpromazine (552 mg/day). Incidence of EPS-related AEs in relation to quetiapine dose was also analysed using a subset of data from fixed-dose studies.. Data from 4956 patients were analysed. Quetiapine was well tolerated, and did not increase EPS-related AEs when compared with placebo (9.6 vs. 10.6%, respectively). The incidence of EPS-related AEs with quetiapine was consistent across the dose range (4.2-13.2% vs. 11.1% with placebo). Patients receiving haloperidol, risperidone and chlorpromazine experienced significantly higher levels of EPS-related AEs than those on quetiapine. The most common quetiapine- associated AEs, with significantly higher incidence than placebo, were sedation, somnolence and orthostatic hypotension.. Quetiapine is generally well tolerated in patients with schizophrenia or related disorders, with placebo-level EPS-related AEs. Quetiapine has a more favourable EPS profile than haloperidol, chlorpromazine or risperidone.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Basal Ganglia Diseases; Chlorpromazine; Dibenzothiazepines; Female; Haloperidol; Humans; Incidence; Male; Middle Aged; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia

Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics.. We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library), and data combined for analysis where there was clinical homogeneity, with a special reference to trial duration.. In five trials (2,206 patients) participants presented with a depressive episode, and in 25 trials (6,174 patients) the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5-6, but more adverse event withdrawals (NNH 12). With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6-12 weeks, but more adverse event withdrawals (NNH of about 22) in studies of 6-12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10). In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of >or=7% (mainly olanzapine trials), somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence.. Atypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine). There is insufficient data confidently to distinguish between different atypical antipsychotics.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Humans; Lamotrigine; Olanzapine; Prevalence; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Treatment Outcome; Triazines

As many as half of obsessive-compulsive disorder (OCD) patients treated with an adequate trial of serotonin reuptake inhibitors (SRIs) fail to fully respond to treatment and continue to exhibit significant symptoms. Many studies have assessed the effectiveness of antipsychotic augmentation in SRI-refractory OCD. In this systematic review, we evaluate the efficacy of antipsychotic augmentation in treatment-refractory OCD. The electronic databases of PubMed, PsychINFO (1967-2005), Embase (1974-2000) and the Cochrane Central Register of Controlled Trials (CENTRAL, as of 2005, Issue 3) were searched for relevant double-blind trials using keywords 'antipsychotic agents' or 'neuroleptics' and 'obsessive-compulsive disorder'. Search results and analysis were limited to double-blind, randomized control trials involving the adult population. The proportion of subjects designated as treatment responders was defined by a greater than 35% reduction in Yale Brown Obsessive-Compulsive Scale (Y-BOCS) rating during the course of augmentation therapy. Nine studies involving 278 participants were included in the analysis. The meta-analysis of these studies demonstrated a significant absolute risk difference (ARD) in favor of antipsychotic augmentation of 0.22 (95% confidence interval (CI): 0.13, 0.31). The subgroup of OCD patients with comorbid tics have a particularly beneficial response to this intervention, ARD=0.43 (95% CI: 0.19, 0.68). There was also evidence suggesting OCD patients should be treated with at least 3 months of maximal-tolerated therapy of an SRI before initiating antipsychotic augmentation owing to the high rate of treatment response to continued SRI monotherapy (25.6%). Antipsychotic augmentation in SRI-refractory OCD is indicated in patients who have been treated for at least 3 months of maximal-tolerated therapy of an SRI. Unfortunately, only one-third of treatment-refractory OCD patients show a meaningful treatment response to antipsychotic augmentation. There is sufficient evidence in the published literature, demonstrating the efficacy of haloperidol and risperidone, and evidence regarding the efficacy of quetiapine and olanzapine is inconclusive. Patients with comorbid tics are likely to have a differential benefit to antipsychotic augmentation.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Comorbidity; Depressive Disorder; Dibenzothiazepines; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Haloperidol; Humans; Middle Aged; Obsessive-Compulsive Disorder; Olanzapine; Patient Dropouts; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Selective Serotonin Reuptake Inhibitors; Tic Disorders; Treatment Outcome

A key goal of the pharmacologic treatment of acute bipolar mania is rapid symptom improvement. Medications commonly used to attain this goal include lithium, several anticonvulsants, and both first- and second-generation antipsychotics. Second-generation antipsychotics, which are associated with substantially lower rates of extrapyramidal side effects than first-generation agents, are becoming a mainstay in the treatment of acute mania. Although their efficacy appears to be comparable, second-generation antipsychotics may differ in time to onset and in their side effect profiles. Therefore, selecting a second-generation antipsychotic requires consideration of how an agent's efficacy, onset of action, and adverse events profile influence its appropriateness for each patient.

Topics: Acute Disease; Anticonvulsants; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Double-Blind Method; Humans; Lithium; Olanzapine; Piperazines; Placebos; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Treatment Outcome

Atypical antipsychotic medications (second-generation antipsychotics) have been increasingly used in the treatment of a number of psychotic disorders since their introduction in 1988, with the newest medication introduced in 2002. Justification for their use includes claims of equal or improved antipsychotic activity over first-generation antipsychotics, increased tolerability, and decreased side effects. However, there are still significant adverse effects and toxicities with this class of medications. Toxicologic exposures and fatalities associated with atypical antipsychotics continue to increase in the United States, with 32,422 exposures and 72 deaths in 2003. There have also been Food and Drug Administration warnings in the past year about how some atypical antipsychotics have been marketed to minimize the potentially fatal risks and claiming superior safety to other atypical antipsychotics without adequate substantiation, indicating the toxicologic potential of these agents may be underestimated.. Continued research to evaluate adverse effects and tolerability of atypical antipsychotics compared with first-generation antipsychotics and each other is reviewed. This article also reviews the pharmacodynamics, pharmacokinetics, and drug interactions with these medications. New therapeutic monitoring recommendations for this class of medications have also been proposed. Finally, clinical toxicity in overdose and management are reviewed.. While new atypical antipsychotic medications may have a safer therapeutic and overdose profile than first-generation antipsychotic medications, many adverse and toxic effects still need to be considered in therapeutic monitoring and overdose management.

Topics: Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Cardiomyopathies; Child; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Drug Interactions; Drug Overdose; Dry Eye Syndromes; Humans; Hyperlipidemias; Hypotension; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Seizures; Thiazoles

Pharmacotherapy in patients with dementia aims to improve distressing behavioral and psychological signs of dementia after nonpharmacologic interventions fail, without causing unacceptable side effects or exacerbating underlying cognitive impairment. We review data describing risperidone (3 published placebo-controlled trials), olanzapine (1 abstract regarding a placebo-controlled trial and a published placebo-controlled trial), quetiapine (1 published open-label trial and an abstract regarding a placebo-controlled trial), and aripiprazole (1 abstract regarding a placebo-controlled trial). For example, a 12-week study of risperidone in patients with Alzheimer's disease showed a dose-related improvement in psychosis and agitation. The frequency of extrapyramidal symptoms (EPS) was also significantly greater in patients receiving the highest doses. A 6-week study of olanzapine showed greater improvement than placebo in agitation/aggression and psychosis with doses of 5 and 10 mg/day, but not 15 mg/day, with side effects including gait disturbance and sedation at all doses. A 52-week, open-label trial of quetiapine (median dose = 138 mg/day) in elderly patients with psychosis suggested good tolerability with apparent behavioral benefit; EPS improved or remained unchanged in most patients. Limited data describing aripiprazole have shown inconclusive evidence regarding relief of psychosis in elderly patients with Alzheimer's disease-related dementia, with apparently good tolerability over the short term. It appears that, in the aggregate, atypical antipsychotics are efficacious for treatment of agitation in dementia, with less clear impact on psychosis, but their tolerability profiles clearly differ. The National Institute of Mental Health-funded Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease project will provide the first head-to-head comparisons of atypicals in dementia and will examine possible drug-drug differences between efficacy and effectiveness.

Topics: Aged; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Treatment Outcome

Lewy body dementia, also referred to as dementia with Lewy bodies (DLB), is a neurodegenerative disorder now considered to be the second most common cause of dementia after Alzheimer's disease. Postmortem findings suggest that DLB accounts for 20% to 34% of all dementia cases and is often underdiagnosed. Salient features of DLB include fluctuations in cognition, perceptual abnormalities (e.g., visual hallucinations), and mild parkinsonism. Other symptoms include frequent falls, nighttime agitation, and depression. DLB symptomatology can be partly explained by the extensive destruction of dopaminergic and acetylcholinergic pathways caused by neurodegeneration. For this reason, DLB patients are especially vulnerable to the antidopaminergic and anticholinergic actions of most conventional antipsychotics, which makes treatment of the psychotic symptoms of DLB extremely difficult. Patients are particularly sensitive to developing extrapyramidal symptoms (EPS) and also to the potentially fatal complication of neuroleptic sensitivity, which affects approximately 50% of DLB patients. Therefore, a need exists for antipsychotic drugs with less propensity to induce EPS and reduced affinity for dopamine and acetylcholine receptors. Here we review studies evaluating the efficacy and tolerability of atypical antipsychotics for the treatment of psychoses associated with DLB. Olanzapine appears to be poorly tolerated, and risperidone has been associated with high risk of neuroleptic malignant syndrome. Clozapine use remains controversial because of its potent anticholinergic action and risk of agranulocytosis. Quetiapine has been shown to reduce psychiatric manifestations of DLB without causing neuroleptic sensitivity or increasing EPS. Hence, quetiapine is an attractive candidate for the treatment of psychoses in DLB and other dementias.

Topics: Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Humans; Lewy Body Disease; Olanzapine; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome

Although life prevalence of substance use disorders among patients with schizophrenia is close to 50%, few studies have been carried out to date to identify an integrated pharmacological treatment for this comorbidity. So far, the most promising results, that we report here, have been obtained with clozapine. To a lesser extent, quetiapine and olanzapine, both clozapine analogues, have also shown promising results. Further to these observations, the present paper critically reviews the advantages associated with clozapine, quetiapine and olanzapine, and their relevance to the treatment of addiction among schizophrenic patients. Six characteristics seem to distinguish clozapine, quetiapine and olanzapine from the first-generation antipsychotics: (1) acting preferentially on the reward system, these second-generation antipsychotics (mainly clozapine and quetiapine) induce almost no extrapyramidal symptoms; (2) quickly dissociating from D(2), theses drugs (mainly clozapine and quetiapine) seem not to induce dysphoria, unlike conventional antipsychotics like haloperidol;(3) these drugs (mainly clozapine) seem more effective in the treatment of negative symptoms than conventional antipsychotics; (4) because of a diversified activity on several serotoninergic and noradrenergic receptors, these drugs positively alter mood, which does not seem to be the case with conventional antipsychotics, except for flupenthixol; (5) these drugs have a positive impact on cognition, which is not the case with the first-generation antipsychotics; (6) unlike conventional antipsychotics, these drugs seem to have a moderate affinity for 5-HT(3), the receptor on which ondansetron, an anti-craving medication, acts.

Topics: Affect; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Cognition; Comorbidity; Dibenzothiazepines; Drug Therapy, Combination; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Schizophrenia; Substance-Related Disorders; Treatment Outcome

Pharmacological treatment remains the mainstay of the management of schizophrenia. Older, "typical" antipsychotics carry a significant burden of side effects, notably extrapyramidal and neurocognitive side effects. Newer, "atypical" agents carry a lower risk of extrapyramidal side effects. They appear to have added benefit for treating negative and cognitive symptoms of schizophrenia, and hence can enhance the quality of life of some patients. The choice of particular agents for individual patients requires a balancing of efficacy and side effects. Medication is only one element of what should be an individualised comprehensive treatment plan for people with schizophrenia.

Topics: Amisulpride; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia; Sulpiride

Topics: Acute Disease; Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Dystonia; Humans; Indoles; Isoindoles; Parkinsonian Disorders; Quetiapine Fumarate; Receptors, Muscarinic; Receptors, Serotonin; Risperidone; Serotonin Antagonists; Syndrome; Thiazoles

Schizophrenia is a serious and disabling psychiatric disorder affecting approximately 1% of the world's population, with its economic cost in the United States alone estimated to exceed that of all cancers combined. The new generation of atypical antipsychotics introduced over the past decade have comparable or greater efficacy than traditional antipsychotics in treating the psychotic symptoms of schizophrenia and a much improved neurologic side effect profile. Quetiapine, the fourth atypical antipsychotic marketed in the United States, was approved by the U.S. Food and Drug Administration in September 1997 and is also currently approved in over 70 countries worldwide for the treatment of psychosis associated with schizophrenia. This article will review the clinical trials examining the efficacy, safety, and tolerability of quetiapine in the treatment of patients with schizophrenia.

Topics: Affect; Aggression; Antipsychotic Agents; Basal Ganglia Diseases; Cognition; Dibenzothiazepines; Double-Blind Method; Humans; Hyperprolactinemia; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Behavioral problems associated with psychosis in the elderly have a significant negative impact on patients' quality of life and can lead to placement in a nursing home. Because of their decreased propensity to produce extrapyramidal symptoms, atypical antipsychotics such as quetiapine hold promise in the treatment of these vulnerable patients. Quetiapine may, in theory, be particularly advantageous in this regard because of its lack of anticholinergic activity and its relatively loose binding to dopamine receptors. This article reviews the somewhat limited number of clinical studies of the use of quetiapine in treating older patients with schizophrenia and other psychotic disorders, patients with psychosis associated with Alzheimer's disease or dementia with Lewy bodies, and patients with Parkinson's disease and drug-induced psychosis.

Topics: Age Factors; Aged; Antiparkinson Agents; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Dementia; Dibenzothiazepines; Double-Blind Method; Humans; Parkinson Disease; Psychoses, Substance-Induced; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Treatment Outcome

The atypical antipsychotic quetiapine has been examined in children and adolescents in a randomized clinical trial, a number of open-label studies, and several chart review studies. Although only a small amount of information exists, most studies indicate that quetiapine is effective and well tolerated in various pediatric populations. Because quetiapine appears to be well tolerated in the young and associated with manifest salutary effects, it seems to be a promising agent that has potential for use in children and adolescents. This article reviews studies of quetiapine in the treatment of children and adolescents with a variety of psychiatric disorders. Despite these encouraging findings, the number of studies is small, and some have methodological limitations. Methodologically rigorous studies with substantive numbers of subjects are needed to confirm or refute these preliminary impressions.

Topics: Adolescent; Age Factors; Antipsychotic Agents; Autistic Disorder; Basal Ganglia Diseases; Child; Clinical Trials as Topic; Dibenzothiazepines; Humans; Medical Records; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Treatment Outcome

The atypical antipsychotics have a low incidence of extrapyramidal side effects (EPS), have improved tardive dyskinesia profiles, and have a broad range of therapeutic efficacy. These agents offer important therapeutic advantages that extend beyond their initial regulatory approval in several conditions and patient groups. The use of atypical antipsychotics is most relevant in the treatment of mood disorders, where these medications are being used increasingly for acute mood stabilization and in patients who are resistant to other treatments. Similar circumstances and clinical advantages pertain to the use of atypical antipsychotics in the treatment of behavioral disturbances in patients with dementia and in the management of personality disorders-both circumstances where conventional antipsychotics were initially poorly tolerated because of EPS. The low incidence of EPS associated with atypical antipsychotics is highly beneficial in several neuropsychiatric conditions. The extent to which endocrine and metabolic dysregulations associated with atypical antipsychotics will influence antipsychotics' role remains to be determined. As therapeutic opportunities evolve and diversify, atypical antipsychotics, because of favorable adverse-effect profiles, will have enhanced patient tolerability and use in nonpsychiatric conditions.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Child; Child Development Disorders, Pervasive; Clozapine; Dementia; Dibenzothiazepines; Humans; Mood Disorders; Olanzapine; Personality Disorders; Pirenzepine; Quetiapine Fumarate; Risperidone

The most frequent problems associated with the older generation of antipsychotic agents are extrapyramidal side effects (EPS) and tardive dyskinesia. Neuroleptic-induced EPS are thought to be caused by blockade of nigrostriatal dopamine tracts resulting in a relative increase in cholinergic activity; tardive dyskinesia is less well understood but is thought to be a supersensitivity response to chronic dopamine blockade. The leading hypothesis for the mechanism of action of the newer generation of atypical antipsychotics is the presence of a high serotonin-to-dopamine receptor blockade ratio in the brain. When serotonergic activity is blocked-as is the case with atypical antipsychotics-dopamine release increases and balances out the dopamine blockade effect at postsynaptic receptor sites, which results in few or no EPS. Prospective data indicate that the risk of tardive dyskinesia in patients taking atypical antipsychotics is less than that for those taking typical antipsychotics. This article reviews the mechanisms of neuroleptic-induced EPS and tardive dyskinesia and discusses the relationship between these movement disorders and atypical antipsychotic agents.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brain; Clozapine; Dibenzothiazepines; Humans; Movement Disorders; Olanzapine; Pirenzepine; Quetiapine Fumarate; Receptors, Dopamine; Receptors, Serotonin; Risk Factors; Risperidone

The objective of this meta-analysis is to summarize the efficacy and tolerability of the new antipsychotics risperidone, olanzapine, sertindole and quetiapine in schizophrenia compared to placebo and conventional antipsychotics. The main results are: (1) All of the 4 new drugs are more effective than placebo, but the magnitude of the effect is only moderate [mean effect size, r, of all antipsychotics vs. placebo = 0.25, with a 95% confidence interval (CI) = 0.22-0.28, n = 2477]. (2) According to the studies published to date, sertindole and quetiapine are as effective as haloperidol, and risperidone and olanzapine are slightly more effective than haloperidol in the treatment of global schizophrenic symptomatology. (3) With respect to negative symptoms, all new antipsychotics are more effective than placebo. However, contrary to widespread opinion, so is the 'conventional' antipsychotic haloperidol. Risperidone and olanzapine are slightly superior, sertindole is as effective and--according to the only study fully published to date--quetiapine is even slightly less effective than haloperidol in this regard. (4) All new antipsychotics are associated with less frequent use of antiparkinson medication than haloperidol, with risperidone appearing to have a slightly less favourable EPS-profile than the other new antipsychotics. The methodological limitations of this review, the generalizability of the results and expectations from future research are discussed.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Haloperidol; Humans; Imidazoles; Indoles; Olanzapine; Pirenzepine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia

The majority of patients with schizophrenia are likely to experience multiple episodes. Furthermore, because schizophrenia may be a progressive encephalopathy, the longer patients experience symptoms, the more likely they are to suffer lasting impairment. Early identification and pharmacologic intervention to relieve symptoms and prevent relapse are likely to have a profound effect on the long-term clinical outcomes. The choice of antipsychotic can be critical in determining long-term treatment outcomes for first-episode patients who are often particularly sensitive to the potential side effects of treatment such as extrapyramidal symptoms (EPS). Atypical antipsychotics have proven efficacy against both the positive and negative symptoms of schizophrenia, have a lower propensity to cause EPS than conventional agents, and may also improve cognitive functioning. Their use is therefore recommended, particularly for those patients experiencing their first episode.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Brief Psychiatric Rating Scale; Clinical Trials as Topic; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Secondary Prevention; Treatment Outcome

While approximately 70% of patients with schizophrenia and other psychotic disorders show a clear-cut reduction of symptoms in clinical trials, there is considerable variation in individual patient outcome, ranging from complete remission to absolute refractoriness. When additional indicators of treatment outcome are considered, such as cognitive and occupational and social functioning, it is clear that the overall outcome for schizophrenia is far from satisfactory. For many schizophrenic patients, treatment with conventional antipsychotic agents is not fully effective, and one approach has been to increase the administered dose. However, raising the dose increases the likelihood of side effects and may significantly compromise patient compliance. The availability of atypical antipsychotic agents represents a significant step forward for those patients who are nonresponsive to conventional antipsychotics, offering proven efficacy, a lower risk of extrapyramidal symptoms, and improved clinical outcomes.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Patient Compliance; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Antipsychotic agents remain the most effective treatment for both acute and chronic schizophrenia. However, conventional antipsychotic agents are frequently associated with significant side effects including, perhaps most notably, extrapyramidal symptoms (EPS). The emergence of EPS can significantly compromise patient compliance with treatment and can have profound effects on long-term treatment outcomes. Providing effective symptom relief with minimal side effects and without inducing EPS is, therefore, a primary goal in the treatment of schizophrenia. Atypical antipsychotic agents are now regarded as first-line therapies for the treatment of schizophrenia because of their lower propensity to induce EPS compared with conventional antipsychotics, and evidence exists that these agents are associated with a lower relapse rate, which perhaps reflects an improvement in patient compliance.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Dystonia; Female; Humans; Male; Movement Disorders; Parkinsonian Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The clinical management of older schizophrenic patients presents particular clinical challenges. Antipsychotics are among the most widely prescribed class of medications for elderly patients. However, the increased frequency of chronic illnesses and thus the potential need for polypharmacy means that the most appropriate treatment strategy for the older schizophrenic patient is not easily extrapolated from the wealth of clinical trials conducted in younger patients. The development of atypical antipsychotics, with their lower propensity to cause adverse effects and cognitive impairment, offers considerable potential benefits to the older schizophrenic patient. The particular problems and key issues that should be addressed when selecting an appropriate antipsychotic for schizophrenic patients in this sensitive population, as well as the place of the new atypical antipsychotic agents in treating this population, are discussed.

Topics: Age Factors; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Drug Administration Schedule; Humans; Hypotension, Orthostatic; Male; Osteoporosis; Quetiapine Fumarate; Schizophrenia

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

This analysis of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study (NCT01157351) compared outcomes after administration of once-monthly paliperidone palmitate (PP) vs conventional oral antipsychotics (COAs) or atypical oral antipsychotics (AOAs).. PRIDE was a 15-month study of 444 individuals with schizophrenia and a history of incarceration. They were randomly assigned to PP or to 1 of 7 commonly prescribed OAs. Primary endpoint was time to first treatment failure (TF). Event-free probabilities were estimated using the Kaplan-Meier method; treatment group differences (PP vs COAs, PP vs AOAs, and PP vs oral paliperidone/risperidone) were assessed using a log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No adjustment was made for multiplicity.. Compared with PP, risk for first TF was 34% higher with COAs (HR: 1.34; 95% CI: 0.80-2.25), 41% higher with AOAs (HR: 1.41; 95% CI: 1.06-1.88), and 39% higher with paliperidone/risperidone (HR: 1.39; 95% CI: 0.97-1.99). Incidences of extrapyramidal symptom-related adverse events (AEs) were 45.7%, 13.7%, and 10.6% in the COA, AOA, and oral paliperidone/risperidone groups vs 23.9% in the PP group. Incidences of prolactin-related AEs were 5.7%, 3.8%, and 3.5% vs 23.5%, and incidences of ≥7% weight increase were 11.4%, 14.9%, and 16.0% vs 32.4%.. Results suggest a lower risk of TF but a higher rate of some AEs after treatment with PP vs COAs, AOAs, and paliperidone/risperidone. Deselection of specific OAs and low patient-compliance rates with OAs likely biased the safety results.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Delayed-Action Preparations; Female; Haloperidol; Humans; Hyperprolactinemia; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Perphenazine; Proportional Hazards Models; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Failure; Treatment Outcome

This study was designed to evaluate the short-term efficacy and safety of once-daily lurasidone (80 mg/day and 160 mg/day) in the treatment of an acute exacerbation of schizophrenia.. Participants, who were recently admitted inpatients with schizophrenia with an acute exacerbation of psychotic symptoms, were randomly assigned to 6 weeks of fixed-dose, double-blind treatment with lurasidone 80 mg (n=125), lurasidone 160 mg (n=121), quetiapine XR 600 mg (QXR-600 mg; n=119; active control included to test for assay sensitivity), or placebo (n=121), all dosed once daily in the evening. Efficacy was evaluated using a mixed-model repeated-measures analysis of the change from Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) total score (the primary efficacy measure) and Clinical Global Impressions severity (CGI-S) score (the key secondary efficacy measure).. Treatment with both doses of lurasidone or with QXR-600 mg was associated with significantly greater improvement at Week 6 on PANSS total score, PANSS positive and negative subscale scores, and CGI-S score compared with placebo. The endpoint responder rate (≥ 20% improvement in PANSS total score) was higher in subjects treated with lurasidone 80 mg (65%; p<0.001), lurasidone 160 mg (79%; p<0.001), and QXR-600 mg (79%; p<0.001) compared with placebo (41%). The proportion of patients experiencing ≥ 7% weight gain was 4% for each lurasidone group, 15% for the QXR-600 mg group, and 3% for the placebo group. Endpoint changes in levels of cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol were comparable for both lurasidone groups and placebo, while the QXR-600 mg group showed a significant median increase compared with the placebo group in levels of cholesterol (p<0.001), LDL cholesterol (p<0.01), and triglycerides (p<0.05).. Lurasidone 80 mg and 160 mg doses administered once-daily in the evening, were safe and effective treatments for subjects with acute schizophrenia, with increased response rates observed at the higher dose. Dose-related adverse effects were limited, and both doses were generally well-tolerated.

Topics: Adolescent; Adult; Aged; Akathisia, Drug-Induced; Analysis of Variance; Antipsychotic Agents; Basal Ganglia Diseases; Body Mass Index; Body Weight; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Middle Aged; Models, Statistical; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Thiazoles; Time Factors; Waist Circumference; Young Adult

The authors compared paliperidone extended-release and quetiapine in patients with recently exacerbated schizophrenia requiring hospitalization.. In a 6-week double-blind study, inpatients with a recent exacerbation of schizophrenia were randomly assigned to treatment with paliperidone extended-release, quetiapine, or placebo. A 2-week monotherapy phase was followed by a 4-week additive-therapy phase. Target doses were at the upper end of recommended ranges: paliperidone extended-release, 9 or 12 mg/day, and quetiapine, 600 or 800 mg/day. The primary endpoint was the difference in mean total change score on the Positive and Negative Syndrome Scale (PANSS) between paliperidone extended-release and quetiapine at the 2-week monotherapy phase endpoint.. Six-week completion rates were 77.5% (124/160) with paliperidone extended-release, 66.7% (106/159) quetiapine, and 63.8% (51/80) placebo. Improvement in mean PANSS total change score was greater with paliperidone extended-release than with quetiapine from day 5 (-11.4 versus -8.2) through the monotherapy phase endpoint (-23.4 versus -17.1). Only paliperidone extended-release showed significantly greater PANSS improvement compared with placebo at 2 weeks. At the 6-week study endpoint, there was a significantly greater improvement with paliperidone extended-release compared with quetiapine despite similar use of additive therapy (predominantly other antipsychotics). Common adverse events with paliperidone extended-release, quetiapine, and placebo, respectively, were tremor (13.9%, 5.0%, 7.5%), somnolence (8.9%, 11.9%, 1.3%), insomnia (10.1%, 9.4%, 11.3%), and headache (12.0%, 7.5%, 13.8%). Six-week adverse event-related discontinuation rates were 6.3%, 10.1%, and 6.3%, respectively, in the paliperidone extended-release, quetiapine, and placebo groups.. Compared with quetiapine, paliperidone extended-release improved symptoms earlier and to a greater degree in patients with recently exacerbated schizophrenia requiring hospitalization, with no unexpected tolerability findings.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Pyrimidines; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Young Adult

To investigate the efficacy and safety of quetiapine for depressive symptoms in patients with schizophrenia.. Thirty-nine patients fulfilling DSM-IV-TR diagnostic criteria for schizophrenia and had depressive symptoms were studied in a prospective 6-week open-label design using quetiapine monotherapy. The brief psychiatric rating scale (BPRS), 17-item Hamilton depression rating scale (HAMD-17), Simpson-Angus rating scale, and the Barnes Akathisia rating scale (BARS) were used to assess patients at baseline, week 1, 2, 4, and 6.. Thirty patients (76.9%) completed this study. The dose of quetiapine at endpoint was 583 (+/-235 SD) mg/day. Treatment with Quetiapine was associated with significantly reduced depressive symptoms (HAMD-17 total score and BPRS depression/anxiety subscale) from the first week of treatment. Changes of mean score from baseline to endpoint were 7.8 +/- 6.2 for HAMD-17 total score and 3.4 +/- 3.6 for BPRS depression/anxiety subscale (LOCF, n = 39, p < 0.001). Quetiapine was well tolerated, with minimal extrapyramidal symptoms and non-significant increase in body weight (mean increase of 0.8 kg).. While the interpretation of findings from the open-label design of this study warrants appropriate caution, the results suggest that quetiapine may be an effective and tolerable treatment for depression in patients with schizophrenia.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Body Weight; Depressive Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Prospective Studies; Psychiatric Status Rating Scales; Psychometrics; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Acute agitation is a common presentation in emergency departments and is often secondary to an underlying psychotic condition. The aim of this study was to compare the effectiveness of three second generation antipsychotics (risperidone, olanzapine, quetiapine) versus haloperidol in the treatment of psychotic agitation for up to 72 h.. We recruited 101 patients with acute psychosis who were admitted at the Mental Health Department 1 South of Turin, Psychiatric Emergency Service of San Giovanni Battista Hospital, from June 2004 to June 2005.. Aggressive behavior, as measured by Modified Overt Aggression Scale and Hostility-suspiciousness factor derived from the Brief Psychiatric Rating Scale, significantly improved in all groups, with no significant between-group differences. Extrapyramidal symptoms were more common in haloperidol treated patients compared with patients receiving risperidone, olanzapine or quetiapine.. Our results show that in the clinical practice setting of emergency psychiatry olanzapine, risperidone, quetiapine are as effective as haloperidol and better tolerated.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aggression; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Dibenzothiazepines; Emergency Services, Psychiatric; Female; Haloperidol; Hostility; Humans; Italy; Male; Middle Aged; Olanzapine; Prospective Studies; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

This was a randomized, flexible-dose, rater-blind, parallel-group, quasi-naturalistic trial comparing the efficacy, safety, and tolerability of quetiapine, risperidone, and olanzapine in patients with schizophrenia hospitalized for severe psychotic symptoms. Seventy-five patients were randomized to quetiapine (n=25), risperidone (n=25), or olanzapine (n=25). Mean doses at Week 8 were: 590.0 mg/day quetiapine; 5.1 mg/day risperidone; 15.1 mg/day olanzapine. Four quetiapine, five risperidone, and five olanzapine patients discontinued prior to Week 8. There were no significant differences between groups in the primary efficacy measures of improvement from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 8 in the per protocol (PP) population and the number of completers who experienced >or=40% improvement on the same scale. PP and intent-to-treat analyses showed significant improvement from baseline in each component of a PANSS-derived battery, without significant differences between treatments. No quetiapine patients, one risperidone, and four olanzapine patients reported an adverse event (AE) of moderate intensity; no severe AEs were reported. A linear mixed model for repeated measures showed an effect of treatment on body weight, with significant differences favoring quetiapine over risperidone and olanzapine. Simpson-Angus Scale scores were significantly worse with risperidone compared with both olanzapine and quetiapine at Week 3 and compared with quetiapine thereafter. Use of concomitant medications for anxiety or tension was significantly less frequent with quetiapine. In conclusion, quetiapine, risperidone, and olanzapine have similar efficacy in schizophrenia, but there are drug-specific differences for some AEs and in the use of concomitant medication that differentiate these agents.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Drug Therapy, Combination; Drug Tolerance; Female; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

This multicentre, observational, prospective, nonrandomized study compared the effectiveness and tolerability of quetiapine and risperidone in the acute and long-term treatment of schizophrenia in a clinical setting. Patients admitted to an acute unit with schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV), who were prescribed quetiapine or risperidone (3 : 1 ratio) within the first week of treatment, according to the physician's usual practice, were recruited. In total, 492 patients (quetiapine: 367; risperidone: 125) were followed up at weeks 1 and 2, discharge and 6 and 12 months thereafter. Mean doses at 12 months were: quetiapine 718.5 mg/day and risperidone 7.0 mg/day. Efficacy measures (Brief Psychiatric Rating Scale, Clinical Global Impression Severity of Illness and Improvement) indicated similar results for both agents. No difference was found in rehospitalization rate with either drug. In terms of tolerability, orthostatic hypotension was more frequent with quetiapine, but extrapyramidal symptoms and male sexual dysfunction were more frequent with risperidone. In conclusion, quetiapine and risperidone had comparable effectiveness, but there were differences between treatments in their side effect profile.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Sexual Dysfunction, Physiological; Spain; Time Factors; Treatment Outcome

To evaluate the effects of quetiapine treatment in patients with delirium.. All patients with delirium were assessed. The diagnosis of delirium was confirmed by using the Confusion Assessment Method (CAM). Quetiapine at the dose between 25 and 100 mg/day was given for 7 days. The efficacy of quetiapine on delirium was evaluated by using the Delirium Rating Scale (DRS) and the Clinical Global Impression-Severity scale (CGI-S). The extrapyramidal side effects were assessed by using the Modified (9-item) Simpson-Angus Scale (MSAS).. Twenty-two patients had delirium. Seventeen (10 males and 7 females) subjects with a mean age (SD) of 55.6 (18.6) years were included in the present study. Means (SDs) dose and duration (SD) of quetiapine treatment were 45.7 (28.7) mg/day and 6.5 (2.0) days, respectively. The DRS and CGI-S scores of days 2-7 were significantly lower than those of day 0 (p < 0. 001) for all comparisons). Only two subjects were shown to have mild tremor.. Quetiapine within the range of 25-100 mg/day improves delirious condition within 24 hours of treatment. It is well-tolerated and has a very low propensity to induce extrapyramidal side effects. Further randomized, placebo-controlled trials are warranted.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Delirium; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Prospective Studies; Psychological Tests; Psychometrics; Quetiapine Fumarate; Treatment Outcome

To compare the efficacy and tolerability of quetiapine and risperidone in the treatment of schizophrenia.. In this 8-week, double-blind, multicenter, flexible-dose study, patients with schizophrenia (DSM-IV diagnosis) were randomly assigned to quetiapine (200-800 mg/day) or risperidone (2-8 mg/day). The primary hypothesis was that quetiapine was not inferior to risperidone. The primary efficacy measure was change from baseline in Positive and Negative Syndrome Scale (PANSS) total scores; secondary outcomes included response rate (> or = 40% reduction in PANSS scores), Clinical Global Impression-Change (CGI-C), and cognitive and social functioning. Tolerability assessments included treatment-emergent adverse events and changes in weight, glucose, and prolactin. Patients were recruited from June 2001 to September 2002.. Patients (N = 673) were randomly assigned to quetiapine (N = 338, mean dose = 525 mg/day) or risperidone (N = 335, mean dose = 5.2 mg/day). The primary analysis demonstrated noninferiority between treatments (p < .05). Improvements with both treatments were comparable on PANSS total, negative, and general psychopathology subscales. Risperidone-treated patients had a significantly (p = .03) greater improvement in PANSS positive subscale score among all patients, but not among completers. Improvements in PANSS response rates, CGI-C, and cognitive function were similar between treatment groups. Changes in serum glucose and weight were minimal and comparable. The rate of extrapyramidal symptom (EPS)-related adverse events was significantly higher with risperidone (22%) than quetiapine (13%; p < .01). Somnolence was more common with quetiapine (26%) than risperidone (20%; p = .04). Prolactin levels increased with risperidone (+35.5 ng/mL), but decreased with quetiapine (-11.5 ng/mL; p < .001).. Quetiapine and risperidone had broadly comparable clinical efficacy. Both agents improved cognitive and social functioning, and neither had a clinically significant effect on weight or glucose. Somnolence was more common with quetiapine; EPS and elevated prolactin rates were significantly higher with risperidone.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Cognition Disorders; Dibenzothiazepines; Disorders of Excessive Somnolence; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hyperprolactinemia; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The objectives of this study were to evaluate the efficacy, safety, and tolerability of quetiapine for treating psychosis in patients with probable/possible Alzheimer disease and assess its impact on other psychopathology and social and daily functioning.. The authors conducted a multicenter, double-blind, placebo-controlled, randomized trial of flexibly dosed quetiapine and haloperidol. Primary outcomes were change in total Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impressions-Severity of Illness (CGI-S) scores at week 10. Secondary outcomes included BPRS factors, Neuropsychiatric Inventory (NPI), Multidimensional Observation Scale for Elderly Subjects (MOSES), and Physical Self-Maintenance Scale (PSMS).. Two hundred eighty-four participants (mean age: 83.2 years) were randomized; 63.4% completed; and mean Mini-Mental State Examination score was 12.8. Median of the mean daily dose was 96.9 mg for quetiapine and 1.9 mg for haloperidol. No differential benefit was seen on any psychosis measure. BPRS agitation factor scores improved with quetiapine versus placebo and not quetiapine versus haloperidol. BPRS anergia scores worsened with haloperidol versus quetiapine but not quetiapine versus placebo. No NPI factors showed change, including the agitation factor. MOSES Withdrawal Subscale and PSMS total scores worsened with haloperidol versus quetiapine. Somnolence occurred in 25.3%, 36.2%, and 4.1% of the quetiapine, haloperidol, and placebo groups, respectively; parkinsonism was most prevalent in the haloperidol group; other safety and tolerability measures differed little among groups.. All treatment groups showed improvement in measures of psychosis without significant differences between them when planned comparisons were performed. Participants treated with quetiapine or haloperidol showed inconsistent evidence of improvement in agitation. Tolerability was better with quetiapine compared with haloperidol.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Basal Ganglia Diseases; Brain; Brief Psychiatric Rating Scale; Cholinesterase Inhibitors; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Drug Tolerance; Female; Haloperidol; Humans; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease, Secondary; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index; Substance Withdrawal Syndrome

Replacement of antipsychotic drugs with quetiapine (QTP) was tried in a naturalistic setting in chronic schizophrenic patients who still showed moderate psychiatric symptoms and either showed extrapyramidal symptoms (EPS) or took anti-parkinson drugs for the EPS. QTP was added on and gradually increased while the previous drugs were tapered and discontinued whenever possible. Clinical symptoms, objective and subjective QOL, and EPS were measured before and 6 months after QTP addition, using Brief Psychiatric Rating Scale (BPRS), Quality of Life Scale (QLS), Schizophrenia Quality of Life Scale (SQLS) and Drug-Induced Extrapyramidal Symptom Scale (DIEPSS), respectively. Twenty-one patients completed the trial and received the assessment. It was found that replacement with QTP-improved clinical symptoms, objective and subjective QOL and EPS. This improvement was equally observed in not only patients who switched to QTP monotherapy (n = 11) but also patients who took QTP together with reduced small doses (4.4 +/- 4.3 mg/day) of previous drugs (n = 11). The results suggest that replacement with QTP improves symptoms as well as objective and subjective QOL in a subgroup of schizophrenia.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quality of Life; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

To evaluate the efficacy and tolerability of quetiapine monotherapy versus placebo for the treatment of mania associated with bipolar disorder.. In an international, multicenter, double-blind, parallel-group, 12-week study, patients with a DSM-IV diagnosis of bipolar I disorder (manic episode) were randomly assigned to treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or lithium. The primary efficacy measure was change from baseline in Young Mania Rating Scale (YMRS) score at day 21. Data were gathered from April 2001 to May 2002.. More patients in the quetiapine (72/107) and lithium (67/98) groups completed the study compared with the placebo group (35/97). Improvement (reduction) in YMRS score was significantly greater for quetiapine than placebo at day 7 (-8.03 vs. -4.89; p < .01), and the difference between groups continued to increase over time to day 21 (-14.6 vs. -6.7; p < .001) and to endpoint at day 84 (-20.3 vs. -9.0; p < .001). Significantly more quetiapine patients compared with placebo patients fulfilled YMRS response criteria at day 21 (53.3% vs. 27.4%; p < .001) and at day 84 (72.0% vs. 41.1%; p < .001). Quetiapine was also superior to placebo in efficacy at day 21 and day 84 by all secondary measures. Lithium-treated patients improved significantly compared with placebo patients and similarly to quetiapine-treated patients on the primary efficacy measure. The most common adverse events for quetiapine were dry mouth, somnolence, and weight gain, while lithium was associated with tremor and insomnia. The quetiapine and placebo groups had similar, low levels of extrapyramidal symptom-related adverse events.. Quetiapine demonstrated superior efficacy to placebo in patients with bipolar mania and was well tolerated.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Hospitalization; Humans; Hyperprolactinemia; Lithium; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

To compare the long-term efficacy and tolerability of oral quetiapine with those of intramuscular haloperidol.. Patients with DSM-IV-diagnosed schizophrenia or schizoaffective disorder requiring long-term antipsychotic treatment were randomly assigned to open-label oral quetiapine or intramuscular haloperidol decanoate for 48 weeks. Clinicians were instructed to target dosing at 500 mg/day of quetiapine or 200 mg of haloperidol decanoate every 4 weeks. The Positive and Negative Syndrome Scale was used to assess efficacy; the Simpson-Angus Scale and the Barnes Akathisia Scale were used to assess safety and tolerability. For statistical analyses, a general linear mixed-model repeated-measures analysis of covariance was used, with change scores for dependent variables computed with the baseline score as covariate. Data were collected from 1998 to 2001.. Thirty-five patients were enrolled, but 6 did not participate after being informed of their treatment assignment; 4 of the 6 withdrawals were assigned to haloperidol decanoate. Mean doses at week 48 were 493 mg/day of quetiapine (N = 16) and 170 mg/28 days of haloperidol decanoate (N = 9). Survival analysis showed no between-group differences in estimates of the number of patients remaining exacerbation-free over time. Both drugs were efficacious, but quetiapine was significantly better than haloperidol decanoate in controlling negative symptoms (p < .05). The incidence of extrapyramidal symptoms was low in both groups; patients receiving quetiapine showed significantly greater improvement in rigidity and akathisia (p < .05).. Oral quetiapine was as efficacious as intramuscular haloperidol in preventing symptom exacerbation over 48 weeks in patients with schizophrenia or schizoaffective disorder, with fewer extrapyramidal symptoms, especially rigidity and akathisia. Quetiapine was more efficacious than haloperidol decanoate in treating negative symptoms.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Female; Haloperidol; Humans; Incidence; Injections, Intramuscular; Long-Term Care; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Survival Analysis; Treatment Outcome

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

Topics: Basal Ganglia Diseases; Benzodiazepines; Body Weight; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Quetiapine Fumarate; Weight Loss

As schizophrenia is a chronic disorder, it is important that treatment be given over a long period of time to avoid relapse. Quetiapine, an atypical antipsychotic, has established efficacy and good tolerability in the short-term treatment of schizophrenia. This study investigated the long-term efficacy and safety of quetiapine in 674 patients with schizophrenia using combined data from the open-label extension phase of four Phase IIIa trials. The results showed that quetiapine, at a mean daily dose of 472.4 mg, provided progressive improvement and maintenance in the Brief Psychiatric Rating Scale total, positive- and negative-symptoms cluster, Clinical Global Impression Severity of Illness, and Scale for the Assessment of Negative Symptoms total scores over 208 weeks and beyond. Furthermore, quetiapine was well tolerated throughout the study period, with a low incidence of extrapyramidal symptom-related adverse events. In conclusion, quetiapine may be a suitable therapy in the long-term treatment of schizophrenia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Treatment Outcome

To compare the tolerability of quetiapine with risperidone in older outpatients.. Post hoc analysis of a subset of older patients (aged 60-80; n = 92) from a randomized, 4-month, multicenter, open-label trial comparing quetiapine and risperidone in an outpatient setting. Participants had various neuropsychiatric disorders associated with psychosis as defined by criteria from the Diagnostic and Statistical Manual of Mental Disorders (4th edn).. The main outcome measure was an extrapyramidal symptoms (EPS) checklist, used to assess motor symptoms, including parkinsonism, at baseline and after treatment. The Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression scale were used to assess therapeutic efficacy.. Substantial EPS (defined as EPS requiring a dosage adjustment or use of medication to reduce EPS) occurred less often with quetiapine (median dosage, 200 mg/day) than with risperidone (median dosage, 3 mg/day); odds ratio, 0.31 (P < 0.03). Quetiapine was also less likely than risperidone to cause akathisia or hypertonia. Both compounds produced comparable reductions in PANSS scores.. Interpretation of findings in this report is limited by the open-label design of the study and the post hoc nature of this analysis. However, the results suggest that quetiapine, when given within the recommended dosage range, has a benign EPS profile, with potentially greater tolerability and comparable efficacy to risperidone in older outpatients with psychotic disorders.

Topics: Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Risperidone

This is the first investigation of the pharmacokinetics, tolerability, and efficacy of quetiapine fumarate in adolescents with chronic or intermittent psychotic disorders.. Ten patients with DSM-IV chronic or intermittent psychotic disorders (ages 12.3 through 15.9 years) participated in an open-label, rising-dose trial and received oral doses of quetiapine twice daily (b.i.d.), starting at 25 mg b.i.d. and reaching 400 mg b.i.d. by day 20. The trial ended on day 23. Key assessments were pharmacokinetic analysis of plasma quetiapine concentrations and neurologic, safety, and efficacy evaluations.. No statistically significant differences were observed between 100-mg b.i.d. and 400-mg b.i.d. quetiapine regimens for total body clearance, dose-normalized area under the plasma concentration-time curve, or dose-normalized premorning- or postmorning-dose trough plasma values obtained under steady-state conditions after multiple-dose regimens. No unexpected side effects occurred with quetiapine therapy, and no statistically significant changes from baseline were observed for the UKU Side Effect Rating Scale items that were rated. No serious adverse events or clinically important changes in hematology or clinical chemistry variables were reported. The most common adverse events were postural tachycardia and insomnia. Extrapyramidal side effects improved, as evidenced by significant (p < .05) decreases from baseline to endpoint in the mean Simpson-Angus Scale total scores and Barnes Akathisia Scale scores. Quetiapine improved positive and negative symptoms, as shown by significant (p < .05) decreases from baseline to endpoint in the mean Brief Psychiatric Rating Scale total score, the Clinical Global Impressions-Severity of Illness scale, and the Modified Scale for the Assessment of Negative Symptoms summary score.. Quetiapine pharmacokinetics were dose proportional in adolescents and were similar to those previously reported for adults. Quetiapine was well tolerated and effective in the small number of adolescents studied.

Topics: Adolescent; Adult; Age Factors; Antipsychotic Agents; Basal Ganglia Diseases; Brief Psychiatric Rating Scale; Child; Dibenzothiazepines; Drug Administration Schedule; Humans; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sleep Initiation and Maintenance Disorders; Tachycardia; Treatment Outcome

Quetiapine is a new atypical antipsychotic medication. As such, relatively little has been published regarding its in vivo effects at the dopamine type 2 (D2) and serotonin type 2a (5-HT2a) receptor systems. The following study was undertaken to explore these effects across the clinical dose range and relate this information to its clinical profile.. Twelve patients with schizophrenia were randomly assigned to doses of 150 to 600 mg/d (n=3, at 150, 300, 450, and 600 mg/d) of quetiapine. After 3 weeks of treatment, D2 and 5-HT2a occupancy were measured using positron emission tomography (PET) imaging, 12 to 14 hours after the last dose. Clinical efficacy and adverse effect ratings were obtained at baseline, at the time of PET scanning, and at 12 weeks. Two additional patients were included to examine the effects of the drug 2 to 3 hours after last dose.. Quetiapine was an effective antipsychotic and improved the extrapyramidal symptoms and prolactin level elevation noted at baseline. It achieved these results with minimal (0%-27%) D2 occupancy 12 hours after the last dose. Study of the additional subjects revealed that quetiapine does give rise to transiently high (58%-64%) D2 occupancy 2 to 3 hours after a single dose that then decreases to minimal levels in 12 hours.. Quetiapine shows a transiently high D2 occupancy, which decreases to very low levels by the end of the dosing interval. Quetiapine's low D2 occupancy can explain its freedom from extrapyramidal symptoms and prolactin level elevation. The data suggest that transient D2 occupancy may be sufficient for its antipsychotic effect. Future studies controlling for nonpharmacological effects as well as activities on other receptors will be necessary to confirm this suggestion.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Brain; Carbon Radioisotopes; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Prolactin; Psychiatric Status Rating Scales; Quetiapine Fumarate; Raclopride; Receptors, Dopamine D2; Receptors, Serotonin; Schizophrenia; Serotonin Antagonists; Tomography, Emission-Computed; Treatment Outcome

A 6-week, double-blind, randomized, multicentre, parallel-group study was conducted to compare the efficacy of quetiapine ('Seroquel') (n=101) with that of chlorpromazine (n=100) in hospitalized patients with acute exacerbation of subchronic or chronic schizophrenia, or schizophreniform disorder. The tolerabilities of the two treatments were also compared. The mean daily doses of quetiapine and chlorpromazine at the end of the study were 407 mg and 384 mg, respectively. Both treatments were effective in the treatment of positive and negative symptoms, with a trend towards superior efficacy for quetiapine. The quetiapine group had a lower incidence of adverse events than the chlorpromazine group, and a low incidence of treatment-emergent extrapyramidal symptoms. Quetiapine was not associated with a sustained increase in serum prolactin. These clinical data support the preclinical profile of quetiapine as an atypical antipsychotic agent.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Chlorpromazine; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Weight Gain

To describe a cohort of young users of risperidone and quetiapine in the province of Manitoba (Canada) and assess the risk for movement disorders in the two treatments.. This was a population-based study conducted on all residents of the province of 19 years of age and younger who received prescriptions for risperidone or quetiapine between April 1, 1996, and March 31, 2011. Incident rates of antipsychotic use were reported. The risk for movement disorders in patients treated with quetiapine compared with those treated with risperidone was assessed by time-to-event analysis using Cox proportional hazards models.. Between April 1, 1996, and March 31, 2011, 23,888 youth (age ≤19 years) were prescribed an antipsychotic agent. Among them, 8756 were identified as new incident users. After applying exclusion criteria, 2594 individuals comprised the cohort of users of risperidone and quetiapine. The use of quetiapine was associated with a lower risk of extrapyramidal symptoms (EPSs) adverse events. The unadjusted and adjusted hazard ratios (95% confidence interval [CI]) for quetiapine versus risperidone were 0.83 (0.56-1.25) and 0.53 (0.34-0.83), respectively.. EPS diagnoses have been detected in children treated with quetiapine; however, the risk of movement disorders appears to be higher with treatment with risperidone. Clinicians should always take into consideration the risk-benefit before treating children with antipsychotic medications and should be vigilant of the onset of drug-induced adverse events.

Topics: Adolescent; Antipsychotic Agents; Basal Ganglia Diseases; Child; Cohort Studies; Female; Humans; Male; Manitoba; Movement Disorders; Population Surveillance; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone

To compare rates of specific adverse outcomes between patients starting quetiapine, olanzapine, or risperidone use in the Netherlands.. Observational study using the PHARMO Database Network, including patients starting quetiapine (4658), olanzapine (5856), or risperidone (7229) in 2000-2009, comparing rates of all-cause mortality, failed suicide attempts, extrapyrimidal symptoms (EPS), diabetes mellitus (DM), hypothyroidism, and acute myocardial infarction (AMI).. Median follow-up until discontinuation/end of follow-up was 0.6 years. Prescribed doses were generally lower than the approved defined daily doses, especially for quetiapine. Quetiapine was significantly associated with lower EPS rates (HR 0.18; 95% CI 0.13-0.24), but higher failed suicide attempt rates (HR 2.07; 95% CI 1.35-3.16) compared to risperidone. Quetiapine was significantly associated with lower EPS rates (HR 0.59; 95% CI 0.42-0.84) and DM rates (HR 0.66; 95% CI 0.44-0.97) compared to olanzapine. Rates for all-cause mortality, hypothyroidism, and stroke were similar between groups. AMI events were too infrequent to draw conclusions.. Quetiapine was associated with lower EPS, but higher failed suicide attempt rates compared to risperidone. Quetiapine was associated with lower EPS and DM rates compared to olanzapine. The results should be interpreted with caution because of possible channelling and residual confounding. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mortality; Netherlands; Olanzapine; Product Surveillance, Postmarketing; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia

Mrs A, a 68-year-old woman with paranoid schizophrenia, was on long-term psychiatric treatment with long-acting intramuscular zuclopenthixol, quetiapine and alprazolam when, in April 2012, she was diagnosed with right breast infiltrating ductal carcinoma. After starting treatment with letrozole on 4 July, Mrs A progressively developed extrapyramidal symptoms and these were particularly evident after each zuclopenthixol administration. On 9 January, both quetiapine and alprazolam were stopped due to excessive lethargy. After the administration of the last dose of zuclopenthixol on 26 January, she presented with sedation, sialorrhea, festinant gait, axial dystonia and dysphagia, all of which were severe. The introduction of letrozole was the only change that had been made to her pharmacotherapeutic regimen in that period. The rest of the findings on neurological examination were normal. Renal function was adequate. Slow symptom onset and progressive worsening until full-blown clinical presentation after 6 months, and the dramatic improvement in the clinical picture achieved 2 days after treatment with biperiden, suggests a long-term insidious interaction leading to zuclopenthixol accumulation. To the best of our knowledge, this is the first report of a possible interaction between letrozole and zuclopenthixol. We consider that it warrants further investigation. In the meanwhile, physicians should be aware of the occurrence of this potentially serious drug-drug interaction.

Topics: Aged; Antineoplastic Agents; Antipsychotic Agents; Basal Ganglia Diseases; Clopenthixol; Dibenzothiazepines; Drug Interactions; Female; Humans; Letrozole; Nitriles; Quetiapine Fumarate; Schizophrenia; Triazoles

The purpose of the study was to determine the downstream implications of atypical antipsychotic (AAP) prescribing in the intensive care unit (ICU), including discharge prescribing practices, monitoring, and attributable adverse drug events.. This retrospective cohort study included patients at least 18 years of age admitted to an ICU that received at least 2 doses of an AAP for documented delirium or avoidance of a deliriogenic medication. Exclusion criteria were documentation of an AAP as a home medication or initiation for a psychiatric indication unrelated to delirium (eg, schizophrenia).. During the 8-month study period, 156 patients were included and 133 (85.2%) patients survived to hospital discharge. Of the survivors, AAP therapy was continued for 112 (84.2%) patients upon ICU transfer and for 38 (28.6%) patients upon hospital discharge. A majority of these patients had evidence of delirium resolution or no indication for continuation documented at discharge. Of the 127 patients with an electrocardiogram ordered during AAP therapy, QTc prolongation occurred in 49 (31.4%) patients. An adverse drug event leading to drug discontinuation was documented in 16 (10.2%) patients.. Because of significant patient-centered implications, AAPs initiated in the ICU require continued evaluation for indication to avoid prolonged and possibly unnecessary use.

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Basal Ganglia Diseases; Benzodiazepines; Cohort Studies; Delirium; Disorders of Excessive Somnolence; Female; Humans; Inappropriate Prescribing; Intensive Care Units; Male; Middle Aged; Olanzapine; Patient Discharge; Piperazines; Quetiapine Fumarate; Retrospective Studies; Risperidone; Survivors; Thiazoles

The frequency of severe adverse drug reactions (ADRs) from psychotropic drugs was investigated in hospitalised psychiatric patients in relation to their age. Specifically, the incidence of ADRs in patients up to 60 years was compared to that of patients older than 60 years.. Prescription rates of psychotropic drugs and reports of severe ADRs were collected in psychiatric hospitals in Switzerland between 2001 and 2010. The data stem from the drug surveillance programme AMSP.. A total of 699 patients exhibited severe ADRs: 517 out of 28,282 patients up to 60 years (1.8%); 182 out of 11,446 elderly patients (1.6%, ns). Logistic regression analyses showed a significantly negative relationship between the incidence of ADRs and patients' age in general and in particular for weight gain, extrapyramidal motor system (EPMS) symptoms, increased liver enzymes and galactorrhoea. A significantly negative relationship was observed for age and the dosages of olanzapine, quetiapine, risperidone, valproic acid and lamotrigine. When comparing age groups, frequency of ADRs was lower in general for antipsychotic drugs and anticonvulsants, in particular for valproic acid in the elderly. Weight gain was found to be lower in the elderly for antipsychotic drugs, in particular for olanzapine. For the group of mood-stabilising anticonvulsants (carbamazepine, lamotrigine and valproic acid) the elderly exhibited a lower incidence of reported allergic skin reactions.. The results suggest that for psychiatric inpatients the incidence of common severe ADRs (e.g., weight gain or EPMS symptoms) arising from psychotropic medication decreases with the age of patients.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Age Factors; Aged; Aged, 80 and over; Antimanic Agents; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Carbamazepine; Causality; Dibenzothiazepines; Drug-Related Side Effects and Adverse Reactions; Female; Galactorrhea; Humans; Lamotrigine; Logistic Models; Male; Middle Aged; Neuroleptic Malignant Syndrome; Olanzapine; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Switzerland; Triazines; Valproic Acid; Weight Gain; Young Adult

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Female; Humans; Myasthenia Gravis; Quetiapine Fumarate; Schizophrenia

The aim of the study was to evaluate the adherence and efficacy of quetiapine treatment in a 6-month, multicentre, noninterventional naturalistic design. Overall, 710 schizophrenia patients using quetiapine or who had switched to quetiapine were included. The continuation rate for quetiapine treatment during 6-month follow-up period was 69%. Adherence improved with each subsequent visit for continued patients, 92.9% at the second visit to 96.1% at the last. Treatment adherence was correlated to improvement of symptoms, though not significantly. Patients having lower clinical global impression severity scores at the beginning were twice as likely to improve compared with patients with higher clinical global impression scores. Schizophrenia patients with antisocial behaviour problems had two and a half times higher drop-out rates. In conclusion, this naturalistic study showed that adherence to quetiapine treatment was high, and treatment was effective in schizophrenia patients during long-term treatment. Remission of symptoms in schizophrenia is much related to severity of symptoms at baseline, treatment adherence and characteristics of patients such as antisocial behavioural patterns.

Topics: Adult; Age of Onset; Aging; Antipsychotic Agents; Antisocial Personality Disorder; Basal Ganglia Diseases; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Medication Adherence; Middle Aged; Obsessive-Compulsive Disorder; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Turkey; Young Adult

The aim of this study was to evaluate the tolerability and efficacy of rapid quetiapine loading in youth diagnosed with pediatric bipolar disorder (PBD).. Quetiapine was started at 100 mg/day, and increased to 400 mg/day by day 5 in 75 bipolar children (6-16 years), presenting in an acute manic or hypomanic episode. Subsequent dose adjustments were predicated on the clinical picture. Response was defined as a ≥ 50% reduction in baseline scores on the Young Mania Rating Scale (YMRS). Clinical Global Impression-Improvement Scale (CGI-I) scores of "2 much improved" or "1 very much improved" were used as secondary measures of response. Remission was defined as a YMRS score of ≤ 12. Adverse events, blood pressure, weight change, somnolence, extrapyramidal syndrome (EPS), and akathisia were monitored to determine tolerability.. At 8 weeks, 94% of the sample had a CGI-I score ≤ 2, and 70% were in remission at 6 months. Sedation was reported by 50% of subjects during the first week; this rate dropped to 5.6% at 6 months.. The findings indicate that rapid dose administration of quetiapine in children and adolescents with PBD is generally well tolerated and efficacious.

Topics: Adolescent; Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Child; Dibenzothiazepines; Female; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; Time Factors; Treatment Outcome

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

Clinical trials suggest between 30-50% of depressed patients have an inadequate outcome to antidepressant pharmacotherapy. Among the approaches to improve outcome has been augmentation with antipsychotic medications. We aim to investigate the efficacy and tolerability of augmentation with quetiapine in depressed patients with a partial response to antidepressants.. Patients with a Major Depressive Disorder (DSMIV) who had partial/no response to a stable dose of an Selective Serotonin Reuptake Inhibitors (SSRI)/SNRI were recruited. All patients received add-on quetiapine (200-600 mg nocte) in a 6-week trial. Outcome measures (HAMD, MADRS) were assessed at screening, baseline, weeks 1, 2, 4 and 6. Extrapyramidal symptoms (EPSEs) were assessed at baseline, weeks 2, 4 and 6. A neuropsychological battery of tests was administered at baseline, weeks 3 and 6.. Nineteen patients entered the trial and 18 completed the trial per protocol. We report a rapid improvement in depression ratings over 6 weeks (p < 0.0005) and remission rates of 67% at week 1 and 94% at week 6. There was no evidence of EPSE and no worsening (and some improvement) of cognition.. This suggests clinical benefits of quetiapine augmentation of SSRI/SNRI antidepressants with no worsening, and possible improvements in cognition.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Cognition; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate; Remission Induction; Selective Serotonin Reuptake Inhibitors; Young Adult

The International Schizophrenia Outpatient Health Outcomes study, IC-SOHO is a three-year international observational study that investigates clinical and health outcomes of antipsychotic treatments. 7658 outpatients treated for schizophrenia were enrolled in the study, who needed an antipsychotic therapy to initiate or switch. The primary analysis compared the group taking olanzapine with the group taking any other antipsychotics, while the secondary comparison was performed between those treated with olanzapine and those with risperidone. Efficacy analysis was carried out based on changes in Clinical Global Impression of Severity scale (CGI-S), which was performed at a global symptom level, as well as with respect to the patients' positive, negative, cognitive and depressive symptoms. In addition, adverse events were also evaluated. Results of the analysis of the 3- and 6-month data from Hungary are disclosed in this publication. 200 patients were enrolled in the country. Demographics of the treatment groups were not significantly different. At 3 and 6 months after treatment initiation, there were no significant between-group differences in improvement of global symptomatology, however, cognitive symptoms improved more in the Olanzapine-group compared to those taking other antipsychotics (p<0.05). In patients showing Extrapyramidal Symptoms (EPS) at baseline, these symptoms finished to a greater extent among those receiving olanzapine than in those receiving other antipsychotics (after 6 months D<0.0001). Half a year later, significantly less patients showed extrapyramidal adverse events (p=0,0007), and the previous EPS terminated to a greater extent (p=0.0016) in the olanzapine group, as compared to those taking risperidone. No between-group differences were found in changes of sexual functions, as well as of weight and Body Mass Index measures. Switching antipsychotic initiated at study baseline, and adding-on one or more other antipsychotic to the initial one, were significantly less frequent in the Olanzapine-group compared to those initiated other antipsychotics. In the first 3 months, treatment compliance was significantly higher with olanzapine therapy than with other antipsychotic treatments, and with risperidone respectively. Results from the Hungarian sample correspond with results from higher analysis levels of wider patient populations of IC-SOHO study. Olanzapine showed outstanding efficacy in lessening cognitive disturbances and global cli

Topics: Adult; Aggression; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dibenzothiazepines; Erectile Dysfunction; Female; Galactorrhea; Gynecomastia; Haloperidol; Humans; Hungary; International Cooperation; Libido; Male; Menstruation Disturbances; Middle Aged; Olanzapine; Outpatients; Patient Admission; Patient Compliance; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index

To determine whether atypical antipsychotic polytherapy is a risk factor for drug treatment for extrapyramidal side-effects (anti-EPS drugs) and whether the risk is attributable to antipsychotic dose.. We studied Iowa Medicaid beneficiaries aged 18-64 years with an active atypical and no conventional antipsychotic on January 1, 2001. The association of atypical antipsychotic polytherapy with anti-EPS drug treatment was determined. Multiple logistic regression was utilized to adjust for covariates in two models, the first adjusting for age, sex and the specific antipsychotic(s) prescribed, and the second also adjusting for doses.. Among 4400 patients, the unadjusted odds of anti-EPS treatment were increased two-fold with polytherapy. Polytherapy remained a risk factor in the first model (OR 1.5, 95% CI 1.1-2.0), but not after adjusting for doses (OR 1.0, 95% CI 0.7-1.4).. Atypical antipsychotic polytherapy is a risk factor for anti-EPS drug treatment, apparently because of higher cumulative doses.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Cross-Sectional Studies; Delayed-Action Preparations; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Iowa; Male; Mathematical Computing; Medicaid; Middle Aged; Models, Statistical; Olanzapine; Product Surveillance, Postmarketing; Psychotic Disorders; Quetiapine Fumarate; Regression Analysis; Risk Factors; Risperidone; Statistics as Topic

To evaluate extrapyramidal symptoms (EPS), including akathisia, with quetiapine in patients with bipolar mania.. Data were analyzed from four similarly designed, randomized, double-blind, 3- to 12-week studies. Two studies evaluated quetiapine monotherapy (up to 800 mg/day) (n = 209) versus placebo (n = 198), with lithium or haloperidol monotherapy as respective active controls. Two studies evaluated quetiapine (up to 800 mg/day) in combination with a mood stabilizer (lithium or divalproex, QTP + Li/DVP) (n = 196) compared to placebo and mood stabilizer (PBO + Li/DVP) (n = 203). Extrapyramidal symptoms were evaluated using the Simpson-Angus Scale (SAS), the Barnes Akathisia Rating Scale (BARS), adverse event reports and anticholinergic drug usage.. The incidence of EPS-related adverse events, including akathisia, was no different with quetiapine monotherapy (12.9%) than with placebo (13.1%). Similarly, EPS-related adverse events with QTP + Li/DVP (21.4%) were no different than with PBO + Li/DVP (19.2%). Adverse events related to EPS occurred in 59.6% of patients treated with haloperidol (n = 99) monotherapy, whereas 26.5% of patients treated with lithium (n = 98) monotherapy experienced adverse events related to EPS. The incidence of akathisia was low and similar with quetiapine monotherapy (3.3%) and placebo (6.1%), and with QTP + Li/DVP (3.6%) and PBO + Li/DVP (4.9%). Lithium was associated with a significantly higher incidence (p < 0.05) of tremor (18.4%) than quetiapine (5.6%); cerebellar tremor, which is a known adverse effect of lithium, may have contributed to the elevated rate of tremor in patients receiving lithium therapy. Haloperidol induced a significantly higher incidence (p < 0.001) of akathisia (33.3% versus 5.9%), tremor (30.3% versus 7.8%), and extrapyramidal syndrome (35.4% versus 5.9%) than quetiapine. No significant differences were observed between quetiapine and placebo on SAS and BARS scores. Anticholinergic use was low and similar with quetiapine or placebo.. In bipolar mania, the incidence of EPS, including akathisia, with quetiapine therapy is similar to that with placebo.

Topics: Adult; Akathisia, Drug-Induced; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Female; Haloperidol; Humans; Lithium Compounds; Male; Middle Aged; Multicenter Studies as Topic; Neurologic Examination; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risk; Treatment Outcome; Valproic Acid

We aimed to analyze the risks of extrapyramidal symptoms (EPS) induced by typical and atypical antipsychotic drugs using a common pharmacokinetic-pharmacodynamic (PK-PD) model based on the receptor occupancy. We collected the data for EPS induced by atypical antipsychotics, risperidone, olanzapine and quetiapine, and a typical antipsychotic, haloperidol from literature and analyzed the following five indices of EPS, the ratio of patients obliged to take anticholinergic medication, the occurrence rates of plural extrapyramidal symptoms (more than one of tremor, dystonia, hypokinesia, akathisia, extrapyramidal syndrome, etc.), parkinsonism, akathisia, and extrapyramidal syndrome. We tested two models, i.e., a model incorporating endogenous dopamine release owing to 5-HT2A receptor inhibition and a model not considering the endogenous dopamine release, and used them to examine the relationship between the D2 receptor occupancy of endogenous dopamine and the extent of drug-induced EPS. The model incorporating endogenous dopamine release better described the relationship between the mean D2 receptor occupancy of endogenous dopamine and the extent of EPS than the other model, as assessed by the final sum of squares of residuals (final SS) and Akaike's Information Criteria (AIC). Furthermore, the former model could appropriately predict the risks of EPS induced by two other atypical antipsychotics, clozapine and ziprasidone, which were not incorporated into the model development. The developed model incorporating endogenous dopamine release owing to 5-HT2A receptor inhibition may be useful for the prediction of antipsychotics-induced EPS.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D2; Risperidone; Schizophrenia; Thiazoles

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

Quetiapine, an atypical neuroleptic, has beneficial antipsychotic effects in schizophrenic patients, but with a lower incidence of extrapyramidal symptoms (EPS) compared with typical antipsychotics. While typical antipsychotics are often switched to atypical agents when adverse effects become limiting, there is little preclinical information to support this strategy, both in terms of efficacy and side effects.. The antipsychotic effects and EPS during concomitant administration of quetiapine with haloperidol, a typical antipsychotic agent, were evaluated in mice and compared with chlorpromazine and risperidone.. We first investigated the antipsychotic effects and EPS liability of quetiapine, risperidone, chlorpromazine, and haloperidol when administered alone to select optimal doses for subsequent combination studies. The second study was designed to evaluate the antipsychotic efficacy and EPS profile of concomitant administration of quetiapine, risperidone, or chlorpromazine with haloperidol. Antipsychotic effects were evaluated with the methamphetamine-induced hyperlocomotion test, and EPS liability was evaluated in a catalepsy-induction model.. Quetiapine, risperidone, chlorpromazine, and haloperidol dose-dependently reduced methamphetamine-induced hyperlocomotion, with ED50 values of 5.6, 0.020, 1.8, 0.035 mg/kg, respectively. In the catalepsy test, quetiapine only weakly induced catalepsy at the highest dose of 100 mg/kg, whereas risperidone, chlorpromazine, and haloperidol dose-dependently induced catalepsy with ED50 values of 0.25, 4.6, and 0.10 mg/kg, respectively. While the combination of quetiapine (6 mg/kg) and haloperidol (0.04 mg/kg) significantly reduced methamphetamine-induced hyperlocomotion in comparison with haloperidol alone, quetiapine (10, 32 mg/kg) plus haloperidol did not potentiate the cataleptogenic activity of haloperidol. In contrast, risperidone (0.1, 0.32 mg/kg) or chlorpromazine (3.2 mg/kg) significantly augmented catalepsy induced by haloperidol. Catalepsy induced by co-administration of quetiapine (10 mg/kg) and haloperidol (0.1 mg/kg) was significantly potentiated by WAY100635, a 5-HT1A antagonist, and catalepsy induced by co-administration of risperidone (0.1 mg/kg) and haloperidol (0.1 mg/kg) was significantly antagonized by 8-OH-DPAT, a 5-HT1A agonist.. The present study demonstrated that the combined administration of quetiapine with haloperidol did not aggravate EPS, possibly because of its affinity for 5-HT1A receptors. This finding may have the clinical implication that quetiapine could provide a successful regimen in switching from typical antipsychotic agents in the symptom management of schizophrenia, or even in adjunctive therapy with other antipsychotic agents.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Administration, Oral; Animals; Antipsychotic Agents; Basal Ganglia Diseases; Catalepsy; Chlorpromazine; Dibenzothiazepines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Haloperidol; Hyperkinesis; Injections, Intraperitoneal; Male; Methamphetamine; Mice; Piperazines; Pyridines; Quetiapine Fumarate; Receptor, Serotonin, 5-HT1A; Risperidone; Schizophrenia; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT1 Receptor Antagonists

Topics: Aged; Amisulpride; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Humans; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Sulpiride

Weight gain is a serious problem with recently introduced atypical antipsychotic agents. Nizatidine, a histamine2 (H2)-receptor antagonist, may help reduce this weight gain. To our knowledge, no adverse effects have been reported when nizatidine is given at recommended doses with atypical antipyschotic agents. We describe, however, an adolescent who was receiving quetiapine and paroxetine for schizophrenia and depression, and developed extrapyramidal symptoms (EPS; parkinsonism and akathisia) after taking nizatidine for weight loss. Based on a report of another patient who developed EPS after taking higher-than-recommended doses of nizatidine, we reviewed the literature on treatment with H2-receptor antagonists for weight gain and on central nervous system adverse effects of nizatidine. Nizatidine may be effective for reducing weight gain associated with both medical and psychiatric conditions. Its safety profile is usually benign, although some patients may develop serious adverse effects, such as EPS and delirium. Therefore, the drug is recommended for short-term management of weight gain associated with atypical antipsychotic agents. Patients receiving nizatidine therapy should be monitored closely for development of EPS, particularly when high doses are prescribed.

Topics: Adolescent; Basal Ganglia Diseases; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Nizatidine; Paroxetine; Quetiapine Fumarate

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Comorbidity; Depression, Postpartum; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles; Treatment Outcome

Second-generation 'atypical' antipsychotics appear to be more effective than first-generation 'typical' antipsychotics in improving negative symptoms in schizophrenia; it is unclear, however, if this greater improvement represents a direct beneficial effect or is mediated indirectly by an antidepressant effect or the absence of extrapyramidal symptoms (EPS). To address this issue with reference to quetiapine ('Seroquel'), data were evaluated from four randomized, controlled clinical studies involving 1106 patients employing a path analysis model. The total effect of quetiapine on negative symptoms was measured using the Scale for Assessment of Negative Symptoms (SANS) total score. Indirect effects on negative symptoms via positive, depressive and EPS were assessed using appropriate instruments. Effect sizes were calculated by path analysis for the difference between treatment groups in change from baseline to endpoint in SANS total score. Analysis confirmed that quetiapine produced a greater overall improvement in negative symptoms than placebo (effect size 1.96); this was explained by a significant direct effect (p = 0.001; 44.2% of total improvement), and a secondary effect of improved positive symptoms (p < 0.001; 47.5% of total improvement), but was not a consequence of changes in depressive symptoms or EPS. Within the constraints of the path analysis methodology, these results indicate that quetiapine has a substantial direct effect on improving the negative symptoms of schizophrenia.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Brief Psychiatric Rating Scale; Depression; Dibenzothiazepines; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Basal Ganglia Diseases; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Quetiapine Fumarate

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Child; Dibenzothiazepines; Female; Humans; Male; Piperazines; Quetiapine Fumarate; Thiazoles

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia, Paranoid; Severity of Illness Index

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Dibenzothiazepines; Family Practice; Humans; Multicenter Studies as Topic; Psychotic Disorders; Quetiapine Fumarate; Risperidone

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

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: Agranulocytosis; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Patient Compliance; Pirenzepine; Practice Patterns, Physicians'; Quality of Life; Quetiapine Fumarate; Risperidone

Side effects of antipsychotic medications are particularly problematic in elderly patients, who experience many age-related changes that may exacerbate medication side effects. Side effects of particular concern in the elderly include anticholinergic reactions, parkinsonian events, tardive dyskinesia, orthostatic hypotension, cardiac conduction disturbances, reduced bone mineral density, sedation, and cognitive slowing. In addition, elderly patients with schizophrenia often have comorbid medical illnesses-such as cardiovascular disease and dementia of the Alzheimer's type-and are thus likely to be taking multiple medications. The effects of polypharmacy must be carefully considered. Patients, caregivers, and family often have different perspectives on side effects. This article addresses the side effects of the currently available antipsychotic medications in light of these concerns.

Topics: Age Factors; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Clozapine; Comorbidity; Dementia; Dibenzothiazepines; Humans; Movement Disorders; Neuroleptic Malignant Syndrome; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Aged; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Imidazoles; Indoles; Movement Disorders; Psychotic Disorders; Quetiapine Fumarate; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine; Receptors, Serotonin; Schizophrenia; Treatment Outcome

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