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Quetiapine
Selected AbstractsEfficacy and safety of quetiapine for depressive symptoms in patients with schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2009Kyoung-Uk Lee Abstract Objective To investigate the efficacy and safety of quetiapine for depressive symptoms in patients with schizophrenia. Method 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. Results 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). Conclusions 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. Copyright © 2009 John Wiley & Sons, Ltd. [source] Quetiapine versus olanzapine for the treatment of negative symptoms in patients with schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2006Pinkhas Sirota Abstract Negative symptoms are considered the most debilitating and refractory aspect of schizophrenia, being associated with poor social, occupational and global outcomes. Conventional antipsychotics have limited efficacy against these symptoms and poor tolerability profiles. Atypical antipsychotics are an alternative treatment, and this 12-week, randomised, flexibly dosed study compared the efficacy, safety and tolerability of quetiapine and olanzapine in this regard. Of the 40 patients who entered the study (32 male; 8 female), 19 were randomised to quetiapine (mean dose 637,mg/day, mean treatment duration 80 days) and 21 to olanzapine (mean dose 16,mg/day, mean treatment duration 78 days). Quetiapine and olanzapine were similarly effective: in each treatment group significant improvements at Week 12 were observed for negative symptom scores on the SANS and the PANSS, and for subscale scores of affective flattening and alogia on the SANS. Both treatments were well tolerated in this patient population, with no worsening of extrapyramidal symptoms in either case. Anxiety and insomnia were the most common adverse events (,7% of patients in each group), but were not drug-related. Although this is a small study with limited power, the results support the effectiveness of quetiapine and olanzapine in treating the negative symptoms of schizophrenia. Copyright © 2006 John Wiley & Sons, Ltd. [source] The effect of quetiapine on aggression and hostility in patients with schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2005Celso Arango Abstract A post hoc analysis of data from three placebo-controlled, double-blind, randomized trials was carried out to determine the efficacy of quetiapine in aggression and hostility in patients with schizophrenia. Quetiapine treatment induced statistically significantly greater improvements in BPRS positive symptom cluster scores and three measures of hostility derived from the BPRS, compared with placebo, in patients symptomatic at baseline. A path analysis showed that the improvements in hostility were highly correlated with improvements in positive symptoms and there was no consistent relationship between sedation and hostility. Aggressive behaviour appears to be related to positive symptoms of schizophrenia. Quetiapine may be a suitable option for patients with schizophrenia and aggressive behaviour. Copyright © 2005 John Wiley & Sons, Ltd. [source] Quetiapine indication shift in the elderly: diagnosis and dosage in 208 psychogeriatric patients from 2000 to 2006INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2007Lorenz Hilwerling Abstract Rationale Quetiapine was approved in Germany as an atypical antipsychotic for treatment of schizophrenia in 2000, followed by the approval as an antipsychotic for treatment of bipolar mania in 2003. The approval of quetiapine for treatment of bipolar depression is expected. We hypothesized that the psychogeriatric prescription pattern for quetiapine shifts from the psychotic to the affective spectrum. Methods Retrospectively we screened discharge reports of all geriatric inpatients of the psychiatric department of the Ruhr-University of Bochum in the period from January 2001 until March 2006 and identified 208 individual patients aged over 60 years, who had received quetiapine as final medication. Age, gender, daily drug dose, year of treatment and diagnosis (according to ICD-10) were recorded and analyzed. Results Over the six-year time span, the proportion of affective disorders (F3) as indication for quetiapine in the elderly increased, whereas the proportion of dementia (F0) as indication for quetiapine decreased significantly. The proportion of schizophrenic disorders (F2) treated with quetiapine did not change significantly. Discussion Since the decision of the German Federal Court in 2002 ,off label' use goes to the expenses of the prescriber. So the decrease of quetiapine in dementia is probably due to its ,off label' status in dementia. The psychogeriatric indication shift for quetiapine towards affective disorders could be the consequence of good clinical experiences with the drug and growing evidence for its antidepressant effect. Conclusion In addition to controlled pharmacological trials prospective clinical research is needed to evaluate the prescription attitudes of clinicians. Copyright © 2006 John Wiley & Sons, Ltd. [source] A Double-Blind, Placebo-Controlled Study With Quetiapine as Adjunct Therapy With Lithium or Divalproex in Bipolar I Patients With Coexisting Alcohol DependenceALCOHOLISM, Issue 10 2010Mary Stedman Background:, This study evaluated the efficacy of quetiapine versus placebo as an adjunct to lithium or divalproex in reducing alcohol consumption in patients with bipolar I disorder and coexisting alcohol dependence. Methods:, Male and female outpatients (21 to 60 years) with a history of bipolar I disorder and alcohol dependence were included in this 12-week, placebo-controlled study. Patients treated with lithium or divalproex (ongoing or assigned at screening) were randomized to receive quetiapine (dosed up to 400 mg/d over 7 days, followed by 300 to 800 mg/d flexible dosing until study end) or placebo. The primary outcome measure was the change in the proportion of heavy drinking days from baseline to Week 12 (as derived from the Timeline Followback method). Secondary outcome measures included time to the first consecutive 2 weeks of abstinence, changes from baseline to Week 12 in the proportion of nondrinking days, mean number of standardized drinks per day, and Clinical Global Impressions-Severity of Illness score. Results:, Of 362 enrolled patients (mean 38.6 years), 176 were randomized to receive quetiapine and 186 to placebo. The mean proportion of heavy drinking days at baseline was 0.66 in the quetiapine group and 0.67 in the placebo group. At Week 12, the mean change in the proportion of heavy drinking days was ,0.36 with quetiapine and ,0.36 with placebo (p = 0.93). No statistically significant differences in any of the secondary outcome measures were noted between the quetiapine and placebo groups. The incidence of adverse events was consistent with the previously known tolerability profile of quetiapine. Conclusions:, The efficacy of quetiapine in the treatment of bipolar disorder is already well established. In this study, however, quetiapine added to lithium or divalproex did not result in significantly greater improvement compared with placebo in measures of alcohol use and dependence in patients with bipolar I disorder and alcohol dependence. [source] Quetiapine as treatment for dopaminergic-induced dyskinesias in Parkinson's diseaseMOVEMENT DISORDERS, Issue 10 2003Mark S. Baron MD [source] An Open Pilot Study Assessing the Benefits of Quetiapine for the Prevention of Migraine Refractory to the Combination of Atenolol, Nortriptyline, and FlunarizinePAIN MEDICINE, Issue 1 2010Abouch V. Krymchantowski MD, FAHS ABSTRACT Background., Migraine is a prevalent neurological disorder. Although prevention is the core of treatment for most, some patients are refractory to standard therapies. Accordingly, the aim of this study was to evaluate the use of Quetiapine (QTP) in the preventive treatment of refractory migraine, defined as previous unresponsiveness to the combination of atenolol, nortriptyline, and flunarizine. Methods., Thirty-four consecutive patients (30 women and 4 men) with migraine (ICHD-II), fewer than 15 days of headache per month, and not overusing symptomatic medications were studied. All participants had failed to the combination of atenolol (60 mg/day), nortriptyline (25 mg/day), and flunarizine (3 mg/day). Failure was defined as <50% reduction in attack frequency after 10 weeks of treatment. After other medications were discontinued, QTP was initiated at a single daily dose of 25 mg, and then titrated to 75 mg. After 10 weeks, headache frequency, consumption of rescue medications, and adverse events were analyzed. Results., Twenty-nine patients completed the study. Three patients withdrew and two were lost to follow-up. Among those who completed, 22 (75.9%; 64.7% of the intention-to-treat population) had greater than 50% headache reduction. The mean frequency of migraine days decreased from 10.2 to 6.2 per month. Use of rescue medications decreased from 2.3 to 1.2 days/week. Adverse events were reported by nine (31%) patients. Conclusions., Although limited by the open design, this study provides pilot data to support the use of QTP in the preventive treatment of refractory migraine. Controlled studies are necessary to confirm these observations. [source] Prolactin, Subjective Well-Being and Sexual Dysfunction: An Open Label Observational Study Comparing Quetiapine with RisperidoneTHE JOURNAL OF SEXUAL MEDICINE, Issue 12 2008Jens Westheide PhD ABSTRACT Introduction., Sexual dysfunction is a frequent side effect of antipsychotic treatment. Increased prolactin levels are believed to be responsible for this sexual impairment despite contradictory results. Aim., The primary objective of the present study was to examine the relationship between sexual dysfunction, subjective well-being and prolactin levels in patients with schizophrenia treated either with risperidone or quetiapine. The secondary objective was to explore the relationship between testosterone and the severity of positive and negative symptoms of schizophrenia in male patients. Methods., In a 4-week nonrandomized open label observational study, 102 inpatients with schizophrenia were recruited. Sexual functioning, subjective well-being and endocrinological parameters were assessed as well as psychopathological characteristics. Main Outcome Measures., Two self-rating questionnaires concerned with sexual functioning ("Essener Fragebogen zur Sexualität") and Subjective Well-Being Under Neuroleptic Treatment Scale (SWN) were completed by the patients. Plasma levels of prolactin in male and female patients were measured. Furthermore, in male patients testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined. Positive and Negative Symptom Scale (PANSS) was applied. Results., After 4 weeks, patients treated with quetiapine reported less severe sexual impairment, as well as lower PANSS negative and general score compared with patients treated with risperidone. Additionally, emotional regulation as measured with the SWN was higher in patients treated with quetiapine. Risperidone was significantly associated with elevated prolactin levels. Prolactin levels were not correlated either with sexual dysfunction or PANSS. However, in the group of patients treated risperidone, sexual impairment was significantly associated with the SWN subscale emotional regulation. Conclusions., Increased prolactin levels do not seem to be decisive for antipsychotic induced sexual dysfunction. Improvement of severity of illness and regaining the ability to regulate one's own emotion have positive influence on sexual functioning. Westheide J, Cvetanovska G, Albrecht C, Bliesener N, Cooper-Mahkorn D, Creutz C, Hornung W-P, Klingmüller D, Lemke MR, Maier W, Schubert M, Sträter B, and Kühn K-U. Prolactin, subjective well-being and sexual dysfunction: An open label observational study comparing Quetiapine with Risperidone. J Sex Med **;**:**,**. [source] Quetiapine for the treatment of bipolar mania in older adultsBIPOLAR DISORDERS, Issue 6 2008Martha Sajatovic Objectives:, A post hoc analysis of pooled data from two quetiapine monotherapy clinical trials was conducted to evaluate the efficacy and tolerability of quetiapine therapy (twice daily, 400,800 mg/day) among bipolar manic adults aged 55 years and older. The primary efficacy endpoint was the change from baseline in Young Mania Rating Scale (YMRS) total score at Day 21. A secondary endpoint was change from baseline in YMRS score at Day 84. Methods:, A total of 407 patients made up the safety population, consisting of 59 older adults (aged ,55 years) and 348 younger adults. A total of 403 patients made up the efficacy population, consisting of 59 older adults and 344 younger adults. Efficacy outcomes were analyzed using covariance models (ANCOVA); descriptive statistics are presented for safety outcomes. Results:, Both older and younger individuals treated with quetiapine had significant improvement from baseline on YMRS scores compared with placebo-treated patients. The older adult group demonstrated a sustained reduction in YMRS score compared with placebo that was apparent by Day 4 of treatment. For the quetiapine treatment groups, the most common adverse effects (at a frequency ,10%) were dry mouth, somnolence, postural hypotension, insomnia, weight gain, and dizziness in older adults, and dry mouth, somnolence, and insomnia in younger adults. For the placebo treatment groups, insomnia was the most common adverse event in both older and younger adults. Conclusions:, This secondary analysis suggests that quetiapine represents a potentially useful treatment option among older adults with bipolar I mania. Studies with a primary focus of geriatric bipolar mania, and including larger patient numbers, are needed to confirm these findings. [source] Safety, tolerability and efficacy of a rapid dose escalation of quetiapine in bipolar I mania: the FATIMA studyACTA NEUROPSYCHIATRICA, Issue 3 2009Eric Constant Objective: The FATIMA study (FAst TItration of quetiapine fumarate in bipolar I MAnia) evaluated the safety, tolerability and efficacy of a rapid dose escalation of quetiapine in acutely ill bipolar I patients experiencing a manic episode. Methods: In an open-label, phase II pilot study, 29 patients aged 18 years or older, hospitalised with a bipolar I manic episode, received quetiapine twice daily for 21 days. Quetiapine was administered at 200, 400, 600, then 800 mg/day on the first 4 days, with flexible dosing (400,800 mg/day) subsequently. The primary endpoint was the proportion of patient dropouts because of adverse drug reactions during the first 7 days. Secondary safety assessments included incidences of adverse drug reactions and significant changes in vital signs. Efficacy assessments included Young Mania Rating Scale (YMRS) and Clinical Global Impressions Severity of Illness (CGI-S) score changes from day 1 to day 21. Results: Twenty patients (69%) completed the study. No patients withdrew as a result of drug-related adverse events (AEs) during the first 7 days. Twenty-three patients reported 58 adverse events, and most of the adverse events were mild or moderate. No clinically relevant abnormalities in vital signs were reported. Mean YMRS and CGI-S scores decreased significantly from baseline to day 21 (p < 0.001). Response and remission rates were 78 and 70%, respectively, at the end of the study. Conclusion: Rapid dose escalation of quetiapine to 800 mg/day over 4 days was well tolerated and effective in reducing symptoms within 5 days in acutely ill bipolar I patients with a manic episode. [source] Effect of quetiapine on cognitive function in schizophrenia: a mismatch negativity potentials studyACTA NEUROPSYCHIATRICA, Issue 1 2009Guo-zhen Yuan Objective:, The purpose of this study was to investigate whether the effects of quetiapine on abnormalities of early auditory processing in patients with schizophrenia were reflected by mismatch negativity (MMN). Methods:, Subjects were 23 patients with schizophrenia and 23 controls. Psychopathology was rated in patients with the Positive and Negative Syndrome Scale (PANSS) at baseline and after 4-week and after 8-week treatments with quetiapine. Auditory stimuli for event-related potentials consisted of 100 ms/1000 Hz standards, intermixed with 100 ms/1500 Hz frequency deviants and 250 ms/ 1000 Hz duration deviants. A stimulus onset asynchrony of each was 300 ms. Electroencephalograph was recorded at Fz. BESA 5.1.8 was used to perform data analysis. MMN waveforms were obtained by subtracting waveforms elicited by standards from those elicited by frequency- or duration-deviant stimuli. Results:, Quetiapine decreased all PANSS scores. Patients showed smaller mean amplitudes of frequency and duration MMN at baseline than did controls. A repeated measure analysis of variance with sessions (i.e. baseline and 4- and 8-week treatments) and MMN type (frequency versus duration) as within-subject factors revealed no significant MMN type or MMN type × session main effect for MMN amplitudes (for MMN type: F = 0.704, df = 1, p = 0.403; for MMN type × session: F = 0.299, df = 2, p = 0.796). Session main effect was significant (F = 3.576, df = 2, p = 0.031). Least square difference tests showed significant differences between MMN amplitudes at 8 weeks and those at both baseline (p = 0.025) and 4 weeks (p = 0.020). MMN amplitudes at 8 weeks were higher than those at baseline. Conclusions:, Quetiapine improved the amplitudes of MMN after the 8-week treatment. MMN offers objective evidence that treatment with the quetiapine may ameliorate preattentive deficits in schizophrenia. [source] Somnolence effects of antipsychotic medications and the risk of unintentional injury,,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2008Qayyim Said PhD Abstract Purpose This study examined the relationship between antipsychotic medications, categorized by published somnolence effects, and unintentional injury (UI). Methods The study population included patients of 18,64 years of age in a healthcare insurance database with claims from 2001 to 2004 and diagnoses of schizophrenia or affective disorder. A nested case-control design was used with cases defined by an E-code claim (a specified external cause of injury) for selected UIs. For cases, the index date referred to the first injury. For controls, the "control index date" was the date of claim if there was only a single medical claim; for patients with ,2 claims, one was selected at random as the "control index date." Both groups had a prescription for a first-generation antipsychotic (FGA) or second-generation antipsychotic (SGA) overlapping the index date. Potential somnolence effects were defined as: low (referent) , aripiprazole/ziprasidone; medium , risperidone; high , olanzapine/quetiapine: or any single FGA. Logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for UI, adjusted for gender, age, concomitant drug, and psychiatric diagnosis. Results Among 648 cases and 5214 controls, high-somnolence SGAs were associated with an OR of 1.41 95%CI (1.03,1.93) for risk of UI, while medium-somnolence SGAs, and FGAs had ORs of 1.17 95%CI (0.83,1.64) and 1.17 95%CI (0.79,1.74), respectively. When quetiapine and olanzapine were disaggregated, ORs were 1.61 95%CI (1.15,2.25) and 1.25 95%CI (0.89,1.74), respectively. Conclusions High-somnolence SGAs may lead to UI among patients. When prescribing antipsychotics, clinicians should consider potential somnolence. Copyright © 2008 John Wiley & Sons, Ltd. [source] Treatment of unipolar psychotic depression: a randomized, double-blind study comparing imipramine, venlafaxine, and venlafaxine plus quetiapineACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2010J. Wijkstra Wijkstra J, Burger H, van den Broek WW, Birkenhäger TK, Janzing JGE, Boks MPM, Bruijn JA, van der Loos MLM, Breteler LMT, Ramaekers GMGI, Verkes RJ, Nolen WA. Treatment of unipolar psychotic depression: a randomized, double-blind study comparing imipramine, venlafaxine, and venlafaxine plus quetiapine. Objective:, It remains unclear whether unipolar psychotic depression should be treated with an antidepressant and an antipsychotic or with an antidepressant alone. Method:, In a multi-center RCT, 122 patients (18,65 years) with DSM-IV-TR psychotic major depression and HAM-D-17 , 18 were randomized to 7 weeks imipramine (plasma-levels 200,300 ,g/l), venlafaxine (375 mg/day) or venlafaxine,quetiapine (375 mg/day, 600 mg/day). Primary outcome was response on HAM-D-17. Secondary outcomes were response on CGI and remission (HAM-D-17). Results:, Venlafaxine,quetiapine was more effective than venlafaxine with no significant differences between venlafaxine,quetiapine and imipramine, or between imipramine and venlafaxine. Secondary outcomes followed the same pattern. Conclusion:, That unipolar psychotic depression should be treated with a combination of an antidepressant and an antipsychotic and not with an antidepressant alone, can be considered evidence based with regard to venlafaxine,quetiapine vs. venlafaxine monotherapy. Whether this is also the case for imipramine monotherapy is likely, but cannot be concluded from the data. [source] Achieving symptomatic remission in out-patients with schizophrenia , a naturalistic study with quetiapineACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2009T. Wobrock Objective:, Symptomatic remission was defined as a score of mild or less on each of eight key schizophrenia symptoms on the Positive and Negative Syndrome Scale (PANSS-8). To evaluate the symptomatic remission criterion in clinical practice and to determine predictors for achieving symptomatic remission, a 12-week non-interventional study (NIS) with quetiapine was conducted in Germany. Method:, For the comparison of patients with and without symptomatic remission, sociodemographic and clinical variables of 693 patients were analyzed by logistic regression for their predictive value to achieve remission. Results:, Four hundred and four patients (58.3%) achieved symptomatic remission after 12 weeks' treatment with quetiapine. Remission was significantly predicted by a low degree of PANSS-8 total score, PANSS single items blunted affect (N1), social withdrawal (N4), lack of spontaneity (N6), mannerism and posturing (G5), and low disease severity (CGI-S) at baseline. Predictors of non-remission were older age, diagnosis of schizophrenic residuum, multiple previous episodes, longer duration of current episode, presence of concomitant diseases, and alcohol abuse. Conclusion:, This study demonstrated that the majority of schizophrenia out-patients achieved symptomatic remission after 12 weeks treatment and confirms the importance of managing negative symptoms in order to achieve disease remission. [source] Weight gain in bipolar disorder: pharmacological treatment as a contributing factorACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2008C. Torrent Objective:, The aim of this paper was to review the association of most commonly used psychopharmacological drugs with weight gain in bipolar disorder. Method:, Information was retrieved from a PubMed/Medline literature search reviewing weight gain in pharmacological studies in bipolar disorder. Results:, Obesity and overweight in bipolar disorder are partly related to prescribed drugs with a strong effect of clozapine and olanzapine. Lesser but still relevant weight gain is caused by quetiapine, risperidone, lithium, valproate, gabapentin and by some antidepressants. Ziprasidone, aripiprazole, carbamazepine and lamotrigine do not seem to cause significant overweight. Conclusion:, Careful monitoring of weight changes in patients before and after drug prescription should be implemented in the clinical routine and drugs which potentially cause weight gain should be avoided in overweight patients with bipolar disorder. Furthermore, eating habits and daily activities should be targeted as they may also have a significant impact on overall health and weight-related issues. [source] Medication decisions and clinical outcomes in the Canadian National Outcomes Measurement Study in SchizophreniaACTA PSYCHIATRICA SCANDINAVICA, Issue 2006R. Williams Objective:, To evaluate over a 2-year period, patients from academic/non-academic centres, from each region of Canada, to determine whether location or other variables such as medication type, gender or income was associated with outcome as defined by non-hospitalization and persistence on original treatment. Method:, A total of 448 patients were recruited from academic and non-academic centres across all provinces of Canada and followed up for 2 years. Results:, Patients from British Columbia had significantly lower rates of hospitalization than patients from other provinces. Male patients showed greater symptomatic improvement at 2 years from initial assessment compared to females. Patients on clozapine, risperidone and olanzapine were least likely to be hospitalized. Conclusion:, There were some regional differences noted in both utilization of types of antipsychotic medications and hospitalization rates. In this sample of stable out-patients over 70% who started on monotherapy with clozapine, risperidone, olanzapine and quetiapine remained on the same medication over the 2-year study period. [source] Torsade de pointes in a patient with complex medical and psychiatric conditions receiving low-dose quetiapineACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2005W. V. R. Vieweg Objective:, Describe potential cardiac complications of low-dose quetiapine and other atypical antipsychotic drugs. Method:, We present a case report of a 45-year-old Black woman with multiple medical and psychiatric problems taking low-dose quetiapine. Results:, Coincident with a generalized seizure, the patient developed ,ventricular fibrillation'. She was countershocked with restoration of normal sinus rhythm. The initial electrocardiogram showed QT interval prolongation. Shortly thereafter, classical torsade de pointes appeared, lasted 10 min, and resolved spontaneously. Hypomagnesemia was present. A cardiac electrophysiologist was concerned that the very slow shortening of the prolonged QTc interval after magnesium replacement implicated quetiapine as a risk factor for QTc interval prolongation and torsade de pointes. A psychosomatic medicine consultant asserted that the fragmented medical and psychiatric care almost certainly contributed to the patient's medical problems. We discuss other cases of QT interval prolongation by newer antipsychotic drugs and previous reports by our group concerning the association of psychotropic drugs, QT interval prolongation, and torsade de pointes. Conclusion:, Atypical antipsychotic drug administration, when accompanied by risk factors, may contribute to cardiac arrhythmias including torsade de pointes. [source] Atypical antipsychotics and weightgain , a systematic reviewACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2000D. M. Taylor Objective: To review systematically data relating to weight changes with atypical antipsychotics. Method: We conducted a Medline search on October 29 1999 and covered the period 1980,99. All recovered papers were examined for further relevant reports. In addition, we wrote to pharmaceutical manufacturers and 10 practising clinicians to ask them to provide other relevant reports known to them. Results: Eighty reports mentioning change in body weight were retrieved. Data relating to weight changes were of variable quality. Weight changes were indicated by a variety of measures. The majority of reports related to short-term changes. Conclusion: All atypical drugs, with the exception of ziprasidone, have been associated with weight increases. Clozapine seems to have the highest risk of weight gain, followed by olanzapine and quetiapine. There is probably a lower risk with risperidone, sertindole and zotepine and a still lower risk with amisulpride. Ziprasidone appears not to be associated with weight gain. In the absence of more compelling data, these rankings must be considered approximate and preliminary. Longer, more robust trials are needed. [source] Early intervention with second-generation antipsychotics in first-episode psychosis: results of an 8-week naturalistic studyEARLY INTERVENTION IN PSYCHIATRY, Issue 1 2010Richard C. Josiassen Abstract Objective: The objective was to compare short-term effectiveness of aripiprazole with three other second-generation antipsychotics (SGAs) in the treatment of first-episode psychosis. Method: In a naturalistic, ,single-blind' design, 60 subjects experiencing their first psychotic episode were treated for 8 weeks with aripiprazole (n = 19), risperidone (n = 16), olanzapine (n = 14) or quetiapine (n = 11). Medication and dosing decisions were made by treating psychiatrists, constrained to once-a-day dosing, low initial doses and no clozapine. Weekly ratings were obtained using the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Rating Scale and Barnes Akathasia Rating Scale. Weight and vital signs were also collected weekly. Results: The group presented with severe psychotic symptoms (mean baseline PANSS total score of 105.2), which were reduced rapidly (P < 0.0005). The between-group and group by time interaction terms were non-significant. Similar reductions were seen across all PANSS sub-scales. At Week 1 the mean PANSS Activation Scale score was reduced more with olanzapine than in the other groups (P < 0.002). Few instances of extrapyramidal symptoms occurred; all were sporadic and did not require treatment. Group body weight increased by 7.3% over the study. Vital signs remained unchanged. Conclusions: Early intervention with low doses of four SGAs led to rapid symptom reduction in first-episode psychotic patients with severe psychopathology. Although no clear medication advantages were observed in the short term, longer duration studies with larger samples will be required for determining efficacy, rates of compliance, relapse prevention and diminished incidence of extrapyramidal signs and symptoms. [source] Atypical antipsychotics and anorexia nervosa: A reviewEUROPEAN EATING DISORDERS REVIEW, Issue 1 2010Rebecca F. McKnight Abstract Background There is currently mixed opinion regarding the value of using atypical antipsychotics to treat anorexia nervosa (AN). Aims To evaluate the literature on the use of atypical antipsychotics in AN. Method A review of all studies and clinical guidelines published before September 2009 involving use of an atypical antipsychotic in patients with AN. Analysis is by narrative synthesis. Results Forty-three publications or study protocols were found, including four randomized-controlled trials, five open-label trials and 26 case reports. The most studied drugs were olanzapine, quetiapine and risperidone. Atypical antipsychotics appear safe and there is some evidence of positive effects on depression, anxiety and core eating disordered psychopathology in patients with anorexia nervosa. Currently there is insufficient evidence to confirm atypical antipsychotics enhance weight gain in this setting. Conclusions Further high quality evidence is needed in this area in order to provide practical guidance to clinicians. However, the main challenge is to persuade adequate numbers of AN patients to participate in research trials. Copyright © 2010 John Wiley & Sons, Ltd and Eating Disorders Association. [source] Metabolic drug interactions with new psychotropic agentsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2003Edoardo Spina Abstract New psychotropic drugs introduced in clinical practice in recent years include new antidepressants, such as selective serotonin reuptake inhibitors (SSRI) and ,third generation' antidepressants, and atypical antipsychotics, i.e. clozapine, risperidone, olanzapine, quetiapine, ziprasidone and amisulpride. These agents are extensively metabolized in the liver by cytochrome P450 (CYP) enzymes and are therefore susceptible to metabolically based drug interactions with other psychotropic medications or with compounds used for the treatment of concomitant somatic illnesses. New antidepressants differ in their potential for metabolic drug interactions. Fluoxetine and paroxetine are potent inhibitors of CYP2D6, fluvoxamine markedly inhibits CYP1A2 and CYP2C19, while nefazodone is a potent inhibitor of CYP3A4. These antidepressants may be involved in clinically significant interactions when coadministered with substrates of these isoforms, especially those with a narrow therapeutic index. Other new antidepressants including sertraline, citalopram, venlafaxine, mirtazapine and reboxetine are weak in vitro inhibitors of the different CYP isoforms and appear to have less propensity for important metabolic interactions. The new atypical antipsychotics do not affect significantly the activity of CYP isoenzymes and are not expected to impair the elimination of other medications. Conversely, coadministration of inhibitors or inducers of the CYP isoenzymes involved in metabolism of the various antipsychotic compounds may alter their plasma concentrations, possibly leading to clinically significant effects. The potential for metabolically based drug interactions of any new psychotropic agent may be anticipated on the basis of knowledge about the CYP enzymes responsible for its metabolism and about its effect on the activity of these enzymes. This information is essential for rational prescribing and may guide selection of an appropriate compound which is less likely to interact with already taken medication(s). [source] Safety and tolerability of once-daily extended release quetiapine fumarate in acute schizophrenia: pooled data from randomised, double-blind, placebo-controlled studiesHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2010Didier Meulien Abstract Introduction Extended release quetiapine fumarate (quetiapine XR) is a new formulation that allows once-daily dosing and a titration regimen that is simpler than that of immediate release quetiapine (quetiapine IR) and may potentially increase patients' adherence to their prescribed medication. Methods The tolerability of quetiapine XR was examined in an analysis of pooled data from three Phase III, double-blind, placebo-controlled, randomised studies with quetiapine IR as a reference treatment. Results The overall incidence of adverse events (AEs) was similar for quetiapine XR (69.5%) and quetiapine IR (72.5%). Most AEs were mild to moderate in severity and in line with those observed with quetiapine IR. The more rapid dose titration of quetiapine XR did not produce any new safety concerns and was as well tolerated as the regimen for quetiapine IR. Conclusions The results of this pooled analysis show that quetiapine XR administered once daily is generally as well tolerated as quetiapine IR given twice daily. These data, together with the simpler dose-titration of quetiapine XR that allowed therapeutically effective doses to be reached by Day 2, suggest that this formulation potentially may improve adherence in patients with schizophrenia. Copyright © 2010 John Wiley & Sons, Ltd. [source] Neurocognition and its influencing factors in the treatment of schizophrenia,effects of aripiprazole, olanzapine, quetiapine and risperidoneHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2010M. Riedel Abstract Background To examine influencing variables of neurocognition in patients with schizophrenia and to predict cognition during antipsychotic treatment. Methods Data were obtained from patients with an acute episode of schizophrenia participating in two double-blind and one open label trial comparing the effects of different atypical antipsychotics on cognition. In total, 129 patients were enrolled in this analysis. Cognitive function was assessed at admission, week 4 and 8. Efficacy and tolerability were assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and the Simpson Angus Sale (SAS). Patients were treated with aripirazole, olanzapine, quetiapine and risperidone. Regression analysis including mixed effect models was performed. Results A significant improvement in all cognitive domains was observed from baseline to week 8. Regarding the antipsychotic treatment applied quetiapine seemed to achieve the most favourable cognitive improvement. Negative and depressive symptoms, the patient's age and the concomitant and antipsychotic treatment applied were observed to significantly influence and predict neurocognition. Conclusion The results may indicate that schizophrenia is a static disorder with trait and state dependent cognitive components especially in the memory domains. The influence of negative and depressive symptoms should be considered in daily clinical routine. Copyright © 2010 John Wiley & Sons, Ltd. [source] Efficacy and safety of quetiapine for depressive symptoms in patients with schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2009Kyoung-Uk Lee Abstract Objective To investigate the efficacy and safety of quetiapine for depressive symptoms in patients with schizophrenia. Method 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. Results 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). Conclusions 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. Copyright © 2009 John Wiley & Sons, Ltd. [source] Quetiapine augmentation in depressed patients with partial response to antidepressants,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2008James S Olver Abstract Objective 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. Methods 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. Results 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. Conclusion This suggests clinical benefits of quetiapine augmentation of SSRI/SNRI antidepressants with no worsening, and possible improvements in cognition. Copyright © 2008 John Wiley & Sons, Ltd. [source] Effectiveness of antipsychotic polypharmacy for patients with treatment refractory schizophrenia: an open-label trial of olanzapine plus risperidone for those who failed to respond to a sequential treatment with olanzapine, quetiapine and risperidoneHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2008Takefumi Suzuki Abstract Objective To evaluate the effectiveness of antipsychotic polypharmacy in a methodologically sound manner. Methods In this open-label study, 17 patients with treatment-refractory schizophrenia, who failed to respond to a sequential monotherapy with olanzapine, quetiapine and risperidone, were subsequently treated with a combination therapy with olanzapine plus risperidone for at least 8 weeks. Results Seven responded according to the primary endpoint defined as the post-treatment Brief Psychiatric Rating Scale being less than 70% of the pretreatment values, and they were classified as such an average of 10 weeks after the initiation of polypharmacy. Two of them were successful in a later conversion to monotherapy. None dropped out prematurely. Four (out of 13 inpatients) got better enough to be discharged from the hospital, while six patients did not show any response. The Global Assessment of Functioning score improved from 37.1 to 53.0 in responders (mean maximum dose: olanzapine 12.9,mg; risperidone 3.14,mg), while it showed non-significant changes among others (mean maximum dose: olanzapine 14.5,mg; risperidone 5.50,mg). Body weight, prolactin, and total cholesterol increased significantly. Conclusions Antipsychotic polypharmacy might be sometimes helpful for difficult populations but at the cost of adverse effects. More studies of antipsychotic combination therapy versus clozapine, augmentation strategies or tenacious longer- term monotherapy are warranted for refractory schizophrenia. Copyright © 2008 John Wiley & Sons, Ltd. [source] Effect of antipsychotic replacement with quetiapine on the symptoms and quality of life of schizophrenic patients with extrapyramidal symptomsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2006Takahide Taniguchi Abstract 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. Copyright © 2006 John Wiley & Sons, Ltd. [source] Quetiapine versus olanzapine for the treatment of negative symptoms in patients with schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2006Pinkhas Sirota Abstract Negative symptoms are considered the most debilitating and refractory aspect of schizophrenia, being associated with poor social, occupational and global outcomes. Conventional antipsychotics have limited efficacy against these symptoms and poor tolerability profiles. Atypical antipsychotics are an alternative treatment, and this 12-week, randomised, flexibly dosed study compared the efficacy, safety and tolerability of quetiapine and olanzapine in this regard. Of the 40 patients who entered the study (32 male; 8 female), 19 were randomised to quetiapine (mean dose 637,mg/day, mean treatment duration 80 days) and 21 to olanzapine (mean dose 16,mg/day, mean treatment duration 78 days). Quetiapine and olanzapine were similarly effective: in each treatment group significant improvements at Week 12 were observed for negative symptom scores on the SANS and the PANSS, and for subscale scores of affective flattening and alogia on the SANS. Both treatments were well tolerated in this patient population, with no worsening of extrapyramidal symptoms in either case. Anxiety and insomnia were the most common adverse events (,7% of patients in each group), but were not drug-related. Although this is a small study with limited power, the results support the effectiveness of quetiapine and olanzapine in treating the negative symptoms of schizophrenia. Copyright © 2006 John Wiley & Sons, Ltd. [source] Efficacy and tolerability of quetiapine in patients with schizophrenia who switched from haloperidol, olanzapine or risperidoneHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2005Ilkka Larmo Abstract A post hoc analysis of the SPECTRUM trial was carried out to evaluate whether the improvements in efficacy and tolerability gained on switching to quetiapine occurred consistently for patients previously treated with either: haloperidol (n,=,43); olanzapine (n,=,66); or risperidone (n,=,55) monotherapy. Patients were initiated with quetiapine to 400,mg/day over 7 days, and then flexibly dosed (300,750,mg/day) for 11 weeks. The mean (SD) modal dose of quetiapine was 501 (138),mg/day in the haloperidol subgroup, 472 (147),mg/day in the olanzapine subgroup and 485 (141),mg/day in the risperidone subgroup at the study endpoint. Switching to quetiapine induced significant improvements from baseline in PANSS scores, with least square mean changes in total scores of ,32.5, ,15.4, and ,18.5 for patients previously treated with haloperidol, olanzapine and risperidone, respectively, (all p,<,0.001 vs baseline). Significant improvements were also noted in CDSS scores, particularly for patients clinically depressed at baseline (all p,<,0.001 vs baseline). There were significant reductions in EPS on the SAS and BAS for all subgroups (all p,<,0.001 vs baseline). Switching to quetiapine produced efficacy and tolerability benefits regardless of whether their previous antipsychotic was haloperidol, olanzapine or risperidone. Copyright © 2005 John Wiley & Sons, Ltd. [source] The effect of quetiapine on aggression and hostility in patients with schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2005Celso Arango Abstract A post hoc analysis of data from three placebo-controlled, double-blind, randomized trials was carried out to determine the efficacy of quetiapine in aggression and hostility in patients with schizophrenia. Quetiapine treatment induced statistically significantly greater improvements in BPRS positive symptom cluster scores and three measures of hostility derived from the BPRS, compared with placebo, in patients symptomatic at baseline. A path analysis showed that the improvements in hostility were highly correlated with improvements in positive symptoms and there was no consistent relationship between sedation and hostility. Aggressive behaviour appears to be related to positive symptoms of schizophrenia. Quetiapine may be a suitable option for patients with schizophrenia and aggressive behaviour. 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