Seroquel quetiapineWhat is Seroquel? Does Seroquel stimulate the appetite? Is Seroquel used for bipolar mania besides schizophrenia? How does Seroquel work? What is the latest research on Seroquel? Does Seroquel have a potential in treating Alzheimer's?
Seroquel is an atypical antipsychotic. Atypical antipsychotics such as Seroquel have less side effect such as tardive kinesis as the older antipsychotics have. AstraZeneca (AZN) announced that the U.S. Food and Drug Administration (FDA) has approved additional efficacy labeling information based on 12-week data for Seroquel (quetiapine fumarate), a psychotropic medication indicated for the treatment of acute manic episodes associated with bipolar I disorder.Seroquel is thought to work by maintaining the imbalances of chemicals in the brain, in particular the neurotransmitters in particular serotonin and dopamine. Seroquel is used for schizophrenia Some bipolars, including me, use Seroquel at night to help sleep. Seroquel usually gives me four hours of uninterrupted sleep. It can give one the munchies or increase ones appetite and thus be a weight gainer.. My doctor prescribed Seroquel in conjunction with Risperdal which I take during the day and which does not cause sleepiness, at least in this person.
Recent clinical testing of Seroquel has shown the drug may have potential in treating dementia associated with Alzheimer's diseaseDon't be threatened by the technical material in these research abstracts. Usually one can read the conclusion to get the gist of the article on Seroquel. Hopefully you will be at least as up to date as your doctor on what you might be taking or considering taking. The articles lean towards Seroquel and bipolar disorder.
J Anal Toxicol. 2004 Sep;28(6):520-5.:
Fatal overdoses associated with quetiapine.
Langman LJ, Kaliciak HA, Carlyle S.
Provincial Toxicology Centre, Riverview Hospital, Coquitlam, British Columbia V3C 4J2, Canada.
llangman@bcmhs.bc.ca
Quetiapine (Seroquel) is an atypical antipsychotic drug belonging to a new chemical class, the benzothiazepine derivatives. We present three cases from the Provincial Toxicology Center of British Columbia, Canada in which suicidal overdose deaths were associated with quetiapine. The blood specimens were initially subjected to a thorough qualitative analysis. Basic drugs were screened for by liquid-liquid extraction followed by gas chromatography-nitrogen-phosphorus (GC-NPD) and gas chromatography-mass spectrometry-electron impact detection utilizing both in-house and commercial search libraries. Acidic and neutral drugs were screened for by liquid-liquid extraction followed by high-performance liquid chromatography-diode-array detection. Volatiles were assayed by gas chromatography-flame-ionization detection. Quetiapine was assayed in biological specimens by basic extraction with n-butyl chloride and derivatized with 50 microL of MTBSTFA and separation by GC-NPD. Linearity was observed up to 2.0 mg/L. Samples with concentrations exceeding the linearity were diluted. These cases were chosen for study because they were all deaths as a result of suicidal ingestion of drugs in which quetiapine was considered a significant factor. The concentrations of quetiapine in these cases are 6-16 times greater than the upper reported therapeutic range (0.1-1.0 mg/L). In case #1, the concentrations of quetiapine found were 7.20 mg/L (19 micromol/L) in blood and 0.93 mg/L (2.4 micromol/L) in vitreous fluid. In case #2, the concentrations of quetiapine found were 16 mg/L in blood (42 micromol/L), 120 mg/kg (310 micromol/kg) in liver, and 1.8 mg/L (4.6 micromol/L) in vitreous fluid. In case #3, the concentrations of quetiapine found in femoral blood was 5.90 mg/L (15 micromol/L). In all cases, drugs in addition to quetiapine were detected, but in cases #1 and #2, the cause of death was considered to be a quetiapine overdose and the other drugs were not considered to be contributory. Case #3 was considered a mixed drug overdose.
Hum Psychopharmacol. 2004 Oct 15; :
Quetiapine has a direct effect on the negative symptoms of schizophrenia.
Tandon R.
State of Florida, Department of Children and Families, 1317 Winewood Blvd, Bldg 6, Room 235, Tallahassee, FL 32399, USA.
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. Copyright (c) 2004 John Wiley & Sons, Ltd.
Am J Psychiatry. 2004 Sep;161(9):1709-11.:
Incidence of newly diagnosed diabetes attributable to atypical antipsychotic medications.
Leslie DL, Rosenheck RA.
Department of Veterans Affairs Connecticut Mental Illness Research, Education and Clinical Center, West Haven, CT, USA.
douglas.leslie@yale.edu
OBJECTIVE: The purpose of the study was to determine the proportion of patients with schizophrenia with a stable regimen of antipsychotic monotherapy who developed diabetes or were hospitalized for ketoacidosis. METHOD: Patients with schizophrenia for whom a stable regimen of antipsychotic monotherapy was consistently prescribed during any 3-month period between June 1999 and September 2000 and who had no diabetes were followed through September 2001 by using administrative data from the Department of Veterans Affairs. Cox proportional hazards models were developed to identify the characteristics associated with newly diagnosed diabetes and ketoacidosis. RESULTS: Of the 56,849 patients identified, 4,132 (7.3%) developed diabetes and 88 (0.2%) were hospitalized for ketoacidosis. Diabetes risk was highest for clozapine (hazard ratio=1.57) and olanzapine (hazard ratio=1.15); the diabetes risks for quetiapine (hazard ratio=1.20) and risperidone (hazard ratio=1.01) were not significantly different from that for conventional antipsychotics. The attributable risks of diabetes mellitus associated with atypical antipsychotics were small, ranging from 0.05% (risperidone) to 2.03% (clozapine). CONCLUSIONS: Although clozapine and olanzapine have greater diabetes risk, the attributable risk of diabetes mellitus with atypical antipsychotics is small.
Clin Psychiatry. 2004 Aug;65(8):1040-8. :
A double-blind, randomized, placebo-controlled trial of quetiapine addition in patients with obsessive-compulsive disorder refractory to serotonin reuptake inhibitors.
Denys D, de Geus F, van Megen HJ, Westenberg HG.
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands.
D.A.J.P.denys@azu.nl
BACKGROUND: Although serotonin reuptake inhibitors (SRIs) are the most effective pharmacologic treatment currently available for patients with obsessive-compulsive disorder (OCD), 40% to 60% of patients do not respond to this treatment. This study was conducted to evaluate the efficacy and tolerability of quetiapine in addition to an SRI for treatment-refractory patients with OCD. METHOD: Forty patients (10 men/30 women, mean +/- SD age = 35.2 +/- 12.1 years; range, 18-60 years) with primary OCD according to DSM-IV criteria who were recruited between February 2001 and December 2002 were randomly assigned in an 8-week, double-blind, placebo-controlled trial to receive dosages titrated upward to 300 mg/day of quetiapine (N = 20) or placebo (N = 20) in addition to their SRI treatment. At entry, all patients were unresponsive to courses of treatment with at least 2 different SRIs at a maximum tolerated dose for 8 weeks. During the study, primary efficacy was assessed according to change from baseline on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A responder was defined as having a final Clinical Global Impressions-Improvement scale rating of "very much improved" or "much improved" and a decrease of > or = 35% in Y-BOCS score. RESULTS: An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean +/- SD decrease in Y-BOCS score of 9.0 +/- 7.0 (31%) in the quetiapine group and 1.8 +/- 3.4 (7%) in the placebo group (F=16.99, df=1,38; p <.001). Eight (40%) of 20 patients in the quetiapine group and 2 (10%) of 20 patients in the placebo group were responders (chi2=4.8, df=1, p=.028). The most common side effects in the quetiapine group were somnolence, dry mouth, weight gain, and dizziness. CONCLUSION: The results of this study show that quetiapine in addition to an SRI is beneficial for patients with OCD who do not respond to SRI treatment alone.
Pharmacotherapy. 2004 Jul;24(7):824-30. :
A retrospective analysis of the short-term effects of olanzapine and quetiapine on weight and body mass index in children and adolescents.
Patel NC, Kistler JS, James EB, Crismon ML.
College of Pharmacy, University of Texas at Austin, 78712, USA.
STUDY OBJECTIVE: To evaluate changes in short-term weight and body mass index (BMI) in children and adolescents receiving olanzapine or quetiapine. DESIGN: Retrospective study Setting. Austin State Hospital, Austin, Texas. PATIENTS: One hundred three patients younger than 18 years who were admitted to the hospital and treated with olanzapine (50 patients) or quetiapine (53) for at least 2 weeks between October 1, 1997, and October 31, 2001. INTERVENTION: Treatment with at least 2 weeks of olanzapine or quetiapine. MEASUREMENTS AND MAIN RESULTS: Mean+/-SD daily doses of olandzapine and quetiapine were 13.9+/-7.3 and 510.9+/-250.3 mg, respectively Weight and height were measured at baseline and 14 or more days after baseline. Body mass index (in kg/m2) was calculated using serial measurements of weight and height, and change in BMI was determined. The olanzapine group gained an average of 3.8 kg, the quetiapine group 0.03 kg. In the olanzapine group, BMI increased by an average of 1.3 kg/m2; in the quetiapine group, BMI decreased by 0.2 kg/m2. After controlling for baseline differences, significant between-group differences in weight and BMI change were noted. Change in BMI correlated significantly with baseline BMI in quetiapine-treated girls. CONCLUSION: Patients taking olanzapine had greater increases in weight and BMI than those taking quetiapine. Further studies are necessary to determine the relative risk, magnitude, and time course of antipsychotic-induced weight gain in this patient population.
J Clin Psychiatry. 2004 Jul;65(7):975-81.:
The effectiveness of olanzapine, risperidone, quetiapine, and ziprasidone as augmentation agents in treatment-resistant major depressive disorder.
Barbee JG, Conrad EJ, Jamhour NJ.
Department of Psychiatry, Louisiana State University Health Sciences Center, New Orleans 70112, USA.
jbarbe@lsuhsc.edu
BACKGROUND: Many questions remain regarding the use of atypical neuroleptics as antidepressant augmentation agents. To date, there have been no reports in the literature regarding the effectiveness of these drugs when trials of one or more of them have failed previously as antidepressant augmentation. METHOD: This retrospective chart review was conducted to determine the effectiveness of olanzapine, risperidone, quetiapine, and ziprasidone when given in a fee-for-service setting as anti-depressant augmentation agents to patients with treatment-resistant, nonpsychotic major depressive disorder (DSM-IV). Prospective (Global Assessment of Functioning [GAF]) along with retrospective (Clinical Global Impressions-Improvement [CGI-I] and -Severity of Illness scales) ratings were completed for each patient. Analyses were conducted in an attempt to identify factors that appeared to correlate with response, including order of administration and Thase-Rush staging of treatment resistance. RESULTS: In this study of 76 medication trials in 49 patients, the overall response rate based on the CGI-I ratings was 65% (32/49). Individual rates of response were 57% (21/37) for olanzapine, 50% (7/14) for risperidone, 33% (6/18) for quetiapine, and 10% (1/10) for ziprasidone. None of the differences between neuroleptics in rates of response were significant. The difference between baseline and final GAF scores was statistically significant only in the olanzapine (p <.001) and risperidone (p =.047) groups. Rates of discontinuation did not vary significantly between agents, though trends were present. Crossover trials from one atypical neuroleptic to another in the event of nonresponse appeared to be effective. CONCLUSIONS: Although limited by its design, this study suggests atypical neuroleptic augmentation of antidepressants may be a viable option in treatment-resistant major depressive disorder.
J Clin Psychiatry. 2004 Jun;65(6):857-63.:
A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus.
Koller EA, Weber J, Doraiswamy PM, Schneider BS.
Division of Metabolic and Endocrine Drug Products, Center for Drug Evaluation and Review, US Food and Drug Administration, Rockville, MD, USA.
OBJECTIVE: To explore the clinical characteristics of hyperglycemia in patients treated with quetiapine. METHOD: A pharmacovigilance survey of spontaneously reported adverse events in quetiapine-treated patients was conducted using reports from the U.S. Food and Drug Administration MedWatch program (January 1, 1997, through July 31, 2002) and published cases using the search terms hyperglycemia, diabetes, acidosis, ketosis, and ketoacidosis. RESULTS: We identified 46 reports of quetiapine-associated hyperglycemia or diabetes and 9 additional reports of acidosis that occurred in the absence of hyperglycemia and were excluded from the immediate analyses. Of the reports of quetiapine-associated hyperglycemia, 34 patients had newly diagnosed hyperglycemia, 8 had exacerbation of preexisting diabetes mellitus, and 4 could not be classified. The mean +/- SD age was 35.3 +/- 16.2 years (range, 5-76 years). New-onset patients (aged 31.2 +/- 14.8 years) tended to be younger than those with preexisting diabetes (43.5 +/- 16.4 years, p = .08). The overall male:female ratio was 1.9. Most cases appeared within 6 months of quetiapine initiation. The severity of cases ranged from mild glucose intolerance to diabetic ketoacidosis or hyperosmolar coma. There were 21 cases of ketoacidosis or ketosis. There were 11 deaths. CONCLUSION: Atypical antipsychotic use may unmask or precipitate hyperglycemia. UPDATE: An additional 23 cases were identified since August 1, 2002, the end of the first survey, by extending the search through November 30, 2003, bringing the total to 69.
J Psychopharmacol. 2004 Jun;18(2):281-4.:
Does quetiapine have mood altering properties?
Mishra A, Moore PB, Hobbs R
.
Mental Health Unit, Leazes Wing, Royal Victoria Infirmary, Newcastle Upon Tyne, UK.
achdoc@aol.com
We present a series of three cases who developed manic symptoms on introduction of quetiapine to their medication regime. All were male, with long-standing psychotic illnesses (schizophrenia/schizoaffective disorder), relatively well maintained on medication until their deterioration which prompted a review of their medication. The dose range of prescribed quetiapine was 300-800 mg daily. Two patients had previously received antidepressants without displaying manic symptoms. The mania subsided on withdrawal of quetiapine in two patients. The third patient continued on quetiapine but with the addition of zuclopenthixol depot. Sodium valproate was prescribed to the other two patients, and quetiapine was discontinued. These cases indicate that a side-effect of quetiapine may be mood elevation. An ability to elevate mood while controlling psychoses would be helpful in the treatment of post-psychotic and bipolar depression. Its clinical importance in the control of manic episodes, for which atypical antipsychotics are used increasingly, is uncertain
Ann Clin Psychiatry. 2004 Jan-Mar;16(1):3-13. :
Atypical antipsychotics in the treatment of affective symptoms: a review.
Masan PS.
Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27702-3319, USA.
masan001@mc.duke.edu
Atypical antipsychotics have demonstrated beneficial effects on affective symptoms, in addition to antipsychotic activity. Consequently, their role in the treatment of bipolar disorder and treatment-resistant or psychotic depression has been explored. Adjunctive atypical antipsychotic therapy appears to benefit patients experiencing manic episodes of bipolar disorder, and some studies suggest that monotherapy may also be efficacious. Clinical studies of patients with schizoaffective disorder and major depression support the use of atypical antipsychotics to treat depression. This review focuses on risperidone, olanzapine, quetiapine, and ziprasidone and provides evidence that these drugs demonstrate activity against manic episodes of bipolar disorder when used as adjunctive therapy and possibly as monotherapy and that depression in patients with schizoaffective disorder also responds to these agents.
Int Clin Psychopharmacol. 2004 May;19(3):173-4. :
Use of quetiapine in bipolar disorder: a case series with prospective evaluation.
Suppes T, McElroy SL, Keck PE, Altshuler L, Frye MA, Grunze H, Leverich GS, Nolen WA, Chisholm K, Dennehy EB, Post RM.
Quetiapine, a new atypical antipsychotic, was added to ongoing treatment of bipolar I outpatients (n=15) for symptoms of illness (mood lability, irritability, psychosis and/or difficulty sleeping). All evaluations were prospectively obtained, with the majority of patients (n=9) showing much or very much improvement on the Clinical Global Impression for Bipolar Disorder (CGI-BP). Somatic complaints were limited. Mean (SD) duration before changes in medication regimens was 134 (100) days. Studies of the use of quetiapine in maintenance treatment of bipolar disorder are warranted.
Am J Ophthalmol. 2004 Nov;138(5):870-1.:
Twice-yearly exams unnecessary for patients taking quetiapine.
Fraunfelder FW.
Casey Eye Institute, Oregon Health & Science University, Portland, Oregon USA.
PURPOSE: To determine the necessity for the heightened level of monitoring for cataract development in patients taking quetiapine (Seroquel, AstraZeneca Pharmaceuticals, Wilmington, Delaware) dictated by the Physicians' Desk Reference. Also, to explore the possibility of cataractogenesis because of quetiapine therapy. DESIGN: Observational case series. METHODS: Data were garnered from a series of 80 case reports collected at the National Registry of Drug-Induced Ocular Side Effects (Portland, Oregon). The World Health Organization (WHO) causality assessment guidelines were used to assess the relationship between quetiapine and cataractogenesis. RESULTS: There were 34 reports of cataracts associated with quetiapine therapy. Average age was 44 years with 23 females and 11 males studied. Average duration of therapy was 29.3 weeks on standard doses. CONCLUSIONS: Cataractogenesis secondary to quetiapine is "unlikely" by WHO guidelines. This probably makes it unnecessary to require biannual ophthalmic examinations as routine eye examinations are sufficient to screen for this condition.
Hum Psychopharmacol. 2004 Oct 15 [Epub ahead of print] :
Quetiapine has a direct effect on the negative symptoms of schizophrenia.
Tandon R.
State of Florida, Department of Children and Families, 1317 Winewood Blvd, Bldg 6, Room 235, Tallahassee, FL 32399, USA.
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. Copyright (c) 2004 John Wiley & Sons, Ltd.
Am J Psychiatry. 2004 Sep;161(9):1709-11. :
Incidence of newly diagnosed diabetes attributable to atypical antipsychotic medications.
Leslie DL, Rosenheck RA.
Department of Veterans Affairs Connecticut Mental Illness Research, Education and Clinical Center, West Haven, CT, USA. douglas.leslie@yale.edu
OBJECTIVE: The purpose of the study was to determine the proportion of patients with schizophrenia with a stable regimen of antipsychotic monotherapy who developed diabetes or were hospitalized for ketoacidosis. METHOD: Patients with schizophrenia for whom a stable regimen of antipsychotic monotherapy was consistently prescribed during any 3-month period between June 1999 and September 2000 and who had no diabetes were followed through September 2001 by using administrative data from the Department of Veterans Affairs. Cox proportional hazards models were developed to identify the characteristics associated with newly diagnosed diabetes and ketoacidosis. RESULTS: Of the 56,849 patients identified, 4,132 (7.3%) developed diabetes and 88 (0.2%) were hospitalized for ketoacidosis. Diabetes risk was highest for clozapine (hazard ratio=1.57) and olanzapine (hazard ratio=1.15); the diabetes risks for quetiapine (hazard ratio=1.20) and risperidone (hazard ratio=1.01) were not significantly different from that for conventional antipsychotics. The attributable risks of diabetes mellitus associated with atypical antipsychotics were small, ranging from 0.05% (risperidone) to 2.03% (clozapine). CONCLUSIONS: Although clozapine and olanzapine have greater diabetes risk, the attributable risk of diabetes mellitus with atypical antipsychotics is small.
Am J Psychiatry. 2004 Sep;161(9):1620-5. :
Equivalent occupancy of dopamine D1 and D2 receptors with clozapine: differentiation from other atypical antipsychotics.
Tauscher J, Hussain T, Agid O, Verhoeff NP, Wilson AA, Houle S, Remington G, Zipursky RB, Kapur S.
University of Toronto Department of Psychiatry, Schizophrenia Program.
johannes.tauscher@meduniwien.ac.at
OBJECTIVE: Clozapine, the prototype of atypical antipsychotics, remains unique in its efficacy in the treatment of refractory schizophrenia. Its affinity for dopamine D(4) receptors, serotonin 5-HT(2A) receptor antagonism, effects on the noradrenergic system, and its relatively moderate occupancy of D(2) receptors are unlikely to be the critical mechanism underlying its efficacy. In an attempt to elucidate the molecular/synaptic mechanism underlying clozapine's distinctiveness in refractory schizophrenia, the authors studied the in vivo D(1) and D(2) receptor profile of clozapine compared with other atypical antipsychotics. METHOD: Positron emission tomography with the radioligands [(11)C]SCH23390 and [(11)C]raclopride was used to investigate D(1) and D(2) receptor occupancy in vivo in 25 schizophrenia patients receiving atypical antipsychotic treatment with clozapine, olanzapine, quetiapine, or risperidone. RESULTS: Mean striatal D(1) occupancies ranged from 55% with clozapine to 12% with quetiapine (rank order: clozapine > olanzapine > risperidone > quetiapine). The striatal D(2) occupancy ranged from 81% with risperidone to 30% with quetiapine (rank order: risperidone > olanzapine > clozapine > quetiapine). The ratio of striatal D(1)/D(2) occupancy was significantly higher for clozapine (0.88) relative to olanzapine (0.54), quetiapine (0.41), or risperidone (0.31). CONCLUSIONS: Among the atypical antipsychotics, clozapine appears to have a simultaneous and equivalent occupancy of dopamine D(1) and D(2) receptors. Whether its effect on D(1) receptors represents agonism or antagonism is not yet clear, as this issue is still unresolved in the preclinical arena. This distinctive effect on D(1)/D(2) receptors may be responsible for clozapine's unique effectiveness in patients with schizophrenia refractory to other typical and atypical antipsychotics.
J Anal Toxicol. 2004 Sep;28(6):520-5.:
Fatal overdoses associated with quetiapine.
Langman LJ, Kaliciak HA, Carlyle S.
Provincial Toxicology Centre, Riverview Hospital, Coquitlam, British Columbia, Canada.
Quetiapine (Seroquel(R)) is an atypical antipsychotic drug belonging to a new chemical class, the benzothiazepine derivatives. We present three cases from the Provincial Toxicology Center of British Columbia, Canada in which suicidal overdose deaths were associated with quetiapine. The blood specimens were initially subjected to a thorough qualitative analysis. Basic drugs were screened for by liquid-liquid extraction followed by gas chromatography-nitrogen-phosphorus (GC-NPD) and gas chromatography-mass spectrometry-electron impact detection utilizing both in-house and commercial search libraries. Acidic and neutral drugs were screened for by liquid-liquid extraction followed by high-performance liquid chromatography-diode-array detection. Volatiles were assayed by gas chromatography-flame-ionization detection. Quetiapine was assayed in biological specimens by basic extraction with n-butyl chloride and derivatized with 50 microL of MTBSTFA and separation by GC-NPD. Linearity was observed up to 2.0 mg/L. Samples with concentrations exceeding the linearity were diluted. These cases were chosen for study because they were all deaths as a result of suicidal ingestion of drugs in which quetiapine was considered a significant factor. The concentrations of quetiapine in these cases are 6-16 times greater than the upper reported therapeutic range (0.1-1.0 mg/L). In case #1, the concentrations of quetiapine found were 7.20 mg/L (19 micromol/L) in blood and 0.93 mg/L (2.4 micromol/L) in vitreous fluid. In case #2, the concentrations of quetiapine found were 16 mg/L in blood (42 micromol/L), 120 mg/kg (310 micromol/kg) in liver, and 1.8 mg/L (4.6 micromol/L) in vitreous fluid. In case #3, the concentrations of quetiapine found in femoral blood was 5.90 mg/L (15 micromol/L). In all cases, drugs in addition to quetiapine were detected, but in cases #1 and #2, the cause of death was considered to be a quetiapine overdose and the other drugs were not considered to be contributory. Case #3 was considered a mixed drug overdose.
Schizophr Res. 2004 Sep 1;70(1):57-62. :
Weight decline in patients switching from olanzapine to quetiapine.
Gupta S, Masand PS, Virk S, Schwartz T, Hameed A, Frank BL, Lockwood K.
Department of Psychiatry, University of Buffalo, School of Medicine and Biomedical Sciences, Buffalo, NY, USA.
sgupta1@adelphia.net
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.
J Clin Psychiatry. 2004 Aug;65(8):1040-8. :
A double-blind, randomized, placebo-controlled trial of quetiapine addition in patients with obsessive-compulsive disorder refractory to serotonin reuptake inhibitors.
Denys D, de Geus F, van Megen HJ, Westenberg HG.
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands.
D.A.J.P.denys@azu.nl
BACKGROUND: Although serotonin reuptake inhibitors (SRIs) are the most effective pharmacologic treatment currently available for patients with obsessive-compulsive disorder (OCD), 40% to 60% of patients do not respond to this treatment. This study was conducted to evaluate the efficacy and tolerability of quetiapine in addition to an SRI for treatment-refractory patients with OCD. METHOD: Forty patients (10 men/30 women, mean +/- SD age = 35.2 +/- 12.1 years; range, 18-60 years) with primary OCD according to DSM-IV criteria who were recruited between February 2001 and December 2002 were randomly assigned in an 8-week, double-blind, placebo-controlled trial to receive dosages titrated upward to 300 mg/day of quetiapine (N = 20) or placebo (N = 20) in addition to their SRI treatment. At entry, all patients were unresponsive to courses of treatment with at least 2 different SRIs at a maximum tolerated dose for 8 weeks. During the study, primary efficacy was assessed according to change from baseline on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A responder was defined as having a final Clinical Global Impressions-Improvement scale rating of "very much improved" or "much improved" and a decrease of > or = 35% in Y-BOCS score. RESULTS: An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean +/- SD decrease in Y-BOCS score of 9.0 +/- 7.0 (31%) in the quetiapine group and 1.8 +/- 3.4 (7%) in the placebo group (F=16.99, df=1,38; p <.001). Eight (40%) of 20 patients in the quetiapine group and 2 (10%) of 20 patients in the placebo group were responders (chi2=4.8, df=1, p=.028). The most common side effects in the quetiapine group were somnolence, dry mouth, weight gain, and dizziness. CONCLUSION: The results of this study show that quetiapine in addition to an SRI is beneficial for patients with OCD who do not respond to SRI treatment alone.
Bipolar Disord. 2004 Jun;6(3):213-23. :
Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind, placebo-controlled study.
Sachs G, Chengappa KN, Suppes T, Mullen JA, Brecher M, Devine NA, Sweitzer DE.
Harvard Bipolar Research Program, Massachusetts General Hospital, Boston, 02114, USA.
sachsg@aol.com
OBJECTIVE: Evaluate the efficacy and tolerability of quetiapine (QTP) combined with lithium (Li) or divalproex (DVP) in the treatment of acute mania. METHODS: Patients were randomized to 21 days of double-blind treatment with QTP plus Li/DVP, or placebo (PBO) plus Li/DVP. QTP was rapidly dosed up to a maximum of 800 mg/day; Li was dosed to 0.7-1.0 mEq/L; or DVP to 50-100 microg/mL. RESULTS: Fifty-six of 91 (61.5%) individuals in the QTP + Li/DVP group compared with 49 of 100 (49%) taking PBO + Li/DVP completed the study. A significantly greater mean reduction in total Young Mania Rating Scale (YMRS) score was observed at end-point in patients receiving QTP + Li/DVP compared with those in the PBO + Li/DVP group (-13.76 versus -9.93; p = 0.021). The response rate (> or =50% YMRS improvement) was significantly higher in the QTP + Li/DVP group than in PBO + Li/DVP-treated patients (54.3% versus 32.6%; p = 0.005), as was the proportion of patients achieving clinical remission (YMRS < 12) (45.7% versus 25.8%; p = 0.007). Patients receiving QTP + Li/DVP also had a significantly greater improvement in Clinical Global Impressions-Bipolar (CGI-BP) Severity of Illness scores (-1.38 versus -0.78; p = 0.001). The mean last-week dose of QTP was 584 mg/day in patients meeting response criteria. Common adverse events (at least 10% and twice the rate of Li/DVP) in the QTP + Li/DVP group included somnolence, dry mouth, asthenia, and postural hypotension. CONCLUSIONS: Quetiapine combined with either Li or DVP has superior efficacy compared with Li or DVP monotherapy for treating patients with bipolar mania. Combination therapy was well-tolerated and most adverse events were mild, withdrawal because of adverse events being only 5% compared with 6% on Li or DVP monotherapy.
Hum Psychopharmacol. 2004 Apr;19(3):181-5.:
Combination of mood stabilizers with quetiapine for treatment of acute bipolar disorder: an open label study.
Bahk WM, Yoon BH, Lee KU, Chae JH.
Department of Psychiatry, College of Medicine, The Catholic University of Korea, St Mary's Hospital, 62 Yoido-Dong, Youngdeungpo-Gu, Seoul 150-713, Korea.
OBJECTIVES: The atypical antipsychotics are being increasingly used to control acute manic episodes, and data are emerging to support their mood-stabilizing and antidepressant properties. This study investigated the short-term efficacy of quetiapine as an add-on therapy in the treatment of acute mania. METHOD: This study was a 4-week, open-label, add-on, prospective investigation using quetiapine in addition to mood stabilizers. Data on 18 patients fulfilling DSM-IV diagnostic criteria for bipolar I disorder were analysed. The Young mania rating scale (YMRS), the Hamilton scale for depression (HDRS), the brief psychiatric rating scale (BPRS) and extrapyramidal symptom rating scale (ESRS) were applied at baseline and at weeks 1, 2 and 4. The clinical global impression scale (CGI) was evaluated at baseline and week 4. RESULTS: The addition of quetiapine produced a statistically significant improvement on the YMRS, HDRS, BPRS and CGI score at week 4 from baseline (p<0.005). Quetiapine was well tolerated, with no subjects discontinuing because of side effects. CONCLUSIONS: The combination of quetiapine was associated with a substantial symptomatic improvement in patients with acute mania. Randomized placebo-controlled prospective studies are needed. Copyright 2004 John Wiley & Sons, Ltd.
Prog Neuropsychopharmacol Biol Psychiatry. 2004 Mar;28(2):413-5.:
Weight gain and improvement with quetiapine in bipolar I disorder: a case report.
Ozcan ME, Kaya B, Polat R.
Department of Psychiatry, Inonu University Medical School, Malatya, Turkey.
eozcan@inonu.edu.tr
Observations made with quetiapine (QUET) in this case give clues for some aspects of its use for patients with bipolar disorder. Weight gain (11 kg; 16.6% increase in 21 weeks) and improvement in manic symptoms occurred after QUET add-on to lithium (Li). Patient's mood improved after QUET add-on without causing extrapyramidal symptoms (EPS), while QUET was discontinued due to weight gain. Short-term QUET add-on to Li may help mood stabilization in bipolar I disorder. Weight changes must be observed carefully.