Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new zyprexa research articles will be listed here shortly after becoming available to us.
Related Sponsors
Medical research on zyprexa
[Atypical antipsychotics in first-episode psychosis: A review.]
Encephale. 2008 Apr; 34(2): 194-204
Rotgé JY, Aouizerate B, Tignol J
BACKGROUND: The management of patients with first-episode psychosis (FEP) is a difficult, but challenging task. Early and efficient treatment may influence long-term clinical outcome. Atypical antipsychotics (A-AP) are commonly prescribed in this population, but few data exist to establish their appropriate usage in the management of FEP. Our purpose is to review the literature and to summarize current data on the prescription of A-AP in FEP. METHODS: Studies assessing efficacy or safety of A-AP in FEP were identified by searches in Medline (up to April 2006). The following nine drugs were considered for this review: clozapine, olanzapine, risperidone, amisulpride, aripiprazole, quetiapine, ziprasidone, zotepine, and sertindole. RESULTS: Only four A-AP (clozapine, quetiapine, olanzapine, and risperidone) were evaluated as treatment of FEP. All of them show the same efficacy as conventional antipsychotics (C-AP). Clozapine has no benefit over C-AP in the treatment of naive patients. It entails a high rate of treatment discontinuation because of the need for regular white blood cell monitoring explained by the risk of agranulocytosis. Hence, clozapine may not be a first-line treatment of FEP. Tolerance to quetiapine and olanzapine is better than C-AP regarding extrapyramidal side effects, but weight gain induced by these two A-AP may be very disabling in a young population. Considering results from head-to-head comparative studies, olanzapine may be more effective than risperidone when an affective component is associated with the FEP symptomatology, but more data are needed to demonstrate this point. Risperidone is a relatively well-tolerated compound when it is prescribed at doses lower than 4mg/d. It is the only A-AP that showed greater efficacy than C-AP to prevent relapse in patients with FEP. Unfortunately, information regarding the preventive efficacy of the other A-AP are lacking. CONCLUSIONS: Further studies, particularly longer-term studies, are needed to explore the impact of A-AP prescription in FEP on the course of psychotic disorders. The common use of A-AP as treatment of FEP is justified by a relatively better tolerance compared to C-AP, and by the hypothesis-not demonstrated-of a better effect on long-term outcome.
Psychopharmacology (Berl). 2008 Jul 3;
Amato D, Stasi MA, Borsini F, Nencini P
RATIONALE: Polydipsia is a severe complication of long-term schizophrenia and, despite its unknown pathogenesis, is empirically treated with typical or atypical antipsychotics. In the rat, nonregulatory water intake is induced by repeated administration of amphetamine-like compounds or by the D2/3 agonist, quinpirole. OBJECTIVE: This study is aimed at determining the potential activity of antipsychotic compounds with different affinities for D2 receptors in preventing and/or reversing quinpirole-induced polydipsia. MATERIALS AND METHODS: Male Sprague-Dawley rats were treated with five injections of quinpirole (0.5 mg/kg i.p.) to induce polydipsia. The oral effects of haloperidol, olanzapine, clozapine, and ST2472 on QNP-induced polydipsia were analyzed in the following two schedules. In the preventive schedule, haloperidol (0.2, 0.4, and 0.8 mg/kg), olanzapine (1.5, 3, and 6 mg/kg), ST2472 (1 and 2 mg/kg), and clomipramine (5, 10, and 20 mg/kg) were given in combination with quinpirole from day 1 to day 5. In the reversal schedule, rats showing quinpirole-induced polydipsia on the third day received haloperidol (0.4 mg/kg), olanzapine (1.5 and 3 mg/kg), clozapine (10, 20, and 40 mg/kg), ST2472 (1, 2, 5, and 10 mg/kg), and clomipramine (5, 10, and 20 mg/kg) before quinpirole on days 4 and 5. RESULTS: Haloperidol both prevented and reversed quinpirole-induced polydipsia, whereas olanzapine and ST2472 only reversed it. Clomipramine prevented but did not reverse quinpirole-induced polydipsia, and clozapine did not reverse it either. CONCLUSIONS: We suggest that, once developed, polydipsia is governed by dopaminergic D2 mechanisms. In contrast, either an increase in the serotoninergic tone or an inhibition of D2 receptors can modulate the development of quinpirole-induced excessive drinking.
J Am Pharm Assoc (2003). 2008 May-Jun; 48(3): 393-400
Hsu C, Ried LD, Bengtson MA, Garman PM, McConkey JR, Rahnavard F
Objectives: To describe the proportions of veterans living with schizophreniarelated disorders monitored for dyslipidemia and hyperglycemia and to investigate whether the likelihood of metabolic dysregulation monitoring was influenced by veterans' sociodemographic characteristics, preswitch pharmacologic treatment, and monitoring before the switch from one second-generation antipsychotic (SGA) to another.Design: Retrospective, observational, descriptive study.Setting: Veterans Affairs (VA) Healthcare System between October 1, 2001, and December 31, 2003.Patients: 1,826 veterans with schizophrenia-related disorders.Intervention: Veterans who were dispensed two or more prescriptions for one of five SGAs (i.e., clozapine, olanzapine, quetiapine, risperidone, and ziprasidone) on the VA Healthcare System formulary were identified. Of these veterans, a subset that was switched from one SGA to another was identified. From this subset, veterans were identified who were on the first SGA continuously for at least 90 days before the index date and the new SGA for 180 or more days after. Finally, among these veterans, ICD-9 codes were used to identify veterans with a schizophrenia or schizoaffective disorder diagnosis (ICD-9 code 295.xx or 296).Main outcome measures: Proportions of veterans with lipid (i.e., low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides) and blood glucose (i.e., fasting blood glucose [FBG], glycosylated hemoglobin [A1C]) laboratory results.Results: Nearly 39% of the veterans had at least one of three lipid fractions monitored 6 months or less before their SGA switch and 59% during the 12 months after. The corresponding proportions of veterans monitored were 57% and 80% for FBG and 19% and 31% for A1C. Pharmacologic agent for metabolic dysregulation, monitoring during the 6 months before the switch, and age 50 years or older were significant predictors of monitoring after the SGA switch for all three laboratory parameters.Conclusion: These findings serve as a benchmark for lipid and blood glucose monitoring among patients who switch SGA therapy. Veterans' metabolic dysregulation was more likely to be monitored after SGA switch for those receiving pharmacologic treatment for metabolic dysregulation, monitored before the switch, and aged 50 years or older. Implementation of monitoring guidelines in daily practice is emphasized to ensure that individuals living with schizophrenia-related disorders and taking SGAs achieve optimal physical health.
Eur J Pharmacol. 2008 Jun 19;
Knauer CS, Campbell JE, Galvan B, Bowman C, Osgood S, Buist S, Buchholz L, Henry B, Wong E, Shahid M, Grimwood S
An in vivo binding assay is characterized for [(3)H]M100907 binding to rat brain, as a measure of 5-HT(2A) receptor occupancy. Dose-response analyses were performed for various 5-HT(2A) antagonist reference agents, providing receptor occupancy ED(50) values in conjunction with plasma and brain concentration levels. Ketanserin and M100907 yielded dose-dependent increases in 5-HT(2A) receptor occupancy with ED(50)s of 0.316 mg/kg and 0.100 mg/kg, respectively. The atypical antipsychotics risperidone, olanzapine, and clozapine dose-dependently inhibited in vivo [(3)H]M100907 binding with ED(50) values of 0.051, 0.144, and 1.17 mg/kg, respectively. In contrast, the typical antipsychotic haloperidol exhibited only 20.1% receptor occupancy at 10 mg/kg despite producing dose-dependent increases in plasma and brain exposure levels. The novel psychopharmacologic agent asenapine dose-dependently occupied 5-HT(2A) receptors in rat brain with an ED(50) of 0.011 mg/kg, demonstrating higher 5-HT(2A) receptor potency compared with the other atypical antipsychotics tested. This enhanced potency was supported by a lower plasma exposure EC(50) of 0.477 ng/ml, compared with risperidone (1.57 ng/ml) and olanzapine (7.81 ng/ml) and was confirmed in time course studies. The validated [(3)H]M100907 rat in vivo binding assay allows for preclinical measurement of 5-HT(2A) receptor occupancy, providing essential data for understanding the pharmacological profile of novel antipsychotic agents. Additionally, the corresponding plasma and brain drug exposure data analyses provides a valuable data set for 5-HT(2A) reference agents by enabling direct comparison with any complementary studies performed in rats, thus providing a foundation for predictive pharmacokinetic/pharmacodynamic models and, importantly, allowing for translation to human receptor occupancy studies using [(11)C]M100907 positron emission tomography.
Olanzapine, but not haloperidol, enhances PSA-NCAM immunoreactivity in rat prefrontal cortex.
Int J Neuropsychopharmacol. 2008 Aug; 11(5): 591-5
Frasca A, Fumagalli F, Ter Horst J, Racagni G, Murphy KJ, Riva MA
Repeated antipsychotic treatment may produce adaptive changes ranging from cytoarchitectural rearrangements to synaptic modifications that might contribute to clinical improvement. We performed a prolonged treatment (2 wk) with the first-generation antipsychotic (FGA) haloperidol (1 mg/kg) and the second-generation antipsychotic (SGA) olanzapine (2 mg/kg twice daily) and analysed the expression of the polysialylated form of neural cell adhesion molecule (PSA-NCAM) in rat hippocampus and prefrontal cortex via immunohistochemistry. We found a regional- and drug-selective increase of PSA-NCAM expression in prefrontal cortex of olanzapine-treated rats with no effects in hippocampus; conversely, haloperidol did not produce a change in either brain region. Our findings reveal a possible role for PSA-NCAM in the mechanism of action of the SGA olanzapine adding complexity as well as specificity to the molecular changes set in motion by this drug.
BMC Med. 2008 Jun 30; 6(1): 17
Ganguli R, Brar JS, Mahmoud R, Berry SA, Pandina GJ
ABSTRACT: BACKGROUND: In clinical practice, physicians often need to change the antipsychotic medications they give to patients because of an inadequate response or the presence of unacceptable or unsafe side effects. However, there is a lack of consensus in the field as to the optimal switching strategy for antipsychotics, especially with regards to the speed at which the dose of the previous antipsychotic should be reduced. This paper assesses the short-term results of strategies for the discontinuation of olanzapine when initiating risperidone. METHODS: In a 6-week, randomized, open-label, rater-blinded study, patients with schizophrenia or schizoaffective disorder, on a stable drug dose for more than 30 days at entry, who were intolerant of or exhibiting a suboptimal symptom response to more than 30 days of olanzapine treatment, were randomly assigned to the following switch strategies (common risperidone initiation scheme; varying olanzapine discontinuation): (i) abrupt strategy, where olanzapine was discontinued at risperidone initiation; (ii) gradual 1 strategy, where olanzapine was given at 50% entry dose for 1 week after risperidone initiation and then discontinued; or (iii) gradual 2 strategy, where olanzapine was given at 100% entry dose for 1 week, then at 50% in the second week, and then discontinued. RESULTS: The study enrolled 123 patients on stable doses of olanzapine. Their mean age was 40.3 years and mean (+/- standard deviation (SD)) baseline Positive and Negative Syndrome Scale (PANSS) total score of 75.6 +/- 11.5. All-cause treatment discontinuation was lowest (12%) in the group with the slowest olanzapine dose reduction (gradual 2) and occurred at half the discontinuation rate in the other two groups (25% in abrupt and 28% in gradual 1). The relative risk of early discontinuation was 0.77 (confidence interval 0.61-0.99) for the slowest dose reduction compared with the other two strategies. After the medication was changed, improvements at endpoint were seen in PANSS total score (-7.3; p < 0.0001) and in PANSS positive (-3.0; p < 0.0001), negative (-0.9; p = 0.171) and anxiety/depression (-1.4; p = 0.0005) subscale scores. Severity of movement disorders and weight changes were minimal. CONCLUSIONS: When switching patients from olanzapine to risperidone, a gradual reduction in the dose of olanzapine over 2 weeks was associated with higher rates of retention compared with abrupt or less gradual discontinuation. Switching via any strategy was associated with significant improvements in positive and anxiety symptoms and was generally well tolerated. Trial registration: ClinicalTrials.gov NCT00378183.
Psychiatry Clin Neurosci. 2008 Jun; 62(3): 370
Nakaaki S, Murata Y, Furukawa TA
Two cases of burning mouth syndrome treated with olanzapine.
Psychiatry Clin Neurosci. 2008 Jun; 62(3): 359-61
Ueda N, Kodama Y, Hori H, Umene W, Sugita A, Nakano H, Yoshimura R, Nakamura J
Two case reports of patients suffering from burning mouth syndrome (BMS), a type of somatoform disorder, who were treated with olanzapine are discussed. One case was a 54-year-old female with BMS who failed to respond to milnacipran treatment. Olanzapine (2.5 mg/day) brought about dramatic improvement in the patient's symptoms, and thereafter milnacipran withdrawal further eliminated her symptoms. The second case was a 51-year-old male with BMS who failed to respond to paroxetine treatment. Olanzapine (2.5 mg/day) was added to the treatment regimen and increased to 5.0 mg/day the following week. The patient noted a reduction in symptoms and continued to live normally thereafter without experiencing severe symptoms. These findings suggest that olanzapine may be useful in the treatment of BMS.
J Clin Psychiatry. 2008 Jun 3; e1-e10
Fraguas D, Merchán-Naranjo J, Laita P, Parellada M, Moreno D, Ruiz-Sancho A, Cifuentes A, Giráldez M, Arango C
OBJECTIVE: The aim of this study was to evaluate metabolic and hormonal side effects in children and adolescents after 6 months of treatment with 3 different second-generation antipsychotics (SGAs). METHOD: 66 children and adolescents (44 male [66.7%], mean +/- SD age = 15.2 +/- 2.9 years) treated for 6 months with risperidone (N = 22), olanzapine (N = 20), or quetiapine (N = 24) composed the study sample. 34 patients (51.5%) suffered from schizophrenia or other psychosis (according to DSM-IV criteria). Patients were consecutively attending different programs from March 2005 to October 2006. Prior to enrollment in the study, patients were either antipsychotic-naive (37.9%, N = 25) or had been taking an antipsychotic drug for fewer than 30 days. Significant weight gain was defined as a >/= 0.5 increase in body mass index (BMI) z score (adjusted for age and gender) at 6 months. Based on recent criteria for pediatric populations, patients were considered "at risk for adverse health outcome" if they met at least 1 of the following criteria: (1) >/= 85th BMI percentile plus presence of 1 or more negative weight-related clinical outcomes, or (2) >/= 95th BMI percentile. RESULTS: After the 6 months, BMI z scores increased significantly in patients receiving olanzapine and risperidone. At the 6-month follow-up, 33 patients (50.0%) showed significant weight gain. The number of patients at risk for adverse health outcome increased from 11 (16.7%) to 25 (37.9%) (p = .018). The latter increase was significant only in the olanzapine group (p = .012). Total cholesterol levels increased significantly in patients receiving olanzapine (p = .047) and quetiapine (p = .016). Treatment with quetiapine was associated with a significant decrease in free thyroxin (p = .011). CONCLUSION: Metabolic and hormonal side effects of SGAs in children and adolescents should be carefully monitored when prescribing these drugs.
Schizophr Res. 2008 Jun 26;
Fatemi SH, Folsom TD, Reutiman TJ, Pandian T, Braun NN, Haug K
Astrocytic markers glial fibrillary acidic protein (GFAP) and connexin 43 (CX43) are known to have altered expression in brains of subjects with psychiatric disorders including autism and major depression. The current study investigated whether GFAP and CX43 expressions are affected by several commonly used psychotropic medications (clozapine, fluoxetine, haloperidol, lithium, olanzapine, and valproic acid). Using SDS-PAGE and western blotting technique, we observed that CX43 protein expression in prefrontal cortex was significantly increased following chronic treatment with fluoxetine and clozapine, while it was significantly decreased by haloperidol and lithium. GFAP protein expression was significantly decreased following chronic treatment with clozapine and valproic acid. These results suggest that astroglial markers GFAP and CX43 could be potential targets for therapeutic intervention.