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.
Medical research on zyprexa
Paediatr Drugs. 2010 Mar 19;
Lobo ED, Robertson-Plouch C, Quinlan T, Hong Q, Bergstrom RF
Olanzapine is an atypical antipsychotic approved for the treatment of adults and adolescents (aged 13 -17 years) with schizophrenia or bipolar I disorder (manic or mixed episodes). To characterize the pharmacokinetics of olanzapine in adolescents, to estimate the sources of variability, and to identify significant co-variates. In addition, olanzapine pharmacokinetic parameters in adolescents were compared with those in adults to guide appropriate dosing recommendations for adolescent patients. A population pharmacokinetic modeling study was performed. The majority of pharmacokinetic data for the model came from a multicenter, open-label study in which 4.5 weeks of oral olanzapine 2.5-20 mg once daily was administered to a total of 105 patients aged 13-17 years (41.1-148 kg) who had a diagnosis of schizophrenia or bipolar I disorder. Four blood samples at steady state were obtained from each patient. Olanzapine concentrations in plasma were determined using a validated high-performance liquid chromatography method with electrochemical detection. Similar data from 11 adolescents from three previous studies were also included. A pharmacokinetic model was developed and the potential effects of patient characteristics (sex, bodyweight, age, ethnic origin) were investigated using a nonlinear mixed effects modeling program. The distributions of pharmacokinetic parameters for olanzapine in adolescents were compared with those previously reported in adults (n = 912, diagnosis of schizophrenia, olanzapine 5-20 mg/day) using the Kolmogorov-Smirnov 2-sample test. A visual predictive check was performed using Monte Carlo simulations on an external validation dataset. The pharmacokinetics of oral olanzapine in adolescent patients were described by a one-compartment pharmacokinetic model. The typical model estimates were 13.6 L/h (70 kg female patient) for oral clearance (CL/F) and 899 L for oral volume of distribution (V/F). Interpatient variability (40.5% for CL/F, 65.4% for V/F) and residual error (27%) were moderate. Bodyweight and sex had a significant influence on CL/F, which was lower in patients with lower weights and approximately 30% higher in males than females. Olanzapine exposure was typically 27% higher in adolescents versus adults. Approximately 77% of adolescents and adults had comparable CL/F values and 69% had comparable V/F values. The pharmacokinetics of oral olanzapine in adolescent patients are similar to those in adults, and are linear in the dosage range of 2.5-20 mg/day. Given the small magnitude of co-variate effects and the interpatient variability, dose adjustments based on bodyweight or sex are not necessary in adolescents.
Olanzapine versus other atypical antipsychotics for schizophrenia.
Cochrane Database Syst Rev. 2010; 3: CD006654
Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, Duggan L, Kissling W, Leucht S
BACKGROUND: In many countries of the industrialised world second generation ("atypical") antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics. OBJECTIVES: To evaluate the effects of olanzapine compared to other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. SEARCH STRATEGY: 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO.2. Reference searching We inspected the reference of all identified studies for more trials.3. Personal contact We contacted the first author of each included study for missing information.4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. SELECTION CRITERIA: We included all randomised trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. MAIN RESULTS: The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole, clozapine, quetiapine, risperidone or ziprasidone). The overall attrition from the included studies was considerable (49.2%) leaving the interpretation of results problematic.Olanzapine improved the general mental state (PANSS total score) more than aripiprazole (2 RCTs, n=794, WMD -4.96 CI -8.06 to -1.85), quetiapine (10 RCTs, n=1449, WMD -3.66 CI -5.39 to -1.93), risperidone (15 RCTs, n=2390, WMD -1.94 CI -3.31 to -0.58) and ziprasidone (4 RCTs, n=1291, WMD -8.32 CI -10.99 to -5.64), but not more than amisulpride or clozapine. This somewhat better efficacy was confirmed by fewer participants in the olanzapine groups leaving the studies early due to inefficacy of treatment compared to quetiapine (8 RCTs, n=1563, RR 0.56 CI 0.44 to 0.70, NNT 11 CI 6 to 50), risperidone (14 RCTs, n=2744, RR 0.78 CI 0.62 to 0.98, NNT 50 CI 17 to 100) and ziprasidone (5 RCTs, n=1937, RR 0.64 CI 0.51 to 0.79, NNT 17, CI 11 to 33).Fewer participants in the olanzapine group than in the quetiapine (2 RCTs, n=876, RR 0.56 CI 0.41 to 0.77, NNT 11 CI 7 to 25) and ziprasidone (2 RCTs, n=766, RR 0.65 CI 0.45 to 0.93, NNT 17 CI 9 to 100) treatment groups, but not in the clozapine group (1 RCT, n=980, RR 1.28 CI 1.02 to 1.61, NNH not estimable), had to be re-hospitalised in the trials.Except for clozapine, all comparators induced less weight gain than olanzapine (olanzapine compared to amisulpride: 3 RCTs, n=671, WMD 2.11kg CI 1.29kg to 2.94kg; aripiprazole: 1 RCT, n=90, WMD 5.60kg CI 2.15kg to 9.05kg; quetiapine: 7 RCTs, n=1173, WMD 2.68kg CI 1.10kg to 4.26kg; risperidone: 13 RCTs, n=2116, WMD 2.61kg CI 1.48kg to 3.74kg; ziprasidone: 5 RCTs, n=1659, WMD 3.82kg CI 2.96kg to 4.69kg). Associated problems such as glucose and cholesterol increase were usually also more frequent in the olanzapine group.Other differences in adverse effects were less well documented. Nevertheless, olanzapine may be associated with slightly more extrapyramidal side effects than quetiapine (use of antiparkinson medication (6 RCTs, n=1090, RR 2.05 CI 1.26 to 3.32, NNH 25 CI 14 to 100), but less than risperidone (use of antiparkinson medication 13 RCTs, n=2599, RR 0.78 CI 0.65 to 0.95, NNH 17 CI 9 to 100) and ziprasidone (use of antiparkinson medication 4 RCTs, n=1732, RR 0.70 CI 0.50 to 0.97, NNH not estimable). It may also increase prolactin somewhat more than aripiprazole, clozapine and quetiapine, but clearly less so than risperidone (6 RCTs, n=1291, WMD -22.84 CI -27.98 to -17.69). AUTHORS' CONCLUSIONS: Olanzapine may be a somewhat more efficacious drug than some other second generation antipsychotic drugs. This small superiority in efficacy needs to be weighed against a larger weight gain and associated metabolic problems than most other second generation antipsychotic drugs, except clozapine. These conclusions are tentative due to the large number of people leaving the studies early which possibly limits the validity of the findings. Further large, well-designed trials are necessary to establish the relative effects of different second generation antipsychotic drugs.
Weight Gain in Asian Patients on Second-generation Antipsychotics.
Ann Acad Med Singapore. 2010 Feb; 39(2): 118-4
Mahendran R, Hendricks M, Chan YH
Introduction: There is increasing evidence that second-generation antipsychotics are associated with weight gain. However almost all available literature has been for Caucasian populations. Materials and Methods: A health quality improvement project was undertaken at the Institute of Mental Health/Woodbridge Hospital to monitor patients who were started on second-generation antipsychotics. This 2-year survey of 266 patients on second-generation antipsychotics closely tracked weight gain and other physical and biochemical parameters. Results: Of the 222 patients regularly monitored, 78.4% had weight gain (mean weight gain 1.9 kg, maximum weight gain 20.1 kg). Weight gain group liability was highest for clozapine (72.4%), followed by olanzapine (66.7%) and risperidone (65%). Most of the weight gain occurred in the fi rst 4 weeks of treatment and 95.9% of those who gained weight had done so in the fi rst 6 months. The maximum weight gain was seen at 12 weeks for risperidone and 8 weeks for clozapine, quetiapine and olanzapine; the latter having another peak at 6 months. Conclusion: The survey confi rms that weight gain is also a problem for Asian patients treated with second-generation antipsychotics. It reinforces the need for the regular monitoring of patients and the need for psychoeducation and advice on diet and a healthy lifestyle.
Impact of Tobacco Smoking Cessation on Stable Clozapine or Olanzapine Treatment (April).
Ann Pharmacother. 2010 Mar 16;
Lowe EJ, Ackman ML
OBJECTIVE: To examine the pharmacokinetic implications and potential clinical effects of tobacco smoking cessation in patients on stable clozapine or olanzapine treatment. DATA SOURCES: A literature search of MEDLINE (1950-November 2009) and EMBASE (1980-November 2009) was conducted using the search terms smoking, tobacco, cigarette, cannabis, smoking cessation, cytochrome P450, antipsychotic, clozapine, and olanzapine. In addition, reference lists from publications identified were searched manually. STUDY SELECTION AND DATA EXTRACTION: English-language articles and human studies were identified, yielding 111 returns. Articles that reported clinical outcomes following smoking cessation were selected. Pharmacokinetic data for these drugs were reviewed and articles that provided relevant background information were also included. DATA SYNTHESIS: Pharmacokinetic studies have demonstrated more rapid clearance of olanzapine and lower clozapine and norclozapine (desmethylclozapine) concentrations in smokers compared to nonsmokers. These studies also found that smokers require higher doses of these agents than nonsmokers. There are case reports of adverse clinical outcomes following smoking cessation in patients being treated with olanzapine and clozapine. Reports that included serum concentrations consistently found elevations following smoking cessation, and dosage reductions of 30-40% were required to achieve pre-cessation concentrations. Worsening psychiatric symptoms, somnolence, hypersalivation, extreme fatigue, extrapyramidal effects, and seizures have all been reported following smoking cessation in this patient group. CONCLUSIONS: Pharmacists need to be aware of potential risks associated with smoking cessation in patients stabilized on clozapine or olanzapine. Toxicity as a result of recent smoking reduction or cessation may be a reason for hospital admission. For hospitalized patients, pharmacists should obtain information concerning smoking status, including cessation attempts. Nonspecific signs and symptoms of elevated clozapine or olanzapine concentrations should be considered in relation to clinical status while the patient is hospitalized. Measurement of baseline serum clozapine concentrations and/or empiric dosage adjustment in patients expected to have a prolonged hospital stay with forced smoking cessation may be appropriate.
Drugs and dilated cardiomyopathies: a case/noncase study in the French PharmacoVigilance Database.
Br J Clin Pharmacol. 2010 Mar; 69(3): 287-94
Montastruc G, Favreliere S, Sommet A, Pathak A, Lapeyre-Mestre M, Perault-Pochat MC, Montastruc JL,
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Dilated cardiomyopathy is a frequent disease, responsible for 40-50% of cases of heart failure. * Several aetiologies have been reported: idiopathic, familial/genetic, viral and/or immune but also toxic agents (alcohol, cobalt, carbon monoxide, lead, cocaine, mercury or drugs). * Among drugs, anthracyclines are well known to induce such an adverse drug reaction. WHAT THIS STUDY ADDS * This study describes an association with already suspected drugs (anthracyclines, antiretrovirals). * It also found a signal with other drugs (antipsychotics, lithium, antidepressants, retinoids). * This pharmacovigilance signal should be confirmed by further prospective studies. AIMS To evaluate putative associations between drugs and dilated cardiomyopathy. METHODS We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were all the observations with dilated cardiomyopathy registered into the FPVD between 1 January 1990 and 30 June 2007. Noncases were all other reports other than those studied. Anthracyclines were used as positive controls. Data were expressed as reporting odds ratio (ROR) with their 95% confidence intervals. RESULTS Out of the 258 729 adverse drug reaction (ADR) reports recorded in the FPVD between 1 January 1990 and 30 June 2007, 47 (22 men, mean age 49 years) were defined as dilated cardiomyopathy. In these 47 patients, 67 drugs were 'suspect'. A significant ROR was found with cytotoxic (epirubicin, mitoxantrone, cyclophosphamide, gemcitabine, fluorouracil) and antiretroviral (lamividune, zidovudine, abacavir) but also with isotretinoin, prednisone, appetite suppressant (clobenzorex) and psychotropic [antipsychotic (clozapine, olanzapine), lithium, antidepressant (clomipramine, amitriptyline, fluvoxamine)] drugs. CONCLUSIONS The present study describes an association between some drugs and reports of dilated cardiomyopathies. This relationship involves not only some already suspected drugs (anthracyclines, antiretrovirals), but also other drugs (antipsychotics, lithium, antidepressants, retinoids) less known to induce such an ADR. Despite the mandatory limits of this kind of study (underreporting, confounding factors . . .), these data represent a pharmacovigilance signal and could contribute to establish further prospective studies in order to confirm such signals.
Synapse. 2010 Mar 10; 64(7): 550-555
Fatemi SH, Folsom TD, Reutiman TJ, Braun NN, Lavergne LG
Our laboratory has recently demonstrated altered expression of phosphodiesterase (PDE) 4A and 4B in subjects with autism, bipolar disorder, and schizophrenia, suggesting disrupted cAMP signaling in these diagnostic groups. In the current study, we measured expression of PDEs in rat frontal cortex (FC) following chronic treatment with clozapine, fluoxetine, haloperidol, lithium, olanzapine, valproic acid (VPA), or sterile saline for 21 days. Western blotting experiments showed decreased expression of PDE4A subtypes in FC following treatment with clozapine, haloperidol, lithium, and VPA. PDE4B subtypes were similarly reduced in FC following treatment with clozapine, fluoxetine, and lithium. We also measured levels of nine PDE subtypes via qRT-PCR in FC and found significant upregulation of PDE1A and PDE8B following treatment with olanzapine, while treatment with lithium reduced expression of mRNA for PDE8B. Our results demonstrate altered expression of PDE4A and PDE4B in response to a variety of psychotropic medications suggesting potentially new therapeutic avenues for treatment of neuropsychiatric diseases. Synapse 64:550-555, 2010. (c) 2010 Wiley-Liss, Inc.
The first- and second-generation antipsychotic drugs affect ADP-induced platelet aggregation.
World J Biol Psychiatry. 2010 Mar; 11(2 Pt 2): 268-75
Dietrich-Muszalska A, Rabe-Jablonska J, Nowak P, Kontek B
OBJECTIVE: Blood platelets play an important role in haemostasis and their hyperaggregability may lead to thrombosis and cardiovascular diseases. Increased incidence of mortality, caused by cardiovascular disease, and the increased risk of thrombotic complication in schizophrenic patients treated with antipsychotics have been reported. The effects of antipsychotic drugs on blood platelet function are not fully explained, therefore the purpose of the present study was to examine and compare the effects of the second-generation antipsychotic drugs used in schizophrenia (clozapine, risperidone and olanzapine), with the effects of the first generation antipsychotic, haloperidol, on the platelet aggregation induced by ADP in vitro. METHODS: Blood obtained from healthy volunteers (n=25) collected into sodium citrate was centrifuged (250xg, 10 min) at room temperature to obtain platelet-rich plasma. Aggregation of blood platelets (10 microM ADP) was recorded (Chrono-log aggregometer) in platelet-rich plasma preincubated with antipsychotic drugs (final concentration: clozapine 420 ng/ml, risperidone 65 ng/ml, olanzapine 40 ng/ml, haloperidol 20 ng/ml) for 30 min. RESULTS: Our results showed that all tested drugs inhibit platelet aggregation induced by ADP in vitro. Among studied antipsychotic drugs clozapine and olanzapine significantly reduced platelet aggregability in vitro. In comparison with control platelets (without the drug), clozapine inhibited ADP-induced platelet aggregation by 21% (P=3.7x10(-6)) and olanzapine by 18% (P=2.8x10(-4)), respectively. CONCLUSION: The obtained results indicate that antipsychotic drugs, especially clozapine and olanzapine, contrary to haloperidol, reduced response of blood platelets to ADP measured as platelet aggregation. This suggests that therapy with such antipsychotics, particularly with second-generation antipsychotics, may partly reduce prothrombotic events associated with the increased platelet activation observed in schizophrenic patients. The mechanism of antiaggregatory influence of antipsychotics requires further studies.
World J Biol Psychiatry. 2010 Mar; 11(2 Pt 2): 256-61
Yoshimura R, Ueda N, Hori H, Ikenouchi-Sugita A, Umene-Nakano W, Nakamura J
In the present study, we longitudinally investigated the effects of risperidone, olanzapine, and aripiprazole on plasma levels of catecholamine metabolites and brain-derived neurotrophic factor (BDNF) in first-episode unmedicated schizophrenic patients. The subjects were 59 Japanese schizophrenic patients (35 males and 24 females; age range: 18-46 years; mean+/-SD: 25+/-16 years). The patients were treated with risperidone (n=32) in a dose range of 2-6 mg/day (mean+/-SD=3.4+/-1.9), olanzapine (n=18) in a dose range of 5-20 mg/day (mean+/-SD=12.1+/-5.8), or aripiprazole (n=9) in a dose range of 12-30 mg/day (mean+/-SD=22.8+/-10.1). All three drugs significantly decreased plasma homovanillic acid (HVA) levels within 8 weeks, although aripiprazole transiently raised this level before 8 weeks. All three drugs also significantly increased plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels within 8 weeks. On the other hand, none of them altered plasma BDNF levels. These results indicate that risperidone, olanzapine, and aripiprazole affect catecholaminergic systems in the brain, that the effects of aripiprazole on the dopaminergic systems seem to slightly different than those of risperidone and olanzapine, and that these atypical antipsychotic drugs might not alter BDNF levels, at least within 8 weeks of treatment.
World J Biol Psychiatry. 2010 Mar; 11(2 Pt 2): 251-5
Rizos EN, Papadopoulou A, Laskos E, Michalopoulou PG, Kastania A, Vasilopoulos D, Katsafouros K, Lykouras L
Brain-derived neurotrophic factor signals and dopaminergic function in the brain are strongly associated, and research on BDNF in schizophrenia may enhance our insights on the pathophysiological mechanisms of this disease. In the present study we aimed to investigate the possible association between serum BDNF levels and schizophrenic relapses and the possible differential effects of treatment with typical and atypical antipsychotics on serum BDNF levels in the same group of patients. We measured serum BDNF levels in 47 patients with schizophrenia during a relapse and again 6 weeks after administration of antipsychotic treatment (14 on risperidone, 18 on haloperidol, 10 on olanzapine and five on amisulpride) and in 44 healthy volunteers. Patients with schizophrenia showed reduced serum BDNF levels in relation to healthy volunteers at study entry. No significant differences were revealed in BDNF serum levels after 6 weeks of antipsychotic treatment in the patients compared to their own levels at study entry. However, serum BDNF was significantly increased in the subgroup receiving olanzapine compared to the other antipsychotics. Our findings may indicate a differential effect of olanzapine on BDNF levels compared to haloperidol, risperidone, and amisulpride.
[Pharmacotherapy in the treatment of borderline personality disorder]
Riv Psichiatr. 2009 Nov-Dec; 44(6): 357-73
Alliani D, Tarantelli S
The aim of this study is to bring together the previous studies on pharmacotherapy of borderline disorder from the oldest to the recent ones, mainly focusing on atypical antipsychotic, whose success has been underlined in recent medical literature with peculiar reference to olanzapine. Since the '80 the pharmacotherapy in borderline personality disorder has been playing an increasing role in the interest of scientific community and in the medical practice as indicated by APA guidelines (2000). Nowadays the pharmacological approach, supported by some experimental outcomes, follow a so called "dimensional" standard. The targets of this standard drug approach are specific psychopathological "dimensions" of the disorder and related neurotransmitters' changes in particular linked to serotoninergic and dopaminergic systems, both supported by experimental outcomes. The psychopathological dimensions to which pharmacological approach is more suitable are: impulsiveness and emotional dysregulation. During the last past years, effectiveness of atypical antipsychotic drugs became of major interest in medical treatment of borderline disorder, mainly related to their action toward the serotoninergic and dopaminergic systems.