Research and Clinical Trials on Olanzapine (Zyprexa)

By Dr Greg Mulhauser
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This list of current clinical research trials on Olanzapine (Zyprexa) is followed by a short set of abstracts from the most recent research articles published on the drug.

Article Contents

Olanzapine (Zyprexa) Clinical Research Trials

From our searchable database at ClinicalTrialsFeeds.org, this list includes all the latest information about clinical trials involving Olanzapine (Zyprexa).

 

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Current Research Literature on Olanzapine (Zyprexa)

Here are abstracts for some of the latest research articles to have appeared on Olanzapine (Zyprexa):

Prescribing Patterns and the Use of Therapeutic Drug Monitoring of Psychotropic Medication in a Psychiatric High-Security Unit.

Ther Drug Monit. 2008 Aug 14;
Castberg I, Spigset O
The aim of this study was to investigate the use of psychotropic medication and therapeutic drug monitoring in a high-security psychiatric unit and to compare the doses and serum concentrations both with the recommended intervals and with the doses and serum concentrations in a control group. One hundred thirty-two patients were admitted in the period from January 2000 to December 2005. All available samples were used when comparing serum concentrations and doses with the recommended ranges. For the comparison of doses and serum concentration-to-dose (C:D) ratios with the control group only 1 sample from each patient was used. A total of 459 analyses of 27 different drugs in samples from 8 women and 73 men were included. The median number of therapeutic drug monitoring analyses per patient was 4 (range 1-29). Thirty-seven of the 81 patients (46%) used 2 or more antipsychotics at the same time. Clozapine, lamotrigine, olanzapine, quetiapine, ziprasidone, and zuclopenthixol were often given in doses above the recommended. The serum levels were frequently above those recommended for clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and zuclopenthixol. The serum levels were significantly higher in the study group than in the control group for clozapine, lamotrigine, quetiapine, and zuclopenthixol. The given dose was significantly higher in the study group than in the control group for clozapine, lamotrigine and zuclopenthixol. The C:D ratio was significantly lower in the study group than in the control group for olanzapine but higher for quetiapine. The non-evidence based practice of high-dose polypharmacy with several antipsychotics is widely used in this unit. The use of higher doses in the study group than in the control group was not due to differences in metabolism or adherence to treatment between the 2 groups. The frequent use of therapeutic drug monitoring did not seem to have a great impact on the prescribed doses.

Does stimulation of 5-HT(1A) receptors improve cognition in schizophrenia?

Behav Brain Res. 2008 May 29;
Meltzer HY, Sumiyoshi T
Cognitive impairment is a key feature of schizophrenia and may be the most important determinant of outcome in schizophrenia. This impairment is diffuse and may reflect abnormalities in frontal cortex, hippocampus and other brain regions. While deficits in glutamatergic, GABAergic, dopaminergic and cholinergic impairment have received the most attention as the basis of this impairment, there are many reasons for considering the role of serotonin (5-HT) in contributing to these deficits. This may be via its influence on dopaminergic, cholinergic, glutamatergic and GABAergic function, as well as various growth factors that have been implicated in schizophrenia. Of the 14 known serotonin receptors, the 5-HT(1A) receptor is a key candidate for mediating at least some of the influence 5-HT has on cognition. 5-HT(1A) receptors are upregulated in postmortem specimens from patients with schizophrenia, suggesting a deficit in 5-HT(1A) function in this disorder. Atypical but not typical antipsychotic drugs stimulate the efflux of dopamine from cortex by a 5-HT(1A)-dependent mechanism. A series of studies from this laboratory involving the 5-HT(1A) partial agonists tandospirone and buspirone have reported a modest ability of these agents to improve some domains of cognition in patients receiving typical or atypical antipsychotic drugs. Preclinical studies have been mixed in regard to the ability of 5-HT(1A) partial agonists to improve cognition in various paradigms; some studies report that 5-HT(1A) antagonists are effective to improve cognition. Aripiprazole, clozapine, olanzapine, perospirone, quetiapine risperidone, and ziprasidone are examples of atypical antipsychotic drugs which are either direct or indirect 5-HT(1A) agonists which have been shown to improve cognitive function in patients with schizophrenia. Further study is needed to determine the role of the 5-HT(1A) receptor to improve cognitive function in schizophrenia.

Differential Effects of Various Typical and Atypical Antipsychotics on Plasma Glucose and Insulin Levels in the Mouse: Evidence for the Involvement of Sympathetic Regulation.

Schizophr Bull. 2008 Aug 14;
Savoy YE, Ashton MA, Miller MW, Nedza FM, Spracklin DK, Hawthorn MH, Rollema H, Matos FF, Hajos-Korcsok E
Atypical antipsychotic treatment has been associated with serious metabolic adverse events, such as glucose dysregulation and development of type 2 diabetes. As part of our studies on possible underlying mechanisms, we investigated the acute effects of various typical and atypical antipsychotics on plasma glucose and insulin in FVB/N mice, a strain that showed a more pronounced hyperglycemic response to clozapine than C57BL/6 and CD-1 mice. Acute administration of high doses of clozapine, olanzapine, quetiapine, perphenazine, or chlorpromazine significantly increased plasma glucose by 100%-140% above basal levels without significant effects on insulin levels. In contrast, risperidone reduced plasma glucose (-30%) and markedly enhanced plasma insulin levels. Doses of ziprasidone that gave 50-fold higher free plasma concentrations than therapeutic plasma levels, as well as high doses of aripiprazole and haloperidol, did not significantly alter either glucose or insulin levels. Clozapine- and olanzapine-induced hyperglycemia occurred at free plasma concentrations that were within, or one order of magnitude above, the range of therapeutic plasma levels. Pretreatment with either the ganglionic blocker hexamethonium, or the alpha(2) adrenergic receptor antagonist yohimbine, blocked the clozapine- and chlorpromazine-induced increase in glucose levels. Taken together, these results suggest that typical and atypical antipsychotics with known metabolic liability produce acute hyperglycemia in mice and that this effect is likely driven by activation of the sympathetic autonomic nervous system via a central mechanism.

Massive pulmonary emboli associated with olanzapine.

Ir Med J. 2008 Jun; 101(6): 186
Hilli MA, MacRedmond R, Hollywood P, O'Neill S, Morgan R

A 12-month follow-up study of treating overweight schizophrenic patients with aripiprazole.

Acta Psychiatr Scand. 2008 Sep; 118(3): 246-50
Schorr SG, Slooff CJ, Postema R, Van Oven W, Schilthuis M, Bruggeman R, Taxis K
OBJECTIVE: To investigate the feasibility of switching overweight schizophrenic patients to aripiprazole and to assess the impact of 12 months of aripiprazole treatment on weight in routine practice. METHOD: This was a non-controlled cohort study in overweight schizophrenic patients. Data were collected before treatment with aripiprazole was started and at 12-month follow-up. RESULTS: A total of 53 patients were included; of these 55% continued using aripiprazole for 12 months. Aripiprazole treatment for 12 months (P = 0.027) and stopping clozapine or olanzapine treatment (P = 0.038) predicted weight loss (> or =3 kg). Patients receiving aripiprazole monotherapy (n = 16, mean -3.0 kg) had similar weight loss than patients receiving aripiprazole in addition to another antipsychotic drug (n = 13, mean -4.4 kg). CONCLUSION: In routine practice once aripiprazole treatment was started, more than half of the patients remained on aripiprazole and most of them lost weight. Adding aripiprazole to clozapine gave similar weight loss as monotherapy with aripiprazole.

 

This page was last reviewed by Dr Greg Mulhauser, Friday, 4 July 2008.

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