Olanzapine observational studies

Initial trials and other observational studies with olanzapine detected transient rises in liver transaminases (SEDA-23, 65). Several other cases have further illustrated this. 

Strom BL, Eng SM, Faich G, Reynolds RF, D Agostino RB, Ruskin J, Kane JM. Comparative mortality associated with ziprasidone and olanzapine in real-world use among 18,154 patients with schizophrenia the Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC). Am J Psychiatry 2011 168 193-201. 

Choure BK, Gosavi D, Nanotkar S (2014) Comparative cardiovascular safety of risperidone and olanzapine, based on electrocardiographic parameters and blood pressure a prospective open label observational study. Indian J Pharmacol 46 493 97... 

Observational studies The use of antipsychotic drugs in children and adolescents is of particular concern. In a 24-week, multicenter, open study supported by Eli-Lilly, the marketing authorization holder, 96 adolescents with schizophrenic disorder (mean age 16 years 68% boys) were given olanzapine 10 mg/day [83 ]. BPRS scores fell from baseline to week 6 by a mean of 17. The most common adverse events were weight gain and increased prolactin. Weight... 

Observational studies Numerous open studies of ziprasidone promoted by Pfeer, the marketing authorization holder, have previously been published [SEDA-32, 111] and further studies, similarly promoted, have emerged. Of 185 subjects who were switched from olanzapine or risperidone to ziprasidone, 72 completed a 1-year extension study [136 ]. The most common adverse effects were insomnia (23%) and somnolence (11%) no patient had a corrected QT interval over 500 ms at any time during the study. 

Antipsychotics in a few small studies have been shown to be helpful. To date this research is limited to typical antipsychotics. Nevertheless, the excellent track record of atypical antipsychotics in treating schizophrenia and the lower burden of side effects lead us to recommend atypical antipsychotics as a first-line treatment for STPD as well. Low doses of risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole are all reasonable options. If no therapeutic effect is observed, doses should be increased. 

An international, multicenter, double-blind trial addressed the acute efficacy and safety of a single-dose range of olanzapine (5 to 20 mg/day) compared with a single-dose range of haloperidol (5 to 20 mg/day) (11.6). A total of 1996 patients with a DSM-lll-R diagnosis of schizophrenia (83.1%), schizophreniform disorder (1.9%), or schizoaffective disorder (15%) participated in this study. The primary overall efficacy analysis (i.e., the difference in baseline to endpoint (last observation carried forward [LOCF]) mean change on the BPRS) found olanzapine to be statistically superior to haloperidol (HPDL) (i.e., -10.98 -7.93 p < 0.015). 

Namjoshi and coworkers (297) reported the results of an extension phase study comparing olanzapine with placebo. The initial reduction achieved in YMS scores continued during this period and by the end of the extension phase reached a mean reduction of 18-points. The authors also conducted an economic analysis of the drug trial (excluding the acute treatment period) and found that the cost per month seen in the open-label extension phase (i.e., 649) was about half of that observed during the 12 months before entering the study (i.e., 1,533.)... 

In one study, excessive appetite was a more frequent adverse event in patients treated with olanzapine versus haloperidol (24 versus 12%) (817). Loss of weight has been observed after withdrawal of neuroleptic drugs (818). 

There was a significant rise in baseline serum prolactin concentration in 10 patients after they had taken risperidone for a mean of 12 weeks compared with 10 patients who were tested after a neuroleptic drug-free wash-out period of at least 2 weeks (1014). A non-significant increase in serum prolactin has also been observed in an open comparison of risperidone with other neuroleptic drugs in 28 patients (1015). However, in a meta-analysis of two independent studies (n = 404), prolactin was greatly increased by risperidone (mean change 45-80 ng/ml), a larger effect than with olanzapine and haloperidol (1016). 

There has been one comprehensive meta-analysis including over 80 studies and over 30 000 patients (489). A meta-analysis of trials of neuroleptic drugs showed the following mean weight gains in kg after 10 weeks of treatment clozapine, 4.5 olanzapine, 4.2 thioridazine, 3.2 sertindole, 2.9 chlorpromazine, 2.6 risperidone, 2.1 haloperidol, 1.1 fluphenazine, 0.43 ziprasidone 0.04 molindone, —0.39 placebo, —0.74 (490,491). In one study, excessive appetite was a more frequent adverse event in patients treated with olanzapine versus haloperidol (24 versus 12%) (185). Loss of weight has been observed after withdrawal of neuroleptic drugs (492). 

Layton D, Harris S, Wilton LV, Shakir SA. Comparison of incidence rates of cerebrovascular accidents and transient ischaemic attacks in observational cohort studies of patients prescribed risperidone, quetiapine or olanzapine in general practice in England including patients with dementia. J Psychopharmacol 2005 19 473-82. 

Although hemotoxicity was not observed during premarketing studies of olanzapine (202), cases of neutropenia (neutrophil count below 1.5 x 109/1) (203) or agranulocytosis (neutrophil count below 0.5 x 109/1) (204) have been published. 

Gomez JC, Sacristan JA, Hernandez J, Breier A, Ruiz Carrasco P, Anton Saiz C, Fontova Carbonell E. The safety of olanzapine compared with other antipsychotic drugs results of an observational prospective study in... 

Olanzapine and clozapine have been compared in a double-blind study by Lilly Research Laboratories for 18 weeks in 220 patients with schizophrenia conclusions were based on the one-sided lower 95% confidence limit of the treatment effect observed from the primary efficacy... 

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