Olanzapine adverse effects

Clozapine and olanzapine are atypical antipsychotic drugs used in the treatment of schizophrenia. Their strnctnres are depicted in Scheme 2.36. The use of clozapine and olanzapine, which are more effective than standard neuroleptic drugs in the treatment of refractory schizophrenia, is, however, limited becanse of their adverse effects. These adverse effects are ascribed to the formation of the corresponding cation-radicals in living organisms under oxidation by bone marrow cells. These cation-radicals eliminate protons from the NH fragments and generate their nitrenium cations. The nitreninm cations are covalently bonnd to the life-important proteins. This results in the toxic effects of clozapine and olanzapine (Sikora et al. 2007). 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

In 48 patients with schizophrenia taking clozapine, olanzapine, risperidone, or typical neuroleptic drugs, and 31 untreated healthy control subjects newer neuroleptic drugs, such as clozapine and olanzapine, compared with typical agents, were associated with adverse effects on blood glucose regulation (774). 

Weight gain related to the use of atypical neuroleptic drugs in children and adolescents, in whom this adverse effect is of particular concern, has been reviewed (804). The published data suggest that clozapine and olanzapine... 

Two women with neuroleptic-drug induced hyperprolactinemia, menstrual dysfunction, and galactorrhea had improvement in these adverse effects during treatment with olanzapine (855). 

Bronson BD, Lindenmayer JP. Adverse effects of high-dose olanzapine in treatment-refractory schizophrenia. J Chn Psychopharmacol 2000 20(3) 382-4. 

Note that perphenazine (Trilafon) is in the middle of the pack there was no statistical difference between it and the leader, olanzapine (Zy-prexa). But Zyprexa had the worst adverse effect profile (see subsequent sections). 

There was a highly significant reduction in rating scale scores for the syndrome with olanzapine 10 mg versus baseline and versus pimozide 2 mg, and a significant reduction with olanzapine 5 mg versus pimozide 4 mg only moderate sedation was reported by one patient during olanzapine treatment while three complained of minor motor adverse effects and sedation during pimozide treatment. 

The results of one of the clinical trials in which olanzapine (Eli Lilly) was compared with risperidone (Janssen Pharmaceutica) (SEDA-22, 64) gave rise to a debate between researchers of the two pharmaceuticals companies on some of the possible flaws (100-105). Since the modal dosage over the 28-week trial was 7.2 mg/day, significantly higher than that used in actual clinical practice (average dose 4.6 mg/day), the higher incidence of risperidone-associated adverse effects could have been explained by this dosage difference. 

Olanzapine, mean dose 5.4 mg/day, has been given to 21 patients with apathy in the absence of depression after long-term treatment with SSRIs for non-psychotic depression in an open, flexible-dose study (111). The more frequent adverse effects were sedation (n = 12), increased appetite (n = 8), stiffness (n = 7), edema (n = 6), and dry mouth (n = 5). 

Several studies have shown a relation between neuroleptic drug dosages, extrapyramidal adverse effects, and the degree of dopamine D2 receptor occupancy (SEDA-18, 48) (181,182). Atypical neuroleptic drugs, such as olanzapine, quetiapine, risperidone, and sertindole, which have lower affinities for D2 receptors, cause fewer extrapyramidal effects than typical neuroleptic drugs (183,185,186). However, there are reports of extrapyramidal effects associated with these atypical neuroleptic drugs (187-189). 

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