Olanzapine dosage

In 11 healthy volunteers carbamazepine (400 mg/day for 2 weeks) reduces by about 30% the AUC of olanzapine, presumably by induction of olanzapine metabolism (104). Although the interaction was considered of little relevance, it cannot be excluded that some patients on carbamazepine may require higher olanzapine dosages than usual. 

Administer once daily in the evening, generally beginning with the 6 mg/25 mg capsule. While food has no appreciable effect on the absorption of olanzapine and fluoxetine given individually, the effect of food on the absorption of olanzapine/fluoxetine has not been studied. Dosage adjustments, if indicated, can be made according to efficacy and tolerability. Antidepressant efficacy was demonstrated with olanzapine/fluoxetine in a dose range of olanzapine 6 to 12 mg and fluoxetine 25 to 50 mg. The safety of doses above 18 mg/75 mg has not been... 

In the total sample of 609 patients the mean (SD) prescribed dosages of study drugs were 16.8 (7.4) mg for olanzapine and 306 (166) mg for clozapine. 

Olanzapine had significantly positive diabetic effects, based on both duration of treatment and dosage. All patients had been exposed to antipsychotic drugs for more than 60 days because there was less awareness of the diabetic effects of atypical antipsychotic drugs during that period, the use of these data reduced the possibility of selection bias. 

A 50-year-old man developed acute ketoacidosis with de novo diabetes mellitus after 8 months of adjunctive olanzapine (865). His dosage was then gradually titrated to 30 mg/day over 6 months, and after withdrawal of olanzapine his diabetes mellitus disappeared completely. 

A meta-analysis of four comparisons of olanzapine and haloperidol showed similar efficacy, with fewer extrapyramidal effects with olanzapine (17). Similar conclusions were reached in another meta-analysis of three randomized, double-bhnd, controlled comparisons of olanzapine and haloperidol (53). Only 15% of olanzapine-treated patients (n = 1620, dosage 5-20 mg/day) needed anticholinergic drugs compared with 49% of those treated with haloperidol (n = 786, dosage 5-20 mg/day). 

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. 

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). 

Olanzapine has fewer extrapyramidal effects than typical neuroleptic drugs such as haloperidol (SEDA-24, 66). Even some cases of tardive dystonia have been successfully managed with atypical neuroleptic drugs. The anti-dystonic efficacy of olanzapine has been studied in an open video-blinded study in four patients with tardive cervical dystonia after several years of neuroleptic drug treatment (35). There was moderate to marked improvement in dystonia in all of them, and no serious adverse effects at the maximum dosage reached (7.5 mg/day). 

Two cases of light-headedness or fainting in patients taking olanzapine have been reported (80). Electrocardiograms showed first-degree heart block and AV conduction delay, which normalized after dosage reduction. 

Akathisia has been reported in 16% of patients taking olanzapine (SEDA-21, 56). Three patients developed severe akathisia during treatment with olanzapine (20-25 mg/day) (87). In two, the akathisia resolved after withdrawal of olanzapine and in one of those olanzapine was well tolerated when reintroduced in combination with lorazepam. In the third patient, the akathisia was controlled by dosage reduction. A 33-year-old man with AIDS and a prior history of extrapyramidal symptoms with both typical antipsychotic drugs and risperidone developed dose-dependent akathisia with olanzapine 15-19 mg/day the akathisia responded to dosage reduction and beta-blockade (88). 

Worsening parkinsonism was observed in two patients after treatment with olanzapine 5 mg/day (114). In contrast, coarse tremors induced by fluphenazine or haloper-idol disappeared in three patients within days of the start of treatment with olanzapine (10 mg/day), without discontinuation or reduction in the dosage of fluphenazine or haloperidol (115). Olanzapine is active at muscarinic cholinergic receptors, which may account for the observed suppression of neuroleptic drug-induced tremor however, two of the three patients had been taking ben-zatropine, an antagonist at muscarinic acetylcholine receptors, with little tremor relief, suggesting that olanzapine could suppress tremor by means of an action other than muscarinic blockade. 

A 27-year-old woman had a seizure while taking a stable dosage of olanzapine 15 mg/day 1 day after the introduction of quetiapine 100 mg in the evening (130). She suddenly fell to the ground and had generalized shaking and inarticulate vocalization for about 30-60 seconds. 

Fluvoxamine under steady-state conditions increases the systemic availability of olanzapine and inhibits the metabolism of clozapine, as shown in 21 male non-smoking Chinese volunteers (mean age 27 years) (277). This could be related to the different metabolic pathways and secretion rates of the two drugs it would be advisable to reduce the dosage of olanzapine and to extend the dosing interval of clozapine when they are combined with fluvoxamine. 

Gurovich I, Vempaty A, Lippmann S. QTc prolongation chlorpromazine and high-dosage olanzapine. Can J Psychiatry 2003 48 348. 

Alevizos B, Papageorgiou C, Christodoulou GN. Acute dystonia caused by low dosage of olanzapine. J Neuropsychiatry Clin Neurosci 2003 15 241. 

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