Weight Gain with Olanzapine: Drug, Gender or Age?

Article excerpt

Byline: Sanjay. Jain, Manish. Bhargava, Shiv. Gautam

Background: The introduction of atypical antipsychotics was a big step forward in the treatment of schizophrenia and other psychoses. Their limitations, however, became evident over time. Aim To study the causes of weight gain associated with the use of olanzapine-an atypical antipsychotic drug. Methods: Eighty patients fulfilling the ICD-10 criteria for schizophrenia, predominantly with negative symptoms, were included in this study to evaluate weight gain as an adverse effect of treatment with olanzapine in relation to age, gender, dose and body mass index (BMI). Sociodemographic data and baseline weight along with height (to calculate the BMI) were recorded before the initiation of treatment. The patients were administered a flexible dose of olanzapine (5-15 mg) as monotherapy. Pregnant patients, smokers and those with endocrine disorders, cardiac problems and organic brain dysfunction were excluded from the study. The increase in weight as a neuroleptic side-effect of olanzapine was recorded and analysed in relation to age, gender, dose and BMI. Results: Of the patients receiving olanzapine, 66.6% had a weight gain of 1-5 kg over a period of 4 weeks. The weight gain was not related to the dose of the drug or BMI. The interesting finding was that the increase in weight was significantly related to age ?40 years and female sex, indicating that women> 40 years of age are more prone to gain weight with olanzapine therapy in comparison with women < 40 years and men of any age group. Conclusion: The potential for weight gain associated with the use of atypical antipsychotics to cause long-term complications will need further study. Clinicians are encouraged to monitor weight, plasma glucose and leptin levels, and lipid parameters in patients receiving olanzapine.

Introduction

The introduction of antipsychotic drugs during the 1950s was a big step forward in the treatment of schizophrenia and other psychoses of these drugs effectiveness as well as adverse effect profile, however, became evident over time. Until a few years ago, these novel antipsychotics demonstrated an improved therapeutic profile compared with that of conventional antipsychotics in terms of effectiveness and adverse effect profile. With regard to endocrine and metabolic effects, there are no surprises at this stage with conventional antipsychotics. The adverse effect profile of these drugs is well known and can generally be anticipated. Accordingly, clinicians are now focusing away from concerns of motor effects and their emphasis has shifted to weight gain, drug-induced glucose imbalance and other emerging metabolic effects associated with the use of atypical antipsychotics.

A national survey in the USA, which evaluated the patterns of use and emerging adverse effect profile of atypical antipsychotics, found that 70% of patients were prescribed an atypical antipsychotic drug and only 30% a typical antipsychotic. Thirty-four per cent of the patients on atypical antipsychotics reported weight gain in comparison to 16% on typical antipsychotics; weight gain was more evident in females (54%).[1]

Since weight gain contributes to non-compliance with treatment and may lead to medical morbidity, it is important to know and study the causes of weight gain associated with the use of the atypical antipsychotic olanzapine.

Olanzapine, a thienobenzodiazepine, is an atypical antipsychotic drug with a high affinity for the serotoninergic receptors 5-HT[sub] 2 and 5-HT[sub] 6 , and a low affinity for 5-HT[sub] 3 receptors in vitro. It also has a high affinity for dopaminergic receptors, mainly D2, D3 and D4; muscarinic M1-5; a[sub] 1 adrenergic; and histaminergic H1 receptors in vitro.[sup] 2 The drug reaches peak plasma levels in 5-8 hours and is metabolized through cytochrome p450 cyp1a2 and p450 cyp2d6. It has a half-life of about 45 hours, depending on the rate of metabolism. …