Analysis published in The Lancet Psychiatry has shown that there is significant difference in the way antipsychotic drugs affect body weight and levels of sugar, cholesterol and other fats in the blood.
Antipsychotics are commonly used to treat patients with schizophrenia, but some newer drugs – the so-called second-generation antipsychotics – are associated with a range of side effects known to put individuals at risk of diabetes and cardiovascular disease. This is particularly relevant because, compared with the general population, people with schizophrenia are twice as likely to have a diagnosis and die from cardiovascular disease.
This new study, undertaken by a team of researchers including Professor Andrea Cipriani from Oxford Health Biomedical Research Centre, is the first time that the medications have been ranked according to these side effects. The researchers aimed to investigate the possible contribution of antipsychotics to the poorer physical health of people with schizophrenia.
The analysis included 100 randomised controlled trials examining antipsychotics and placebo in the short-term treatment of schizophrenia, the level of metabolic side effects and their relationship to changes in the symptoms of schizophrenia. The side effects that were studied were increases in weight and body mass index (BMI), and increases in levels of glucose, cholesterol and other fats in the blood.
Although antipsychotic drugs all work on the same chemical system in the brain, they interact differently with other systems in the body. This may influence the risk of side effects.
Clozapine and olanzapine were shown to have the worst side effect profiles, but the research also demonstrated that a high level of metabolic side effects was linked to an improvement in the symptoms of schizophrenia. Clozapine is the only drug recommended for use in those who do not respond to other antipsychotics (treatment-resistant schizophrenia), so there may be no alternative for some patients.
Interestingly previous research has shown that, in spite of the side effects, people with schizophrenia treated with antipsychotics have better cardiovascular outcomes and live longer. This may be because improvements in their mental health from medication allow them to better look after themselves in the longer term.
The research also investigated which patient characteristics might predict a high level of these metabolic side effects. Professor Cipriani explains “we found that baseline body-weight, male gender, and non-Caucasian ethnicity predict greater vulnerability to antipsychotic-induced metabolic dysregulation. This suggests overlap between risk-factors for metabolic disease in the general population and in antipsychotic-induced metabolic disease. We also showed that improvements in the overall severity of symptoms are associated with increases in weight, BMI, total-cholesterol and LDL-cholesterol levels, and decreases in HDL cholesterol levels.”
It is hoped that the results of the study will be reflected in treatment guidelines to help doctors and patients choose the best drug treatment weighing up treatment benefits for symptoms against the risk of metabolic and other side effects.