The summer before Mark started his studies at the Engineering Faculty, his behaviour drastically changed. Not that he would have noticed it he started avoiding even his best friends convinced they were spying on him in order to help the authorities to come after him. His distrust soon spread to his brother and other family members, who then realised that Mark needed medical assistance. The prescribed medication eased Mark’s psychiatric problems, once the dosage was finetuned, but as a consequence Mark put on lots of weight.

Mark’s diagnosis is Schizophrenia, a mental disorder characterised by abnormal social behaviour, whose onset typically occurs during late adolescence and early adulthood. Common symptoms are false beliefs, unclear or confused thinking, hearing imaginary voices.

The causes of schizophrenia are a combination of genetic and environmental factors. From a genetic point of view, the heritability contributes around 80%, although environmental factors, such as living environment, drug use and prenatal stress are also considered to be significant contributors.

Clinically, schizophrenia is a worldwide spread mental disease which results in a decreased life expectancy by around 20%, primarily because of its association with obesity arising from a sedentary lifestyle and antipsychotic drug-related side effects.1

Many drugs that best control Schizophrenia symptoms make patients obese and more likely to develop metabolic side-effects with a higher risk to develop diabetes and cardiovascular diseases. The mechanisms causing the onset of these severe metabolic side effects are still unknown and are currently being also investigated by a consortium ITN Treatment funded by the grant from the European Union.

Discovery of early metabolic modifications will provide a foundation to develop diagnostics of metabolic changes and enable a timely switch to another drug before metabolic derangements are manifested as side effects. It will also contribute to the assessment of novel drugs for these side effects.

Switching from widely used antipsychotics that are known to be associated with adverse weight and metabolic effects (olanzapine, quetiapine, and risperidone) to treatment with aripiprazole, which is associated with a lower rate of such effects, seems to improve the metabolic parameters. For example, a three-year study at 27 clinical research centres in the USA on 215 patients (129 completed the entire 24-week protocol on assigned treatment) that were assessed for clinical manifestations of metabolic changes (metabolic syndrome) and risk of cardiovascular disease development has reported a reduction in both parameters in participating men and women.

Encouraging results of reduction of cardiovascular disease risk, by about 10%, however, cannot be attributed only to the medication switch, as study participants were also on a diet improvement and exercise program. Nevertheless, it is important that the applied lifestyle interventions improved the metabolic parameters even in the patients that remained treated with drugs with the associated adverse metabolic effects.

Improvement of metabolic effects after changed medication was also confirmed by other studies, but needs some more testing, because of the relatively short duration of the studies.2

While changing medication may help patients after the adverse symptoms are developed, it would be better if a timely detection of possible metabolic derangements were possible. The results of the clinical trial mentioned above also imply that the appropriate lifestyle modifications can reduce the side-effects also in the patients on drugs associated with substantial weight gain and adverse metabolic effects. It is therefore important to explore the possibility of providing sufficient care and support to enable the patient to adhere to a healthy lifestyle regime.

Francesca Forno and Irina Milisav

  1. Stroup TS, et al. 2013. Effects of switching from olanzapine, quetiapine, and risperidone to aripiprazole on 10-year coronary heart disease risk and metabolic syndrome status: results from a randomized controlled trial. Schizophr Res. 2013 May;146(1-3):190-5. doi: 10.1016/j.schres.2013.01.013. PMID: 23434503; PMCID: PMC3622801. 
  2. Wani RA, et al. 2015. Effects of switching from olanzapine to aripiprazole on the metabolic profiles of patients with schizophrenia and metabolic syndrome: a double-blind, randomized, open-label study. Neuropsychiatr Dis Treat. 2015 Mar 13;11:685-93. doi: 10.2147/NDT.S80925. PMID:25792838; PubMed Central PMCID: PMC4364593.