A Probiotic Strategy for Antipsychotic-induced Metabolic Dysfunction

Schizophrenia is a mental illness associated with psychosis and is treated with antipsychotic medication. These medications are very effective; however, they are associated with side-effects that impact people's physical health. Substantial body weight gain occurs in up to half of people during long-term antipsychotic treatment. Antipsychotics can also increase glucose (sugar) and lipid (fat) levels in the blood, and the ones that do this the most, tend to be the same ones that cause the most weight gain. People taking antipsychotics regard weight gain as one of the most distressing side-effects caused by their medication. This weight gain often leads people to stop taking their antipsychotic treatment with a risk of their psychosis returning. People with psychosis die 15-20 years earlier than the general population. The leading cause of 'years of life' lost in this population is poor physical health. Heart disease and metabolic disorders are 1.4-2-fold more common in this population. Being overweight increases the risk of heart attack, stroke, and developing many physical illnesses and cancers. Furthermore, being overweight and experiencing psychosis are associated with reduced self-esteem, reduced quality of life, and stigma.

In a previous study by the investigating team, the investigators found that a bacteria found in the gut of healthy individuals, Bifidobacterium longum APC1472, was able to prevent obesity in mice treated with an antipsychotic. A second study conducted by the investigating team with people who were overweight or obese found that this type of bacteria, which may be developed into a new probiotic, improved sugar levels. The investigators are now looking to examine the impact this bacteria could have on the weight, blood sugars, and wellbeing of people treated with antipsychotic medication. Having access to a probiotic capsule that alleviates the most distressing side-effects of antipsychotic medications will benefit people who need these medications greatly.

Antipsychotic drugs are used to treat a range of psychiatric disorders including schizophrenia, bipolar disorders, and psychotic depression. Most antipsychotics are associated with significant weight gain and metabolic disturbances, which increase the risks for other diseases (obesity, diabetes, coronary diseases, etc.) and negatively impact medication adherence and quality of life. Evidence has shown that olanzapine, for example, increases appetite, food intake, and food reward and modulates the gut microbiota. The gut microbiota can modulate adiposity, metabolism and immune-endocrine signals that impact host's energy balance and feeding behaviour. This, together with the fact that antipsychotics induced remodeling of the gut microbiota has been associated with weight gain, suggests that microbiota-targeted interventions could help to alleviate or prevent the distressing side-effects of antipsychotic medications. The investigators have previously published promising data demonstrating anti-obesity effects of a novel Bifidobacterium longum APC1472, in a mouse model of obesity and in an overweight/obese population of humans, reducing levels of glucose and normalizing ghrelin levels. Because atypical antipsychotic medications are often used in people experiencing psychosis and the mechanisms of antipsychotic-induced weight gain and metabolic dysfunction have been suggested to include glucose intolerance (hyperglycaemia) and aberrant ghrelin signalling, the investigators propose to assess if adjunct supplementation of Bifidobacterium longum APC1472 can attenuate weight gain and metabolic side-effects associated with the use of atypical antipsychotic medication in people with non- affective psychosis. The investigators propose an exploratory patient-oriented research study, to assess the potential of adjunct Bifidobacterium longum APC1472 supplementation in individuals with psychosis receiving antipsychotic treatment, to ameliorate the liability to gain weight and/or normalize metabolic disturbances. Findings from this study will support clinical decision-making, increasing patient choice, and increase medication adherence, which will ultimately improve health and quality of life, and overall wellbeing of individuals as they pass through normal life stages.

A high percentage of individuals experiencing affective or a non-affective psychotic episode are treated with second-generation antipsychotics. While effective, most are associated with a significant liability for weight gain and metabolic disorders, negatively impacting adherence, health and quality of life. This study will explore the potential of a metabolically beneficial Bifidobacterium longum APC1472 to attenuate weight gain and metabolic side-effects in individuals with a non-affective psychosis, treated with antipsychotics.