Intervening to prevent serious side effects
For people with schizophrenia, their mental illness comes with a physical toll: they have roughly a 20 per cent reduced life expectancy on average compared with the general population, mainly because of a higher risk of heart disease.
Several factors contribute to this bigger heart risk. Commonly prescribed to treat schizophrenia, newer antipsychotic drugs are linked with significant weight gain and higher risks of obesity and diabetes.
"There are people who refuse to take their medication because of the side effects. It's a very serious issue," says CAMH's Dr. Margaret Hahn, Clinician Scientist in the Schizophrenia Program and Co-director of the Mental Health and Metabolic Clinic.
In three new studies, Dr. Hahn is investigating how to prevent these side effects in people with schizophrenia, for whom there are very few treatments to date other than diet and exercise. A key target of her work is metabolism – how our bodies break down and convert what we eat and drink into energy.
Changes in metabolism
What's driving Dr. Hahn's interest in metabolism is the fact that people with schizophrenia are two times more likely than the general population to develop metabolic syndrome, and three to five times more likely to develop type 2 diabetes. Metabolic syndrome is a cluster of metabolism "abnormalities," including high blood pressure, a low level of "good" or HDL cholesterol and excess fat in the stomach area. "Diabetes is irreversible and associated with heart disease, kidney failure, blindness and amputations," says Dr. Hahn. "We want to do everything we can to prevent it.”
"High sugar levels also impair cognition," says Dr. Hahn. "And we know that cognitive deficits are a core symptom of schizophrenia."
Few existing treatments
Researching new possible treatments is important because, other than research into interventions targeting antipsychotic-induced weight gain, "there are virtually no studies looking at interventions for these modifiable cardiovascular risk factors in people with severe mental illness," says Dr. Hahn. Exercise and diet alone may not be enough.
As well, the underlying causes of these metabolism changes may be different in people with schizophrenia than in the general population. In addition to medications, factors related to lifestyle, health care services and genes may be involved, says Dr. Hahn. For example, lifestyle factors affecting people with schizophrenia may include poor dietary habits, lower levels of physical activity and higher rates of smoking. Individuals may have reduced access to medical care. In some cases, ambiguity or poor coordination between mental health services and physical health services may mean that metabolism changes may not be appropriately monitored or treated. A genetic link also exists between schizophrenia and type 2 diabetes.
Dr. Hahn is leading three clinical trials to test new interventions and better understand early changes that increase heart and metabolic risks.
In a randomized controlled trial, Dr. Hahn is studying a medication called topiramate in people aged 17 to 49 who are taking the antipsychotic drug clozapine and have experienced weight gain. “Clozapine is the last-line medication for people with schizophrenia who have not responded to other treatments," says Dr. Hahn. Topiramate, an anti-seizure medication, has also been shown to help with weight loss and improve psychiatric symptoms. In addition to looking at topiramate's impact on blood sugars and weight, the study will include magnetic resonance imaging (MRI) scans of the brain related to cognition and of the stomach to look at effects on visceral fat, the "bad fat" that surrounds organs in the stomach area and is a risk factor for heart disease and diabetes, says Dr. Hahn.
Working as part of the Slaight Family Centre for Youth in Transition at CAMH, Dr. Hahn is testing an anti-diabetic drug called metformin paired with a lifestyle intervention, which involves seeing a dietitian. The study is examining people aged 40 years or younger who take an antipsychotic medication and have early abnormalities in how their body regulates blood-sugar levels. The goal is to assess how this new medication will affect weight, sugar (glucose) metabolism, fat distribution and brain health. Participants will receive an MRI brain scan to assess whether high glucose levels are linked with a reduction in brain volume.
In another study, she is also investigating metabolism changes in new users of antipsychotic medications who are aged 12 to 35 years. Combining blood and sugar tests and MRI imaging, the study seeks to understand what happens in young people when they begin taking antipsychotic drugs for the first time.
Throughout her research, her main goal is the same: “If we can treat blood sugars, prevent or reduce weight gain, and lower the risk of diabetes, we may be able to change the long-term symptoms of schizophrenia,” says Dr. Hahn. “Most importantly, we can also improve the quality of lives of young people already burdened with this serious mental illness.”