A new research effort investigates the medical side-effects of new or second generation antipsychotic medications prescribed for schizophrenia.
While the medicines have proven effective in treating the disease, individuals often gain weight and develop other risk factors of metabolic syndrome, placing an individual at greater risk of heart disease and type 2 diabetes.
Schizophrenia is a complex type of psychotic mental illness characterized by thoughts that are uncoupled from reality. Huge gains in the effective treatment of individuals with the disease began in the 1950s with the development of the first generation of antipsychotic drugs.
The new class of medications, known as atypical antipsychotic (AAP), were put into use in the 1990s.
These medications allowed physicians to treat the “positive” effects of the illness (delusions and hallucinations) and, to a lesser extent, the “negative” symptoms (apathy).
Prior research on animal models discovered the consumption of at least one atypical antipsychotic may increase the risks for metabolic syndrome. The model allowed researchers to explore the sequence of early metabolic events that may result from atypical medications.
In the new study, scientist built upon the model allowing a clear distinction between the antipsychotic drugs that produce some weight gain, moderate weight gain or no gain at all. According to the scientists, these distinctions corresponded to the response in humans.
In the study 18 male rats were randomly assigned to one of three groups: (1) those receiving the conventional antipsychotic drug haloperidol (HA); (2) those receiving the atypical antipsychotic drug olanzapine (OL); or (3) the control (CO) group which did not receive either drug.
The medicines were given in food for a period of six weeks. Female rats were excluded to eliminate bias in the study since antipsychotic-induced weight gain in female rodents is likely related to an interaction of the drugs with estrogens.
Testing after four weeks found that the concentration of blood sugar (as glucose) was higher in OL rats (0.87 g/l) than in CO rats (0.75 g/l) and the levels increased more rapidly after a glucose meal. Testing six weeks later found fasting blood sugar levels continued to rise in OL rats (1.46 g/l vs. 1.25 g/l in CO rats) while the level of lipids (fats) in the blood was similar for both groups.
Although there was no difference in body weight gain or food intake, the proportion of fat stored in the abdominal cavity was higher in OL rats (1.63%) vs. CO rats (1.44%).
The HA rats did not vary in any way with the control group at any time. They exhibited a lower blood sugar level after a glucose meal and a lower proportion of intraabdominal fat store (1.44%) than OL rats.
Senior study author Dominique Hermier said, “Based on these findings we concluded that male rats treated with olanzapine experienced an early disruption of energy metabolism. This was a result of the fat tissue we observed and the impairment in blood sugar regulation which are both associated with metabolic syndrome and subsequent risk of diabetes.”
She added, “Atypical medications like olanzapine are of tremendous value in treating individuals with certain kinds of mental illness. Our hope is that through discoveries such as this one, such life-enhancing medicines can be further optimized.”
Source: American Physiological Society