Antipsychotic medications are used in the management of
schizophrenia and a growing number of off-label conditions. While effective at reducing
psychoses, these drugs possess noted metabolic side effects including
weight gain, liver
lipid accumulation and disturbances in
glucose and lipid metabolism. To counter the side effects of
antipsychotics standard of care has typically included
metformin. Unfortunately,
metformin does not protect against
antipsychotic induced metabolic disturbances in all patients and thus additional treatment approaches are needed. One potential candidate could be
salsalate, the
prodrug of
salicylate, which acts synergistically with
metformin to improve indices of
glucose and lipid metabolism in obese mice. The purpose of the current investigation was to compare the effects of
salsalate,
metformin and a combination of both drugs, on
weight gain and indices of metabolic health in female mice treated with the
antipsychotic,
olanzapine. Herein we demonstrate that
salsalate was equally as effective as
metformin in protecting against
olanzapine induced
weight gain and liver
lipid accumulation with no additional benefit of combining both drugs. Conversely,
metformin treatment, either alone or in combination with
salsalate, improved indices of
glucose metabolism and increased energy expenditure in
olanzapine treated mice. Collectively, our findings provide evidence that dual
therapy with both
metformin and
salsalate could be an efficacious approach with which to dampen the metabolic consequences of
antipsychotic medications.