NIH Study Shows Antidepressants May Enhance Drug Delivery to Brain

A new study from the United States National Institutes of Health (NIH) found that pairing the antidepressant amitriptyline with drugs designed to treat central nervous system diseases, enhances drug delivery to the brain by inhibiting the blood-brain barrier in rats. The blood-brain barrier serves as a natural, protective boundary, preventing most drugs from entering the brain. The research, performed in rats, appeared online April 27, 2017 in the Journal of Cerebral Blood Flow and Metabolism.

According to a press release from NIH, the new finding has the potential to revolutionize treatment for multiple brain-centered conditions including epilepsy, stroke, human amyotrophic lateral sclerosis (ALS), depression, and others. Although NIH says more research is needed to confirm the benefit in humans, a provisional patent application has been filed for methods of co-administration of amitriptyline with central nervous system drugs.

According to Ronald Cannon, PhD, staff scientist at NIH’s National Institute of Environmental Health Sciences (NIEHS), the biggest obstacle to efficiently delivering drugs to the brain is P-glycoprotein. Located along the inner lining of brain blood vessels, P-glycoprotein directs toxins and pharmaceuticals back into the body’s circulation before they pass into the brain.

Cannon and his NIEHS colleagues initially found that amitriptyline significantly reduced P-glycoprotein’s pump activity in brain capillaries from wild-type rats. Later, they saw amitriptyline had the same effect in brain capillaries from genetically modified rats designed to mimic human ALS. In both rat models, amitriptyline turned off P-glycoprotein within 10–15 minutes. When amitriptyline was removed, P-glycoprotein pump activity returned to full-strength.

NIEHS post baccalaureate fellow David Banks is lead author on the paper and described amitriptyline’s action on P-glycoprotein as rapid and reversible. “Most inventions developed at the bench don’t make it to the clinic, but I’m hopeful that our findings will translate into better treatment options for doctors and their patients,” Banks said in a statement.

Cannon anticipates that administering amitriptyline along with a lower dose of an opioid could relieve pain and reduce the negative side effects, such as constipation and addiction, usually seen with higher doses of prescribed opioids.

Source: NIH