ECT as Used in Psychiatry Temporarily Opens the Blood"Brain Barrier: Could This be Used to Better Deliver Chemotherapy for Glioblastoma

Abstract

Glioblastoma remains a poor"prognosis cancer. We review research showing evanescent opening of the blood"brain barrier, BBB, after electroconvulsive treatment, ECT. ECT as currently used in psychiatry for treatment"resistant depression has been in continuous use throughout the world since introduction in the late 1930’s. Post-ictal BBB opening phenomenon might be safe enough to use to deliver chemotherapeutic agents that would not otherwise cross the BBB. Although the main mass of tumor in glioblastoma has a relatively leaky BBB, the invasive paucicellular migratory microsatellite glioblastoma cells that become the origin of recurrent tumor are supplied by normal poorly"permeable capillaries, preventing ready access of potentially useful chemotherapy drugs like doxorubicin or methotrexate. These microsatellites go on to kill. Modern ECT uses deep neuromuscular blockade and cardiovascular stabilizing drugs such that muscular contractions and increases in intracranial pressure are minimized, yet the electroencephalogram shows a typical grand mal seizure. Post"ECT BBB opening allows transgression of > 4 kDa peptides, potentially comfortable enough to give free access to brain tissue of doxorubicin or methotrexate for example. Even drugs that are said to cross the BBB, such as temozolomide, the current mainstay chemotherapy drug in glioblastoma, do so only at ~20% of plasma levels. Many potentially useful drugs achieve brain tissue levels <1% of blood levels. We conclude that if careful step-wise study can establish safety, by delivering chemotherapy immediately after ECT we may open new and more effective treatment avenues for glioblastoma.