Medical electrical lead systems and related methods are described. The lead systems may be configured to be at least partially implanted in neural tissue of a subject, such as a brain of a subject. Some variations of the lead systems may comprise a lead body, an electrode connected to the lead body, and a bioactive agent. The electrode and/or lead body may comprise a substrate, and the bioactive agent may be supported by the substrate (e.g., by a substantial portion of the area of the substrate). Examples of bioactive agents that may be used in the lead system include antiproliferative agents, bactericidal agents, bacteriostatic agents, antiepileptic agents, and/or antifungal agents. Methods described herein may comprise coating a lead body and/or an electrode of a medical electrical lead system with at least one bioactive agent, where the lead body and the electrode are connected to each other.