Maniac tells the story of Annie Landsberg and Owen Milgrim, two strangers who follow a mysterious medical process, each for a different reason. Annie goes through life aimlessly and dissatisfied after losing contact with her mother and sister. Owen, the fifth son of a wealthy New York family, has struggled with schizophrenia all his life. Their lives are not going as they planned and only the arrival of a new, radical treatment in the medical world could restore their brains.