One system includes a stimulation device such as a vagus nerve stimulation lead, and a controller for controlling the stimulation device according to a set of stimulation parameters. A memory of the stimulation device contains a state transition model, and for each state defines a set of stimulation parameters and at least one expected response during the application of stimulation with the parameters. A matrix determines the transition rules between states based on physiological levels measured versus target levels. A state transition control unit determines, in an organized timely method, possible transitions between states according to the rules on physiological levels obtained in response to the implementation of the stimulation parameters of the current state, and a transition from a current state to a new state causes a corresponding change in the parameter set used for stimulation.