The present invention is directed to CNS pharmaceutical compositions and methods of use. The pharmaceutical compositions comprise a CNS active agent and preferably at least two vagal neuromodulators, one of which is a mechanoreceptor stimulator. The vagal neuromodulators are preferably in an amount sufficient to reduce a somnolence side-effect of the CNS active agent without changing its therapeutic efficacy/activity. The invention further encompasses a method of reducing CNS active agent side-effects. The method typically comprises oral administration of at least one CNS active agent to a patient at the conventionally accepted dose; and administration of at least two vagal neuromodulators to the patient so that at least one neuromodulator is administered or released from dosage form after the CNS active agent is administered and/or released.