Abstract: Methods and compositions are provided for preventing or reversing loss of the therapeutic effect of a drug, where the loss is associated with the repeated administration of the drug to a patient. The method includes administering to the patient a dopamine receptor agonist or partial agonist or a drug that increases the extracellular level of dopamine by enhancing release of dopamine, decreasing the removal of dopamine from the extracellular space, enhancing the synthesis of dopamine within the brain, or decreasing metabolic degradation of dopamine; and also administering to the patient an opioid receptor antagonist in an ultra-low dose amount, wherein the ultra-low dose amount is effective to prevent or reverse loss of therapeutic effects associated with the repeated administration of the drug to the patient. The methods are useful for various treatments, including treating Parkinson's Disease, Restless Leg Syndrome, depression, schizophrenia, psychostimulant drug abuse, or attention deficit disorder.

Abstract: A combination of a pro-agonist first medication in timed release form, and a sequestered second non-antagonist medication allows the first medication to be effective if taken according to medical directions. If the combination is tampered with or otherwise taken in a manner not according to medical directions, the second medication is released and prevents the first medication from becoming effective. The non-antagonist second medication does not precipitate immediate withdrawal in a dependent patient.

Abstract: Pharmaceutical dosage forms are provided for use in deterring abuse of opioids or other medications, which help avoid harm to a patient dependent on the medication. In one case, a pharmaceutical oral dosage form is provided that includes a plurality of microcapsules, each microcapsule of the plurality containing an opioid agonist medication in a controlled release form, and a partial opioid agonist sequestered in the pharmaceutical dosage form, such that upon oral administration of the pharmaceutical oral dosage form the partial opioid agonist will pass through the gastrointestinal tract without uptake by the body.