A group of physiologic consequences that occur when chronic drug treatment is
terminated or an antagonist is administered. Typically, the withdrawal syndrome
has characteristics that are opposite in nature to the acute effects of the chronically
administered drug. In most cases, the longer the drug is administered and the
higher the dose, the more intense the withdrawal syndrome. Withdrawal is believed
to be a result of the removal of the drug from its site of action (e.g.,
receptor). The more rapid the removal of the drug from its site of action, the
more rapid the onset of withdrawal and the more severe the syndrome. As such,
drugs with rapid elimination kinetics often have intense, but shorter lasting
withdrawal syndrome. Similarly, the longer the elimination kinetics, the less
intense, but longer lasting the withdrawal syndrome. In cases where a withdrawal
syndrome occurs following administration of a drug that rapidly removes the chronic
drug from its site of action, the syndrome can be explosive and particularly unpleasant.