The nocebo effect: a reason for patients' non-adherence to generic substitution?

Substituting generic formulations of the same chemical agent is a common practice in German health care on the basis of so called rebate contracts. The substitution of a medication may affect the patients' adherence or result in adverse events. While adverse events which may be caused by the pharmacological activity of the agent itself can be explained, some non-specific side effects cannot be substantiated referring to pharmacological factors.

Substitution of theophylline slow-release formulations according to the rebate contracts in the German statutory health insurance.

On the basis of the rebate contracts between individual statutory health insurance funds and pharmaceutical enterprises, the generic substitution of prescribed medications is economically attractive and is advocated for statutory health insurees in Germany. In addition to the drugs whose substitution can be considered to be uncritical, rebate contracts also include controversial substances such as the bronchodilator theophylline (CAS 58-55-9), which has a narrow therapeutic range and should only be substituted under certain conditions. The objective of this article was to check the safety of the substitution of theophylline by means of a comparative evaluation of bioequivalence studies carried out on theophylline slow-release preparations.