The recent commentary by Carpenter et al1 was timely and important. Some of their points regarding the necessity of medication-free research in new drug development merit additional discussion. Their arguments for medication-free periods can be classified into 2 groups: the initial lead-in period and the parallel placebo control group.
Their rationale for the initial medication-free lead-in period was (1) to prevent carry-forward effects of prestudy medication; (2) to establish a medication-free baseline; and (3) to minimize the risk of adverse drug-drug interactions.
Volavka J. Are Medication-Free Periods Necessary for Phase 3 Trials of New Antipsychotic Drugs?. Arch Gen Psychiatry. 1998;55(3):280-281. doi: