NEED FOR A NEW PARADIGM FOR THE CLINICAL-TRIALS OF ANTIDEPRESSANTS

The current clinical trials model for antidepressants (AD) was develop ed in the 1960s. It views major depression as a unitary disorder, and ''antidepressants'' as having illness-specific therapeutic actions. Th e established efficacy measures are the Hamilton symptom rating scale and the CGI, which provide summary measures of improvement. In contras t, the DSM IV defines depression as heterogeneous, with such broad cla sses as unipolar and bipolar showing different response to treatments. Research further indicates depression to be comprised of major affect ive and behavioral components which vary in intensity across patients, and the tricyclic ADs to have multiple actions that affect various co mponents sequentially. ''New'' ADs, products of rapid advancements in the neurosciences, are more precise in their actions on brain monoamin e systems, targeted to affect behaviors with greater specificity. A ne w trials model sensitive to the varied behavioral effects needs to be developed to adapt to these quicker acting, targeted antidepressants. A componential model is recommended that employs an array of behaviora l methods, and subtype classification and statistical approaches to es timate onset and sequence of multiple drug actions. The NIMH can inter vene to accelerate improvements by initiating funding programs to impl ement move effective clinical methods and models. (C) 1998 American Co llege of Neuropsychopharmacology. Published by Elsevier Science Inc.