Strategies for the testing of antidepressants: trials and tribulations. An overview

Short-term, long-term and prophylactic trials are all important for the thorough assessment of a new antidepressant. Patients are carefully selected for such trials according to rigidly applied selection criteria, and their depressive disorder should be rated using a standard classification system. Multicentre trials are often a useful means of obtaining sufficient numbers of patients for valid conclusions to be drawn, but different assessors obtain quite different results even on the same rating scales. Thus, ideally, the assessors should undergo centralized training in such rating. A useful method of circumventing these problems is to use a more objective test, such as the dexamethasone suppression test. Trials should also compare the new drug with placebo and standard antidepressants (e.g. 150 mg/day amitriptyline). The safety profile should be carefully established by monitoring side-effects and investigating interactions with commonly used drugs (including alcohol). Most new antidepressants are found to be equally as effective as, but no better than, standard antidepressant therapy. However, many new antidepressants have the advantage of causing fewer side-effects.