ANTIDEPRESSANT DRUG SELECTION - CRITERIA AND OPTIONS

The dilemma of developing new medications rationally-as opposed to dis covering them through serendipity-is to create an optimal balance betw een the number of mechanisms of action needed for the widest spectrum of antidepressant activity while maximizing safety and tolerability. N ewer antidepressants, such as serotonin selective reuptake inhibitors (SSRIs) and venlafaxine, have a wider therapeutic index than the older tricyclic antidepressants. Fewer types of adverse effects and a reduc tion in the potential for pharmacodynamic interactions are the distinc t benefits of all the newer targeted antidepressants, such as venlafax ine, SSRIs, and bupropion, in comparison with older drugs. However, th ere are important differences among the newer antidepressants in terms of effects of P450 enzymes, dose-response curves for antidepressant r esponse and adverse effects, and dosing schedules. One of the main ben efits of having a wide array of options is the evidence that there may be different forms of the illness, which respond to different mechani sms of action. More research is needed to test this concept and to dev elop predictors of differential responsiveness.