Serotonin specific reuptake inhibitor antidepressants (SSRIs) have become t
he de facto first line treatment in pharmacotherapy of major depression. Al
beit SSRIs have the advantage in tolerance and safety over older treatments
, their ease of use does not circumvent the major enduring clinical problem
of treatment resistant depression (TRD), For TRD in the setting of an SSRI
failure recent data supports a range of strategies including switching, ei
ther to a second SSRI or out of the class to a non-SSRI antidepressant, or
augmentation with the addition of lithium carbonate. Data concerning use of
buspirone and pindolol, serotonin 1A receptor partial agonists, as augment
ation agents in SSRI failure remains mixed. In contrast venlafaxine continu
es to look quite promising in TRD, Curr Opin Psychiatry 13:93-98. (C) 2000
Lippincott Williams & Wilkins.