The number of previous treatments with antidepressants was negatively correlated with treatment outcome .
After a first SSRI , any switch within or between classes of antidepressants appears legitimate ( second SSRI , novel dual-acting antidepressants , selective norepinephrine or nor-adrenergic/dopaminergic agents , or tricyclic anti-depressant or mianserin ) .
No unequivocal evidence is available to prove an advantage of a between-class switch .
OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are frequently used as a first antidepressant for major depressive disorder but have response rates of 50 % to 60 % in daily practice .
For patients with insufficient response to SSRIs , switching is often applied .
This article aims to systematic ally review the evidence for switching pharmacotherapy after a first SSRI .
Lithium Augmentation of Nortriptyline for Subjects Resistant to Multiple Antidepressants
Lithium augmentation , the most studied augmentation strategy for depression , has not been evaluated in patients with a history of non-response to multiple antidepressants . The objective of this study was to assess the efficacy of lithium augmentation for patients with a history of treatment resistant depression who also failed a prospect i ve trial of nortriptyline .  We enrolled 92 subjects with treatment resistant depression . Treatment resistance was defined by at least one , but no more than five , adequate trials of antidepressants during the current episode . Subjects were treated with nortriptyline ( NT ) for 6 weeks . Those subjects who tolerated NT for 6 weeks and whose depression did not respond ( n=35 ) were r and omized to receive either lithium ( n=18 ) or placebo ( N=17 ) augmentation of nortriptyline for an additional 6 weeks . Response was defined as an equal to or greater than 50 % decrease in HAM-D-17 scores . After 6 weeks of double-blind augmentation , 12.5 % of subjects responded to lithium and 20.0 % to placebo . Our results revealed no significant difference between lithium and placebo augmentation . While lithium augmentation seems to be useful in depression refractory to a single medication in some studies , our data suggest limited usefulness of this option for patients refractory to multiple treatments . More definitive data await the outcome of the NIMH Sequential Treatment Alternatives to Relieve Depression ( STAR*D ) study
The number of previous treatments with antidepressants was negatively correlated with treatment outcome .
After a first SSRI , any switch within or between classes of antidepressants appears legitimate ( second SSRI , novel dual-acting antidepressants , selective norepinephrine or nor-adrenergic/dopaminergic agents , or tricyclic anti-depressant or mianserin ) .
No unequivocal evidence is available to prove an advantage of a between-class switch .
OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are frequently used as a first antidepressant for major depressive disorder but have response rates of 50 % to 60 % in daily practice .
For patients with insufficient response to SSRIs , switching is often applied .
This article aims to systematic ally review the evidence for switching pharmacotherapy after a first SSRI .