Treatment of resistant depression by adding noradrenergic agents to lithium augmentation of SSRIs

OBJECTIVE: To examine the efficacy of second-line augmentation with noradrenergic antidepressants (NAs) in depressed patients who partially responded to lithium augmentation of selective serotonin-reuptake inhibitors (SSRIs). CASE SUMMARY: Six patients with major depression or double depression (major depression and dysthymia) who were partially responsive to lithium and SSRI treatment were given either bupropion or desipramine, in an open clinical manner. Improvement was determined and rated by a psychiatrist based on clinical judgment guided by the Clinical Global Impression (CGI) improvement scale and by the Global Assessment of Functioning (GAF) as described in Axis V in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. RESULTS: Among the 6 depressed patients with partial remission (much improved in symptoms and moderate functional improvement: CGI score 2, GAF score 51-60) while taking the SSRI and lithium combination, 2 showed complete remission (very much improved in symptoms and good functioning: CGI 1, GAF 80-100) and 3 achieved near-complete remission (very much improved in symptoms and significant functional recovery: CGI 1, GAF 61-80) when given either bupropion or desipramine. One patient did not show any additional clinical or functional improvement. Second-line augmentation with bupropion was better tolerated than desipramine. CONCLUSIONS: This clinical observation suggests that second-line augmentation with NAs may be a viable option to optimize recovery in depressed patients with a partial response to lithium augmentation of SSRIs.

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