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Do Depressed Subjects Who Have Failed Both Fluoxetine and a Tricyclic Antidepressant Respond to the Combination?

J Clin Psychiatry 1999;60(9):613–616

Background: Recent evidence suggests that the combination of fluoxetine and desipramine may provide a rapid and effective treatment for depression.

Method: The current study evaluated 13 subjects with DSM-III-R nonpsychotic major depression who had previously failed either desipramine or imipramine and who were currently unsuccessfully treated with fluoxetine. Desipramine or imipramine was added to fluoxetine and Hamilton Rating Scale for Depression (HAM-D) scores, Beck Depression Inventory (BDI) scores, and plasma tricyclic levels were monitored for 3 weeks.

Results: Of the 13 subjects, 7 (54%) had a greater than 40% decline in HAM-D scores and 4 of these (31%) had 50% or greater decline in HAM-D. At week 3, responders (767 ± 282 nmol/L) had a significantly higher mean tricyclic level as compared with nonresponders (515 ± 95 nmol/L, F = 25.1, p < .0001), and change in BDI scores was significantly correlated with tricyclic level (r = –0.60, p < .05).

Conclusion: These findings suggest that in some subjects the positive clinical effect of combining fluoxetine and a tricyclic antidepressant may be related to the plasma levels of the tricyclic compound.