Clomipramine augmentation in treatment‐resistant depression

Abstract

In depression that is resistant to tricyclic antidepressant (TCA) therapy, the substitution of a selective serotonin re-uptake inhibitor (SSRI), clomipramine, or a monoamine oxidase (MAO) inhibitor has been recommended. However, adding an additional antidepressant medication from a different drug class may produce even more rapid efficacy. In this regard, the combination of a MAO inhibitor or a SSRI plus a TCA has been shown to be of value in treatment-resistant depression (TRD). In this report, we examined the efficacy of clomipramine augmentation in 20 patients who failed to respond to either a MAO inhibitor or fluoxetine therapy for at least a 6-week period, and compared this to a third group given MAO inhibitor plus a conventional TCA. Two out of 9 (22%) MAO inhibitor/clomipramine patients and 4 out of 11 (36%) fluoxetine/clomipramine patients improved (Fisher's Exact test, P = ns), compared to 3 out of 7 (43%) patients taking MAO inhibitor/TCA (P = ns). However, the MAO inhibitor/clomipramine group experienced significantly more adverse events which necessitated stopping treatment (56%) when compared to the fluoxetine/clomipramine (9%) and compared to the MAO inhibitor/TCA group (0%) (chi 2 = 8.9, df = 2, P < 0.05). These adverse events included several cases of serotonin syndrome of mild to moderate severity. These observations indicate that clomipramine augmentation of a failed MAO inhibitor trial is of marginal efficacy (compared to augmentation with a conventional TCA) and should be employed with extreme caution.

Tricyclic antidepressant pharmacology and therapeutic drug interactions updated

“…Psychiatrists continue to struggle to understand the antidepressant drug–drug interactions of TCAs. Disagreements of both opinion and fact are evident in reference texts ( Ellis, 2004 ; Anon, 2005 ; Cowen, 2005 ; Rossi, 2007 ) and in review papers ( Amsterdam et al ., 1997 ; DeBattista et al ., 1998 ; Bonnet, 2003 ). This applies particularly to TCA interactions with MAOIs ( Gillman, 1998 , 2006a ; Gillman and Whyte, 2004 ).…”

Reboxetine Combination in Treatment-resistant Depression to Selective Serotonin Reuptake Inhibitors

“…Although the number of publications in combination treatments has seen a marked increase, the effectiveness has not yet been suffi ciently demonstrated in many controlled trials [12,13,28,38,41] . The combination strategies most well documented in the scientifi c literature are SSRI with tricyclic antidepressants (TCA) [2,16,32,33,47] , SSRI with mirtazapine [7,8] and SSRI with bupropion [6,22,24,43] . One of the drugs most widely used in recent years in combination treatments is reboxetine, an antidepressant from the family of selective noradrenaline reuptake inhibitors.…”

Transcriptomic profiling of human hippocampal progenitor cells treated with antidepressants and its application in drug repositioning

“…Our results also revealed that the drug clomipramine had the highest connectivity score, suggesting it evokes similar changes to mRNA in neural progenitor cells as we identify in our study (Figure 3). Clomipramine is a tricyclic antidepressant used in the treatment of MDD with both serotonergic and noradrenergic effects (Amsterdam et al, 1997), and thus our results suggest that we may have identified a functionally valid set of mRNA changes, which can be used to identify compounds which elicit similar functional effects.…”