Fluoxetine-clonazepam cotherapy for anxious depression: an exploratory, post-hoc analysis of a randomized, double blind study

Abstract

Anxious depression, defined as major depressive disorder (MDD) accompanied by high levels of anxiety, seems to be both common and difficult to treat, with antidepressant monotherapy often yielding modest results. We sought to examine the relative benefits of antidepressant-anxiolytic cotherapy versus antidepressant monotherapy for patients with anxious depression versus without anxious depression. We conducted a post-hoc analysis of an existing dataset (N=80), from a 3-week, randomized, double-blind trial which demonstrated cotherapy with fluoxetine and clonazepam to result in superior efficacy than fluoxetine monotherapy in MDD. The present analysis involved examining whether anxious depression status served as a predictor and moderator of symptom improvement. Anxious depression status was not found to predict symptom improvement, or serve as a moderator of clinical improvement to cotherapy versus monotherapy. However, the advantage in remission rates in favor of cotherapy versus monotherapy was, numerically, much larger for patients with anxious depression (32.2%) than it was for patients without anxious MDD (9.7%). The respective number needed to treat statistic for these two differences in response rates were, approximately, one in three for patients with anxious depression versus one in 10 for patients without anxious depression. The efficacy of fluoxetine-clonazepam cotherapy compared with fluoxetine monotherapy was numerically but not statistically enhanced for patients with anxious depression than those without anxious depression.

The effect of desvenlafaxine 50 mg/day on a subpopulation of anxious/depressed patients: a pooled analysis of seven randomized, placebo‐controlled studies

“…Anxious depression has been reported to be more difficult to treat compared with nonanxious depression (Fava et al ., ; Wiethoff et al ., ), but the current analysis is not the first to find otherwise (Farabaugh et al ., ; Nelson, ; Papakostas et al ., ; Papakostas et al ., ; Russell et al ., ; Uher et al ., ). Although the criterion for anxious depression used in this study (HAM‐D 17 A/S factor ≥7) was the same as that applied in previous trials, the anxious population in this analysis may have differed from populations in which efficacy was reduced.…”

“…The use of a scale designed specifically to measure symptoms of anxiety independent of other disorders, such as the HAM-A (Hamilton, 1959), would have been preferable, but no anxiety scale was administered in these studies. Although the HAM-D 17 is designed to assess symptoms of depression and not anxious states, the HAM-D A/S factor is commonly used to identify patients with anxious depression and to measure drug effects on anxious symptoms (Fava et al, 2000b;Russell et al, 2001;Fava et al, 2008;Farabaugh et al, 2010;Papakostas et al, 2010;Wiethoff et al, 2010;Papakostas et al, 2011;Uher et al, 2011). It should be noted that the HAM-D A/S factor used to categorize patients in the pooled population and HAM-D 17 total scores, used as the primary endpoint, are not independent, and also that an anxiety scale such as the HAM-A would include additional dimensions of anxiety that are not captured in the items that make up the HAM-D A/S factor.…”

“…Not all analyses have demonstrated differences in clinical outcomes for anxious depressed patients compared with nonanxious patients, however. Both in post hoc analyses of individual antidepressant clinical trials (Farabaugh et al ., ; Papakostas et al ., ; Uher et al ., ) and in pooled analyses of duloxetine (Nelson, ) and escitalopram trials (Papakostas et al ., ), there were no significant differences in primary efficacy outcomes between anxious and nonanxious depressed patient populations.…”

The chicken and egg of anxiety and depression

“…For example, clonazepam added to the Selective Serotonin Reuptake Inhibitor (SSRI) fluoxetine appears to produce greater response than the SSRI alone (Papakostas et al 2010). Benefit has also been reported with the atypical antipsychotic quetiapine (Montgomery et al 2014) and the antidepressant mirtazapine (Schatzberg et al 2002) both of which have potent 5-HT2 antagonist effects and thus are calming and potentially sedating.…”

A new logical insight and putative mechanism behind fluoxetine-induced amenorrhea, hyperprolactinemia and galactorrhea in a case series

“…Patients Sex/age [Papakostas et al 2010;Eric et al 2003]. However, there is a dearth of literature correlating the impact of this cotherapy in hypochondriasis, even though this combination therapy is often used in regular clinical practice with satisfactory clinical outcomes.…”