Only one third of patients prescribed SSRI s achieve full remission. Are dual reuptake inhibitors ( SNRIs: nor adrenaline and serotonin) better than SSRIs?. When medications differ in efficacy by modest degrees only, it is difficult to show the difference unless you have very large trials. Metaanalysis and systemtic review of these metaanalysis offer an opportunity to look at this question closely.
Andrew J Bradley and Alan J Lenox-Smith reviewed comparison trials of SSRis against the SNRIs in acute treatment of deprsssion (duloxetine, desvenlafaxine, milnacipran and venlafaxine). They systematically reviewed the meta analysis reports and pragmatic trials of significance.
49 efficacy-related meta-analyses were identified. Fifteen meta-analyses were with summary data and seven meta-analyses provided individual patient data.
Venlafaxine: Venlafaxine was consistently found to be superior in remission rates compared to pooled SSRIs with OR for remission ranging from 1.12–1.43. Pragmatic trials like STAR D showed remission rates of 17.6% for sertraline and 24.8% for venlafaxine XR at level 2 treatment ( ie after first line ,citalopram). This difference was not statistically significant.ARGO study (open-label, randomised, multicentre study comparing the efficacy of venlafaxine XR and ‘conventional antidepressants’ in conventional non-responders) showed that patients treated with venlafaxine XR had a statistically significant superior rate of remission compared with those receiving CAs (which included mirtazapine) (59% vs 51%; p<0.0001)
Duloxetine: RCT summary-level meta-analyses and two patient-level meta-analyses comparing duloxetine with SSRIs met inclusion criteria .A remission rate in favour of duloxetine was found OR 1.1≥1 (95% CI 0.91–1.34) from the analysis of summary data from nine RCTs but this was not statistically significant .The benefit was not staistically significant against paroxetine, fluoxetine or citolapram. One pragmatic trial that was included also did not find significant benefits.
Desvenlafaxine: No meta-analysis of any type or any pragmatic studies was found comparing desvenlafaxine with SSRIs.
Data comparing venlafaxine to pooled SSRIs was consistently supportive of increased efficacy of dual reuptake inhibition in both remission and response rates .Venlafaxine showed superior efficacy compared to fluoxetine and paroxetine and was generally in favour of venlafaxine when compared to fluvoxamine and sertraline. With citalopram results were equivocal.Mixed results from the existing data mean a definitive conclusion regarding additional efficacy of the addition of NA reuptake inhibition to that of 5-HT cannot currently made.
Summary of the article:
Does adding noradrenaline reuptake inhibition to selective serotonin reuptake inhibition improve efficacy in patients withdepression? A systematic review of meta-analyses and large randomised pragmatic trials.
Bradley AJ, Lenox-Smith AJ. J Psychopharmacol. 2013 Aug;27(8):740-58