Evidence from meta- analysis of r and omised controlled trials ( RCTs ) and r and omised pragmatic trials was found in support of greater efficacy of the serotonin noradrenaline reuptake inhibitors ( SNRIs ) , venlafaxine and duloxetine , in moderate to severe depression compared to SSRIs but no evidence was found for superiority of milnacipran .
There is sufficient current evidence that demonstrates an increase in efficacy , when noradrenaline reuptake is added to serotonin ( 5-HT ) reuptake , to suggest that patients with severe depression or those who have failed to reach remission with a SSRI may benefit from treatment with a SNRI .
Selective serotonin reuptake inhibitors ( SSRIs ) are recommended as first-line pharmacological treatment for depression and are the most commonly prescribed class of antidepressants .
However , there is substantial evidence that noradrenaline has a role in the pathogenesis and treatment of depression .
This review aims to examine the evidence of including noradrenaline reuptake inhibition with serotonin reuptake inhibition with respect to increasing efficacy in the treatment of depression .
Venlafaxine extended release versus citalopram in patients with depression unresponsive to a selective serotonin reuptake inhibitor
Findings from the National Institute of Mental Health 's Sequenced Treatment Alternatives to Relieve Depression trial indicate that approximately 50 % of patients with major depressive disorder do not experience a treatment response after adequate first-line treatment with a selective serotonin reuptake inhibitor ( SSRI ) . This study was design ed to test the hypothesis that , after treatment failure with an SSRI , switching to venlafaxine extended release ( ER ) would offer advantages over switching to another SSRI , citalopram . The objectives of this trial were to compare the efficacy and safety of venlafaxine ER and citalopram in the treatment of moderate-to-severe depression in patients who did not experience a treatment response to an SSRI other than citalopram  and to investigate the effects of severity of depression by categorizing treatment groups according to baseline severity . This was a 12-week , double-blind , r and omized , parallel-group , multicenter study . Participants were adult out patients who , following 8 weeks of monotherapy with an adequate dosing regimen of an SSRI other than citalopram  and had not responded , met the diagnostic criteria for depression as described in the Diagnostic and statistical manual of mental disorders , fourth edition , and had a score ≥20 on the 21-item Hamilton Rating Scale for Depression ( HAM-D21 ) . After a 7-day screening period , patients were r and omly assigned to receive venlafaxine ER 75 mg/day or citalopram 20 mg/day for the first 2 weeks . Doses could be increased every 2 weeks through week 6 . Treatment lasted 12 weeks and was followed by a 1-week tapering period . Maximum dosages were venlafaxine ER 300 mg/day or citalopram 60 mg/day . The primary end point was the final on-therapy total HAM-D21 score . To investigate the treatment effects of the severity of depression on efficacy , a subgroup analysis was performed for baseline HAM-D21 total score ≤31 and > 31 . The analyses for HAM-D21 , Montgomery – Åsberg Depression Rating Scale ( MADRS ) , Clinical Global Impressions – Severity ( CGI-S ) , and Clinical Global Impressions – Improvement scores were based on intent-to-treat ( ITT ) population , for both the primary analysis and subgroup analysis according to baseline HAM-D21 total scores ≤31 or > 31 . Safety assessment s included the recording of adverse events ( AEs ) . A total of 406 patients ( 200 venlafaxine ER , 206 citalopram ) were r and omly assigned and 396 patients were included in the ITT population ( 194 venlafaxine ER , 202 citalopram ) . Treatment groups were similar in terms of demographics and baseline psychiatric assessment s. Two hundred and eighty-four patients ( 137 venlafaxine ER , 147 citalopram ) were present in the ITT population with a baseline HAM-D21 total score ≤31 and 112 patients ( 57 venlafaxine ER , 55 citalopram ) in the > 31 group . In the primary analysis , there was no statistical difference between groups . The group with a baseline HAM-D21 total score of 20–31 did not differ significantly in any efficacy parameters . In the group with a baseline HAM-D21 total score > 31 , the venlafaxine ER group differed significantly from the citalopram group on the primary end point HAM-D21 total score ( P=0.0121 ) . The secondary end point CGI-S score was statistically significant ( P=0.0359 ) , although the MADRS total score ( P=0.0930 ) was not . AEs were reported by 57.8 and 63.4 % of venlafaxine ER and citalopram patients , respectively . Overall discontinuation rates were 24.5 % for venlafaxine ER and 20.9 % for citalopram  . Discontinuation rates owing to an AE as a primary or secondary reason were 5.5 % for venlafaxine ER and 5.3 % for citalopram . Overall , venlafaxine ER and citalopram showed similar efficacy in patients who had an inadequate response to an SSRI . In the subset of more severely depressed patients , venlafaxine ER was significantly more effective on a number of efficacy measures . Patients who remain severely depressed following treatment with an SSRI may gain more benefit from the dual-action drug venlafaxine , rather than switching to another SSRI
Evidence from meta- analysis of r and omised controlled trials ( RCTs ) and r and omised pragmatic trials was found in support of greater efficacy of the serotonin noradrenaline reuptake inhibitors ( SNRIs ) , venlafaxine and duloxetine , in moderate to severe depression compared to SSRIs but no evidence was found for superiority of milnacipran .
There is sufficient current evidence that demonstrates an increase in efficacy , when noradrenaline reuptake is added to serotonin ( 5-HT ) reuptake , to suggest that patients with severe depression or those who have failed to reach remission with a SSRI may benefit from treatment with a SNRI .
Selective serotonin reuptake inhibitors ( SSRIs ) are recommended as first-line pharmacological treatment for depression and are the most commonly prescribed class of antidepressants .
However , there is substantial evidence that noradrenaline has a role in the pathogenesis and treatment of depression .
This review aims to examine the evidence of including noradrenaline reuptake inhibition with serotonin reuptake inhibition with respect to increasing efficacy in the treatment of depression .