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 .
MMRM vs. LOCF: A Comprehensive Comparison Based on Simulation Study and 25 NDA Datasets
In recent years , the use of the last observation carried forward ( LOCF ) approach in imputing missing data in clinical trials has been greatly criticized , and several likelihood-based modeling approaches are proposed to analyze such incomplete data . One of the proposed likelihood-based methods is the Mixed-Effect Model Repeated Measure ( MMRM ) model . To compare the performance of LOCF and MMRM approaches in analyzing incomplete data , two extensive simulation studies are conducted , and the empirical bias and Type I error rates associated with estimators and tests of treatment effects under three missing data paradigms are evaluated . The simulation studies demonstrate that LOCF analysis can lead to substantial biases in estimators of treatment effects and can greatly inflate Type I error rates of the statistical tests , whereas MMRM analysis on the available data leads to estimators with comparatively small bias , and controls Type I error rates at a nominal level in the presence of missing completely at r and om ( MCAR ) or missing at r and om ( MAR ) and some possibility of missing not at r and om ( MNAR ) data . In a sensitivity analysis of 48 clinical trial data sets obtained from 25 New Drug Applications ( NDA ) su bmi ssions of neurological and psychiatric drug products , MMRM analysis appears to be a superior approach in controlling Type I error rates and minimizing biases , as compared to LOCF ANCOVA analysis . In the exploratory analyses of the data sets , no clear evidence of the presence of MNAR missingness is found
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 .