A Review of the Serotonin-Norepinephrine Reuptake Inhibitors: Pharmacologic Aspects and Clinical Implications for Treatment of Major Depressive Disorder and Associated Painful Physical Symptoms

Abstract

Background: Depression is characterized by low mood, low self-esteem, and loss of interest or pleasure. Painful physical symptoms (PPS) associated with depression have a negative impact on the probability of remission. Because both norepinephrine and serotonin are involved with the central regulation of pain, the serotonin-norepinephrine reuptake inhibitors (SNRIs) may have more success than the selective serotonin reuptake inhibitors (SSRIs) in impacting PPS as well as the core emotional symptoms of depression. Methods: Published preclinical and clinical data on the SNRIs (i.e., milnacipran, venlafaxine, and duloxetine) have been reviewed, paying special attention to the differentiation of the pharmacological aspects of the SNRIs. The efficacy and safety results on depression and associated PPS have also been summarized. Results: Each of the SNRIs has different profiles regarding the inhibition of binding to human serotonin and norepinephrine uptake transporters and clinical pharmacokinetics. All SNRIs have data for alleviating the core symptoms of depression; duloxetine and venlafaxine show efficacy for PPS associated with depression. There are also differences in tolerability and adverse events profiles. Conclusions: Although all SNRIs have the same dual mechanism of action for the treatment of depression, they have different pharmacologic profiles that may impact clinical outcomes.