Siegfried Kasper, Gerald PailDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, AustriaAbstract: Tricyclic antidepressants (TCAs) are among the most effective antidepressants available, although their poor tolerance at usual recommended doses and toxicity in ­overdose make them difficult to use.While selective serotonin reuptake inhibitors (SSRIs) are ­better tolerated than TCAs, they have their own specific problems, such as the aggravation of sexual dysfunction, interaction with coadministered drugs, and for many, a discontinuation syndrome.In addition, some of them appear to be less Soccer - Shoes Outdoor - Senior effective than TCAs in more severely depressed patients.
Increasing evidence of the importance of norepinephrine in the etiology of depression has led to the development of a new generation of antidepressants, the serotonin and ­norepinephrine reuptake inhibitors (SNRIs).Milnacipran, one of the pioneer SNRIs, was designed from theoretic considerations to be more effective than SSRIs and better tolerated than TCAs, and with a simple pharmacokinetic English bridle profile.Milnacipran has the most balanced potency ratio for reuptake inhibition of the two neurotransmitters compared with other SNRIs (1:1.
6 for milnacipran, 1:10 for duloxetine, and 1:30 for venlafaxine), and in some studies milnacipran has been shown to inhibit norepinephrine uptake with greater potency than serotonin (2.2:1).Clinical studies have shown that milnacipran has efficacy comparable with the TCAs and is superior to SSRIs in severe depression.
In addition, milnacipran is well tolerated, with a low potential for pharmacokinetic drug–drug interactions.Milnacipran is a first-line therapy suitable for most depressed patients.It is frequently successful when other treatments fail for reasons of efficacy or tolerability.
Keywords: milnacipran, SNRI, antidepressant efficacy, tolerability.