What are SNRIs?

The acronym SNRI stands for serotonin and norepinephrine reuptake inhibition.

In this sense they are broader acting in the brain that the SSRIs but confusingly this has not translated in practice to they being more effective that the SSRIs. Generally speaking, unless there is a specific reason, it is better to start with an SSRI first.

There are three SNRI antidepressants available. These are: Effexor XR (venlafaxine), Cymbalta (duloxetine) and Fetzima (levomilnacipran). Effexor XR is the longest available, since the mid-19990s and is FDA approved for the treatment of several other disorders in addition to major depression, namely: Panic Disorder, Social Anxiety Disorder, Generalized Anxiety Disorder (GAD), PTSD and Migraine prophylaxis.

It has a particularly wide dose range of 75 mg to 450 mg daily so a lot of adjustment and titration may be needed to find the right dose for you. Nevertheless it is a quite potent antidepressant.

However, my first choice in this category is Cymbalta (duloxetine) which is approved for major depression and GAD. Dosing is quite simple compared to Effexor XR, 60 mg or 120 mg daily. This means that the usual starting dose of Cymbalta 60 mg is also a therapeutic dose but this is not really the case with Effexor. In my practice if two SSRIs have not worked (Lexapro and Zoloft) my next choice is to change the class of antidepressant treatment to an SNRI and pursue a trial of treatment with Cymbalta. Lastly, I have found the newest SNRI Fetzima to be somewhat lacking in efficacy for my patients and have deemphasized it as choice currently.