Milnacipran was marketed earlier in Japan and Europe; later in China and the US. It is the only SNRI with a greater NET effect than SERT. Other SNRIs such as venlafaxine and duloxetine exhibit stronger SNRT effects than NET effects. The strong NET inhibitory pharmacological profile of milnacipran suggests the following possible clinical effects: 1. Possible better efficacy in various pains (somatic symptomatic pain of depression, chronic neuropathic pain, fibromyalgia). 2. Possible energetic recovery promoting effects. 3. May have a psychomotor activating effect. 4. May have a higher rate of transient mania than other SNRIs; and a relatively high incidence of “drug-induced monophasic depression biphasicization”. 5. Strong NET inhibition may be associated with more sweating, urinary retention, and dysuria (theoretically due to “pro-NE” effects caused by alpha-1 on the bladder; alpha-1 receptor antagonists may help).