Venlafaxine was the first SNRI introduced into clinical practice for the treatment of major depression. Only later did its efficacy against a number of pain syndromes become apparent.

Serotonin norepinephrine reuptake inhibitors, SNRI’s are another group of drugs that have found great use in treating chronic pain. They are similar to the selective serotonin reuptake inhibitors, SSRI’s in that both inhibit the reuptake of neuroactive amines at the synaptic junction, but the SNRI’s have a broader spectrum. In low doses they function primarily by inhibiting the reuptake of serotonin, while at moderate doses they block the reuptake of norepinephrine as well. At high doses these compounds begin to block the reuptake of dopamine.

Efficacy in treating major depression is roughly equivalent to the tricyclic antidepressants and the SSRIs, but the side effect profile of the SNRI’s may be slightly better, or at least different. Sedation and sexual side effects appear to be less common with the SNRI’s than with the SSRI’s, but they can produce the opposite effects, increased libido, anxiety and sleep disturbances, which can be just a troubling.

When used to treat chronic pain, the SNRI’s appear to be moderately more effective than SSRIs, but in my experience with this patient population, dysphoric side effects are significantly more common. These dysphoric side effects are the major reason for discontinuing these drugs in my practice.

SNRIs Commonly Used in Chronic Pain


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