Role of antidepressant serotonin-norepinephrine reuptake inhibitors in the treatment of chronic pain
Duloxetine is perhaps the most well-known serotonin-norepinephrine reuptake inhibitor (SNRI) agent used in the treatment of chronic pain. This medication and other SNRI agents have a dual mechanism of action (e.g., inhibition of both the reuptake of norepinephrine as well as serotonin). From an analgesic viewpoint, duloxetine is FDA approved for the treatment of fibromyalgia, painful diabetic neuropathy, and chronic musculoskeletal pain. Nausea and sedation are among the more common side effects. Other reported side effects of note include impaired glucose control, hypertension, and rare hepatic toxicity. Venlafaxine has a dual mechanism of action only at higher doses (>150 mg). At lower doses, it is primarily a SSRI drug, and its analgesic benefit is not as great as documented in clinical trials. This is very important to consider, as many patients placed on venlafaxine for chronic pain have not been titrated to doses likely to be effective in my experience. The most common side effects include nausea, sedation, dizziness, sexual dysfunction, insomnia, and increases in diastolic blood pressure. Minalcipran is FDA approved for the treatment of fibromyalgia only in the United States (not depression).
Preclinical studies suggested that blocking the reuptake of central serotonin alone was not as effective as blocking the reuptake of both central serotonin and norepinephrine for analgesic purposes. These preclinical observations have held true in human clinical trials. Therefore, while there may be published trials showing some benefit of SSRI agents for chronic pain treatment and individual patients who experience benefit, in general, these are not as effective for most patients as the medications described previously.