Nonetheless, the successful use of these agents in clinical practice has been commonly reported.

“Clinicians should quantify the potential benefit to be gained against the substantial side effect profile and risk of overdose when trying to treat neuropathic pain with TCA,” the authors advised.

Clinical Pain Advisor interviewed Dr Urits to glean additional insights and clinical implications regarding this topic.

Clinical Pain Advisor: What are the reasons why off-label antidepressant use for chronic pain has increased in recent years?

Dr Urits: The opioid epidemic has demonstrated to the medical field the need to collectively reduce opioid prescribing and our use of opioids for the management of chronic pain conditions. As such, exploration of nonopioid adjunctive medications is paramount. Many chronic pain conditions have a strong neuropathic component. Antidepressant medications such as TCAs and SNRIs are thought to modulate the serotonergic and noradrenergic neurotransmission in the nervous system, which is likely dysfunctional in patients who experience neuropathic pain.

Clinical Pain Advisor: What are some of the most notable recent findings pertaining to this topic?

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Dr Urits: In addition to known benefits in the treatment of neuropathic pain, in recent years, duloxetine has been demonstrated in numerous studies to be effective in the treatment of osteoarthritic pain.

Clinical Pain Advisor: What are the relevant implications for our physician audience?

Dr Urits: Beneficial effects of antidepressants prescribed for the management of chronic pain may not be immediate, and, in fact, take several weeks to achieve maximum effect. Although TCAs are the most commonly prescribed class of antidepressants for the treatment of chronic pain, common AEs include sedation and difficulty with concentration, which may be particularly problematic for patients. Most patients can achieve benefits with low doses, thus avoiding AEs. In patients with comorbid depression, SNRIs may confer the advantage of relieving both symptoms of depression and pain at effective dosages.

Clinical Pain Advisor: What should be the next steps in this area in terms of research, education, or otherwise?

Dr Urits: Chronic pain is best treated from a multimodal approach, which can include physical rehabilitative therapy, medical management, and minimally invasive interventions. Advances in neurostimulation in recent years have significantly improved the arsenal with which physicians can combat chronic pain. The rate of advancement is ever-increasing, and I expect that our ability to treat chronic pain with minimally invasive interventions such as spinal cord stimulation will continue to improve.  

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References

1. Urits I, Peck J, Orhurhu MS, et al. Off-label antidepressant use for treatment and management of chronic pain: evolving understanding and comprehensive review. Curr Pain Headache Rep. 2019;23(9):66.

2. Semenchuk MR, Sherman S, Davis B. Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain. Neurology. 2001;57(9):1583-1588.

3. Kast RE, Altschuler EL. Remission of Crohn’s disease on bupropion. Gastroenterology. 2001;121(5):1260-1261.

4. Brustolim D, Ribeiro-dos-Santos R, Kast RE, Altschuler EL, Soares MBP. A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon-gamma in mice. Int Immunopharmacol. 2006;6(6):903-907.

5. Hajhashemi V, Khanjani P. Analgesic and anti-inflammatory activities of bupropion in animal models. Res Pharm Sci. 2014;9(4):251-257.

6. Ito S, Suto T, Saito S, Obata H. Repeated administration of duloxetine suppresses neuropathic pain by accumulating effects of noradrenaline in the spinal cord. Anesth Analg. 2018;126(1):298-307.

7. Alev L, Fujikoshi S, Yoshikawa A, et al. Duloxetine 60 mg for chronic low back pain: post hoc responder analysis of double-blind, placebo-controlled trials. J Pain Res. 2017;10:1723-1731.

8. Hiroki T, Suto T, Saito S, Obata H. Repeated administration of amitriptyline in neuropathic pain: Modulation of the noradrenergic descending inhibitory system. Anesth Analg. 2017;125(4):1281-1288.

9. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;(7):CD008242.