New Serotonin-Norepinephrine Reuptake Inhibitors and Their Anesthetic and Analgesic Considerations

Abstract

Serotonin-norepinephrine reuptake inhibitors (SNRIs) inhibit the presynaptic neuronal uptake of serotonin and norepinephrine and prolong the effects of the monoamines in the synaptic cleft within the central nervous system, leading to increased postsynaptic receptor activation and neuronal activities. Serotonin-norepinephrine reuptake inhibitors can have multiple clinical indications, including as the first-line agents for the management of depression and anxiety, and as analgesics in the treatment of chronic pain. The effects of reuptake inhibition of norepinephrine and serotonin are often dose-dependent and agent-dependent. There are five FDA-approved serotonin-norepinephrine reuptake inhibitors (desvenlafaxine, duloxetine, levomilnacipran, milnacipran and sibutramine) currently being marketed in the United States. As the COVID-19 pandemic significantly increased the incidence and prevalence of anxiety and depression across the country, there are significantly increased prescriptions of these medications perioperatively. Thus, anesthesiologists are more likely than ever to have patients administered with these agents and scheduled for elective or emergency surgical procedures. A thorough understanding of these commonly prescribed serotonin-norepinephrine reuptake inhibitors and their interactions with commonly utilized anesthetic agents is paramount. There are two potentially increased risks related to the continuation of SNRIs through the perioperative period: intraoperative bleeding and serotonin syndrome. SNRIs have some off-label uses, more new indications, and ever-increasing new applications in perioperative practice. This article aims to review the commonly prescribed serotonin-norepinephrine reuptake inhibitors and the current clinical evidence regarding their considerations in perioperative anesthesia and analgesia.

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“…And thus, duloxetine being a balanced inhibitor, is more useful for the management of chronic pain conditions 28 . Therefore, duloxetine is approved for the treatment of fibromyalgia, diabetic peripheral neuropathy, and musculoskeletal pain and is used off-label to treat peripheral neuropathy secondary to chemotherapy administration and urinary incontinence 11,29 . In contrast, venlafaxine is used off-label for diabetic neuropathy and peripheral neuropathy secondary to chemotherapy administration but is not approved and is currently evaluated for chronic neuropathic pain 12,29 .…”

Pain management considerations in patients living with both pain syndromes and cardiovascular diseases and disorders

“…34 SNRIs that are used for pain include duloxetine, venlafaxine, and milnacipran, however, duloxetine has the most evidence supporting its use and is the only SNRI that has shown efficacy in nociceptive pain. 34 As a class, SNRIs have been reported to cause an increase in BP and HR. 9 Venlafaxine has been associated with a statistically significant increase in BP in a dose-dependent manner, albeit not clinically significant, and observed at doses of greater than 300 mg. 35 However, treatment doses for venlafaxine range between 75 and 225 mg/day, making this finding most likely not clinically meaningful.…”

“…SNRIs are commonly prescribed for depression, neuropathic pain, and fibromyalgia 34 . SNRIs that are used for pain include duloxetine, venlafaxine, and milnacipran, however, duloxetine has the most evidence supporting its use and is the only SNRI that has shown efficacy in nociceptive pain 34 . As a class, SNRIs have been reported to cause an increase in BP and HR 9 .…”

Could the fibromyalgia syndrome be triggered or enhanced by COVID-19?

“…Duloxetine, another drug approved by the FDA as a therapy for FM, decreased the incidence of COVID-19 in patients (Blanch-Rubió et al 2020 ), and seems to be less likely to interact with treatments recommended for COVID-19 (Plasencia-García et al 2021 ). Furthermore, it is among the most commonly prescribed drugs annually in the United States, has an established safety profile, and is generally well-tolerated (Fanelli et al 2021 ). In contrast, milnacipran, another SNRI used as a first-line treatment for FM (Sarzi-Puttini et al 2020 ), has not been evaluated in the COVID-19 setting.…”

“…In contrast, milnacipran, another SNRI used as a first-line treatment for FM (Sarzi-Puttini et al 2020 ), has not been evaluated in the COVID-19 setting. However, milnacipran may represent a good therapeutic alternative since it lacks interaction with the cytochrome P450 enzymes (frequently involved in the metabolism of antidepressants) (Fanelli et al 2021 ). Therefore, milnacipran is less likely to interact with antiretroviral drugs used in patients with COVID-19 (Plasencia-García et al 2021 ).…”