Anti-Depressants
In the absence of reliable evidence, it is the opinion of the workgroup that a recommendation for or against the use of duloxetine cannot be made given the limited evidence and safety concerns.
Pharmacologic, Physical, and Cognitive Pain Alleviation for Musculoskeletal Extremity/Pelvis Surgery (2021)
This guideline was produced in collaboration with METRC, with funding provided by the US Department of Defense. Endorsed by: SOMOS, OTA

Rationale

There is lack of evidence for the use of duloxetine with only one moderate quality study (YaDeau 2016) included which demonstrated a reduction in opioid consumption but did not demonstrate an improvement in pain after surgery, the primary study outcome.

Benefits/Harms of Implementation

Reducing opioid use in the post-op period mitigates their well-known side-effects such as nausea/vomiting, respiratory depression, tolerance, etc. Pain and symptoms of depression/anxiety are well known to interact clinically such that it is difficult to treat pain when symptoms of depression/anxiety are poorly controlled, and vice versa. There is an FDA Black Box Warning on prescribing duloxetine to patients younger than 25 years old as there is an increased risk of suicidality in this population. Duloxetine may negatively interact with pre-existing therapies for those with mental health disease.

Outcome Importance

The US is in the midst of an opioid epidemic known to contribute to the development of hyperalgesia, tolerance, dependence, addiction, and abuse. Therefore, reducing opioid use is a national priority. Patients with mental health disease can face significant challenges in symptom control after surgery, and maintaining control is essential to pain management and functional improvement.

Cost Effectiveness/Resource Utilization

Duloxetine is a generic medication not requiring significant resources over other medications.

Acceptability

Some orthopaedic surgeons may be hesitant to prescribe duloxetine for pain given its use in anxiety and depression, concern for interference with pre-existing medications, or lack of clinical familiarity with medication treatments for mental health diseases.

Feasibility

Duloxetine is currently widely prescribed in the US and is FDA indicated for chronic musculoskeletal pain, fibromyalgia, diabetic peripheral neuropathic pain, generalized anxiety disorder, and major depressive disorder.

Future Research

Future pain outcomes should be investigated in patients with chronic pain, pre-operative opioid use, generalized anxiety disorder, major depressive disorder.