Responsibility of the doctor who prescribes serotonin and noradrenaline reuptake inhibitors for patients with chronic musculoskeletal pain

Abstract

Duloxetine, a serotonin and noradrenaline reuptake inhibitor (SNRI), is indicated for the management of chronic musculoskeletal pain, as it helps inhibit pain signals by activating descending pain inhibitory pathways.1 Thus, duloxetine is increasingly being prescribed by many doctors who are not familiar with psychopharmacology. We conducted a questionnaire survey on Japanese physicians’ recognition of the severe side-effects of duloxetine. We surveyed 69 physicians who had prescribed duloxetine for chronic musculoskeletal pain and 52 (75.4%) responded. The main specialties of the responders were psychosomatic medicine (n = 26, 50.0%), orthopedics (n = 14, 26.9%), anesthesiology and pain (n = 6, 11.5%), and general internal medicine (n = 6, 11.5%). The average age of the 52 responders was 52.4 years. Seventeen responders reported side-effects in their patients due to duloxetine, as follows: falls (n = 12, 23.1%), hyponatremia (n = 2, 3.8%), and discontinuation syndrome (n = 3, 5.8%). Of the 52 responders, 24 (46.2%) considered falls and syncope as a side-effect, 13 (25.0%) recognized hyponatremia as a serious complication, and only 11 (21.2%) knew about discontinuation syndrome. These results suggest that many prescription doctors are unaware or ignore these side-effects of SNRI. Of the 52 responders, 26 (50.0%) considered duloxetine as an analgesic drug, and 26 (50.0%) recognized it as an SNRI. Duloxetine has some severe side-effects at the same level as other SNRI. Syncope and orthostatic hypotension can occur at any time during treatment, particularly after dose increases. SNRI, as well as selective serotonin reuptake inhibitors (SSRI), are well known to have side-effects, including the syndrome of inappropriate antidiuretic hormone secretion, which results in hyponatremia, the most commonly encountered electrolyte abnormality in clinical practice. Following the abrupt discontinuation of SNRI, discontinuation symptoms, such as dizziness, headache, irritability, insomnia, and fatigue, may occur. Moreover, the majority of patients with chronic musculoskeletal pain are elderly and tend to have a higher underlying risk for falls, such as use of multiple medications and medical comorbidities. In Japan, after the introduction of SSRI and SNRI for depression, pharmaceutical companies initiated educational campaigns. Due to these marketing practices, SSRI and SNRI sales have achieved a tremendous increase, resulting in an increase in severe side-effects.2 We can learn a great deal from this experience with the aggressive marketing of these drugs as a kind of disease mongering. Now, the same risk exists with duloxetine for chronic musculoskeletal pain. The doctor who prescribes SNRI must weigh the benefits against the side-effects. When prescribing an SNRI for chronic musculoskeletal pain, patients should be carefully monitored against side-effects. Discontinuation should be considered in patients who experience side-effects during SNRI therapy. Even then, a gradual reduction in the dose rather than abrupt cessation is recommended, whenever possible, to prevent discontinuation syndrome. The author declares no conflicts of interest.