Which medication should be stopped first, Trintellix (vortioxetine) or Cymbalta (duloxetine), in a patient already on both?

Which Medication to Stop First: Trintellix (vortioxetine) or Cymbalta (duloxetine)

When discontinuing treatment in a patient on both Trintellix (vortioxetine) and Cymbalta (duloxetine), Trintellix should be discontinued first due to its adjunctive role and less established analgesic properties compared to duloxetine.

Rationale for Discontinuing Trintellix First

• When a patient is taking two medications that target the same disorder, the first medication to be removed should be the one that was used adjunctively or as an augmenter 1.
• Duloxetine (Cymbalta) has stronger evidence for analgesic efficacy in various pain conditions compared to vortioxetine, making it more versatile for patients with comorbid pain and depression 1.
• Among SNRIs, the evidence for analgesic effects is strongest for duloxetine, particularly in neuropathic pain conditions, musculoskeletal pain, and headache 1.
• Vortioxetine (Trintellix) is a newer antidepressant with multimodal activity but has less established long-term efficacy data compared to duloxetine 2, 3.

Discontinuation Process Considerations

For Vortioxetine (Trintellix):

• Vortioxetine has a long half-life of approximately 66 hours 2, which may allow for a somewhat smoother discontinuation.
• Despite this long half-life, gradual tapering is still recommended to minimize discontinuation symptoms 1.
• Monitoring should continue for several weeks after discontinuation due to the drug's long half-life 2.

For Duloxetine (Cymbalta):

• If duloxetine needs to be discontinued later, it should be tapered gradually to avoid a discontinuation syndrome 1.
• Duloxetine discontinuation can lead to withdrawal symptoms including dizziness, nausea, headache, paresthesia, and irritability 1.
• The tapering period for duloxetine should be longer than for some other antidepressants due to its shorter half-life and higher risk of discontinuation syndrome 1.

Safety Considerations

• Continuing both medications poses a risk of serotonin syndrome due to the combined serotonergic effects 1.
• Caution should be exercised when combining two or more serotonergic drugs, including monitoring for symptoms of serotonin syndrome, especially during the first 24-48 hours after dosage changes 1.
• Symptoms of serotonin syndrome include mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity 1.

Special Considerations

• If the patient has significant cognitive dysfunction, this might influence the decision, as vortioxetine has shown some specific benefits for cognitive function in depression 4, 5.
• However, the primary consideration should be which medication was added second or as an adjunct, which is typically vortioxetine in clinical practice 1.
• If duloxetine is being used specifically for pain management alongside its antidepressant effects, this would further support keeping duloxetine and discontinuing vortioxetine first 1.

Monitoring During Discontinuation

• Monitor for return of depressive symptoms, which may occur weeks to months after discontinuation 1.
• Watch for discontinuation symptoms including dizziness, fatigue, headaches, nausea, sensory disturbances, anxiety, and irritability 1.
• Develop a specific monitoring plan with more frequent follow-ups during the tapering process 1.
• If symptoms emerge during tapering, consider slowing the taper or temporarily returning to a higher dose before proceeding with a more gradual reduction 1.