What are the management options for leg weakness associated with Trintellix (vortioxetine)?

Management of Leg Weakness Associated with Trintellix (Vortioxetine)

For patients experiencing leg weakness associated with Trintellix (vortioxetine), the recommended approach is to discontinue Trintellix and consider switching to an alternative antidepressant with a different mechanism of action, particularly alpha-2-delta ligands such as gabapentin or pregabalin which have better efficacy and safety profiles for treating both depression and movement disorders.

Assessment of Leg Weakness

• Evaluate for potential Restless Legs Syndrome (RLS), which can manifest as leg weakness and has been reported with serotonergic antidepressants including Trintellix 1
• Assess for hyponatremia, which can be induced by certain medications and manifest as lower extremity weakness 2
• Rule out other neurological causes of leg weakness such as functional neurological disorder or peripheral neuropathy 3
• Consider if symptoms worsen at rest or in the evening, which would suggest RLS rather than pure weakness 4

First-Line Management Options

• Discontinue Trintellix if leg weakness is significantly impacting mobility or quality of life 1
• Consider switching to an alpha-2-delta ligand such as gabapentin, which is strongly recommended by the American Academy of Sleep Medicine for RLS symptoms (if RLS is the underlying cause) 3, 4
• Pregabalin is another strongly recommended alternative that can address both mood symptoms and leg symptoms 3, 4
• Check serum iron studies, including ferritin and transferrin saturation, as iron deficiency can exacerbate RLS symptoms that may present as leg weakness 4

Second-Line Management Options

• If iron deficiency is present (ferritin ≤75 ng/mL or transferrin saturation <20%), consider iron supplementation 4
• For severe symptoms not responding to first-line treatments, IV ferric carboxymaltose may be considered 3, 4
• Consider non-pharmacological approaches such as bilateral high-frequency peroneal nerve stimulation 4
• For patients with both depression and leg symptoms, duloxetine may be considered as it has evidence for treating both neuropathic pain and depression 3

Medications to Avoid

• Other serotonergic antidepressants (SSRIs, SNRIs) may worsen leg symptoms 1
• Dopaminergic agents (levodopa, pramipexole, ropinirole) should be avoided for long-term use due to risk of augmentation 4
• Benzodiazepines should be avoided, particularly during recovery from neurological symptoms 5
• Valproic acid is not recommended for treating leg symptoms related to movement disorders 4, 5

Monitoring and Follow-up

• Monitor for improvement in leg weakness symptoms after discontinuation of Trintellix 1
• If switching to gabapentin or pregabalin, start at low doses and titrate up to minimize side effects such as somnolence and dizziness 3
• Evaluate for improvement in both mood symptoms and leg weakness with the alternative treatment 1
• If symptoms persist despite medication changes, consider referral to neurology for further evaluation 3

Special Considerations

• Vortioxetine has a long half-life of approximately 66 hours, so improvement may not be immediate after discontinuation 6
• Some case reports suggest that vortioxetine may actually improve RLS symptoms in certain patients, so individual response can vary 7, 1
• For patients with both depression and movement disorders, the choice of antidepressant should prioritize agents less likely to exacerbate movement symptoms 1
• Consider that leg weakness could be related to hyponatremia induced by Trintellix, which would resolve with discontinuation and normalization of sodium levels 2