What are the considerations for prescribing Trintellix (vortioxetine) to a patient with a history of epilepsy?

Trintellix (Vortioxetine) in Patients with Epilepsy

Trintellix can be safely prescribed to patients with epilepsy, as the FDA label does not list seizure disorders as a contraindication or warning, and emerging clinical evidence suggests it may actually reduce epileptiform activity rather than provoke seizures. 1, 2, 3

FDA-Approved Safety Profile

• The FDA prescribing information for Trintellix does not include seizures or epilepsy in its warnings, precautions, or contraindications sections, which distinguishes it favorably from other antidepressants like bupropion that explicitly carry seizure warnings 1, 4
• The only absolute contraindications for Trintellix are hypersensitivity reactions and concurrent use with MAOIs 1
• Discontinuation syndrome can occur with abrupt cessation, so doses of 15-20 mg/day should be tapered to 10 mg/day for one week before full discontinuation 1

Clinical Evidence Supporting Safety in Epilepsy

A case series of nine patients with epilepsy treated with vortioxetine 10-20 mg demonstrated complete remission of depressive symptoms with excellent tolerability and no seizure exacerbation in seven of nine patients 2

• In the two patients who experienced seizures during vortioxetine treatment, the seizures were attributed to suboptimal antiepileptic drug therapy rather than vortioxetine itself, and seizure control was achieved after optimizing antiepileptic medications 2
• The observation period ranged from 2 to 48 months, providing substantial follow-up data 2
• All nine patients included those with secondary focal and generalized epilepsy as well as unclassified epilepsy 2

Preclinical Evidence of Anticonvulsant Properties

Animal studies demonstrate that vortioxetine 10 mg/kg significantly reduced spike frequencies of penicillin-induced epileptiform activity, with efficacy comparable to diazepam 5 mg/kg 3

• Vortioxetine reduced acute epileptic discharges without significant difference from the positive control (diazepam) 3
• This suggests vortioxetine may possess mild anticonvulsant properties through its multimodal serotonergic mechanisms 3

Practical Prescribing Recommendations

Start with 10 mg once daily without regard to meals, then increase to 20 mg/day as tolerated, or reduce to 5 mg/day if higher doses are not tolerated 1

• Ensure antiepileptic medications are optimized and at therapeutic levels before initiating vortioxetine 5
• Monitor for increased seizure activity during the first months of treatment and following dosage adjustments, though this is a general precaution rather than a specific vortioxetine concern 5
• Consider EEG monitoring if clinically indicated, particularly if breakthrough seizures occur 5

Advantages Over Alternative Antidepressants

Vortioxetine offers significant advantages compared to other antidepressants in patients with seizure disorders:

• Tricyclic antidepressants carry a 0.4-2% seizure risk and should be avoided entirely 5
• Bupropion lowers seizure threshold and should be avoided in patients with epilepsy 4
• SSRIs like escitalopram require close monitoring for increased seizure activity and should be started at lower doses with slow titration 5
• Vortioxetine has low risk of pharmacokinetic interactions with antiepileptic drugs, unlike enzyme-inducing agents 2

Monitoring Parameters

• Continue baseline antiepileptic drug therapy throughout vortioxetine treatment 6
• Check antiepileptic drug serum levels to ensure therapeutic concentrations are maintained 7
• Monitor for serotonin syndrome if combining with other serotonergic agents, though this is not specific to epilepsy patients 1
• Watch for hyponatremia, which can lower seizure threshold independent of vortioxetine's effects 1

Special Considerations

Vortioxetine is particularly well-suited for epilepsy patients with comorbid depression because:

• It addresses cognitive dysfunction commonly seen in both epilepsy and depression 2, 3
• It has minimal sedation risk, avoiding compounding of cognitive impairment from antiepileptic drugs 2
• It causes minimal sexual dysfunction and metabolic side effects 2
• It does not require dose adjustment in hepatic or renal impairment unless the patient is a known CYP2D6 poor metabolizer (reduce to maximum 10 mg/day) 1