Which antidepressants are not contraindicated with brivaracetam (Briviact) or lacosamide?

Antidepressant Selection with Brivaracetam (Briviact) or Lacosamide

SSRIs (particularly citalopram, escitalopram, and sertraline) and SNRIs (particularly venlafaxine, duloxetine) are not contraindicated with brivaracetam or lacosamide, as these third-generation antiepileptic drugs have minimal propensity for drug-drug interactions.

Preferred Antidepressant Options

First-Line Choices: SSRIs

• Citalopram and escitalopram are the most preferred options due to their minimal effect on CYP450 isoenzymes and lowest propensity for drug interactions among SSRIs 1
• Sertraline is also an excellent choice with minimal CYP450 enzyme inhibition and can be safely combined with antiepileptic medications 2
• These agents demonstrate the lowest potential for pharmacokinetic interactions 1

Alternative First-Line: SNRIs

• Duloxetine is often considered first among SNRIs for its established analgesic efficacy and generally safer profile compared to tricyclic antidepressants 3
• Venlafaxine has the least effect on the CYP450 system compared to SSRIs, making it another reasonable option 1
• Other SNRIs including milnacipran and desvenlafaxine are also viable alternatives 3

Why These Combinations Are Safe

Brivaracetam and Lacosamide Interaction Profile

• Both brivaracetam and lacosamide have little propensity for drug-drug interactions with other medications, including antidepressants 4, 5
• These third-generation antiepileptic drugs lack the significant CYP450 enzyme interactions that characterize older anticonvulsants 6
• Brivaracetam shows high selectivity for its target (SV2A) with minimal off-target effects 7

Pharmacokinetic Stability

• Brivaracetam and lacosamide serum concentrations remain fairly stable and are not significantly affected by most antidepressants 8
• The concentration/dose ratios for both drugs show only minor changes even during physiological stress states 8

Antidepressants to Avoid or Use with Caution

Contraindicated

• MAOIs are absolutely contraindicated with any serotonergic antidepressant due to severe serotonin syndrome risk 1

Use with Caution

• Fluoxetine and paroxetine strongly inhibit CYP2D6, which could theoretically affect medications metabolized by this pathway, though this is less relevant for brivaracetam and lacosamide specifically 1
• Fluvoxamine inhibits multiple CYP enzymes (CYP1A2, CYP2C19, CYP2C9, CYP3A4, CYP2D6), creating the highest risk for drug interactions among SSRIs 1
• Tricyclic antidepressants (TCAs) should generally be avoided due to their anticholinergic effects, orthostatic hypotension, cardiac conduction issues, and increased risk of cardiac arrest, particularly in older adults 3

Critical Safety Monitoring

QT Interval Considerations

• Citalopram can prolong QT interval at doses exceeding 40 mg/day; limit to maximum 40 mg/day and 20 mg/day in patients over 60 years 3, 1
• Escitalopram has similar but less pronounced QT effects; maximum dose restrictions also apply 3
• Baseline ECG should be obtained if risk factors for QT prolongation exist 3

Serotonin Syndrome Prevention

• Avoid combining multiple serotonergic agents due to serotonin syndrome risk 2, 1
• Monitor closely in the first 24-48 hours after any dose change for symptoms including confusion, agitation, tremors, hyperreflexia, muscle rigidity, hypertension, tachycardia, and diaphoresis 2, 1
• Start at low doses and titrate slowly 1

Dosing Recommendations

SSRI Initiation

• Allow at least 2-4 weeks at each dose level to assess response before further titration 2
• Start with the lowest available dose to minimize adverse effects 3

SNRI Considerations

• Duloxetine can often be initiated at target dose without extensive titration 3
• Venlafaxine requires monitoring of blood pressure and pulse 1
• Dose tapering is advisable when discontinuing to reduce risk of discontinuation syndrome 3

Common Pitfalls to Avoid

• Do not assume all antidepressants are equally safe; fluoxetine, paroxetine, and fluvoxamine have significantly higher interaction potential than citalopram, escitalopram, or sertraline 1
• Do not exceed recommended maximum doses of citalopram (40 mg/day, 20 mg/day if >60 years) to avoid QT prolongation 3, 1
• Do not combine multiple serotonergic agents without careful consideration and monitoring 2
• Bupropion and mirtazapine lack comparable evidence of analgesic efficacy if pain is a comorbid concern, though they remain options for depression treatment 3