From the Guidelines
Selective serotonin reuptake inhibitors (SSRIs) are generally the safest antidepressants for patients with epilepsy. Specifically, sertraline (50-200 mg daily), citalopram (20-40 mg daily), and escitalopram (10-20 mg daily) have the lowest risk of seizure exacerbation, as they have minimal impact on lowering seizure threshold through glutamate or GABA pathways 1. When starting these medications, it's best to begin at a low dose and increase gradually while monitoring seizure frequency. Some key points to consider when prescribing antidepressants to patients with epilepsy include:
- Fluoxetine can also be used but has more drug interactions due to its long half-life 1.
- Serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine (75-225 mg daily) and duloxetine (30-60 mg daily) are considered second-line options with moderate safety profiles.
- Medications to avoid include bupropion, maprotiline, and tricyclic antidepressants (especially clomipramine and amitriptyline), as these significantly lower the seizure threshold 1.
- Mirtazapine (15-45 mg daily) is another relatively safe option with minimal impact on seizure threshold. Regular monitoring of both seizure activity and depression symptoms is essential when initiating antidepressant therapy in epilepsy patients.
From the FDA Drug Label
- 3 Drugs That Lower Seizure Threshold
Use extreme caution when coadministering bupropion hydrochloride extended-release tablets (XL) with other drugs that lower the seizure threshold (e.g., other bupropion products, antipsychotics, antidepressants, theophylline, or systemic corticosteroids).
The FDA drug label does not answer the question.
From the Research
Safe Antidepressants for Patients with Epilepsy
The following antidepressants are considered safe for patients with epilepsy:
- SSRIs (Selective Serotonin Reuptake Inhibitors) such as sertraline, citalopram, paroxetine, fluoxetine, escitalopram, and fluvoxamine 2, 3
- SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors) such as venlafaxine and duloxetine 2
- Other antidepressants like mirtazapine and reboxetine 2, 4
Antidepressants to Avoid in Patients with Epilepsy
The following antidepressants are not recommended for patients with epilepsy due to their high risk of inducing seizures:
Key Findings
- A study found that citalopram is a safe and effective antidepressant in the treatment of depressed epileptic patients, with no seizure worsening observed 3
- Another study found that citalopram and reboxetine have an anticonvulsant effect in rats with chronic epilepsy, reducing seizure frequency 4
- The risk of antidepressant-associated seizures is generally considered low, especially for newer antidepressants 6