What antidepressants do not cause seizures?

Antidepressants with Lowest Risk of Seizures

Most selective serotonin reuptake inhibitors (SSRIs), particularly fluoxetine and duloxetine, have a negligible risk of seizures and are the safest antidepressant options for patients concerned about seizure risk.

Understanding Seizure Risk with Antidepressants

Seizures are a relatively rare but serious adverse effect of some antidepressant medications. The risk varies significantly between different classes and individual agents:

Low-Risk Antidepressants (First-Line Options)

• Fluoxetine: Evidence indicates negligible seizure risk 1
• Duloxetine: Demonstrates negligible seizure risk 1
• Sertraline: Low risk (0.0%-0.4%), comparable to background seizure incidence in the general population 2, 3
• Citalopram: Low risk, though slightly higher than fluoxetine 1
• Escitalopram: Low risk, similar to citalopram 1
• Mirtazapine: Low risk with regular dosing 1
• Paroxetine: Low risk with therapeutic dosing 1, 3

Moderate-Risk Antidepressants (Use with Caution)

• Venlafaxine: Moderate risk, especially at higher doses 1
• Trazodone: Moderate risk 1

High-Risk Antidepressants (Avoid if Possible)

• Bupropion: Higher risk compared to SSRIs 4, 1
• Clomipramine and other tricyclic antidepressants: Relatively high risk (0.4% to 1-2%) at therapeutic doses 2, 1
• Amoxapine, maprotiline: Not recommended for patients with epilepsy 3

Risk Factors for Antidepressant-Induced Seizures

Several factors can increase the risk of seizures with antidepressant use:

• Pre-existing seizure disorder: Patients with epilepsy or history of seizures
• Dose-dependent risk: Higher doses generally increase seizure risk 5
• Rapid dose escalation: Gradual titration is safer
• Drug interactions: Especially with other medications that lower seizure threshold
• History of head trauma or brain injury
• Alcohol or sedative withdrawal
• Multiple concomitant medications 5

Clinical Recommendations

1. Screen patients for seizure predisposition before initiating antidepressant therapy

2. For patients with no seizure history:

   • First-line: Fluoxetine or duloxetine (negligible risk)
   • Alternative options: Sertraline, citalopram, escitalopram, or paroxetine

3. For patients with epilepsy or seizure risk factors:

   • First-line: Fluoxetine or duloxetine
   • Alternative: Sertraline (well-studied in epilepsy patients) 3
   • Avoid: Bupropion, clomipramine, amoxapine, and maprotiline 3

4. Dosing considerations:

   • Start with lower doses and titrate slowly
   • Maintain lowest effective dose
   • Monitor for signs of seizure activity, especially during dose adjustments

Important Caveats

• The FDA label for sertraline notes: "No seizures were observed among approximately 3000 patients treated with sertraline in the development program for major depressive disorder" 6
• Contrary to common perception, some antidepressants may actually have anticonvulsant properties at therapeutic doses 7
• The risk of untreated depression may outweigh the small seizure risk from most modern antidepressants
• Most antidepressant-related seizures occur with overdose rather than therapeutic dosing 2

In conclusion, while no antidepressant is completely free from seizure risk, fluoxetine and duloxetine appear to have the lowest risk profile based on current evidence. For patients with epilepsy or seizure risk factors, these agents or sertraline would be the most appropriate choices.