What antidepressant is least likely to cause seizures?

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From the Guidelines

Selective serotonin reuptake inhibitors (SSRIs) are generally the antidepressants least likely to cause seizures, with citalopram and escitalopram having the lowest seizure risk among all antidepressants, with estimated rates of less than 0.1%. These medications work by increasing serotonin levels in the brain without significantly affecting other neurotransmitters that might lower the seizure threshold. Other SSRIs like sertraline and fluoxetine also have low seizure risk but slightly higher than citalopram and escitalopram.

Key Points to Consider

  • When prescribing antidepressants to patients with epilepsy or seizure risk factors, it's essential to start with low doses and increase gradually 1.
  • Certain antidepressants like bupropion, clomipramine, and maprotiline have higher seizure risks, especially at higher doses 1.
  • The seizure risk of any antidepressant increases with higher doses, rapid dose escalation, and in patients with predisposing factors such as history of seizures, head trauma, or substance withdrawal.

Medication Options

  • Citalopram (Celexa) and escitalopram (Lexapro) are preferred due to their low seizure risk and favorable adverse effect profiles 1.
  • Sertraline (Zoloft) and fluoxetine (Prozac) are also options, but with slightly higher seizure risk compared to citalopram and escitalopram.
  • Bupropion (Wellbutrin) and other non-SSRI antidepressants may be considered for patients who do not respond to SSRIs, but with caution due to their higher seizure risk.

From the Research

Antidepressants and Seizure Risk

The risk of antidepressant-associated seizures is generally low, and most antidepressant-related seizures have been associated with either ultra-high doses or overdosing 2.

Recommended Antidepressants for Patients with Epilepsy

For patients with epilepsy, clinicians should consider using SSRIs or SNRIs, particularly:

  • Sertraline
  • Citalopram
  • Mirtazapine
  • Reboxetine
  • Paroxetine
  • Fluoxetine
  • Escitalopram
  • Fluvoxamine
  • Venlafaxine
  • Duloxetine 2

Antidepressants to Avoid in Patients with Epilepsy

The following antidepressants are not recommended for patients with epilepsy:

  • Amoxapine
  • Bupropion
  • Clomipramine
  • Maprotiline 2

Comparison of Fluoxetine with Other Antidepressants

Fluoxetine has been compared with other antidepressants in several studies:

  • Fluoxetine was less effective than sertraline, mirtazapine, and venlafaxine in some studies 3, 4
  • Fluoxetine was better tolerated than tricyclic antidepressants (TCAs) and some other antidepressants 3, 4

Safety Profile of SSRIs

SSRIs, including fluoxetine, have a favorable safety profile and are generally well-tolerated 5, 6. However, they can cause side effects such as gastrointestinal disturbances, headache, and sexual dysfunction 5.

Seizure Risk and Antidepressant Choice

While there is no clear evidence on which antidepressant is least likely to cause seizures, SSRIs and SNRIs are generally considered to be safe and effective options for patients with depression, including those with epilepsy 2. However, the choice of antidepressant should be individualized and based on a patient's specific needs and medical history.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Antidepressants in epilepsy.

Neurologia i neurochirurgia polska, 2018

Research

Fluoxetine versus other types of pharmacotherapy for depression.

The Cochrane database of systematic reviews, 2005

Research

Fluoxetine versus other types of pharmacotherapy for depression.

The Cochrane database of systematic reviews, 2013

Research

Selective serotonin-reuptake inhibitors: an update.

Harvard review of psychiatry, 1999

Research

Fluoxetine: a review on evidence based medicine.

Annals of general hospital psychiatry, 2004

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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