Is Celexa (citalopram) contraindicated in patients with a history of seizure disorders?

Celexa (Citalopram) and Seizure Disorders

Celexa is not absolutely contraindicated in patients with seizure disorders, but it should be introduced with care and close monitoring due to a documented seizure risk. 1

FDA Labeling Position

The FDA label explicitly states that citalopram has not been systematically evaluated in patients with a seizure disorder, as these patients were excluded from premarketing clinical trials. 1 However, the label recommends that "like other antidepressants, citalopram tablets should be introduced with care in patients with a history of seizure disorder." 1

Clinical Trial Data on Seizure Risk

• In clinical trials, seizures occurred in 0.3% of patients treated with citalopram (one patient per 98 years of exposure) compared to 0.5% in placebo-treated patients (one patient per 50 years of exposure). 1
• Notably, animal studies showed anticonvulsant effects of citalopram, though this has not translated to systematic human evaluation. 1

Comparative Seizure Risk Among Antidepressants

Citalopram and its metabolite escitalopram carry among the highest seizure risks of second-generation antidepressants in elderly patients. 2 A large population-based study found:

• Escitalopram had the highest risk (adjusted OR 1.79; 95% CI 1.42-2.25) compared to bupropion. 2
• Citalopram had the second-highest risk (adjusted OR 1.67; 95% CI 1.35-2.07). 2
• Fluoxetine (OR 1.02) and duloxetine (OR 0.94) showed no incremental risk over bupropion. 2

Evidence of Potential Benefit in Epilepsy

Paradoxically, one open-label study in 45 epileptic patients treated with citalopram 20 mg/day for 4 months showed overall improvement in seizure frequency while effectively treating depression. 3 No patients discontinued due to seizure worsening, and plasma antiepileptic drug concentrations remained stable. 3

General Antidepressant Considerations in Epilepsy

• Most antidepressants at therapeutic doses carry a seizure risk <0.1% in non-epileptic patients, similar to first spontaneous seizure rates in the general population. 4
• At high doses, seizure incidence can reach up to 40%. 4
• Drugs that increase serotonergic transmission appear less convulsant or potentially anticonvulsant compared to other mechanisms. 4
• Maprotiline and amoxapine exhibit the greatest seizure risk, while trazodone, fluoxetine, and fluvoxamine exhibit the least. 4

Clinical Management Algorithm

If citalopram must be used in a patient with seizure disorder:

1. Ensure seizures are well-controlled on optimized antiepileptic therapy before initiating citalopram. 1

2. Start at the lowest effective dose (10 mg/day) and titrate slowly while monitoring seizure frequency. 1

3. Monitor for drug interactions: Check for pharmacokinetic interactions between antiepileptic drugs and citalopram that may alter plasma concentrations of either medication. 4

4. Close clinical observation is mandatory for any increase in seizure activity during initiation and dose adjustments. 1

5. Consider alternative SSRIs with lower seizure risk profiles (fluoxetine, sertraline) if depression treatment is essential. 2

Key Caveats

• The comparative seizure risk data comes primarily from elderly populations, so extrapolation to younger patients should be done cautiously. 2
• Overdose situations carry significantly higher seizure risk: A case report documented late-onset seizures with 400 mg citalopram ingestion. 5
• Abrupt discontinuation can also precipitate seizures as part of discontinuation syndrome. 1
• Drug-induced seizures account for approximately 6.1% of first-occurring seizures, making this a clinically relevant consideration. 6