What are the considerations for using bupropion (antidepressant) in patients with Ehlers-Danlos syndrome (EDS)?

Bupropion Use in Ehlers-Danlos Syndrome

Bupropion can be used in patients with Ehlers-Danlos syndrome (EDS) for depression or smoking cessation, but requires heightened vigilance for seizure risk given the potential association between EDS and epilepsy, and careful monitoring for bleeding complications if combined with antiplatelet agents.

Primary Seizure Risk Consideration

The most critical concern when prescribing bupropion to EDS patients is the seizure threshold:

• Bupropion is absolutely contraindicated in patients with seizure disorders and should be used with extreme caution in those at risk of seizures 1.
• EDS has been documented in association with epilepsy, with case series reporting various seizure types including complex partial seizures and grand mal seizures in EDS patients 2.
• The mechanism appears related to congenital or acquired CNS disorders that can accompany EDS, including structural brain abnormalities such as gliosis, vascular malformations, and basilar artery hypoplasia 2.

Before prescribing bupropion to any EDS patient, explicitly screen for:

• Personal history of seizures or epilepsy
• Family history of seizure disorders
• History of head trauma or CNS structural abnormalities
• Concomitant medications that lower seizure threshold 1

Bleeding Risk Considerations

EDS patients have documented hemostatic abnormalities that require consideration:

• Nearly half (41.7%) of EDS patients demonstrate abnormal bleeding scores, with 90% of these cases showing platelet function abnormalities 3.
• The bleeding risk progressively increases with the number of platelet function defects, reaching an odds ratio of 5.19 when more than three abnormalities are present 3.
• While bupropion itself is not a primary bleeding risk, if combined with antiplatelet agents or NSAIDs for chronic pain management (common in EDS), the cumulative bleeding risk becomes clinically significant 3.

Standard Monitoring Protocol

When bupropion is deemed appropriate for an EDS patient:

• Monitor blood pressure and heart rate regularly, particularly during the first 12 weeks, as uncontrolled hypertension is a contraindication 1.
• Screen for suicidal ideation, especially in patients under 24 years, as EDS patients have increased incidence of depression and borderline personality disorder 1, 4.
• Avoid concomitant use with MAO inhibitors (14-day washout required) or opioid medications, the latter being particularly relevant since chronic pain in EDS often involves opioid therapy 1.

Practical Dosing Approach

• The standard FDA-approved dose of 300 mg daily for major depressive disorder is appropriate for EDS patients who pass seizure risk screening 1.
• Start at lower doses and titrate gradually to assess tolerance, given the multisystem nature of EDS and potential for unpredictable drug responses.

Alternative Considerations

If seizure risk is uncertain or concerning:

• SSRIs combined with gabapentin (which also addresses EDS-related pain) represent a safer alternative, as documented in EDS case reports 4.
• Lithium augmentation of SSRIs has been used successfully in EDS patients with recurrent depression 4.