How do Selective Serotonin Reuptake Inhibitors (SSRIs) interact with antiepileptic medications?

From the Guidelines

SSRIs can interact with epilepsy medications, potentially affecting their effectiveness and safety, and careful monitoring is necessary to minimize the risk of adverse interactions, as evidenced by the potential of SSRIs to lower the seizure threshold in some individuals 1. When taking both types of medications, it is essential to be aware of the potential interactions between SSRIs and antiepileptic drugs. Some common interactions occur between SSRIs, such as fluoxetine, sertraline, and paroxetine, and antiepileptic drugs like carbamazepine, phenytoin, and valproate. For example, fluoxetine and fluvoxamine can inhibit the metabolism of phenytoin and carbamazepine, leading to increased blood levels and potential toxicity 1. Conversely, some antiepileptic drugs like carbamazepine can increase the metabolism of certain SSRIs, reducing their effectiveness.

Key Considerations

• The interactions between SSRIs and antiepileptic drugs are complex and can affect the efficacy and safety of both medication types.
• Patients taking both medication types should report any changes in mood, seizure frequency, or new side effects to their healthcare provider.
• Dose adjustments may be necessary when starting, stopping, or changing either medication.
• Blood level monitoring of antiepileptic drugs is often recommended when adding or removing an SSRI from the treatment regimen.

Monitoring and Management

• Healthcare providers should closely monitor patients taking both SSRIs and antiepileptic drugs for signs of adverse interactions, such as increased seizure frequency or changes in mood.
• The use of SSRIs in patients with epilepsy should be carefully considered, and the benefits and risks of treatment should be weighed on an individual basis 1.
• In general, the management of patients taking both SSRIs and antiepileptic drugs requires careful attention to the potential interactions between these medications and regular monitoring to minimize the risk of adverse effects.

From the FDA Drug Label

Anticonvulsants — Patients on stable doses of phenytoin and carbamazepine have developed elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity following initiation of concomitant fluoxetine treatment.

• SSRIs and epilepsy medication interaction: The use of fluoxetine with anticonvulsants such as phenytoin and carbamazepine may lead to elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity.
• Key consideration: When coadministering fluoxetine with epilepsy medications, caution is advised due to the potential for increased anticonvulsant levels and toxicity.
• Clinical decision: Monitor patients closely for signs of anticonvulsant toxicity when initiating concomitant fluoxetine treatment, and consider adjusting the dose of the anticonvulsant medication as needed 2.

From the Research

Effects of SSRIs on Epilepsy Medication

• SSRIs are considered safe for patients with epilepsy at therapeutic doses, with some studies suggesting they may even have antiepileptic properties 3, 4.
• The risk of antidepressant-associated seizures is low, and most seizures associated with antidepressants are due to ultra-high doses or overdosing 3.
• Certain antidepressants, such as amoxapine, bupropion, clomipramine, and maprotiline, are not recommended for patients with epilepsy due to their potential to trigger seizures 3.
• SSRIs like sertraline, citalopram, mirtazapine, reboxetine, paroxetine, fluoxetine, escitalopram, fluvoxamine, venlafaxine, and duloxetine are considered safe and effective for treating depression in patients with epilepsy 3, 4, 5.

Clinical Evidence

• A study published in 2000 found that sertraline can be safely used in the vast majority of patients with epilepsy, with only 6% of patients experiencing an increase in seizure frequency 6.
• Another study published in 2007 found that sertraline and fluoxetine are safe and effective treatments for children and adolescents with epilepsy and depression, with only 2 patients experiencing seizure worsening 7.
• A review article published in 2023 discussed the effects of antidepressant drugs on seizures and epilepsy, highlighting the potential benefits of newer SSRIs and SNRIs in improving epilepsy severity 5.

Considerations for Prescribing SSRIs to Patients with Epilepsy

• Clinicians should consider the potential benefits and risks of prescribing SSRIs to patients with epilepsy, taking into account the individual patient's medical history and seizure frequency 3, 4.
• Patients with epilepsy should be closely monitored for any changes in seizure frequency or severity when starting or adjusting SSRIs 6, 7.
• The use of SSRIs in patients with epilepsy should be carefully weighed against the potential benefits of treating depression, which can have a significant impact on quality of life 5.