What is the safest selective serotonin reuptake inhibitor (SSRI) for a 15-year-old patient with controlled epilepsy, currently on lamotrigine (Lamictal) 125mg twice daily (BD)?

From the Guidelines

For a 15-year-old with controlled epilepsy on lamotrigine 125 mg twice daily, sertraline is generally considered one of the safer SSRI options. This recommendation is based on the fact that sertraline has a relatively low risk of drug interactions compared to other SSRIs, such as fluoxetine, which can increase lamotrigine levels by 20-50% and potentially cause toxicity 1.

When initiating sertraline, it is recommended to start at a low dose of 25-50 mg daily and gradually increase if needed, while closely monitoring for breakthrough seizures, lamotrigine side effects (rash, dizziness, headache), or mood changes. Regular follow-up appointments every 2-4 weeks during the initial treatment period are important to assess the patient's response to the medication and adjust the dose as needed.

Some key points to consider when prescribing SSRIs to patients with epilepsy include:

• The potential for drug interactions, particularly with fluoxetine, which can increase lamotrigine levels and cause toxicity 1
• The risk of suicidal thinking and behavior, which is a boxed warning for all SSRIs in patients through age 24 years 1
• The potential for behavioral activation/agitation, which can occur early in treatment or with dose increases, and may be more common in younger children than adolescents 1
• The importance of educating patients and their families about the potential side effects of SSRIs, including dry mouth, nausea, diarrhea, and changes in appetite or sleep patterns 1

Overall, sertraline is a reasonable choice for an SSRI in a 15-year-old with controlled epilepsy on lamotrigine, due to its relatively low risk of drug interactions and side effects. However, close monitoring and regular follow-up appointments are essential to ensure the patient's safety and adjust the treatment plan as needed.

From the FDA Drug Label

Sertraline has not been evaluated in patients with a seizure disorder. These patients were excluded from clinical studies during the product’s premarket testing. No seizures were observed among approximately 3000 patients treated with sertraline in the development program for major depressive disorder However, 4 patients out of approximately 1800 (220 <18 years of age) exposed during the development program for obsessive-compulsive disorder experienced seizures, representing a crude incidence of 0. 2%. Three of these patients were adolescents, two with a seizure disorder and one with a family history of seizure disorder, none of whom were receiving anticonvulsant medication.

Accordingly, sertraline should be introduced with care in patients with a seizure disorder

The FDA drug label does not answer the question of which SSRI is safer for a 15-year-old epileptic patient on lamotrigine. However, it does provide information on the use of sertraline in patients with seizure disorders, stating that it should be introduced with care in these patients 2.

Key points:

• Sertraline has not been evaluated in patients with a seizure disorder.
• It should be introduced with care in patients with a seizure disorder.
• There is limited information on the use of sertraline in patients with epilepsy, particularly in adolescents. No conclusion can be drawn about the safety of sertraline or other SSRIs in this patient population based on the provided drug labels 2.

From the Research

Safety of SSRIs in Epileptic Patients

• The safety of SSRIs in epileptic patients is a concern due to the potential risk of seizures 3.
• However, the risk of antidepressant-associated seizures is generally low, and some evidence suggests that antidepressants may lower the risk of triggering seizures 3.
• Four antidepressants are not recommended for patients with epilepsy: amoxapine, bupropion, clomipramine, and maprotiline 3.

Recommended SSRIs for Epileptic Patients

• Clinicians should consider using SSRIs or SNRIs, particularly sertraline, citalopram, mirtazapine, reboxetine, paroxetine, fluoxetine, escitalopram, fluvoxamine, venlafaxine, and duloxetine 3.
• Escitalopram has been shown to be effective in treating severe depression and may be a good option for epileptic patients with depression 4.

Fluoxetine and Epilepsy

• Fluoxetine is not recommended for patients with epilepsy, according to some sources.
• However, the evidence does not provide a clear reason for this recommendation, and fluoxetine is listed as a potential option for treating depression in epileptic patients 3.

Lamotrigine and SSRIs

• Lamotrigine is an antiepileptic drug that is also used to treat depression 5, 6.
• The interaction between lamotrigine and SSRIs is not well-studied, but it is generally considered safe to use them together 3.
• The patient in question is already taking lamotrigine, and the addition of an SSRI may be considered to treat depression.