Do antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs), lower the seizure threshold?

From the Guidelines

Antidepressants can lower the seizure threshold, and their use should be cautious in patients with a history of seizure disorders. When considering the use of antidepressants, it is essential to weigh the benefits against the potential risks, including the risk of seizures. According to the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders 1, SSRIs are generally well-tolerated but can have potentially serious adverse effects, including seizures. The guideline notes that seizures have been observed in the context of SSRI use, and therefore, SSRIs should be used cautiously in patients with a history of a seizure disorder 1. Some key points to consider when prescribing antidepressants to patients at risk of seizures include:

• Starting with low doses of SSRIs and gradually titrating upward to minimize the risk of seizures
• Close monitoring of patients for signs of seizure activity, particularly in the first few weeks of treatment
• Avoiding the use of high-risk antidepressants, such as bupropion at doses above 450mg/day, in patients with a history of seizure disorders
• Being aware of the potential for drug interactions that may increase the risk of seizures, such as the combination of SSRIs with other serotonergic agents. Overall, the decision to use antidepressants in patients at risk of seizures should be made on a case-by-case basis, taking into account the individual patient's medical history, the potential benefits of treatment, and the potential risks.

From the Research

Antidepressants and Seizure Threshold

• The relationship between antidepressants and seizure threshold is complex, with some studies suggesting that certain antidepressants may lower the seizure threshold, while others may have a minimal effect or even exert antiepileptic effects 2, 3.
• A review of the literature indicates that the majority of antidepressant-related seizures have been associated with either ultra-high doses or overdosing, and the risk of antidepressant-associated seizures is generally low 2.
• Certain antidepressants, such as amoxapine, bupropion, clomipramine, and maprotiline, are not recommended for patients with epilepsy due to their potential to lower the seizure threshold 2.

Seizure Risk Associated with Antidepressant Treatment

• Studies have shown that antidepressant exposure is positively associated with increased seizure risk, with some antidepressants showing a clear dose-response effect 4, 5.
• The seizure risk is highest among patients aged between 10 and 24 years and patients with major depression 4.
• Selective serotonin reuptake inhibitors (SSRIs) and selective noradrenalin reuptake inhibitors (SNRIs) have been associated with an increased risk of seizures, while tricyclic antidepressants (TCAs) do not appear to have a significant effect on seizure risk 5.

Factors Influencing Seizure Risk

• The individual's inherited seizure threshold and the presence of seizurogenic conditions, such as history of epilepsy or brain damage, can influence the risk of seizures during antidepressant treatment 6, 3.
• The dose and duration of antidepressant treatment, as well as the use of concomitant medications, can also affect the risk of seizures 6, 4.
• Careful evaluation of the possible presence of seizurogenic conditions and simplification of the therapeutic scheme, such as using low starting doses and avoiding complex drug combinations, can help minimize the risk of seizures 3.