Medicines Q&As

Medicines Q&As
In addition, some antidepressants may interact with anticonvulsants; this potential for interactions
would need to be considered when choosing a suitable antidepressant agent for the patient. Plasma
concentrations of the anticonvulsants should be carefully monitored if appropriate, particularly during
the early phase of treatment with the antidepressant and doses adjusted accordingly (6;11;22).
As a general rule, the more sedating a drug is, the more likely it is to induce seizures (22). There is a
dose dependent relationship between antidepressant use and seizures. Patients should be
commenced on a low dose, and this should be increased slowly until a therapeutic dose has been
achieved, to reduce the risk of seizures (7;22). In addition, maximum recommended doses of
antidepressants should not be exceeded.
Summary
• The first consideration should always be to check the patients’ anticonvulsant regimen for
potential drug-induced depression. It may be that the patient would benefit from changing the
anti-convulsant to another agent with a more favourable effect on mood rather than adding in
an antidepressant.
• The risk of seizures with most antidepressants is low, but is probably not zero for any of them,
and patients should be made aware of this when prescribing. The risk of seizures increases
with increasing doses.
• SSRIs are considered the first line antidepressant option in patients with epilepsy. Published
data do not support the recommendation of a specific SSRI, although fluoxetine is not the
best choice due to its long half-life, a possibly greater incidence of seizures and an increased
risk of drug interactions. Citalopram or sertraline may be considered the better option due to
safety and reduced interaction potential with the anticonvulsants.
• Moclobemide, is a good alternative, as it has a low incidence of seizures but due to limited
data it should be reserved as a second choice.
• TCAs should be used cautiously in patients with epilepsy and reserved for patients who
poorly respond to or are intolerant of other antidepressants. Where a TCA is needed, doxepin
would be the agent of choice.
• Clinicians should be aware of the possibility of interactions between antidepressants and
anticonvulsants and should monitor carefully patients with epilepsy who are prescribed
antidepressants.
• Introducing the antidepressant gradually, starting with a low dose, and not exceeding the
maximum recommended doses may reduce the risk of a seizure.
Limitations
In general, very little specific information is available about the use of antidepressants in epilepsy.
Most studies investigating the relationship between antidepressants and seizure activity have
examined the effects of antidepressants in overdose in the general population, making it difficult to
extrapolate the findings to patients with epilepsy. Seizure rates quoted are based on the incidence in
patients with depression rather than patients with epilepsy, and this latter figure would be expected to
be higher. Many of the early estimates of seizure incidence were based on case reports where there
were many influencing variables and poor definitions for what constituted a convulsive event.
Patients were also often taking concomitant medication, which may have affected seizure threshold,
or, through inhibition of antidepressant metabolism, caused higher antidepressant plasma levels.
Newer antidepressants have undergone clinical trials with improved methodology and with systematic
reporting of adverse events. However, even these do not allow accurate comparisons to be made
between the antidepressants. There are few systematic studies of antidepressants in people with
epilepsy. Unless a large-scale trial is conducted, which is unlikely, the best antidepressant in epilepsy
will remain unknown (7).
From the National Electronic Library for Medicines. www.nelm.nhs.uk 4