Medicines Q&As

Medicines Q&As
Doxepin is considered to have the lowest incidence of seizures (5;7;9;21) and therefore is considered
the TCA of choice. The manufacturers of amitriptyline and clomipramine have advised that these
antidepressants should be used with caution in epilepsy but other sources recommend that they
should be avoided completely in epilepsy (22).
Selective Serotonin Reuptake Inhibitors (SSRIs)
In general, the SSRIs have been suggested to have a low pro-convulsive effect (7;22), a favourable
side effect profile and to be less problematic in overdose (6). SSRIs are associated with a lower
incidence of seizures when compared with TCAs (1;11). However, little data are available
concerning the use of SSRIs in patients with epilepsy. Early clinical trials suggested that the SSRIs
were not associated with seizures (6). Seizures have now been reported with all SSRIs (16) and the
risk is considered to be dose related (22). Data on how these antidepressants induce seizures is still
controversial, one theory is that a decreased turnover of serotonin in the central nervous system
(CNS) might be associated with seizures (23). There is some evidence that SSRIs increase the
seizure duration once a seizure has commenced (6).
Fluoxetine is the most studied SSRI and was suggested to exert an anticonvulsant effect in rats, this
has been further supported by data from small-scale controlled studies in humans (23). Fluoxetine
has a probable seizure incidence of 0.2% (7;11;16) and has a long half-life (24). The manufacturers
recommend it should be avoided in patients with unstable seizure disorders and patients with
controlled epilepsy should be monitored (24).
One small-scale study (n=28) reported that fluvoxamine was not epileptogenic at doses ranging from
50 to 200mg, when given to depressed epileptic patients (25) however there have been case reports
of seizures following therapeutic doses of fluvoxamine in patients with and without a previous history
of seizures (26). More recently, a retrospective survey of prescriptions (n=10,401) suggested the
incidence of seizure with fluvoxamine to be 0.2% in the general population (27). It has also been
suggested that fluvoxamine is associated with a higher incidence of seizures in overdose when
compared to other SSRIs but the evidence for this is poor (6). Fluvoxamine should be avoided in
patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored
(28).
Paroxetine appears to have a minimal potential for producing seizures at therapeutic doses (7) but
the manufacturers suggest that it should be used with caution in patients with epilepsy (29). Reviews
suggest paroxetine has a seizure incidence of 0.1% (6;11;30). Seizures have occurred rarely in trials
and no cause-effect relationship has been proven (7).
Citalopram and escitalopram have not been reported to have a pro-convulsive effect (7). In a recent
open label study citalopram 20mg/day was associated with an improvement in depressive symptoms
and a reduction in seizure frequency in 39 patients who had epilepsy and depression (31). A study of
43 patients with epilepsy showed citalopram to be an effective antidepressant without affecting
seizure frequency (32). It is considered one of the first line options due to it is perceived safety in
these patients and lack of interactions with the anticonvulsant agents (11;22) .
Early clinical trials with sertraline suggested that seizures occurred at a similar frequency to placebo
and only in people with a history of seizures (7). The above study in 43 patients showed only 6% of
epileptics taking sertraline had worsening of seizures, which were corrected by adjusting the
antiepileptic dosage (4;32).
Overall, it has been suggested that the risk of seizures with SSRIs at therapeutic doses lies between
0.1-4% (23) but the incidence varies between individual agents. SSRIs are considered the first line
antidepressant option in patients with epilepsy (3;4;11;22;27). Fluoxetine, fluvoxamine and paroxetine
are all potent inhibitors of the cytochrome P450 enzymes (11;22), which means they have interaction
potential with the anticonvulsant agents, which needs to be considered. Citalopram and sertraline
may be considered the safest options due to their lack of interaction potential with the anticonvulsants
(11). The manufacturers of these agents recommend to avoid their use in patients with unstable
epilepsy (33;34).
From the National Electronic Library for Medicines. www.nelm.nhs.uk 2