Medicines Q&As
Q&A 24.5
What is the most appropriate antidepressant to use in persons with
epilepsy?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Published: September 2012
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
anticonvulsant 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. 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
options 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
is possibly of lowest risk and therefore 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.
If seizures occur or if the incidence of seizures increases, the antidepressant should be
discontinued.
Background
Depression is increased in people with epilepsy with a lifetime prevalence of about 30% (1). Patients
with epilepsy are three times more likely to be prescribed an antidepressant than the general
population and two times more likely to report suicidal thoughts (1). The association between epilepsy
and depression may be explained in part by serotonin; depletion of serotonin increases the risk of
both depression and epilepsy (2). Multiple studies have demonstrated that depression has a greater
negative impact on health-related quality of life than seizure activity and it has been associated with
poorer seizure outcomes, increased rates of adverse effects from antiepileptic drugs and increased
medical costs (1).
Answer
Peri-ictal depression (where symptoms are temporally related to seizure activity) should be initially
treated by optimising anticonvulsant therapy. Interictal depression (where symptoms occur
independently of seizures) are likely to require treatment with antidepressants (2). Use of antiepileptic
drugs with mood stabilising properties may be appropriate for selected individuals with mild
depressive symptoms (1). For example, gabapentin, carbamazepine, oxcarbazepine, valproate, and
lamotrigine improve depressive symptoms in epileptic patients (3,4,5,6), whereas phenobarbitone (4),
vigabatrin (4), primidone (7), topiramate (5) and tiagabine (5) have been associated with depression.
From the NHS Evidence website www.evidence.nhs.uk
1
Medicines Q&As
It is important to check the anticonvulsant regimen of an epileptic patient with depression for potential
drug-induced depression before considering adding an antidepressant.
The use of antidepressant medication in patients with epilepsy is a common clinical dilemma, as
some antidepressants, especially the tricyclic antidepressants (TCAs), are well known to lower the
seizure threshold and the risk is dose related (2). However, the perceived risks are often
overestimated and rarely outweigh the risk of leaving depression untreated (1). Antidepressants may
exert proconvulsive effects, the evidence for which comes largely from overdose studies (8,9)
therefore recognising that there is a dose-dependant relationship between antidepressants and
seizures (10). When assessing the relative risk of inducing seizures, predisposing factors must be
taken into account as well as antidepressant dosing and induction rate (11). A slow rate of
introduction reduces the risk of seizures in prone patients (10). There is no ideal ranking for likelihood
of seizures with antidepressants though a number of reviewers have tried to provide some guidance
(2,10,11,12):
High risk of seizure:
amitriptyline (higher doses), clomipramine, dosulepin,
Intermediate risk of seizure:
amitriptyline, doxepin, duloxetine, imipramine, mianserin, mirtazapine,
nortriptyline, trazodone, venlafaxine
Low risk of seizure:
fluvoxamine, fluoxetine, isocarboxazid, moclobemide, paroxetine,
phenelzine, reboxetine, sertraline, tranylcypromine, tryptophan
Selective Serotonin Reuptake Inhibitors (SSRIs)
In general, the SSRIs are considered a good choice in epilepsy because they have a low proconvulsive effect (2,10). The risk of seizures at therapeutic doses is between 0.1-4% (13), though this
varies between individual agents. SSRIs are associated with a lower incidence of seizures when
compared with TCAs (14) and are considered the first line antidepressant option in patients with
epilepsy (2,3,8,9,15,16). However, seizures have now been reported with all SSRIs (17) and the risk
is considered to be dose-related (13). If seizures occur or if the incidence of seizures increases, the
antidepressant should be discontinued. 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 (13). Citalopram and sertraline are considered by some
reviewers as first line agents because of their efficacy and safety and the minimal pharmacokinetic
interaction with antiepileptic drugs (1,3), but unless a large scale trial is carried out, the safest
antidepressant in epilepsy will remain unknown (10).
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 (13). Fluoxetine
has a probable seizure incidence of 0.2% (10,3,17) and has a long half-life (18). The manufacturers
recommend it should be avoided in patients with unstable seizure disorders and patients with
controlled epilepsy should be monitored (18). It should also be noted that fluoxetine can cause
changes in blood levels of phenytoin such that cases of phenytoin toxicity have been reported (18).
One small-scale study (n=28) reported that fluvoxamine was not proconvulsant at doses ranging
from 50 to 200mg, when given to depressed epileptic patients (19), however there have been case
reports of seizures following therapeutic doses of fluvoxamine in patients with and without a previous
history of seizures (20). Pre-marketing studies and a retrospective survey of prescriptions (n=10,401)
suggested the incidence of seizure with fluvoxamine to be 0.2% in the general population (15,16).
Fluvoxamine should be avoided in patients with unstable epilepsy and patients with controlled
epilepsy should be carefully monitored (21). Data from the manufacturers also suggest that the
incidence of seizures with fluvoxamine at therapeutic doses to be less than 0.1%. In addition, dose
adjustments may be necessary when fluvoxamine is used with anticonvulsants such as
carbamazepine and phenytoin (21,22).
Paroxetine appears to have a minimal potential for producing seizures at therapeutic doses (10) but
the manufacturers suggest that it should be used with caution in patients with epilepsy (23). Reviews
From the NHS Evidence website www.evidence.nhs.uk
2
Medicines Q&As
suggest paroxetine has a seizure incidence of less than 0.1% (3,4,9). In addition, paroxetine is not
known to have any effect on the pharmacokinetics and pharmacodynamics of anticonvulsants (23).
Citalopram and escitalopram have not been reported to have a proconvulsive effect post-marketing
(10). In an 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 (24).
A study of 43 patients with epilepsy showed citalopram to be an effective antidepressant without
affecting seizure frequency (5). However, due to the potential for all SSRIs to cause seizures, the
manufacturers advise caution in patients with controlled epilepsy (25,26). Citalopram and
escitalopram should be avoided in patients with unstable epilepsy and patients with controlled
epilepsy should be carefully monitored (25, 26). However, citalopram 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 (2,3).
Early clinical trials with sertraline suggested that seizures occurred at a similar frequency to placebo
and only in people with a history of seizures (10,15). 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 (5,8,). Data from, the manufacturers suggests the incidence of seizures to be
between 0.1% and 1% at therapeutic doses of sertraline. It has the benefit of having no interactions
with carbamazepine but it may interact with phenytoin (27).
Tricyclic Antidepressants (TCAs)
All TCAs appear to lower the seizure threshold with amitriptyline reputed to be the most proconvulsive
and doxepin possibly of lowest risk (10). The overall incidence of seizures at therapeutic doses of
TCAs has been estimated as <1% (15) though the incidence for individual TCAs varies markedly (see
Table 2).
Table 2: Seizure incidence rates and manufacturers advice for individual TCAs
Drug
Incidence
Manufacturers Advice
Amitriptyline
0.3% (therapeutic doses) (3).
Clomipramine
0.5--12.2% (therapeutic doses,
dose dependent) (3,15).
Avoid if possible in patients with a history of
epilepsy (28).
Use with extreme caution in epilepsy (seizure
occurrence appears to be dose dependent) (16).
Dosulepin
Limited data.
Avoid in patients with history of epilepsy (30).
Doxepin
0.1% (therapeutic doses) (15).
Imipramine
0.1% (≤200mg/day) –
(>200mg/day) (15,17).
Lofepramine
Limited data
Nortriptyline
Limited data
Trimipramine
Limited data
Mianserin
Limited data
Trazodone
<0.1% (therapeutic doses) (3)
1.1%
Use with caution in patients with history of epilepsy
(31).
Use with extreme caution in epilepsy (seizure
occurrence appears to be dose dependent) (32).
Use with extreme caution in patients with a history
of epilepsy or recent convulsions (33).
Avoid if possible in patients with a history of
epilepsy (34).
Use with great caution in patients with a history of
epilepsy (35).
Convulsions have been reported at therapeutic
dosage so use with caution in epilepsy (36)
Use with caution in patients with epilepsy.
Specifically abrupt increases or decreases of
dosage should be avoided (37)
Amitriptyline, dosulepin, clomipramine should ideally be avoided completely in epilepsy (2). Most
TCAs are known to potentially interact with anticonvulsants and manufacturers advice should be
consulted for individual TCAs (28-31,32-37)
From the NHS Evidence website www.evidence.nhs.uk
3
Medicines Q&As
Monamine Oxidase Inhibitors (MAOIs)
MAOIs have a low seizure risk but they are seldom used now due to their interactions with certain
foods and drugs and the fact that there are safer alternatives available. It has been suggested that
MAOIs are not administered at the same time as anticonvulsants (22,38).
Moclobemide is a reversible inhibitor of monoamine oxidase type A (RIMA) which is less likely to
interact with foods and drugs, and there have been no reports of problems in epilepsy to date (10). It
is therefore considered a good choice in patients with epilepsy and is not cautioned or contraindicated
in these patients, or reported to cause seizures in overdose (2,39).
Phenelzine is an irreversible MAOI which should be used with caution in patients with epilepsy since
the drug has been reported to cause convulsions at therapeutic doses (38).
Isocarboxazid has been reported to have varying effects in epileptic patients with some patients
experiencing a reduced frequency in seizures and others reporting an increased frequency (40).
Based on this and the potential for convulsions in overdose, isocarboxazid requires caution when
used in epileptics.
Tranylcypromine is cautioned when used in epileptic patients due to animal studies indicating a
varying effect on seizure threshold and convulsions being noted in overdoses (41).
Miscellaneous Antidepressants
Seizures have been reported in 0.26% of depressed patients treated with venlafaxine (a serotoninnoradrenaline reuptake inhibitor) during clinical trials (15,16) but data is limited compared to that
available for SSRIs (2). It is considered to increase seizure risk in overdose (2,42). It should be
introduced with caution in patients with a history of seizures (42).
Rare cases of seizures with Reboxetine (a noradrenaline reuptake inhibitor) have been reported in
clinical studies but it has not been tested in patients with epilepsy; therefore its use is cautioned by
the manufacturer in epilepsy (43). There were no reports of seizures following overdose (43).
Mirtazapine (a centrally active presynaptic alpha-2 antagonist) is also associated with a minimal
incidence of seizures (9,3) with an incidence of less than 0.1% suggested (12,15). However, one
grand mal seizure has been reported in a patient with a history of seizures receiving mirtazapine at a
dose of 80mg/day during a trial (10) (maximum licensed dose in UK is 45mg/day (44)). In one small
study mirtazapine was found to enhance cortical excitability in healthy controls (n=6) and in patients
with epilepsy (n=7). This may be associated with an increase in seizures, although this was not seen
in the study but the small numbers and short duration of the study limit the power of the study in this
respect (45). Although clinical experience indicates that seizures are rare during mirtazapine therapy,
caution is advised in patients with epilepsy (44). In addition, there is a significant interaction with
carbamazepine whereby mirtazapine dosing may have to be increased for therapeutic effect, and
mirtazepine also interacts with phenytoin (44).
Clinical experience and data regarding the safety of duloxetine (a combined serotonin and
noradrenaline reuptake inhibitor) in epileptic patients is limited. Seizures have been reported rarely (2)
and the manufacturer’s advise caution in patients with a history or diagnosis of seizures (46). Cases
of convulsions have been reported on discontinuation of therapy (46).
Flupentixol (Fluanxol®) is licensed for treatment of depression in the UK (47). Its exact mode of
action in this condition is unclear but may involve presynaptic dopamine receptors. Use of Fluanxol® is
cautioned in patients with epilepsy given that convulsions have been reported as an adverse effect at
therapeutic doses (47).
L-tryptophan is neither cautioned nor contraindicated in patients with epilepsy (48). However, its use
is limited to treatment-resistant depression and as an adjunct to other antidepressants. L-tryptophan
does not have any interactions with anticonvulsants and has very few undesirable effects (48).
From the NHS Evidence website www.evidence.nhs.uk
4
Medicines Q&As
Eosinophilia myalgia syndrome (EMS) is a rare but potentially fatal event reported with L-tryptophan
at therapeutic doses (48).
Agomelatine (a melatonergic agonist and 5-HT antagonist) also appears to have no cautions or
contraindications with regards to use in epilepsy (49). However, it is currently under intense
monitoring by the Medicines and Healthcare products Regulatory Agency (MHRA) and there is little
post-marketing data regarding any adverse effects (49).
Lithium is licensed for recurrent depression where treatment with other antidepressants has been
unsuccessful (50). It is also used to augment other antidepressants in patients with treatmentresistant depression (unlicensed indication) (22). Lithium use in epileptics is cautioned due to there
being a potential to increase the frequency of convulsions at therapeutic doses and it has marked
epileptogenic activity in overdose (10,50). In addition, interactions with carbamazepine may cause
neurotoxicity and there are reports of interactions with phenytoin (50).
Other factors to consider
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 (2,3,9,). NICE recommends that
generally SSRIs should be first-line treatment for depression in people with a chronic physical health
problem and of the SSRIs, sertraline and citalopram probably have the lowest interaction potential
(51).
As a general rule, the more sedating a drug is, the more likely it is to induce seizures (2). 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 (2,10). In addition, maximum recommended doses of
antidepressants should not be exceeded.
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 (5).
References
1.
2.
Noe KH, Locke DEC, Sirven JI. Treatment of depression in patients with epilepsy. Current
Treatment Options in Neurology 2011; 13:371-379.
Taylor D, Paton C, Kapur S. The Maudsley Prescribing Guidelines in Psychiatry. The South
London and Maudsley NHS Foundation Trust, Oxleas NHS Foundation. 11th Edition. Wiley
Blackwell. 2012
From the NHS Evidence website www.evidence.nhs.uk
5
Medicines Q&As
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
Prueter C, Norra C. Mood disorders and their treatment in patients with epilepsy. J
Neuropsychiatry Clin Neurosci 2005;17(1):20-8.
Schmitz B. Antidepressant drugs: Indications and guidelines for use in epilepsy. Epilepsia
2002;43(S2):14-18.
Harden CL. The co-morbidity of depression and epilepsy: epidemiology, etiology, and
treatment. Neurology 2002;59(S4):S48-S55.
Mazza M, Marca GD, Di Nicola D et al. Oxcarbazepine improves mood in patients with
epilepsy. Epilepsy & Behaviour 2007;10:397-401.
Trimble MR. Anticonvulsant-induced psychiatric disorders: The role of forced normalisation.
Drug Safety 1996;15(3):159-66.
Jackson MJ, Turkington D. Depression and Anxiety in Epilepsy. J Neurol Neurosurg
Psychiatry 2005;76(Suppl 1):i45-i47.
Curran S, de Pauw K. Selecting an antidepressant for use in a patient with epilepsy. Drug Saf
1998;18(2):125-33.
Bazire S. Psychotropic Drug Directory 2012. Lloyd-Reinhold communications. Warwickshire.
2012
“Comparative incidence of seizures from antidepressants.” In DRUGDEX® Consults.
Micromedex 2.0. Thomson Reuters (Healthcare) Inc. Accessed via
http://www.thomsonhc.com on 19/09/2012.
Mula M, Schmitz B, Sander JW. The pharmacological treatment of depression in adults with
epilepsy. Expert Opin. Pharmacother 2008; 9 (18): 3159-3168
Torta R, Monaco F. Atypical antipsychotics and serotoninergic antidepressants in patients
with epilepsy: pharmacodynamic considerations. Epilepsia 2002;43(S2):8-13.
Seethalakshmi R, Krishnamoorthy ES. Depression in epilepsy: phenomenology, diagnosis
and management. Epilep Disord 2007; 9(1):1-10
Anon. Prompt diagnosis and treatment of depression in patients with epilepsy essential for
patient well-being. Drugs & Therapy Perspectives 2003;19(1):7-10.
Harden CL, Goldstein MA. Mood disorders in patients with epilepsy: epidemiology and
management. CNS Drugs 2002;16(5):291-302.
Duncan D, Taylor D. Which is the safest antidepressant to use in epilepsy? Psychiatric
Bulletin 1995;19:355-6.
Summary of Product Characteristics. Prozac 20mg hard capsules, and 20mg/5ml oral liquid.
Eli Lilly and Company Ltd. Date of revision of text: 26/04/2012. Accessed via:
http://emc.medicines.org.uk. Date accessed: 29/08/2012.
Harmant J, van Rijckevorsel-Harmant K, de Barsy TH et al. Fluvoxamine: an antidepressant
with low (or no) epileptogenic effect. Lancet 1990;336(8711):386.
Wood DM, Rajalingham Y, Greene SL et al. Status epilepticus following intentional overdose
of fluvoxamine: A case report with serum fluvoxamine concentration. Clin Toxicol
2007;45:791-3.
Summary of Product Characteristics. Faverin 50mg film-coated tablets. Abbott Healthcare
Products Ltd. Date of revision of text: 01/03/2012. Accessed via: http://emc.medicines.org.uk.
Date accessed: 29/08/2012.
British National Formulary 64, September 2012. BMJ Group & Pharmaceutical Press. 2012.
Accessed via www.medicinescomplete.com on 03/09/2012
Summary of Product Characteristics. Seroxat 10mg, 20mg, 30mg tablets, 20mg/10ml oral
suspension. GlaxoSmithKline UK. Date of revision of text: 18/06/2012. Accessed via:
http://emc.medicines.org.uk. Date accessed: 29/08/2012.
Specchio LM, Iudice A, Specchio N et al. Citalopram as treatment of depression in patients
with epilepsy. Clin Neuropharmacol 2004;27(3):133-6.
Summary of Product Characteristics. Cipramil Tablets. Lundbeck Ltd. Date of revision of text:
23/01/2012. Accessed via: http://emc.medicines.org.uk. Date accessed: 22/08/2012.
Summary of Product Characteristics. Cipralex 5, 10 and 20mg film-coated tablets and
20mg/ml oral drops, solution. Lundbeck Ltd. Date of revision of text: 16/12/2011. Accessed
via: http://emc.medicines.org.uk. Date accessed: 22/08/2012.
Summary of product Characteristics. Lustral. Pfizer Ltd. Date of revision of text: Feb 2012.
Accessed via: http://emc.medicines.org.uk. Date accessed: 22/08/2012.
From the NHS Evidence website www.evidence.nhs.uk
6
Medicines Q&As
28. Summary of Product Characteristics. Amitriptyline tablets BP 50mg. Actavis UK Ltd. Date of
revision of text: 22/02/2011. Accessed via: http://emc.medicines.org.uk. Date accessed:
22/08/2012.
29. Summary of Product Characteristics. Anafranil Capsules. Novartis Pharmaceuticals UK Ltd.
Date of revision of text: 21/06/2012. Accessed via: http://emc.medicines.org.uk. Date
accessed: 22/08/2012.
30. Summary of Product Characteristics. Dosulepin 25mg capsules.Gerard Laboratories. Date of
revision of text: April 2011. Accessed via: http://emc.medicines.org.uk Date accessed:
24/09/2012.
31. Summary of Product Characteristics. Sinepin Capsules 25mg. Marlborough Pharmaceuticals
Ltd. Date of revision of text: 18/07/2011. Accessed via: http://emc.medicines.org.uk. Date
accessed: 22/08/2012.
32. Summary of Product Characteristics. Imipramine Hydrochloride 25mg/5ml Oral Solution.
Rosemount Pharmaceuticals Ltd. Date of revision of text: 22/03/2011. Accessed via:
http://emc.medicines.org.uk. Date accessed: 22/08/2012.
33. Summary of Product Characteristics. Lofepramine 70mg Tablets. Merck Serono. Date of
revision of text: 16/11/10. Accessed via: http://emc.medicines.org.uk. Date accessed:
22/08/2012.
34. Summary of Product Characteristics. Allegron. King Pharmaceuticals Ltd. Date of revision of
text: June 2010. Accessed via: http://emc.medicines.org.uk. Date accessed: 22/08/2012.
35. Summary of Product Characteristics. Surmontil Capsules 50mg hard capsules. SanofiAventis. Date of revision of text: August 2011. Accessed via: http://emc.medicines.org.uk.
Date accessed: 29/08/2012.
36. Summary of Product Characteristics. Mianserin 10mg & 30mg film coated tablets. Gerard
Laboratories. Date of revision of text: April 2011. Accessed via: http://emc.medicines.org.uk.
Date accessed: 29/08/2012.
37. Summary of Product Characteristics. Molipaxin 50mg Capsules. Zentiva. Date of revision of
text: 27/09/2010. Accessed via: http://emc.medicines.org.uk. Date accessed: 22/08/2012.
38. Summary of Product Characteristics. Nardil Tablets. Archimedes Pharma UK Ltd. Date of
revision of text: October 2008. Accessed via: http://emc.medicines.org.uk. Date accessed:
22/08/2012.
39. Summary of Product Characteristics. Manerix 150mg Tablets. Meda Pharmaceuticals. Date of
revision of text:19/06/1997. Accessed via: http://emc.medicines.org.uk. Date accessed:
22/08/2012.
40. Summary of Product Characteristics. Isocarboxazid Tablets 10mg. Alliance Pharmaceuticals.
Date of revision of text:16/11/2011. Accessed via: http://emc.medicines.org.uk. Date
accessed: 22/08/2012.
41. Summary of Product Characteristics. Tranylcypromine 10mg Tablets. Mercury Pharma Group.
Date of revision of text: 09/12/2010. Accessed via: http://emc.medicines.org.uk. Date
accessed: 03/09/2012.
42. Summary of Product Characteristics. Efexor XL. Pfizer Limited. Date of revision of text:
November 2011. Accessed via: http://emc.medicines.org.uk. Date accessed: 22/08/2012.
43. Summary of Product Characteristics. Edronax 4mg Tablets. Pharmacia Ltd. Date of revision
of text: July 2012. Accessed via: http://emc.medicines.org.uk. Date accessed: 22/08/2012.
44. Summary of Product Characteristics. Zispin SolTab 15mg, 30mg and 45mg Orodispersible
Tablets. Merck Sharp & Dohme Limited. Date of revision of text: October 2010. Accessed via:
http://emc.medicines.org.uk. Date accessed: 22/08/2012.
45. Munchau A, Langosch JM, Gerschlager W et al. Mirtazapine increases cortical excitability in
healthy controls and epilepsy patients with major depression. J Neurol Neurosurg Psychiatry
2005;76:527-33.
46. Summary of Product Characteristics. Cymbalta 30mg hard gastro-resistant capsules,
Cymbalta 60mg hard gastro-resistant capsules. Eli Lilly and Company Ltd. Date of revision of
text: 26/07/2011. Accessed via: http://emc.medicines.org.uk. Date accessed: 22/08/2012.
47. Summary of Product Characteristics. Fluanxol Tablets. Lundbeck Ltd. Date of revision of text:
07/01/2012. Accessed via: http://emc.medicines.org.uk. Date accessed: 22/08/2012.
48. Summary of Product Characteristics. Optimax. Merck Serono. Date of revision of text:
09/10/2009. Accessed via: http://emc.medicines.org.uk. Date accessed: 22/08/2012.
From the NHS Evidence website www.evidence.nhs.uk
7
Medicines Q&As
49. Summary of Product Characteristics. Valdoxan. Servier Laboratories Ltd. Date of revision of
text: March 2012. Accessed via: http://emc.medicines.org.uk. Date accessed: 22/08/2012.
50. Summary of Product Characteristics. Priadel 200mg prolonged release tablets. SanofiAventis. Date of revision of text: 22/06/2011. Accessed via: http://emc.medicines.org.uk. Date
accessed: 22/08/2012.
51. National Collaborating Centre for Mental Health. Depression: The NICE guideline on the
treatment and management of depression in adults with a chronic physical health problem.
October 2009. CG91. Accessed via www.nice.org.uk on 24/09/12
Quality Assurance
Prepared by
Caroline Taylor, London Medicines Information Service (Northwick Park Hospital)
Based on earlier work by Iram Husain, Caroline Fletcher and Varinder Rai
Date Prepared
22nd September 2012
Checked by
Alexandra Denby, London Medicines Information Service (Northwick Park Hospital)
Date of check
15th October 2012
Search strategy
 Embase [AMITRIPTYLINE/ OR CLOMIPRAMINE/ OR DOSULEPIN/ OR DOXEPIN/ OR
IMIPRAMINE/ OR LOFEPRAMINE/ OR NORTRIPTYLINE/ OR TRIMIPRAMINE/ OR
MIANSERIN/ OR TRAZODONE/ OR PHENELZINE/ OR ISOCARBOXAZID/ OR
TRANYLCYPROMINE/ OR MOCLOBEMIDE/ OR CITALOPRAM/ OR ESCITALOPRAM/ OR
FLUOXETINE/ OR FLUVOXAMINE/ OR PAROXETINE/ OR SERTRALINE/ OR
AGOMELATINE/ OR DULOXETINE/ OR FLUPENTIXOL/ OR MIRTAZAPINE/ OR
REBOXETINE/ OR TRYPTOPHAN/ OR VENLAFAXINE/] AND exp EPILEPSY/ [Limit to:
Publication Year 2008-2011]
exp DEPRESSION/dt [Limit to: Publication Year 2008-Current] [dt=Drug Therapy] AND exp
EPILEPSY/ [Limit to: Publication Year 2008-Current] AND ANTIDEPRESSANT AGENT/ae
[Adverse Drug Reaction]
exp ANTIDEPRESSANT AGENT/ [Limit to: Publication Year 2008-Current] AND exp EPILEPSY/
[Limit to: Publication Year 2008-Current] AND exp DEPRESSION/dt [Limit to: Publication Year
2008-Current] [dt=Drug Therapy]



Medline [MOCLOBEMIDE/ OR ISOCARBOXAZID/ OR TRANYLCYPROMINE/ OR
PHENELZINE/ OR CITALOPRAM/ OR FLUOXETINE/ OR FLUVOXAMINE/ OR MIANSERIN/
OR PAROXETINE/ OR TRAZODONE/ OR AMITRIPTYLINE/ OR CLOMIPRAMINE/ OR
DOTHIEPIN/ OR DOXEPIN/ OR IMIPRAMINE/ OR LOFEPRAMINE/ OR NORTRIPTYLINE/ OR
TRIMIPRAMINE/ OR TRYPTOPHAN/ OR escitalopram.af OR SERTRALINE/ OR agomelatine.af
OR duloxetine.af OR FLUPENTHIXOL/ OR mirtazapine.af OR reboxetine.af OR venlafaxine.af =
63460] AND exp EPILEPSY/ exp EPILEPSY/ [Limit to: Publication Year 2008-Current] AND exp
DEPRESSIVE DISORDER/dt [Limit to: Publication Year 2008-Current] [dt=Drug Therapy] (exp
ANTIDEPRESSIVE AGENTS/ OR ESCITALOPRAM.af OR DULOXETINE.af [Limit to:
Publication Year 2008-Current] OR FLUPENTIXOL.af [Limit to: Publication Year 2008-Current]
OR MIRTAZAPINE.af OR REBOXETINE.af OR VENLAFAXINE.af) AND exp EPILEPSY/
In-house resources
Electronic Medicines Compendium
From the NHS Evidence website www.evidence.nhs.uk
8