Download What is the most appropriate antidepressant to use?

Medicines Q&As
Q&A 24.7
What is the most appropriate antidepressant to use in people with
epilepsy?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at https://www.sps.nhs.uk/articles/about-ukmi-medicines-qas/
Published: December 2016
Summary
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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.
Selective Serotonin Reuptake Inhibitors (SSRIs) are considered the first line antidepressant
option in patients with epilepsy. Sertraline may be considered the better option due to safety
data and reduced interaction potential with the anticonvulsants. 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.
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 to SSRIs.
Tricyclic antidepressants (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 within
this group.
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.
Detailed information regarding drug interactions has not been included in this Q&A:
pharmacokinetic and pharmacodynamic drug interactions between antidepressants and
antiepileptic drugs must be checked prior to prescribing.
Background
Depression is the most common co-morbidity in people with epilepsy (PWE) compared with the
general population (1;2). Rates vary from 3-9% in patients with well-controlled epilepsy to much
higher (20-55%) in those with recurrent seizures and those treated at tertiary referral centres (1;3;4).
A population-based study estimated a lifetime prevalence of 17.4% in those with epilepsy compared
to 10.7% in those without epilepsy (3). The presence of depression has been associated with poorer
seizure control and has a greater negative impact on quality of life than the number of prescribed
antidepressants or seizure frequency (5). A higher suicide rate than the general population has also
been documented for PWE (6).
The association between epilepsy and depression may be explained in part by serotonin; depletion of
serotonin increases the risk of both depression and epilepsy (5;7). Abnormalities in other
neurotransmitters such as noradrenaline, dopamine, and GABA are also seen in both conditions (3;5).
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Depressive symptoms present in a number of ways. Peri-ictal depression is relative to seizure
activity, is short-lasting and does not require treatment with antidepressants; this should be treated by
optimising anticonvulsant therapy (3;7). Peri-ictal depression can be divided into three types. Preictal (before a seizure) depressive symptoms manifest hours to days prior to a seizure. Ictal
depression occurs minutes before a complex partial seizure. Post-ictal depression is characterised by
a depressed mood developing in most cases hours to days after a seizure (1;3).
Inter-ictal depression presents as chronic depression; this is not related to seizure activity and is likely
to require treatment with antidepressants (1;3;7). PWE are three times more likely to be prescribed an
antidepressant than the general population and two times more likely to report suicidal thoughts (8).
Many antidepressants may lower the seizure threshold, but there is also evidence that when used
within their therapeutic dosage range, the risk of seizure activity is low (1).
Guidelines suggest that Selective Serotonin Reuptake Inhibitors (SSRIs) are an appropriate first-line
choice for treating depression in PWE (4;9). What data supports this choice, or the choice of
antidepressants from other drug classes?
Answer
Use of antiepileptic drugs (AEDs) with mood stabilising properties may be appropriate for selected
individuals with mild depressive symptoms (3). For example, gabapentin, carbamazepine,
oxcarbazepine, valproate, and lamotrigine improve depressive symptoms in epileptic patients
(1;2;10), whereas phenobarbitone, vigabatrin, primidone, topiramate and tiagabine have negative
psychotropic properties and have been associated with depression (1).
There is a lack of information regarding the safety of antidepressants in PWE (9) and the choice is a
common clinical dilemma. A recent Cochrane review, for example, concluded there is no high quality
evidence to inform the choice of antidepressant drug in treating depression in PWE (11). Some
antidepressants, especially the tricyclic antidepressants (TCAs), are well known to lower the seizure
threshold but the risk is dose related (7). There is no large study comparing seizure frequency in
PWE who take antidepressants with those who do not (12). With few exceptions, all antidepressants
are associated with seizures in overdose; SSRIs are less likely to cause seizures in overdose than
TCAs (13). However, the perceived risks are often overestimated and rarely outweigh the risk of
leaving depression untreated (8). Treatment of depression in PWE can improve their quality of life
and reduce their risk of suicide (5). It is important to check the anticonvulsant regimen of an epileptic
patient with depression for potential drug-induced depression before considering adding an
antidepressant.
Selective Serotonin Reuptake Inhibitors (SSRIs)
In general, the SSRIs are considered the first-line choice in patients with stable epilepsy because they
have a low pro-convulsive effect and are associated with a lower incidence of seizures when
compared with TCAs (1-4;7;8;14). Treatment should be initiated with a low dose and increased
gradually, as necessary (9). If seizures occur, or if the incidence of seizures increases, the
antidepressant should be discontinued (15-20).
The risk of seizures at therapeutic doses of SSRIs is between 0-0.3%, compared with 0.4 to 1-2%
with TCAs (13), though this varies between individual agents. Studies of short and long-term SSRI
treatment (1 month to around 15 months), suggest there is no worsening in seizure frequency and in
some patients improvement in seizure outcomes are seen. It should also be noted that in some
patients, seizure frequency worsened but could be controlled by either increasing the dose of
antiepileptic drug, or discontinuing the antidepressant (2). There is a lack of double-blind, randomised
controlled trials in large patient populations; most have been small studies in highly selected patients
(2).
Drug interactions with SSRIs must be taken into consideration: escitalopram, citalopram, fluoxetine,
fluvoxamine, paroxetine and sertraline inhibit cytochrome P450 enzymes to varying degrees and may
increase the plasma levels of AEDs (5;15-20).
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Fluoxetine is the most studied SSRI and has a probable seizure incidence of 0.2% (14;21).
Fluoxetine should be avoided in patients with unstable seizure disorders and patients with controlled
epilepsy should be monitored (17). It is a potent CYP2D6 enzyme inhibitor and can cause changes in
blood levels of phenytoin such that cases of phenytoin toxicity have been reported (7;17;22). The
long half-life of fluoxetine should be taken into consideration when starting or stopping treatment (17).
Pre-marketing studies and a retrospective survey of prescriptions (n=10,401) suggested the incidence
of seizures with fluvoxamine to be 0.2% in the general population (13;23). One small-scale study
(n=28) reported that fluvoxamine was not proconvulsant at doses ranging from 50 to 200mg, when
given to depressed PWE (24), however there have been case reports of seizures following
therapeutic doses of fluvoxamine in patients with and without a previous history of seizures (25;26).
Fluvoxamine should be avoided in patients with unstable epilepsy and patients with controlled
epilepsy should be carefully monitored (18). Fluvoxamine inhibits CYP1A2 and CYP2C19, and to a
lesser extent, CYP2C9, CYP2D6 and CYP3A4; co-administration with antiepileptics metabolised by
these isoenzymes, such as phenytoin and carbamazepine, may lead to higher plasma levels of the
AED and dose adjustments may be necessary (18).
Paroxetine appears to have a minimal potential for producing seizures at therapeutic doses (14) and
reviews suggest paroxetine has a seizure incidence of less than 0.1% (21). Paroxetine is a potent
inhibitor of several CYP enzyme systems and concurrent use with AEDs may require dosage
adjustments (7;22). Paroxetine dose adjustment may also be necessary if an enzyme inducer (such
as carbamazepine, phenytoin or phenobarbitone) is initiated or discontinued and it should be used
with caution (19).
Citalopram and escitalopram have not been reported to have a proconvulsive effect in postmarketing data except in overdose (7;14). In an open label study citalopram 20mg/day for 4 months
was associated with an improvement in depressive symptoms and a reduction in seizure frequency
(from 1.31 per month to 0.82, p<0.005) in 39 patients who had epilepsy and depression (27). A study
of 43 patients with epilepsy showed citalopram (average dose 22.6mg) to be an effective
antidepressant without affecting monthly seizure frequency or causing de novo generalised tonicclonic seizures when used for 2 months (28). A third study also showed citalopram (mean dose
24mg) to be an effective treatment without causing an increase in seizure frequency in 33 patients
with temporal lobe epilepsy, when used for up to 30 weeks (29). Citalopram is a weak inhibitor of
hepatic CYP enzyme systems and there is a lack of documented interactions with the anticonvulsant
agents (7). However, due to the potential for all SSRIs to cause seizures, and citalopram’s proconvulsive effect in overdose (7), it should be used with caution in patients with controlled epilepsy
(15;16). Citalopram and escitalopram should be avoided in patients with unstable epilepsy and
patients with controlled epilepsy should be carefully monitored (15;16). (7;21).
Early clinical trials with sertraline suggested that seizures occurred at a similar frequency to placebo
and only in people with a history of seizures (14). The seizure frequency in 100 (adult and paediatric)
patients with epilepsy after being started on sertraline (mean dose 108mg) was assessed in one study
(30). The mean treatment duration was 10.3 months (median duration 6 months, range 0.2 to 38
months). Six patients experienced an increase in seizure frequency but this could be definitely linked
with sertraline in only one patient; sertraline was stopped in this patient. There was probable
causality between seizure increase and sertraline in the other five patients; AED doses were adjusted
and four continued with sertraline treatment. Reviews suggest sertraline has a seizure incidence of
less than 0.1% at therapeutic doses of 50-100mg (31). Sertraline may interact with phenytoin due to
reduced sertraline levels and potential inhibition of phenytoin metabolism. It can be considered as one
of the first line options but as with all SSRI’s, itshould be used with caution in PWE (20;22).
Serotonin / Noradrenaline Reuptake Inhibitors (SNRIs)
An SNRI can be used as an alternative to an SSRI (9) but clinical experience and data regarding the
safety of duloxetine in PWE is very limited and for both duloxetine and venlafaxine caution is required
(7).
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A seizure rate of 0.2% with duloxetine therapy was reported in clinical trials (n=2418) (13). There is
limited data and experience with duloxetine , therefore it (7) should still be used with caution in
patients with a history or diagnosis of seizures (32). Cases of convulsions have been reported on
discontinuation of therapy (32). Seizures have been reported in 0.3% of depressed patients (n=3082)
treated with venlafaxine ≤150mg/day in clinical trials (13). In a large cohort study using data from
primary care databases, venlafaxine was associated with a higher risk of epilepsy and seizures
compared to other antidepressants, but as patients with a previous diagnosis of epilepsy/seizures
were excluded, the results are not directly applicable to the scenario in this Q&A (33). Venlafaxine is
also considered to increase seizure risk in overdose (7;34). If venlafaxine is prescribed, it should be
introduced slowly in patients with a history of seizures; no interactions with antiepileptics is anticipated
(14;34).
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 (14). Ideally they should not be used in PWE (7).
The overall incidence of seizures at therapeutic doses of TCAs is estimated at 0.4 to 1-2% (13),
though the incidence for individual TCAs varies markedly (see Appendix 1). TCAs are also more
likely to cause seizures in overdose compared with SSRIs (13). Most TCAs are known to potentially
interact with anticonvulsants and manufacturer’s advice should be consulted for individual TCAs.
Monamine Oxidase Inhibitors (MAOIs)
MAOIs (phenelzine, isocarboxazid and tranylcypromine) 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. However, they should be used with caution in PWE(35) and can increase or
decrease seizure frequency (14).
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
(7;14;35). It is therefore considered a good choice in PWE and is not cautioned or contraindicated in
these patients (7;36).
Miscellaneous Antidepressants
Rare cases of seizures with reboxetine (a noradrenaline reuptake inhibitor) have been reported in
clinical studies but it has been tested in few patients with epilepsy; therefore it should be used with
care in PWE (7;37). One study showed reboxetine (mean dose 6.9mg) to be an effective treatment
without causing an increase in seizure frequency in 15 patients with temporal lobe epilepsy, when
used for up to 30 weeks (29). Premarketing clinical trials suggest a seizure rate of 0.2% (13).
Reboxetine is primarily metabolised by CYP3A4 and enzyme inducers such as phenobarbitone,
carbamazepine and phenytoin, may reduce reboxetine plasma levels (37).
There is limited data and experience with the newer antidepressant vortioxetine (serotonergic
receptor modulator and serotonin re-uptake inhibitor), therefore it should be used with caution in
patients with a history of seizures or unstable epilepsy (7;38). Vortioxetine is metabolised by CYP450,
and enzyme inducers such as carbamazepine and phenytoin, may reduce vortioxetine plasma levels
(38).
Mirtazapine (a centrally active presynaptic alpha-2 antagonist) is associated with a minimal incidence
of seizures of less than 0.1% with a 30mg dose suggested (39). 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 (14;40) (maximum licensed dose in UK is 45mg/day (41)). A second patient, with no
history of seizures, developed generalised tonic-clonic seizures following initiation of mirtazapine
15mg/day, which stopped spontaneously (42). One study however showed mirtazapine (mean dose
32mg) to be an effective treatment without causing an increase in seizure frequency in 27 patients
with temporal lobe epilepsy, when used for up to 30 weeks (29). In another small study, mirtazapine
30mg/day for 3 weeks was found to enhance cortical excitability in seven patients with epilepsy, but
there was no increase in seizure frequency, duration or severity. The small numbers and short
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Medicines Q&As
duration of the study limit the power of the study in this respect (43). Although clinical experience
indicates that seizures are rare during mirtazapine therapy and it is considered a good choice in
epilepsy (7), the manufacturers still advise caution (41). In addition, there is a significant interaction
with carbamazepine and phenytoin (CPYP3A4 inducers), resulting in large reductions in mirtazapine
plasma concentrations of 60% and 45% respectively; in such cases the mirtazapine dose may need
to be increased (41).
Agomelatine (a melatonergic agonist and 5-HT antagonist) appears to have no cautions or
contraindications with regards to use in epilepsy (44) but there are very limited data regarding its
safety in PWE (7).
Other factors to consider
Drug Interactions
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 (7). 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
(45).
Dose initiation
As a general rule, the more sedating a drug is, the more likely it is to induce seizures (7). 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). In addition, maximum recommended doses of
antidepressants should not be exceeded.
Limitations
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In general, very little specific information is available about the use of antidepressants in PWE.
The SSRIs are the most widely studied antidepressants in PWE.
Seizure rates quoted are often based on the incidence in patients with depression rather than
PWE who suffer from depression, and this latter figure would be expected to be higher. 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 PWE.
Seizure frequency often fluctuates and can increase as a result of various clinical conditions,
such as fatigue or non-compliance with AEDs, and it is sometimes difficult to attribute the
observed aggravation of seizures only to antidepressants in the absence of controls (12).
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 is no large study comparing seizure frequency in PWE who take antidepressants with
those who do not (12). Unless a large-scale trial is conducted, which is unlikely, the best
antidepressant in epilepsy will remain unknown.
Detailed information regarding drug interactions has not been included in this Q&A:
pharmacokinetic and pharmacodynamic drug interactions between antidepressants and
antiepileptic drugs must be checked prior to prescribing.
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14/01/2015. Alliance Pharmaceuticals. Accessed via: http://www.medicines.org.uk on
16/11/2016.
(53) Summary of Product Characteristics. Lofepramine 70mg tablets. Date of revision of the text:
5/10/2015. Actavis UK Ltd. Accessed via: http://www.medicines.org.uk on 16/11/2016.
Available through NICE Evidence Search at www.evidence.nhs.uk
8
Medicines Q&As
(54) Summary of Product Characteristics. Mianserin 10mg tablets. Date of revision of the
text:18/04/2012. Teva UK Limited. Accessed via: http://www.mhra.gov.uk/spc-pil/ on
16/11/2016.
(55) Summary of Product Characteristics. Nortriptyline. Date of revision of the text: 11/09/2015.
King Pharmaceuticals Ltd. Accessed via: http://www.medicines.org.uk on 16/11/2016.
(56) Summary of Product Characteristics. Nardil tablets. Date of revision of the text: 10/2015.
Kyowa Kirin Ltd. Accessed via: http://www.medicines.org.uk on 16/11/2016.
(57) Summary of Product Characteristics. Tranylcypromine. Date of revision of the text:
28/10/2015. Concordia International. Accessed via: http://www.medicines.org.uk on
16/11/2016.
(58) Summary of Product Characteristics. Molipaxin 50mg capsules. Date of revision of the text:
29/04/2015. Zentiva. Accessed via: http://www.medicines.org.uk on 16/11/2016.
(59) Summary of Product Characteristics. Trimipramine 50mg capsules. Date of revision of the
text: 09/06/2015. Zentiva. Accessed via: http://www.medicines.org.uk on 16/11/2016.
Quality Assurance
Prepared by
Varinder Rai, Pharmacist, London Medicines Information Service (Northwick Park Hospital)
Date Prepared
November 2016
Checked by
Georgina Glass, Pharmacist, London Medicines Information Service (Northwick Park Hospital)
Date of check
December 2016
Search strategy




Embase: ((DEPRESSION/ AND EPILEPSY/) AND (CITALOPRAM/ OR ESCITALOPRAM/ OR
FLUOXETINE/ OR PAROXETINE/ OR SERTRALINE/ OR VORTIOXETINE/ OR AMITRIPTYLINE/ OR
CLOMIPRAMINE/ OR IMIPRAMINE/ OR LOFEPRAMINE/ OR TRIMIPRAMINE/ OR DOSULEPIN/ OR
DOXEPIN/ OR MOCLOBEMIDE/ OR PHENELZINE/ OR TRANYLCYPROMINE/ OR
NORTRIPTYLINE/ OR AGOMELATINE/ OR DULOXETINE/ OR FLUPENTIXOL/ OR FLUVOXAMINE/
OR ISOCARBOXAZIDE/ OR MIANSERIN/ OR MIRTAZAPINE/ OR REBOXETINE/ OR TRAZODONE/
OR VENLAFAXINE/)) [DT 2014-2016] [English language] [Humans]
Embase: ((DEPRESSION/dt OR *"ANTIDEPRESSANT AGENT"/) AND*EPILEPSY/) [DT 2014-2016]
[English language] [Humans]
Medline: (CITALOPRAM/ OR FLUOXETINE/ OR FLUVOXAMINE/ OR PAROXETINE/ OR
SERTRALINE/ OR TRAZODONE/ OR AMITRIPTYLINE/ OR CLOMIPRAMINE/ OR DOTHIEPIN/ OR
IMIPRAMINE/ OR LOFEPRAMINE/ OR NORTRIPTYLINE/ OR TRIMIPRAMINE/ OR DOXEPIN/ OR
"VENLAFAXINE HYDROCHLORIDE"/ OR "DULOXETINE HYDROCHLORIDE"/ OR
(escitalopram).af OR FLUPENTHIXOL/ OR MIANSERIN/ OR ISOCARBOXAZID/ OR
MOCLOBEMIDE/ OR PHENELZINE/ OR TRANYLCYPROMINE/ OR (mirtazapine).af OR
(reboxetine).af OR (agomelatine).af OR (vortioxetine).af AND EPILEPSY/
Medline: (EPILEPSY/ AND DEPRESSION/dt) [DT 2014-2016] [Languages English] [Humans]
Available through NICE Evidence Search at www.evidence.nhs.uk
9
Medicines Q&As
Appendix 1: Manufacturers information [from Summaries of Product Characteristics]
Drug
Drug class*
Special warnings for patients with epilepsy
Adverse events: incidence of
convulsions†
Agomelatine (44)
MRA/SSRA
None
Not reported
Amitriptyline (46)
TCA
Reported, incidence not stated
Citalopram (16)
SSRI
Avoid if possible.
Avoid in unstable epilepsy. Monitor controlled epilepsy
carefully. Discontinue if seizures occur or frequency
increases.
Clomipramine (47)
TCA
Use with extreme caution.
Uncommon
Dosulepin (48)
TCA
Avoid if possible.
Rare
Doxepin (49)
TCA
Use with caution.
Unlikely
Duloxetine (32)
SNRI
Use with caution.
Rare
Avoid in unstable epilepsy. Monitor controlled epilepsy
carefully. Discontinue if seizures occur or frequency
increases.
Introduce with caution, discontinue if seizures occur or
frequency increases. Avoid in unstable epilepsy. Monitor
controlled epilepsy carefully.
Use with caution.
Avoid in unstable epilepsy. Monitor controlled epilepsy
carefully. Discontinue if seizures occur or frequency
increases.
Rare (grand mal)
Unknown (other convulsions)
Escitalopram (15)
SSRI
Fluoxetine (17)
SSRI
Flupentixol (50)
Neuroleptic
Fluvoxamine (18)
SSRI
Imipramine (51)
TCA
Use with extreme caution.
Rare
Isocarboxazid (52)
MAOI
May increase or decrease seizures.
Not reported
Lofepramine (53)
TCA
Use with extreme caution.
Rare
Mianserin (54)
TeCA
Use with extreme caution.
Reported. Incidence not stated
Mirtazapine (41)
AAA
Use with caution: careful dosing and regular monitoring
required.
Unknown
Moclobemide (36)
RIMA
None
Not reported
Nortriptyline (55)
TCA
Avoid if possible, if not, monitor carefully at the start of
treatment.
Reported, incidence not stated
Paroxetine (19)
SSRI
Use with caution, discontinue if seizures occur.
Rare
Phenelzine (56)
MAOI
Use with great caution.
Uncommon
Use with caution. Monitor epilepsy, discontinue if
seizures occur.
Avoid in unstable epilepsy. Monitor controlled epilepsy
carefully. Discontinue if seizures occur.
Unknown
Rare
Reported, incidence not stated
Rare
Reboxetine (37)
SNI
Sertraline (20)
SSRI
Tranylcypromine (57)
MAOI
Use with great caution.
Not reported
Trazodone (58)
Other
Careful dosing and regular monitoring, avoid abrupt
increases or decreases.
Unknown
Trimipramine (59)
TCA
Avoid if possible
Rare
Venlafaxine (34)
SNRI
Introduce with caution, convulsions may occur. Monitor
epilepsy carefully. Discontinue if seizures occur.
Rare
Other
Introduce with caution. Monitor and discontinue if
seizures occur or frequency increases.
Not reported
Vortioxetine (38)
Rare
Uncommon
Available through NICE Evidence Search at www.evidence.nhs.uk
10
Medicines Q&As
* Drug class
AAA: Alpha2 adrenoceptor antagonist
RIMA: Reversible Inhibitor of Monoamine oxidase preferentially of type A
MAOI: Monoamine Oxidase Inhibitor
MRA/SSRA: Melatonin Receptor Agonist and Selective Serotonin Receptor Antagonist
SNRI: Serotonin and Noradrenaline Reuptake Inhibitor
SNI: Selective Noradrenaline reuptake Inhibitor
SSRI: Selective Serotonin Reuptake Inhibitor
TCA: Tricyclic Antidepressant
TeCA: Tetracyclic Antidepressant
†Incidence of adverse events
Very common: ≥1/10
Common: ≥1/100 - <1/10
Uncommon: ≥1/1,000 - <1/100
Rare: ≥1/10,000 - <1/1,000
Unknown: adverse event has occurred but
incidence cannot be estimated from available data
Available through NICE Evidence Search at www.evidence.nhs.uk
11