Treatment of Depression in Adults with Epilepsy
Publication Date: September 30, 2020
Last Updated: September 17, 2022
RECOMMENDATIONS
FIRST LINE TREATMENT
For mild depressive episodes, psychoeducation or psychotherapies are treatment alternatives to antidepressants. Where medication is used (wish/preference of the patient, positive experience of the patient with response to medication treatment in the past, moderate or severe episodes in the past or if initial non-pharmacological trials failed should be considered), SSRIs are first choice medications. (1, B)
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For moderate to severe depressive episodes, SSRIs are first choice medications. (1, B)
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SPECIAL PRECAUTIONS
The potential risks should be carefully balanced with the benefits of antidepressant treatment. Consideration of the individual past history including risk factors for suicidal behaviour and close observation of the patient during the first weeks of treatment are recommended when starting antidepressant treatment. (, )
(Consensus)
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For severely depressed patients, consider the risk of overdose when antidepressant medications are prescribed. (, )
(Consensus)
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If the patient has suicidal thoughts or intent, s/he should be always be referred to a psychiatrist for urgent review. Close surveillance and specialist treatment are necessary and admission to a psychiatric ward may be considered. Hospital admittance without patient consent may be necessary. Immediate and intensive care should be initiated and should include intensive pharmacotherapy and psychotherapy addressing psychological and psychosocial factors. (, )
(Consensus)
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Patients with psychotic depression should be always referred to a psychiatrist for urgent review and a combination of an antidepressant with an antipsychotic medication is recommended when treatment is initiated. (3, )
(ILAE Consensus)
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SSRIs are not associated with seizure worsening in people with epilepsy. (, C)
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INADEQUATE RESPONSE TO FIRST LINE ANTIDEPRESSANT
In the case of inadequate response to antidepressant treatment, assessing adherence to the current treatment regimen is recommended as a first step. (, )
(Consensus)
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In patients partially or non-responding to first line treatment, switching from an SSRI to venlafaxine appears legitimate. (3, C)
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If antidepressants that are inhibitors of CYP isoenzymes are combined with other drugs metabolized by the same CYP isoenzymes, interactions and dose adjustment according to clinical response should be considered.
(, )(Consensus)
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DURATION OF THE ANTIDEPRESSANT TREATMENT
Antidepressant treatment should be maintained for at least 6 months following remission from a first depressive episode. Antidepressant treatment should be prolonged to 9 months in patients with a history of long previous episodes and should continue even longer in cases of residual symptomatology and until such symptoms have subsided and in severe depression. (, )
(Consensus)
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It is recommended that the same antidepressant successfully used to achieve response/remission in the acute-phase therapy should be continued at the same dose during the continuation phase. If no relapse occurs during continuation therapy, a gradual discontinuation of the antidepressant medication is recommended in case of first episodes. Patients should be carefully monitored during the discontinuation to ensure the stability of the remission. If tapering off results in a return of symptoms, the medication should be reinstated in the original dose for at least another 6 months before attempting discontinuation again. (3, )
(ILAE Consensus)
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Step-down discontinuation within a period of 1 – 4 weeks is recommended rather than abrupt discontinuation, as this may cause discontinuation symptoms. (, )
(Consensus)
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MONOTHERAPY AUGMENTATION STRATEGIES
Combination of an SSRI with an inhibitor of presynaptic autoreceptors like, mirtazapine is can be considered where monotherapy failed. The combination of venlafaxine with mirtazapine may be accompanied by worsening side effects. (2, )
(ILAE Consensus)
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Adding lithium to ongoing antidepressant treatment is recommended in case monotherapy failed. Lithium augmentation should be administered for 2 – 4 weeks in order to allow assessment of the patient’s response. The recommended lithium serum target levels are 0.6 to 0.8 mmol/L. In case of response, lithium augmentation should be continued for at least 12 months.
In the epilepsy population, if lithium needs to be considered after monotherapy failure as augmentation, this should be used with caution given the tolerability profile and should be prescribed only by psychiatrists. Consider interactions with ASMs. (2, )
In the epilepsy population, if lithium needs to be considered after monotherapy failure as augmentation, this should be used with caution given the tolerability profile and should be prescribed only by psychiatrists. Consider interactions with ASMs. (2, )
(ILAE Consensus)
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The augmentation of antidepressants with quetiapine or aripiprazole represents an alternative to lithium augmentation and is recommended in case monotherapy failed. Potential unwanted effects include sedation (quetiapine), weight gain (quetiapine, and to a lesser extent aripiprazole) and akathisia (aripiprazole). (2, )
(ILAE Consensus)
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OTHER PHARMACOLOGICAL TREATMENTS
Hypericum (St. John’s Wort) may be an option in patients with mild depression who prefer “alternative medicine” – but intensive education about potential side effects including seizure relapse and interactions has to be provided and potential drug interactions have to be monitored. (2, )
(ILAE Consensus)
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ELECTROCONVULSIVE THERAPY
Among the indications for electroconvulsive therapy (ECT) as a first-line treatment are: severe major depression with psychotic features, severe major depression with psychomotor retardation, “true” treatment-resistant major depression, refusal of food intake or in other special situations when rapid relief from depression is required (e.g., in severe suicidality) or medication contraindicated (e.g., in pregnancy). ECT as a first-line approach may also be indicated in patients who have experienced a previous positive response to ECT, and in patients who prefer ECT for a specific reason. ECT should only be performed by a psychiatrist who is experienced with this treatment intervention. (4, )
(ILAE Consensus)
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Prior to ECT treatment implementation, a thorough medical evaluation of the patient must be performed in close collaboration with an anaesthesiologist. Caution is indicated in patients with evidence of increased intracranial pressure or cerebrovascular fragility, in patients with cardiovascular disease, e.g., recent myocardial infarction, myocardial ischaemia, congestive heart failure, cardiac arrhythmias or pacemakers, or abdominal aneurysm and in patients with severe osteoporosis. ECT should only be performed by a psychiatrist who is experienced with this treatment intervention. (, )
(Consensus)
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OTHER TREATMENTS
Light therapy is an option in treatment of seasonal affective disorder (SAD) if administration is possible and protocol adherence can be ensured. (3, )
(ILAE Consensus)
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Exercise training can be used as an adjunct to medication treatment for patients with mild to moderate depression.
(3, )(ILAE Consensus)
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Vagal nerve stimulation (VNS) may be an option in patients with depression with insufficient response to trials of pharmacotherapy but consider that parameters used for the treatment of epilepsy may differ from those used for the treatment of depression. (5, )
(ILAE Consensus)
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Repetitive Transcranial magnetic stimulation (rTMS) may be an option in patients with depression with insufficient response to trials of pharmacotherapy but consider that parameters used for the treatment of depression may differ from those safely used in people with epilepsy. (5, )
(ILAE Consensus)
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PSYCHOLOGICAL INTERVENTIONS
Psychotherapy should be considered as an initial treatment modality for patients with mild depression. Furthermore, psychotherapy is recommended in combination with antidepressants for patients with moderate to severe depression and for patients who have had only partial responses to antidepressant medications or who have had problems with adherence to antidepressants. Patient preference for antidepressant medications or psychotherapy and the availability of psychotherapy should be considered when deciding between initiating treatment with antidepressants or psychotherapy. (3, C)
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Recommendation Grading
Overview
Title
Treatment of Depression in Adults with Epilepsy
Authoring Organization
International League Against Epilepsy
Publication Month/Year
September 30, 2020
Last Updated Month/Year
April 1, 2024
Supplemental Implementation Tools
Document Type
Guideline
External Publication Status
Published
Country of Publication
US
Inclusion Criteria
Female, Male, Adult
Health Care Settings
Ambulatory, Long term care, Outpatient
Intended Users
Social worker, psychologist, nurse, nurse practitioner, physician, physician assistant
Scope
Treatment
Diseases/Conditions (MeSH)
D003863 - Depression, D004827 - Epilepsy
Keywords
selective serotonin reuptake inhibitor (SSRI), Antidepressants, epilepsy, Clinical Practice Guidelines, Depression in Adults
Source Citation
Mula M, Brodie MJ, de Toffol B, Guekht A, Hecimovic H, Kanemoto K, Kanner AM, Teixeira AL, Wilson SJ. ILAE clinical practice recommendations for the medical treatment of depression in adults with epilepsy. Epilepsia. 2022 Feb;63(2):316-334. doi:10.1111/epi.17140. Epub 2021 Dec 5. PMID: 34866176.