Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Treatment Options in Neurology
Published in: Current Treatment Options in Neurology 12/2017

01-12-2017 | Epilepsy (E Waterhouse, Section Editor)

Epilepsy and Psychiatric Comorbidities: Drug Selection

Author: Marco Mula, MD, PhD

Published in: Current Treatment Options in Neurology | Issue 12/2017

Login to get access

Abstract

Purpose of review The pharmacological treatment of patients with epilepsy and psychiatric comorbidities may sometimes represent a therapeutic challenge. This review is focused on the pharmacological management of patients with epilepsy and psychiatric problems in terms of rationalization of the antiepileptic drug (AED) treatment and the pharmacological management of the most clinically relevant psychiatric comorbidities, namely mood and anxiety disorders, psychoses, and attention deficit hyperactivity disorder (ADHD).
Recent findings Up to 8% of patients with drug-resistant epilepsy develop treatment-emergent psychiatric adverse events of AED regardless of the mechanism of action of the drug and this is usually related to an underlying predisposition given by the previous psychiatric history and the involvement of mesolimbic structures. Careful history taking, periodic screening for mood and anxiety disorders, low starting doses, and slow titration schedules can reduce the possibility of AED-related problems. A pragmatic checklist for the pharmacological management of patients with epilepsy and psychiatric disorders is presented.
Summary patients should be informed of potential behavioral effects of AEDs but no drugs should be excluded a priori. Any psychiatric comorbidity should be addressed in the appropriate setting and full remission and recovery should always represent the first goal of any therapeutic intervention. Neurologists should be aware of the side effects of major psychotropic drug classes in order to fully counsel their patients and other health professionals involved.
Literature
1.
Duncan JS, Sander JW, Sisodiya SM, Walker MC. Adult epilepsy. Lancet Lond Engl. 2006;367:1087–100.CrossRef
2.
MacDonald BK, Cockerell OC, Sander JW, Shorvon SD. The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK. Brain J Neurol. 2000;123(Pt 4):665–76.CrossRef
3.
Ngugi AK, Kariuki SM, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Incidence of epilepsy: a systematic review and meta-analysis. Neurology. 2011;77:1005–12.CrossRefPubMedPubMedCentral
4.
Forsgren L, Beghi E, Oun A, Sillanpää M. The epidemiology of epilepsy in Europe—a systematic review. Eur J Neurol. 2005;12:245–53.CrossRefPubMed
5.
6.
Cockerell OC, Johnson AL, Sander JW, Shorvon SD. Prognosis of epilepsy: a review and further analysis of the first nine years of the British National General Practice Study of Epilepsy: a prospective population-based study. Epilepsia. 1997;38:31–46.CrossRefPubMed
7.
Mula M, Cock HR. More than seizures: improving the lives of people with refractory epilepsy. Eur J Neurol. 2015;22:24–30.CrossRefPubMed
8.
de Boer HM, Mula M, Sander JW. The global burden and stigma of epilepsy. Epilepsy Behav. 2008;12:540–6.CrossRefPubMed
9.
Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55:475–82.CrossRefPubMed
10.
Tellez-Zenteno JF, Patten SB, Jetté N, Williams J, Wiebe S. Psychiatric comorbidity in epilepsy: a population-based analysis. Epilepsia. 2007;48:2336–44.PubMed
11.
Rai D, Kerr MP, McManus S, Jordanova V, Lewis G, Brugha TS. Epilepsy and psychiatric comorbidity: a nationally representative population-based study. Epilepsia. 2012;53:1095–103.CrossRefPubMed
12.
• Reilly C, Atkinson P, Das KB, Chin RFMC, Aylett SE, Burch V, et al. Neurobehavioral comorbidities in children with active epilepsy: a population-based study. Pediatrics. 2014;133:e1586–93. Population-based study of psychiatric comorbidities in children with epilepsy.CrossRefPubMed
13.
14.
Mula M. Epilepsy: bidirectional link between epilepsy and psychiatric disorders. Nat Rev Neurol. 2012;8:252–3.CrossRefPubMed
15.
Hesdorffer DC, Hauser WA, Annegers JF, Cascino G. Major depression is a risk factor for seizures in older adults. Ann Neurol. 2000;47:246–9.CrossRefPubMed
16.
Hesdorffer DC, Hauser WA, Olafsson E, Ludvigsson P, Kjartansson O. Depression and suicide attempt as risk factors for incident unprovoked seizures. Ann Neurol. 2006;59:35–41.CrossRefPubMed
17.
Hesdorffer DC, Ishihara L, Mynepalli L, Webb DJ, Weil J, Hauser WA. Epilepsy, suicidality, and psychiatric disorders: a bidirectional association. Ann Neurol. 2012;72:184–91.CrossRefPubMed
18.
Chang Y-T, Chen P-C, Tsai I-J, Sung F-C, Chin Z-N, Kuo H-T, et al. Bidirectional relation between schizophrenia and epilepsy: a population-based retrospective cohort study. Epilepsia. 2011;52:2036–42.CrossRefPubMed
19.
Adelow C, Andersson T, Ahlbom A, Tomson T. Hospitalization for psychiatric disorders before and after onset of unprovoked seizures/epilepsy. Neurology. 2012;78:396–401.CrossRefPubMed
20.
Wotton CJ, Goldacre MJ. Coexistence of schizophrenia and epilepsy: record-linkage studies. Epilepsia. 2012;53:e71–4.CrossRefPubMed
21.
22.
23.
Mula M. Neuropsychiatric Symptoms of Epilepsy.London: Springer 2016.
24.
Perucca P, Mula M. Antiepileptic drug effects on mood and behavior: molecular targets. Epilepsy Behav. 2013;26:440–9.CrossRefPubMed
25.
26.
Mula M, Trimble MR, Sander JW. Are psychiatric adverse events of antiepileptic drugs a unique entity? A study on topiramate and levetiracetam. Epilepsia. 2007;48:2322–6.PubMed
27.
Pohlmann-Eden B, Aldenkamp A, Baker GA, Brandt C, Cendes F, Coras R, et al. The relevance of neuropsychiatric symptoms and cognitive problems in new-onset epilepsy—current knowledge and understanding. Epilepsy Behav. 2015;51:199–209.CrossRefPubMed
28.
Mula M, Hesdorffer DC, Trimble M, Sander JW. The role of titration schedule of topiramate for the development of depression in patients with epilepsy. Epilepsia. 2009;50:1072–6.CrossRefPubMed
29.
Mula M. The Landolt’s phenomenon: an update. Epileptologia. 2010;18:39–44.
30.
Mula M, Sander JW. Negative effects of antiepileptic drugs on mood in patients with epilepsy. Drug Saf Int J Med Toxicol Drug Exp. 2007;30:555–67.CrossRef
31.
•• Brodie MJ, Besag F, Ettinger AB, Mula M, Gobbi G, Comai S, et al. Epilepsy, antiepileptic drugs, and aggression: an evidence-based review. Pharmacol Rev. 2016;68:563–602. Systematic review on aggressive behavior as a treatment emergent adverse event of antiepileptic drug treatment.CrossRefPubMedPubMedCentral
32.
Stephen LJ, Wishart A, Brodie MJ. Psychiatric side effects and antiepileptic drugs: observations from prospective audits. Epilepsy Behav. 2017;71:73–8.CrossRefPubMed
33.
Mula M, Trimble MR, Lhatoo SD, Sander JWAS. Topiramate and psychiatric adverse events in patients with epilepsy. Epilepsia. 2003;44:659–63.CrossRefPubMed
34.
White JR, Walczak TS, Leppik IE, Rarick J, Tran T, Beniak TE, et al. Discontinuation of levetiracetam because of behavioral side effects: a case-control study. Neurology. 2003;61:1218–21.CrossRefPubMed
35.
•• Gill SJ, Lukmanji S, Fiest KM, Patten SB, Wiebe S, Jetté N. Depression screening tools in persons with epilepsy: a systematic review of validated tools. Epilepsia. 2017;58:695–705. Systematic review of screening instruments for depression in epilepsy.CrossRefPubMed
36.
Gilliam FG, Barry JJ, Hermann BP, Meador KJ, Vahle V, Kanner AM. Rapid detection of major depression in epilepsy: a multicentre study. Lancet Neurol. 2006;5:399–405.CrossRefPubMed
37.
Seo J-G, Cho YW, Lee S-J, Lee J-J, Kim J-E, Moon H-J, et al. Validation of the generalized anxiety disorder-7 in people with epilepsy: a MEPSY study. Epilepsy Behav. 2014;35:59–63.CrossRefPubMed
38.
Mula M, Cavalheiro E, Guekht A, Kanner AM, Lee HW, Ozkara C, et al. Educational needs of epileptologists regarding psychiatric comorbidities of the epilepsies: a descriptive quantitative survey. Epileptic Disord. 2017;19(2):178–85.PubMed
39.
Kerr MP, Mensah S, Besag F, de Toffol B, Ettinger A, Kanemoto K, et al. International consensus clinical practice statements for the treatment of neuropsychiatric conditions associated with epilepsy. Epilepsia. 2011;52:2133–8.CrossRefPubMed
40.
Mula M, Kanner AM. Introduction—treatment of psychiatric disorders in adults with epilepsy: what every epileptologist should know. Epilepsia. 2013;54(Suppl 1):1–2.CrossRefPubMed
41.
Mula M. The pharmacological management of psychiatric comorbidities in patients with epilepsy. Pharmacol Res. 2016;107:147–53.CrossRefPubMed
42.
Robertson MM, Trimble MR. The treatment of depression in patients with epilepsy: a double-blind trial. J Affect Disord. 1985;9:127–36.CrossRefPubMed
43.
Mula M, Schmitz B, Sander JW. The pharmacological treatment of depression in adults with epilepsy. Expert Opin Pharmacother. 2008;9:3159–68.CrossRefPubMed
44.
Kuhn R. The treatment of depressive states with G 22355 (imipramine hydrochloride). Am J Psychiatry. 1958;115:459–64.CrossRefPubMed
45.
Kiloh LG, Davison K, Osselton JW. An electroencephalographic study of the analeptic effects of imipramine. Electroencephalogr Clin Neurophysiol. 1961;13:216–23.CrossRefPubMed
46.
Davison K. EEG activation after intravenous amitriptyline. Electroencephalogr Clin Neurophysiol. 1965;19:298–300.CrossRefPubMed
47.
Alper K, Schwartz KA, Kolts RL, Khan A. Seizure incidence in psychopharmacological clinical trials: an analysis of Food and Drug Administration (FDA) summary basis of approval reports. Biol Psychiatry. 2007;62:345–54.CrossRefPubMed
48.
Leander JD. Fluoxetine, a selective serotonin-uptake inhibitor, enhances the anticonvulsant effects of phenytoin, carbamazepine, and ameltolide (LY201116). Epilepsia. 1992;33:573–6.CrossRefPubMed
49.
Hamid H, Kanner AM. Should antidepressant drugs of the selective serotonin reuptake inhibitor family be tested as antiepileptic drugs? Epilepsy Behav. 2013;26:261–5.CrossRefPubMed
50.
Kanner AM, Kozak AM, Frey M. The use of sertraline in patients with epilepsy: is it safe? Epilepsy Behav. 2000;1:100–5.CrossRefPubMed
51.
Thomé-Souza MS, Kuczynski E, Valente KD. Sertraline and fluoxetine: safe treatments for children and adolescents with epilepsy and depression. Epilepsy Behav. 2007;10:417–25.CrossRefPubMed
52.
Hovorka J, Herman E, Nemcová I. Treatment of interictal depression with citalopram in patients with epilepsy. Epilepsy Behav. 2000;1:444–7.CrossRefPubMed
53.
Specchio LM, Iudice A, Specchio N, La Neve A, Spinelli A, Galli R, et al. Citalopram as treatment of depression in patients with epilepsy. Clin Neuropharmacol. 2004;27:133–6.CrossRefPubMed
54.
Mula M. Anticonvulsants—antidepressants pharmacokinetic drug interactions: the role of the CYP450 system in psychopharmacology. Curr Drug Metab. 2008;9:730–7.CrossRefPubMed
55.
Devinsky O, Pacia SV. Seizures during clozapine therapy. J Clin Psychiatry. 1994;55(Suppl B):153–6.PubMed
56.
Pacia SV, Devinsky O. Clozapine-related seizures: experience with 5,629 patients. Neurology. 1994;44:2247–9.CrossRefPubMed
57.
Varma S, Bishara D, Besag FMC, Taylor D. Clozapine-related EEG changes and seizures: dose and plasma-level relationships. Ther Adv Psychopharmacol. 2011;1:47–66.CrossRefPubMedPubMedCentral
58.
Fung LK, Mahajan R, Nozzolillo A, Bernal P, Krasner A, Jo B, et al. Pharmacologic treatment of severe irritability and problem behaviors in autism: a systematic review and meta-analysis. Pediatrics. 2016;137(Suppl 2):S124–35.CrossRefPubMed
59.
Nickl-Jockschat T, Paulzen M, Schneider F, Grözinger M. Drug interaction can lead to undetectable serum concentrations of quetiapine in the presence of carbamazepine. Clin Neuropharmacol. 2009;32:55.CrossRefPubMed
60.
Mula M, Monaco F. Antiepileptic-antipsychotic drug interactions: a critical review of the evidence. Clin Neuropharmacol. 2002;25:280–9.CrossRefPubMed
61.
Thapar A, Cooper M. Attention deficit hyperactivity disorder. Lancet Lond Engl. 2016;387:1240–50.CrossRef
62.
Dunn DW, Austin JK, Perkins SM. Prevalence of psychopathology in childhood epilepsy: categorical and dimensional measures. Dev Med Child Neurol. 2009;51:364–72.CrossRefPubMedPubMedCentral
63.
Ettinger AB, Ottman R, Lipton RB, Cramer JA, Fanning KM, Reed ML. Attention-deficit/hyperactivity disorder symptoms in adults with self-reported epilepsy: results from a national epidemiologic survey of epilepsy. Epilepsia. 2015;56:218–24.CrossRefPubMed
64.
Pliszka SR, Crismon ML, Hughes CW, Corners CK, Emslie GJ, Jensen PS, et al. The Texas Children’s medication algorithm project: revision of the algorithm for pharmacotherapy of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2006;45:642–57.CrossRefPubMed
65.
66.
Feldman H, Crumrine P, Handen BL, Alvin R, Teodori J. Methylphenidate in children with seizures and attention-deficit disorder. Am J Dis Child. 1989;143:1081–6.PubMed
67.
Gonzalez-Heydrich J, Whitney J, Waber D, Forbes P, Hsin O, Faraone SV, et al. Adaptive phase I study of OROS methylphenidate treatment of attention deficit hyperactivity disorder with epilepsy. Epilepsy Behav. 2010;18:229–37.CrossRefPubMedPubMedCentral
68.
Santos K, Palmini A, Radziuk AL, Rotert R, Bastos F, Booij L, et al. The impact of methylphenidate on seizure frequency and severity in children with attention-deficit-hyperactivity disorder and difficult-to-treat epilepsies. Dev Med Child Neurol. 2013;55:654–60.CrossRefPubMed
69.
Markowitz JS, Patrick KS. Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder. Clin Pharmacokinet. 2001;40:753–72.CrossRefPubMed
70.
• Nabbout R, Camfield CS, Andrade DM, Arzimanoglou A, Chiron C, Cramer JA, et al. Treatment issues for children with epilepsy transitioning to adult care. Epilepsy Behav. 2017;69:153–60. Review of treatment issues in children with epilepsy transitioning to the adult service.CrossRefPubMed
Metadata
Title
Epilepsy and Psychiatric Comorbidities: Drug Selection
Author
Marco Mula, MD, PhD
Publication date
01-12-2017
Publisher
Springer US
Published in
Current Treatment Options in Neurology / Issue 12/2017
Print ISSN: 1092-8480
Electronic ISSN: 1534-3138
DOI
https://doi.org/10.1007/s11940-017-0483-0

Other articles of this Issue 12/2017

Current Treatment Options in Neurology 12/2017 Go to the issue

Dementia (J Pillai, Section Editor)

Current Role for Biomarkers in Clinical Diagnosis of Alzheimer Disease and Frontotemporal Dementia

Neurologic Manifestations of Systemic Disease (N Scolding, C Rice and A Wilkins, Section Editors)

Treatment of Cerebellar Ataxia in the Context of Systemic Diseases

Neuromuscular Disorders (C Fournier, Section Editor)

Advances in the Treatment of Paraproteinemic Neuropathy

Neuromuscular Disorders (C Fournier, Section Editor)

Acute Flaccid Myelitis: Etiologic Challenges, Diagnostic and Management Considerations

Pediatric Neurology (R-M Boustany, Section Editor)

Current and Future Treatments for Lysosomal Storage Disorders