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Psychiatric comorbidity in patients with epilepsy: a population-based study

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Patients with epilepsy often suffer from concomitant psychiatric disorders. Treatment patterns and the extent of comorbidity are insufficiently investigated and appropriate methods are scarce. The purpose of the study was to estimate the prevalence of psychiatric comorbidity in patients with epilepsy and to investigate prescription patterns of drugs prescribed for psychiatric disorders in epilepsy.

Methods

Prescription data from the Norwegian Prescription Database (NorPD) regarding the use of CNS-active drugs included anonymous data from almost 190,000 patients and 1.1–1.3 million prescriptions per year (2004–2007). Searches were based upon use of specific drugs, defined daily doses, number of patients, prescriptions, gender, and age. Reimbursement codes related to psychiatric diagnosis were used as indicators for clinical use.

Results

The prevalence of psychiatric comorbidity in patients with epilepsy was estimated to be 32%. There were 56% women and 44% men participating in the study. Among patients using antidepressants two thirds were women, but no gender differences were seen with antipsychotic medication. Antidepressants and antipsychotics were used 3.4 (20.9%) and 5.8 (13.4%) times more frequently than in the general population, accounting for 7.88 and 1.99 defined daily doses (DDDs)/1,000 inhabitants/day/year respectively. Lamotrigine was the most commonly used antiepileptic drug (AED) in epilepsy, accounting for 33% of the use of AEDs (in total 5.65 DDDs/1,000 inhabitants/day/year). The use of benzodiazepines was 9.55 DDDs/1,000 inhabitants/day/year. The patients had complex pharmacotherapy with two to eight concomitant drugs.

Conclusion

The present study gives an estimate of psychiatric comorbidity of 32% in patients with epilepsy in a nation-wide population. The pharmacotherapy in this patient population is complex. The results provide valuable data on prescription patterns that contribute to pharmacovigilance on a national scale.

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References

  1. Silberstein SD (2001) Shared mechanisms and comorbidities in neurologic and psychiatric disorders. Headache 41(1):S11–S17

    Article  PubMed  Google Scholar 

  2. Jobe PC (2004) Affective disorder and epilepsy comorbidity: implications for development of treatments, preventions and diagnostic approaches. Clin EEG Neurosci 35:53–68

    PubMed  Google Scholar 

  3. Schmitz B (2005) Depression and mania in patients with epilepsy. Epilepsia 46(4):45–49

    Article  PubMed  Google Scholar 

  4. Kanner MK (2005) Depression in epilepsy: a neurobiologic perspective. Epilepsy Curr 5(1):21–27

    Article  PubMed  Google Scholar 

  5. Tellez-Zenteno JF, Patten SB, Jetté N, Williams J, Wiebe S (2007) Psychiatric comorbidity in epilepsy: a population-based analysis. Epilepsia 48(12):2236–2244

    Google Scholar 

  6. Fuller-Thomson E, Brennenstuhl S (2009) The association between depression and epilepsy in a nationally representative sample. Epilepsia 50(5):1051–1058

    Article  PubMed  Google Scholar 

  7. LaFrance WC, Kanner MK, Hermann B (2008) Psychiatric comorbidities in epilepsy. Int Rev Neurobiol 83:347–383

    Article  PubMed  Google Scholar 

  8. Ettinger A, Reed M, Cramer J (2004) Depression and comorbidity in community-based patients with epilepsy or asthma. Neurology 63:1008–1014

    PubMed  Google Scholar 

  9. Gaitazis A, Trimble MR, Sander JW (2004) The psychiatric comorbidity of epilepsy. Acta Neurol Scand 110:207–220

    Article  Google Scholar 

  10. Stefanello S, Marín-Léon L, Fernandes PT, Li LM, Botega NJ (2009) Psychiatric comorbidity and suicidal behavior in epilepsy: a community-based case-control study. Epilepsia doi:10.1111/j.1528-1167.2009.02386.x

    PubMed  Google Scholar 

  11. Lacey CJ, Salzberg MR, Roberts H, Trauer T, D’Souza WJ (2009) Psychiatric comorbidity and impact on health service utilization in a community sample of patients with epilepsy. Epilepsia 50(8):1991–1994

    Article  PubMed  Google Scholar 

  12. Kanner MK (2008) The use of psychotropic drugs in epilepsy: what every neurologist should know. Semin Neurol 28(3):379–388

    Article  PubMed  Google Scholar 

  13. Ertekin BA, Kulaksizoglu IB, Ertekin E, Gürses C, Bebek N, Gökyiğit A, Baykan B (2009) A comparative study of obsessive-compulsive disorder and other psychiatric comorbidities in patients with temporal lobe epilepsy and idiopathic generalized epilepsy. Epilepsy Behav 14(4):634–639

    Article  PubMed  Google Scholar 

  14. Sperli F, Rentsch D, Despland PA, Foletti G, Jallon P, Picard F, Landis T, Seeck M (2009) Psychiatric comorbidity in patients evaluated for chronic epilepsy: a differential role of the right hemisphere? Eur Neurol 61(6):350–357

    Article  CAS  PubMed  Google Scholar 

  15. Jones JE, Bell B, Fine J, Rutecki P, Seidenberg M, Hermann B (2007) A controlled prospective investigation of psychiatric comorbidity in temporal lobe epilepsy. Epilepsia 48:2357–2360

    PubMed  Google Scholar 

  16. Weber NS, Cowan DN, Milikan AM, Niebuhr DW (2009) Psychiatric and general conditions comorbid with schizophrenia in the National Hospital Discharge Survey. Psychiatr Serv 60(8):1059–1067

    Article  PubMed  Google Scholar 

  17. Weibe S, Bellhouse DR, Fallahay C, Eliasziw M (1999) Burden of epilepsy. The Ontario Health Survey. Can J Neurol Sci 26:263–270

    Google Scholar 

  18. Schachter SC (2006) Quality of life for patients with epilepsy is determined by more than seizure control: the role of psychosocial factors. Expert Rev Neurother 6(1):111–118

    Article  PubMed  Google Scholar 

  19. Thompson AW, Miller JW, Katon W, Chaytor N, Ciechanowski P (2009) Sociodemographic and clinical factors associated with depression in epilepsy. Epilepsy Behav 14(4):655–660

    Article  PubMed  Google Scholar 

  20. Bell GS, Gaitazis A, Bell CL, Johnson AL, Sander JW (2009) Suicide in people with epilepsy: how great is the risk? Epilepsia 50(8):1933–1942

    Article  PubMed  Google Scholar 

  21. Beyenburg S, Mitchell AJ, Schmidt D et al (2005) Anxiety in patients with epilepsy: systematic review and suggestions for clinical management. Epilepsy Behav 7:161–171

    Article  PubMed  Google Scholar 

  22. Tsiropoulos B, Gichangi A, Andersen M, Bjerrum L, Gaist D, Hallas J (2006) Trends in utilization of antiepileptic drugs in Denmark. Acta Neurol Scand 113:405–411

    Article  CAS  PubMed  Google Scholar 

  23. Savica R, Beghi E, Mazzaglia G, Innocenti F, Brignoli O, Cricelli C, Caputi AP, Musolino R, Spina E, Trifirò G (2007) Prescribing patterns of antiepileptic drugs in Italy: a nationwide population-based study in the years 2000–2005. Eur J Neurol 14(12):1317–1321; erratum in: Eur J Neurol 2008, 15(3):313

    Article  CAS  PubMed  Google Scholar 

  24. Johannessen Landmark C, Larsson PG, Rytter E, Johannessen SI (2009) Antiepileptic drugs in epilepsy and other disorders: a population-based study of prescriptions. Epilepsy Res 87:31–39

    Article  CAS  PubMed  Google Scholar 

  25. Rogawski MA, Löscher W (2004) The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions. Nat Med 10:685–692

    Article  CAS  PubMed  Google Scholar 

  26. Johannessen Landmark C (2007) Targets for antiepileptic drugs in the synapse. Med Sci Monit 13(1):1–7

    Google Scholar 

  27. Johannessen Landmark C (2008) Antiepileptic drugs in non-epilepsy disorders: relations between mechanisms of action and clinical efficacy. CNS Drugs 22:27–47

    Article  PubMed  Google Scholar 

  28. Van de Vrie-Hoekstra NW, de Vries TW, van den Berg PB, Brouwer OF, de Jong-van den Berg LT (2008) Antiepileptic drug utilization in children from 1997–2005 a study from the Netherlands. Eur J Clin Pharmacol 64(10):1013–1020

    Article  PubMed  Google Scholar 

  29. Hsia Y, Neubert A, Sturkenboom M, Murray ML, Verhamme KM, Sen F, Giaquinto C, Ceci A, Wong IC; on behalf of the TEDDY Network of Excellence (2010) Comparison of antiepileptic drug prescribing in children in three European countries. Epilepsia 51(5):789–796

    PubMed  Google Scholar 

  30. Furu K, Skurtveit S, Langhammer A, Nafstad P (2007) Use of anti-asthmatic medications as a proxy for prevalence of asthma in children and adolescents in Norway: a nationwide prescription database analysis. Eur J Clin Pharmacol 63(7):693–698

    Article  CAS  PubMed  Google Scholar 

  31. Furu K (2008) Establishment of the nationwide Norwegian Prescription Database (NorPD)—new opportunities for research in pharmacoepidemiology in Norway. Norwegian J Epidemiol 18(2):129–136. Available at: www.ub.ntnu.no/journals/norepid or www.doaj.org

    Google Scholar 

  32. Devold HM, Doung GM, Tvedal A, Furu K, Meyer HE, Falch JA, Sogaard AJ (2010) Prescription of anti-osteoporosis drugs during 2004–2007—a nationwide register study in Norway. Eur J Clin Pharmacol 66(3):299–306

    Article  PubMed  Google Scholar 

  33. Bramness JG, Grøholt B, Engeland A, Furu K (2009) The use of lithium, valproate or lamotrigine for psychiatric conditions in children and adolescents in Norway 2004–2007—a prescription database study. J Affect Disord 117(3):208–211

    Article  CAS  PubMed  Google Scholar 

  34. WHO Collaborating Center. Available at: http://www.whocc.no

  35. Statistics Norway. Available at: http://www.ssb.no

  36. The Norwegian Institute of Public Health, The National Prescription Database (NorPD). Available at: http://www.reseptregisteret.no

  37. Cavanna AE, Cavanna S, Bertero S, Robertson MM (2009) Depression in women with epilepsy: clinical and neurobiological aspects. Funct Neurol 24(2):83–87

    PubMed  Google Scholar 

  38. Johannessen SI, Johannessen Landmark C (2008) Value of therapeutic drug montoring in epilepsy. Expert Rev Neurother 8(6):929–939

    Article  CAS  PubMed  Google Scholar 

  39. Huying F, Klimpe S, Werhahn KJ (2006) Antiepileptic drug use in nursing home residents: a cross-sectional, regional study. Seizure 15(3):194–197

    Article  PubMed  Google Scholar 

  40. Johannessen Landmark C, Patsalos PN (2010) Drug interactions involving the newer second- and third- generation antiepileptic drugs. Exp Rev Neurother 10(1):19–40

    Article  Google Scholar 

  41. Austin JK, Caplan R (2007) Behavioral and psychiatric comorbidities in pediatric epilepsy: toward an integrative model. Epilepsia 48(9):1639–1651

    Article  PubMed  Google Scholar 

  42. Ekinci O, Titus JB, Rodopman AA, Berkem M, Trevathan E (2009) Depression and anxiety in children and adolescents with epilepsy: prevalence, risk factors, and treatment. Epilepsy Behav 14(1):8–18

    Article  PubMed  Google Scholar 

  43. Rytter E, Johannessen Landmark C, Johannessen SI (2009) Admission of children to a referral center for epilepsy—does it make a difference? Seizure 18(8):573–579

    Article  PubMed  Google Scholar 

  44. Goldberg JF, Brooks JO III, Kurita K, Hoblyn JC, Ghaemi SN, Perlis RH, Miklowitz DJ, Ketter TA, Sachs GS, Thase ME (2009) Depressive illness burden associated with complex polypharmacy in patients with bipolar disorder: findings from the STEP-BD. J Clin Psychiatry 70(2):155–162

    Article  PubMed  Google Scholar 

  45. Patsalos PN, Perucca P (2003) Clinically important interactions in epilepsy: interactions between antiepileptic drugs and other drugs. Lancet Neurol 2(8):473–481

    Article  CAS  PubMed  Google Scholar 

  46. Mula M (2008) Anticonvulsants-antidepressants pharmacokinetic drug interactions: the role of the CYP450 system in psychopharmacology. Curr Drug Metab 9(8):730–737

    Article  CAS  PubMed  Google Scholar 

  47. Gidal BE, French JA, Grossman P, Le Teuff G (2009) Assessment of potential drug interactions in patients with epilepsy: impact of age and sex. Neurology 72(5):419–425

    Article  PubMed  Google Scholar 

  48. Thompson C, Peveler RC, Stephenson D, McKendrick J (2000) Compliance with antidepressant medication in the treatment of major depressive disorder in primary care: a randomized comparison of fluoxetine and a tricyclic antidepressant. Am J Psychiatry 157(3):338–343

    Article  CAS  PubMed  Google Scholar 

  49. Normann C, Hummel B, Scharer LO, Hörn M, Grunze H, Walden J (2002) Lamotrigine as adjunct to paroxetine in acute depression: a placebo-controlled, double-blind study. J Clin Psychiatry 63:337–344

    CAS  PubMed  Google Scholar 

  50. Fakhoury TA, Barry JJ, Mitchell Miller J, Hammer AE, Vuong A (2006) Lamotrigine in patients with epilepsy and comorbid depressive symptoms. Epilepsy Behav 10:155–162

    Article  PubMed  Google Scholar 

  51. Miller MJ, Robert PK, Vuong A, Hanner AE, Messenheimer JA (2008) Depressive symptoms in epilepsy. Drugs 68(11):1493–1509

    Article  CAS  PubMed  Google Scholar 

  52. Ettinger AB, Argoff CE (2007) Use of antiepileptic drugs for nonepileptic conditions: psychiatric disorders and chronic pain. Exp Rev Neurother 4:75–83

    CAS  Google Scholar 

  53. Brodtkorb E, Mula M (2006) Optimizing therapy of seizures in adult patients with psychiatric comorbidity. Neurology 67 [12 Suppl 4]:S39–S44

    PubMed  Google Scholar 

  54. Mula M, Trimble MR, Sander JW (2007) Are psychiatric adverse events of antiepileptic drugs a unique entity? A study on topiramate and levetiracetam. Epilepsia 48(12):2322–2326

    CAS  PubMed  Google Scholar 

  55. Haw C, Stubbs J (2005) A survey of off-label prescribing for inpatients with mild intellectual disability and mental illness. J Intellect Disabil Res 49(Pt 11):858–864

    Article  CAS  PubMed  Google Scholar 

  56. Citrome L (2009) Adjunctive lithium and anticonvulsants for the treatment of schizophrenia: what is the evidence? Expert Rev Neurother 9(1):55–71

    Article  CAS  PubMed  Google Scholar 

  57. Goldberg JF, Citrome L (2005) Latest therapies for bipolar disorder. Looking beyond lithium. Postgrad Med 117(2):25–26, 29–32, 35–36

    Article  PubMed  Google Scholar 

  58. Baldessarini R, Henk H, Sklar A, Chang J, Leahy L (2008) Psychotropic medications for patients with bipolar disorder in the United States: polytherapy and adherence. Psychiatr Serv 59(19):1175–1183

    Article  PubMed  Google Scholar 

  59. Snyder EM, Murphy MR (2008) Schizophrenia therapy: beyond atypical antipsychotics. Nat Rev 7:471–472

    Article  CAS  Google Scholar 

  60. Al Jurdi RK, Marangell LB, Petersen NJ, Martinez M, Gyulai L, Sajatovic M (2008) Prescription patterns of psychotropic medications in elderly compared with younger participants who achieved a “recovered” status in the systematic treatment enhancement program for bipolar disorder. Am J Geriatr Psychiatry 16(11):922–933

    Article  PubMed  Google Scholar 

  61. D’Souza WJ, Fryer JL, Quinn SJ, Taylor BV, Ficker DM, O’Brien TJ, Pearce NE, Cook MJ (2007) The Tasmanian Epilepsy Register—a community-based cohort. Background and methodology for patient recruitment from the Australian national prescription database. Neuroepidemiology 29(3–4):255–263

    Article  PubMed  Google Scholar 

  62. Davis KL, Chandrilli SD, Edin HM (2008) Prevalence and cost of nonadherence with antiepileptic drugs in an adult managed care population. Epilepsia 49(3):446–454

    Article  PubMed  Google Scholar 

  63. Cramer JA, Rosenheck R (1998) Compliance with medication regimens for mental and physical disorders. Psychiatr Serv 49(2):196–201

    CAS  PubMed  Google Scholar 

  64. Demyttenaere K, Mesters P, Boulanger B, Dewe W, Delsemme MH, Gregoire J, Van Ganse E (2001) Adherence to treatment regimen in depressed patients treated with amitriptyline or fluoxetine. J Affect Disord 65(3):243–252

    Article  CAS  PubMed  Google Scholar 

  65. Gaudiano BA, Weinstock LM, Miller IW (2008) Improving treatment adherence in bipolar disorder: a review of current psychosocial treatment efficacy and recommendations for future treatment development. Behav Modif 32(3):267–301

    Article  PubMed  Google Scholar 

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Acknowledgement

We would like to acknowledge Prof. Odd Aalen, Department of Basic Medical Sciences, University of Oslo, for helpful statistical discussions.

Conflict of interest

The authors have no conflicts of interest or financial disclosures regarding this manuscript.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Health Sciences, Oslo University College, Pilestredet 50, 0167, Oslo, Norway

    Mohamad Karouni, Subaneesan Arulthas & Cecilie Johannessen Landmark

  2. The National Center for Epilepsy, Sandvika, Oslo University Hospital, Oslo, Norway

    Pål G. Larsson, Elisif Rytter & Svein I. Johannessen

  3. Department of Pharmacology, Oslo University Hospital, Oslo, Norway

    Svein I. Johannessen

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  1. Mohamad Karouni
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  2. Subaneesan Arulthas
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  3. Pål G. Larsson
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  5. Svein I. Johannessen
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  6. Cecilie Johannessen Landmark
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Correspondence to Cecilie Johannessen Landmark.

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Karouni, M., Arulthas, S., Larsson, P.G. et al. Psychiatric comorbidity in patients with epilepsy: a population-based study. Eur J Clin Pharmacol 66, 1151–1160 (2010). https://doi.org/10.1007/s00228-010-0861-y

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  • DOI: https://doi.org/10.1007/s00228-010-0861-y

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