Abstract
Patients with epilepsy are at high risk for depression because of an incompletely understood combination of factors that may be both psychosocial and neurological. Interictal depression in patients with epilepsy is an undertreated condition, in part because of concern regarding drug interactions and the risk of exacerbating seizures with antidepressant treatment. Bipolar disorder is not described as occurring with a higher than expected frequency in the population with epilepsy, but high rates of depression and suicide are well recognised, highlighting the need for more emphasis on antidepressive treatment in this group of at-risk patients.
Neurological factors, including site and lateralisation of seizure focus, may be important for the development of depression, with left-sided seizure foci having a higher association with depressive symptoms. Forced normalisation may be a factor in the paradoxical onset of depression in patients with epilepsy whose seizures suddenly become well controlled by anti-seizure treatment. Lowering of folic acid levels by some antiepileptic drugs (AEDs) may also influence the expression of depression in patients with epilepsy.
New AEDs continue to emerge as beneficial treatments themselves for mood disorders, with lamotrigine, gabapentin and, to a lesser extent, topiramate having clinical trials data to support their use in patients with bipolar disease. Similar positive data are available for vagal nerve stimulation. Mood effects of AEDs can be complicated, however, as many of these drugs (e.g. tiagabine) have also been reported to cause depression as an adverse effect. Electroconvulsive therapy in depressed patients with epilepsy requires special consideration.The selective serotonin reuptake inhibitors (SSRIs) and antidepressants that act at multiple receptors (e.g. nefazodone, venlafaxine) are the most appropriate treatments for depressed patients with epilepsy. Among these agents, citalopram has a low risk of interactions with AEDs. Bupropion, clomipramine and maprotiline are associated with a greater risk of seizures compared with other antidepressants and consequently should be used with caution in the treatment of depression in patients with epilepsy.
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References
Hermann BP, Seidenberg M, Bell M. Psychiatric comorbidity in chronic epilepsy: identification, consequences, and treatment of major depression. Epilepsia 2000; 41 Suppl. 2: S31–41
Edeh J, Toone BK, Corney RH. Epilepsy, psychiatric morbidity, and social dysfunction in general practice. Comparison between clinic patients and clinic nonattenders. Neuropsychiatry Neuropsychol Behav Neurol 1990; 3: 180–92
Edeh J, Toone B. Relationship between interictal psychopathology and type of epilepsy. Results of a survey in general practice. Br J Psychiatry 1987; 151: 95–101
Jacoby A, Baker GA, Steen N, et al. The clinical course of epilepsy and its psychosocial correlates: findings from a U.K. community study. Epilepsia 1996; 37: 148–61
Victoroff JI, Benson DF, Engel Jr J, et al. Interictal depression in patients with medically intractable complex partial seizures: electroencephalography and cerebral metabolic correlates [abstract]. Ann Neurol 1990; 28: 221
Indaco A, Carrieri PB, Nappi C, et al. Interictal depression in epilepsy. Epilepsy Res 1992; 12: 45–50
Victoroff JI, Benson DF, Grafton ST, et al. Depression in complex partial seizures. Electroencephalography and cerebral metabolic correlates. Arch Neurol 1994; 51: 155–63
Robertson MM, Channon S, Baker J. Depressive symptomatology in a general hospital sample of outpatients with temporal lobe epilepsy: a controlled study. Epilepsia 1994; 35: 771–7
Boyd JH, Weissman MM. Epidemiology. In: Paykel ES, editor. Handbook of affective disorders. New York: The Guilford Press, 1982: 25
Blumer D. Postictal depression: significance for the neurobehavioral disorder of epilepsy. J Epilepsy 1992; 5: 214–9
Lambert MV, Robertson MM. Depression in epilepsy: etiology, phenomenology, and treatment. Epilepsia 1999; 40 Suppl. 10: S21–47
Lim J, Yagnik P, Schraeder P, et al. Ictal catatonia as a manifestation of nonconvulsive status epilepticus. J Neurol Neurosurg Psychiatry 1986; 49: 833–6
Betts TA. Neuropsychiatry. In: Laidlaw J, Richens A, Chadwick D, editors. A textbook of epilepsy. 4th ed. Edinburgh: Churchill-Livingston, 1993: 397–458
Mendez MF, Doss RC. Ictal and psychiatric aspects of suicide in epileptic patients. Int J Psychiatry Med 1992; 22: 231–7
Wiegartz P, Seidenberg M, Woodard A, et al. Co-morbid psychiatrie disorder in chronic epilepsy: recognition and etiology of depression. Neurology 1999; 53(5 Suppl. 2): S3–8
Reynolds EH. Interictal psychiatric disorders. Adv Neurol 1991; 55: 47–57
Robertson MM. Affect and mood in epilepsy: an overview with a focus on depression. Acta Neurol Scand 1992; 86: 127–32
Barraclough B. The suicide rate of epilepsy. Acta Psychiatry Scand 1987; 76: 339–45
Kanner AM, Nieto JC. Depressive disorders in epilepsy. Neurology 1999; 53(5 Suppl. 2): S26–32
Manchanda R, Schaefer B, McLachlan RS, et al. Relationship of site of seizure focus to psychiatric morbidity. J Epilepsy 1995; 8: 23–8
Herman BP, Seidenberg M, Haitiner A, et al. Mood state in unilateral temporal lobe epilepsy. Biol Psychiatry 1991; 30: 1205–18
Bromfield EB, Alshuler L, Leiderman DB, et al. Cerebral metabolism and depression in patients with complex partial seizures. Arch Neurol 1992; 59: 617–23
Robertson M. Mood disorders associated with epilepsy. In: McConnell HW, Snyder PJ, editors. Psychiatric comorbidity in epilepsy. Basic mechanisms, diagnosis, and treatment. Washington, DC: American Psychiatric Press, 1998: 132–67
Schmitz EB, Moriarty J, Costa DC, et al. Psychiatric profiles and patterns of cerebral blood flow in focal epilepsy: interactions between depression, obsessionality, and perfusion related to the laterality of the epilepsy. J Neurol Neurosurg Psychiatry 1997; 62: 458–63
Bench CJ, Frackowiak R, Dolan R. Changes in regional cerebral blood flow on recovery from depression. Psychol Med 1995; 25: 247–51
Standage KF, Fenton GW. Psychiatric symptom profiles of patients with epilepsy: a controlled investigation. Psychol Med 1975; 5: 152–60
Betts TA. A follow-up study of a cohort of patients with epilepsy admitted to psychiatric care in a English city. In: Harris P, Mawdsley C, editors. Epilepsy proceedings of the Hans Berger Centenary symposium. Edinburgh: Churchill Livingston, 1974: 326–38
Mendez MF, Doss RC, Taylor JL, et al. Depression in epilepsy: relationship to seizures and anticonvulsant therapy. J Nerv Ment Dis 1993; 181: 444–7
Landolt H. Some clinical electroencephalographical correlations in epileptic psychoses (twilight states) [abstract]. Electroencephalogr Clin Neurophysiol 1953; 5: 121
Landolt H. Serial electroencephalographic investigations during psychotic episodes in epileptic patients and during schizophrenic attacks. In: Lorentz de Haas AM, editor. Lectures on epilepsy. Amsterdam: Elsevier, 1958: 91–133
Smith PF, Darlington CL. Neural mechanisms of psychiatric disturbances in patients with epilepsy. In: McConnell HW, Snyder PJ, editors. Psychiatric comorbidity in epilepsy. Basic mechanisms, diagnosis, and treatment. Washington, DC: American Psychiatric Press, 1998: 15–35
Trimble M. Non-monoamine oxidase inhibitor antidepressants and epilepsy: a review. Epilepsia 1987; 19: 241–51
Goddard GV, McIntyre DC, Leech CK. A permanent change in brain function resulting from electrical stimulation. Exp Neurol 1969; 25: 296–330
Hermann BP, Whitman S. Psychosocial predictors of interictal depression. J Epilepsy 1989; 2: 231–7
Brent D, Crumrine P, Varma R. Phenobarbital treatment and major depressive disorder in children with epilepsy. Pediatrics 1987; 80: 909–17
Barabas G, Matthews W. Barbiturate anticonvulsants as a cause of severe depression. Pediatrics 1988; 82: 284–5
Dodrill CB. Behavioral effects of antiepileptic drugs. In: Smith D, Treiman D, Trimble M, editors. Advances in neurology. Vol. 44. New York: Raven Press, 1991: 213–24
Ben-Menachem E, French J. Vigabatrin. In: Engel Jr J, Pedley TA, editors. Epilepsy: a comprehensive textbook. Philadelphia (PA): Lippincott-Raven Publishers, 1997: 1609–18
French J, Pellock J, Ferrendelli J, et al. Results of a multicenter, placebo-controlled, parallel study of vigabatrin (VGB, Sabril) in patients with focal epilepsy whose seizures are difficult to control [abstract]. Neurology 1993; 43 Suppl. 2: A307
Penry JK, Wilder BJ, Sachdeo RC, et al. Multicenter dose-response study of vigabatrin in brain and CSF of the rat. Brain Res 1980; 190: 288–92
Harden CL, Lazar LM, Pick LH, et al. A beneficial effect on mood in partial epilepsy patients treated with gabapentin. Epilepsia 1999; 40(8): 1129–34
McElroy SL, Soutullo CA, Keck Jr PE, et al. A pilot trial of adjunctive gabapentin in the treatment of bipolar disorder. Clin Psychiatry 1997; 9(2): 99–103
Schaffer CB, Schaffer LC. Gabapentin for the treatment of bipolar disorder [letter]. Am J Psychiatry 1997; 154: 291
Sokolski KN, Green C, Maris DE, et al. Gabapentin as an adjunct to standard mood stabilizers in outpatients with mixed bipolar symptomatology. Ann Clin Psychiatry 1999; 11(4): 217–22
Cabras PL, Hardoy MJ, Hardoy MC, et al. Clinical experience with gabapentin in patients with bipolar or schizoaffective disorder: results of an open-label study. J Clin Psychiatry 1999; 60(4): 245–8
Pande AC, Crockatt JG, Janney CA, et al. Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy. Gabapentin Bipolar Disorder Study Group. Bipolar Disord 2000 Sep; 2 (3 Pt 2): 249–55
Calabrese JR, Bowden CL, Sachs GS, et al. A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. J Clin Psychiatry 1999; 60(2): 79–88
Ichim L, Berk M, Brook S. Lamotrigine compared with lithium in mania: a double-blind randomized controlled trial. Ann Clin Psychiatry 2000; 12(1): 5–10
Calabrese JR, Suppes T, Bowden CL, et al. A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. Lamictal 614 Study Group. J Clin Psychiatry 2000; 61(11): 841–50
Crawford P. An audit of topiramate use in a general neurology clinic. Seizure 1998; 7: 207–11
Marcotte D. Use of topiramate, a new anti-epileptic as a mood stabilizer. J Affect Disord 1998; 50(2–3): 245–51
McElroy SL, Suppes T, Keck Jr PE, et al. Open-label adjunctive topiramate in the treatment of bipolar disorders. Biol Psychiatry 2000; 47(12): 1025–33
Berlant JL. Topiramate in posttraumatic stress disorder: preliminary clinical observations. J Clin Psychiatry 2001; 62 Suppl. 17: 60–3
Leppik IE, Gram L, Deaton R, et al. Safety of tiagabine: summary of 53 trials. Epilepsy Res 1999; 33: 235–46
Dodrill CB, Arnett JL, Shu V, et al. Effects of tiagabine monotherapy on abilities, adjustment, and mood. Epilepsia 1998; 39: 33–42
Meldrum BS, Chapman AG. Basic mechanisms of Gabitril (tiagabine) and future potential developments. Epilepsia 1999; 40 Suppl. 9: S2–6
Grunze H, Erfurth A, Marcuse A, et al. Tiagabine appears not to be effective in the treatment of acute mania. J Clin Psychiatry 1999; 60(11): 759–62
Kaufman KR. Adjunctive tiagabine treatment of psychiatric disorders: three cases. Ann Clin Psychiatry 1998; 10(4): 181–4
Kanba S, Yagi G, Kamijima K, et al. The first open study of zonisamide, a novel anticonvulsant, shows efficacy in mania. Prog Neuropsychopharmacol Biol Psychiatry 1994; 18(4): 707-15
Joca SR, Skalisz LL, Beijamini V, et al. The antidepressive-like effect of oxcarbazepine: possible role of dopaminergic neurotransmission. Eur Neuropsychopharmacol 2000; 10(4): 223–8
Kossoff EH, Bergey GK, Freeman JM, et al. Levetiracetam psychosis in children with epilepsy. Epilepsia 2001; 42(12): 1611–3
Harden CL, Pulver MC, Ravdin LD, et al. A pilot study of mood in epilepsy patients treated with vagus nerve stimulation. Epilepsy Behav 2000; 1: 93–9
Rush AJ, George MS, Sackeim HA, et al. Vagus nerve stimulation (VNS) for treatment-resistant depressions: a multicenter study. Biol Psychiatry 2000; 47: 276–86
Edeh J, Toone BK. Antiepileptic therapy, folate deficiency and psychiatric morbidity: a general practice survey. Epilepsia 1985; 26: 434–40
Froscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995; 18: 165–82
Carney MWP, Chary TKN, Laundy M, et al. Red cell folate concentrations in psychiatric patients. J Affect Disord 1990; 19: 207–13
Torta R, Keller R. Behavioral, psychotic, and anxiety disorders in epilepsy: etiology, clinical features, and therapeutic implications. Epilepsia 1999; 40 Suppl. 10: S2–20
Dell J. Social dimensions of epilepsy: stigma and response. In: Whitman S, Hermann PP, editors. Psychopathology in epilepsy: social perspectives. New York: Oxford University Press, 1986: 185–210
Hermann BP, Wyler AR. Depression, locus of control, and the effects of epilepsy surgery. Epilepsia 1989; 30(3): 332–8
Lefcourt HM. Locus of control. New York: Erlbaum, 1976
Katon W, VonKorff M, Lin E, et al. Adequacy and duration of antidepressant treatment in primary care. Med Care 1992; 30: 67–76
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994
Blumer D, Montouris G, Hermann B. Psychiatric morbidity in seizure patients on a neurodiagnostic monitoring unit. J Neuropsychiatry Clin Neurosci 1995; 7: 445–56
Davidson J. Seizures and bupropion: a review. J Clin Psychiatry 1989; 50: 256–61
Dessain EC, Schatzberg AF, Woods BT, et al. Maprotiline treatment in depression: a perspective on seizures. Arch Gen Psychiatry 1986; 43: 86–90
Jabbari B, Dryan GE, Marsh EE, et al. Incidence of seizures with tricyclic and tetracyclic antidepressants. Arch Neurol 1985; 42: 480–1
Rosenstein DL, Nelson JC, Jacobs SC. Seizures associated with antidepressants: a review. J Clin Psychiatry 1993; 54(8): 289–99
DeVeaugh-Geis J, Landau P, Katz R. Preliminary results from a multicenter trial of clomipramine in obsessive-compulsive disorder. Psychopharmacol Bull 1989; 25: 36–40
Jick H, Dinan BJ, Hunter JR, et al. Tricyclic antidepressants and convulsions. J Clin Psychopharmacol 1983; 3: 182–5
Peck AW, Stern WC, Watkinson C. Incidence of seizures during treatment with tricyclic antidepressant drugs and bupropion. J Clin Psychiatry 1983 May; 44 (5 Pt 2): 197–201
Physician’s desk reference. Montvale (NJ): Medical Economics, 1999
Edwards JG, Inman WHW, Wilton L, et al. Prescription-event monitoring of 10,401 patients treated with fluvoxamine. Br J Psychiatry 1994; 164: 387–95
Physician’s desk reference. Montvale (NJ): Medical Economics, 2000
Dailey JW, Naritoku DK. Antidepressants and seizures: clinical anecdotes overshadow neuroscience. Biochem Pharmacol 1996; 52(9): 1323–9
Prendiville S, Gale K. Anticonvulsant effect of fluoxetine on focally evoked limbic motor seizures in rats. Epilepsia 1993; 34(2): 381–4
Leander JD. Fluoxetine, a selective serotonin-uptake inhibitor, enhances the anticonvulsant effects of phenytoin, carbamazepine, and ameltolide (LY201116). Epilepsia 1992; 33(3): 573–6
Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935-1984. Epilepsia 1993; 34(3): 453–68
The Association of the British Pharmaceutical Industry (ABPI). Compendium of data sheets and summaries of product characteristics. London: Datapharm Publications, 1996
Ketter TA, Post RM, Parakh PI, et al. Addition of monoamine oxidase inhibitors to carbamazepine: preliminary evidence of safety and antidepressant efficacy in treatment-resistant depression. J Clin Psychiatry 1995; 56(10): 471–5
Ereshefsky L. Drug-drug interactions involving antidepressants: focus on venlafaxine. J Clin Psychopharmacol 1996; 19 Suppl. 2: S37–53
Levy RH, Mather GG. Metabolic enzymes and antiepileptic drug interactions. In: French J, Leppik I, Dichter MA, editors. Antiepileptic drug development. Advances in neurology. Vol. 76. Philadelphia (PA): Lippincott-Raven Publishers, 1998: 49–55
Shank RP, Gardocki JF, Streeter AJ, et al. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia 2000; 41 Suppl. 1: S3–9
Kalinowsky LB, Kennedy F. Observations in electroshock therapy applied to the problems of epilepsy. J Nerv Ment Dis 1943; 98: 56–67
Keller CH, Bernstein HJ. ECT as a treatment for neurologic illness. In: Coffey CE, editor. The clinical science of electroconvulsive therapy. Washington, DC: American Psychiatric Press, 1993: 183–210
Weiner RD, Coffey CE. Electroconvulsive therapy in the medical and neurologic patient. In: Stoudemeire A, Fogel BS, editors. Psychiatric care of the medical patient. New York: Oxford University Press, 1993: 207–24
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Harden, C.L., Goldstein, M.A. Mood Disorders in Patients with Epilepsy. CNS Drugs 16, 291–302 (2002). https://doi.org/10.2165/00023210-200216050-00002
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DOI: https://doi.org/10.2165/00023210-200216050-00002