Skip to main content
SpringerLink
Log in

Suicidality and Antiepileptic Drugs

Is there a Link?

  • Review Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

The main purpose of the present article is to review the possible risk factors for suicidal behaviour in epilepsy with a special emphasis on the different antiepileptic drugs (AEDs).

Epidemiological data show that, in general, the suicide rate among patients with epilepsy is 5-fold higher than that in the general population, while in temporal lobe epilepsy and complex partial seizures it is approximately 25-fold higher. A certain psychiatric comorbidity may provoke suicidality in patients with epilepsy, and depression and cognitive impairment seem to be the main risk factors for suicidality in epilepsy. In addition, depression and cognitive deterioration in epilepsy may share common neuropsychological mechanisms in terms of hypofrontality. This may cause similar psychopathological signs in both diagnostic categories, including suicidality.

Analysis of the literature has shown that serotonin metabolism disturbances are involved in the pathogenesis of suicidal behaviour irrespective of primary diagnosis. Serotonin disturbances also seem to be a common link between depression, suicidality and even epilepsy itself.

The various AEDs differ not only in their mechanisms of action, but also in influences on cognition and mood in epileptic patients and suicidality, respectively. Until now, only Ketter’s hypothesis has been proposed to explain the psychotropic effects of different AEDs, although it does not explain the positive psychotropic effects of some AEDs, such as carbamazepine and oxcarbazepine.

According to this model, all psychotropic effects of AEDs may be the result of effects on the function of two types of receptor functions: γ-aminobutyric acid (GABA) ergic and antiglutamatergic; other possible mechanisms have not been incorporated. Presumably, other neurochemical mechanisms, and a serotonergic mechanism in particular, should also be taken into account when explaining the psychotropic effects of different AEDs.

Based on these data, it has been suggested that AEDs with certain serotonergic properties should reduce the suicidality risk because they exert effects similar to antidepressants (i.e. selective serotonin reuptake inhibitors), whereas AEDs that lack serotonergic mechanisms would not be effective in suicidality prevention. In line with this paradigm, phenobarbital and phenytoin seem to be the only drugs with proven suicidality risk. On the other hand, carbamazepine, oxcarbazepine, valproate and lamotrigine could be regarded as drugs with antisuicidal properties because they all improve cognitive functions and mood in epileptic patients, and possess serotonergic mechanisms of action. The other AEDs, including topiramate, tiagabine, vigabatrin, levetiracetam and zonisamide, all exert negative effects on mood and cognition, although their influence on suicidality has not been proven in evidence-based studies yet. Although zonizamide has serotonergic properties, it exerts negative psychotropic effects, whereas gabapentin is devoid of serotonergic properties but has positive psychotropic effects on mood and cognition.

To more fully explain the positive and negative psychotropic effects and influence on suicidality of AEDs, Ketter’s paradigm should be supplemented by an understanding of the serotonergic mechanisms of different AEDs. Further trials are required to prove or refute this model.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III

Similar content being viewed by others

References

  1. Diehl LW. Epilepsie und Suizid. Psychiatr Neurol Med Psychol (Leipz) 1986; 38: 625–33

    CAS  Google Scholar 

  2. Blumer D. Postictal depression: significance for the neurobehavioral disorder of epilepsy. J Epilepsy 1992; 5: 214–9

    Article  Google Scholar 

  3. Blumer D, Montouris G, Davis K, et al. Suicide in epilepsy: psychopathology, pathogenesis, and prevention. Epilepsy Behav 2002; 3(3): 232–41

    Article  PubMed  Google Scholar 

  4. Blumer D. Dysphoric disorders and paroxysmal affects: recognition and treatment of epilepsy-related psychiatric disorders. Harvard Rev Psychiatry 2000; 8(1): 8–17

    CAS  Google Scholar 

  5. Mendez MF, Cummings JL, Benson DE. Depression in epilepsy: significance and phenomenology. Arch Neurol 1986; 43: 766–70

    Article  PubMed  CAS  Google Scholar 

  6. Robertson MM, Trimble MR, Townsend HRA. Phenomenology of depression in epilepsy. Epilepsia 1987; 28: 364–72

    Article  PubMed  CAS  Google Scholar 

  7. Lambert MV, Schmitz EB, Ring HA, et al. Neuropsychiatric aspects of epilepsy. In: Schiffer RB, Rao SM, Fogel BS, editors. Neuropsychiatry. 2nd ed. Philadelphia (PA): LWW, 2003: 1071–131

    Google Scholar 

  8. Lambert MV, Thompson PJ, Trimble M. Neuropsychiatric aspects of epilepsy. In: Rizzo M, Eslinger PJ, editors. Principles and practice of behavioral neurology and neuropsychology. Philadelphia (PA): Saunders, 2004: 763–79

    Google Scholar 

  9. Kalinin V, Polyanskiy D. Gender differences in risk factors of suicidal behavior in epilepsy. Epilepsy Behav 2005; 6: 424–9

    Article  PubMed  Google Scholar 

  10. Kalinin V, Polyanskiy D. Gender and suicidality prediction in epilepsy. Epilepsy Behav 2005; 7, 4: 657–63

    Article  PubMed  Google Scholar 

  11. Steinert T, Froscher W. Aggression bei Epilepsie. Nervenheilkd 1994; 13: S199–205

    Google Scholar 

  12. Rösche J, Uhlmann C, Möller A. Psychische Störungen. In: Fröscher W, Vassella F, Hufnagel A. (Hrsgb.) Die Epilepsien. Grundlagen, Klinik, Behandlung. Stuttgart: Schattauer, 2004: 243–62

    Google Scholar 

  13. Kanner A, Rivas Nieto JC. Depressive disorders in epilepsy. Neurology 1999; 53Suppl. 1: S26–32

    PubMed  CAS  Google Scholar 

  14. Attarian H, Vahle V, Carter J, et al. Relation between depression and intractability of seizures. Epilepsy Behav 2003; 4: 298–301

    Article  PubMed  CAS  Google Scholar 

  15. Kanner A. Depression in epilepsy is much more than a reactive process. Epilepsy currents 2003; 3(3): 202–3

    Article  PubMed  Google Scholar 

  16. Harden CL, Goldstein MA. Mood disorders in patients with epilepsy: epidemiology and management. CNS Drugs 2002; 16(5): 291–302

    Article  PubMed  CAS  Google Scholar 

  17. Altshuler LL, Devinsky O, Post RM, et al. Depression, anxiety and temporal lobe epilepsy: laterality of focus and symptoms. Arch Neurol 1990; 47: 284–8

    Article  PubMed  CAS  Google Scholar 

  18. Mendez MF, Taylor JL, Doss RC, et al. Depression in secondary epilepsy: relation to lesion laterality. J Neurol Neurosurg Psychiatry 1994; 57: 232–3

    Article  PubMed  CAS  Google Scholar 

  19. Victoroff JL, Benson F, Grafton ST, et al. Depression in complex partial seizures: electroencephalography and cerebral metabolic correlates. Arch Neurol 1994; 51: 155–63

    Article  PubMed  CAS  Google Scholar 

  20. Schmitz B. Depressive disorders in epilepsy. In: Trimble M, Schmitz B, editors. Seizures, affective disorders and anticonvulsant drugs. Guildford: Clarius Press Ltd, 2002: 19–34

    Google Scholar 

  21. Ritaccio AL, Devinsky O. Personality disorders in epilepsy. In: Ettinger A, Kanner A, editors. Psychiatric issues in epilepsy: a practical guide to diagnosis and treatment. Philadelphia (PA): LWW, 2001: 147–61

    Google Scholar 

  22. Doval O, Gaviria M, Kanner A. Frontal lobe dysfunction in epilepsy. In: Ettinger A, Kanner A, editors. Psychiatric issues in epilepsy: a practical guide to diagnosis and treatment. Philadelphia (PA): LWW, 2001: 261–71

    Google Scholar 

  23. Castellon SA, Hinkin CH, Satz P. Behavioral disorders associated with central nervous system dysfunction. In: Adams HE, Sutker PB, editors. Comprehensive handbook of psychopathology. 3rd ed. New York: Springer, 2004: 813–40

    Google Scholar 

  24. Herman BP, Seidenberg M, Haltiner A, et al. Mood state in unilateral temporal lobe epilepsy. Biol Psychiatry 1991; 30: 1205–18

    Article  Google Scholar 

  25. Schneider F, Habel U, Bestman S. Affektive Störungen. In: Förstl H. (Hrsg.) Frontalhirn. Funktionen und Erkrankungen, 2 Auflage. Heidelberg: Springer, 2005: 233–65

    Google Scholar 

  26. Helmstaedter C, Sonntag-Dillender M, Hoppe C, et al. Depressed mood and memory impairment in temporal lobe epilepsy as a function of focus lateralization and localization. Epilepsy Behav 2004; 5(5): 696–701

    Article  PubMed  Google Scholar 

  27. Quiske A, Helmstaedter C, Lux S, et al. Depression in patients with temporal lobe epilepsy is related to mesial temporal sclerosis. Epilepsy Res 2000; 39: 121–5

    Article  PubMed  CAS  Google Scholar 

  28. Conwell Y, Burhan A. The neuropsychiatry of suicide. In: Schiffer RB, Rao SM, Fogel BS, editors. Neuropsychiatry. 2nd ed. Philadelphia (PA): LWW, 2003: 679–723

    Google Scholar 

  29. Asberg M, Thoren P, Traskman L, et al. “Serotonin depression”: a biochemical subgroup within the affective disorder? Science 1976; 191: 478–80

    Article  PubMed  CAS  Google Scholar 

  30. Asberg M, Traskman L, Thoren P. 5-HIAA in the cerebrospinal fluid: a biochemical suicide predictor? Arch Gen Psychiatry 1976; 33: 1193–7

    Article  PubMed  CAS  Google Scholar 

  31. Agren H. Symptom patterns in unipolar and bipolar depression correlating with monoamine metabolites in the cerebrospinal fluid: II. Suicide. Psychiatry Res 1980 Oct; 3(2): 225–35

    Article  PubMed  CAS  Google Scholar 

  32. Brown GL, Goodwin FK, Ballenger JC, et al. Aggression in human correlates with cerebrospinal fluid metabolites. Psychiatry Res 1979; 1: 131–9

    Article  PubMed  CAS  Google Scholar 

  33. Brown GL, Ebert ME, Goyer PF, et al. Aggression, suicide and serotonin: relationships to CSF amine metabolites. Am J Psychiatry 1982; 139: 741–6

    PubMed  CAS  Google Scholar 

  34. Lidberg L, Tuck JR, Asberg M, et al. Homocide, suicide and CSF 5-HIAA. Acta Psychiatr Scand 1985; 71: 230–6

    Article  PubMed  CAS  Google Scholar 

  35. Linnoila VM, Virkkunen M. Aggression, suicidality, and serotonin. J Clin Psychiatry 1992; 53Suppl.: 46–51

    PubMed  Google Scholar 

  36. van Praag HM. Biological suicide research: outcome and limitations. Biol Psychiatry 1986; 21(13): 1305–23

    Article  PubMed  Google Scholar 

  37. van Praag HM, Plutchik R. Depression type and depression severity in relation to risk of violent suicide attempt. Psychiatry Res 1984; 12: 333–8

    Article  PubMed  Google Scholar 

  38. Stanley M, Mann JJ. Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet 1983; 1: 214–6

    Article  PubMed  CAS  Google Scholar 

  39. Janicak PG, Davis JM, Preskorn SH, et al. Principles and practice of psychopharmacotherapy. Philadelphia (PA): LWW, 2001: 700

    Google Scholar 

  40. Chugani HT, Chugani DC. Imaging of serotonin mechanisms in epilepsy. Epilepsy Currents 2005; 5(6): 201–6

    Article  PubMed  Google Scholar 

  41. Dailey JW, Reigel CE, Mishra PK, et al. Neurobiology of seizure predisposition in the genetically epilepsy-prone rat. Epilepsy Res 1989; 3: 317–20

    Article  Google Scholar 

  42. Statnick MA, Daile JW, Jobe PC, et al. Abnormalities in brain serotonin concentration, high-affinity uptake, and tryptophan hydroxylase activity in severe-seizure genetically epilepsyprone rats. Epilepsia 1996; 37: 311–21

    Article  PubMed  CAS  Google Scholar 

  43. Wenger GR, Stitzel RE, Craig CR. The role of biogenic amines in the reserpine-induced alteration of minimal electroshock seizure thresholds in the mouse. Neuropharmacology 1983; 12: 693–703

    Article  Google Scholar 

  44. Maynert E, Marczynski T, Browning R. The role of neurotransmitters in the epilepsies. Adv Neurology 1975; 13: 79–143

    CAS  Google Scholar 

  45. Louw D, Sutherland GB, Glavin GB, et al. A study of monoamine metabolism in human epilepsy. Can J Neurol Sci 1989; 16: 394–7

    PubMed  CAS  Google Scholar 

  46. Bercovici E, Cortez MA, Wang X, et al. Serotonine depletion attenuates AY-9944-mediated atypical absence seizures. Epilepsia 2006; 47(2): 240–6

    Article  PubMed  CAS  Google Scholar 

  47. Drevets WC, Frank E, Price JC, et al. PET imaging of serotonin 1A receptor binding in depression. Biological Psychiatry 1999; 46: 1375–87

    Article  PubMed  CAS  Google Scholar 

  48. Gilliam F, Santos J, Vahle V, et al. Depression in epilepsy: ignoring clinical expression of neuronal network dysfunction? Epilepsia 2004; 45Suppl. 2: 28–33

    Article  PubMed  Google Scholar 

  49. Forsgren L, Nystrom L. An incident case referent study of epileptic seizures in adults. Epilepsy Res 1990; 6: 66–81

    Article  PubMed  CAS  Google Scholar 

  50. Hesdorffer DC, Hauser WA, Annegers JF, et al. Major depression is a risk factor for seizures in older adults. Ann Neurol 2000; 47: 246–9

    Article  PubMed  CAS  Google Scholar 

  51. Ketter TA, Post RM, Theodore WH. Positive and negative psychiatric effects of antiepileptic drugs in patients with seizure disorders. Neurology 1999; 53Suppl. 2: 53–67

    Google Scholar 

  52. Hirsch E, Schmitz B, Carreiio M. Epilepsy, antiepileptic drugs (AEDs) and cognition. Acta Neurologica Scand 2003; 108Suppl. 180: 23–32

    Article  Google Scholar 

  53. Frances A, Manning D, Marin D, et al. Relationship of anxiety and depression. Psychopharmacology 1992; 106Suppl.: S82–86

    Article  PubMed  Google Scholar 

  54. Brent D, Crumrine P, Varma R. Phenobarbital treatment and major depressive disorder in children with epilepsy. Pediatrics 1987; 80: 909–17

    PubMed  CAS  Google Scholar 

  55. Ferrari N, Barabas G, Mathews W. Psychological and behavioral disturbance among epileptic children treated with barbiturate anticonvulsants. Am J Psychiatry 1983; 140: 112–3

    PubMed  CAS  Google Scholar 

  56. Smith D, Collins J. Behavioral effects of carbamazepine, phenobarbital, phenitoin and primidone [abstract]. Epilepsia 1987; 28: 598

    Article  Google Scholar 

  57. Barabas G, Mathews W. Barbiturate anticonvulsant as a cause of severe depression. Pediatrics 1988; 82: 284–5

    PubMed  CAS  Google Scholar 

  58. Hawton K, Fagg J, Marsack P. Association between epilepsy and attempted suicide. J Neurol Neurosurg Psychiatry 1980; 43: 168–70

    Article  PubMed  CAS  Google Scholar 

  59. Calandre EP, Dominguez-Granados R, Gomez-Rubio M, et al. Cognitive effects of long-term treatment with Phenobarbital and valproic acid in school children. Acta Neurologica Scandinavica 1990; 81: 504–6

    Article  PubMed  CAS  Google Scholar 

  60. Kanner A, Weisbrot D. Psychiatric evaluation of the patient with epilepsy: a practical approach for the “Nonpsychiatrists”. In: Ettinger A, Kanner A, editors. Psychiatric issues in epilepsy: a practical guide to diagnosis and treatment. Philadelphia (PA): LWW, 2001: 19–43

    Google Scholar 

  61. Brown SW. Dementia and epilepsy. In: Trimble M, Schmitz B, editors. The neuropsychiatry of epilepsy. Cambridge: Cambridge University Press, 2002: 135–51

    Chapter  Google Scholar 

  62. Barry JJ, Lembke A, Huynh N. Affective disorders in epilepsy. In: Ettinger A, Kanner A, editors. Psychiatric issues in epilepsy: a practical guide to diagnosis and treatment. Philadelphia (PA): LWW, 2001: 45–71

    Google Scholar 

  63. Barry JJ. The recognition and management of mood disorders as a comorbidity of epilepsy. Epilepsia 2003; 44Suppl. 4: 30–40

    Article  PubMed  Google Scholar 

  64. Reynolds E, Chanarin I, Milner G, et al. Anticonvulsant therapy, folic acid and vitamin B12 metabolism and mental symptoms. Epilepsia 1966; 7: 261–70

    Article  PubMed  CAS  Google Scholar 

  65. Fröscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995; 18: 165–82

    Article  PubMed  Google Scholar 

  66. Devinsky O. Cognitive and behavioral effects of antiepileptic drugs. Epilepsia 1995; 36Suppl. 2: 46–65

    Article  Google Scholar 

  67. Devinsky O, D’Esposito M. Neurology of cognitive and behavioral disorders. New York: Oxford University Press, 2004: 451

    Google Scholar 

  68. Biggs CS, Pearce BR, Fowler LJ, et al. Regional effects of sodium valproate on extracellular concentrations of 5-hydroxytryptamine, dopamine, and their metabolites in the rat brain: an in vivo microdialysis study. J Neurochem 1992; 59: 1702–8

    Article  PubMed  CAS  Google Scholar 

  69. Parnas J, Flachs H, Gram L. Psychotropic effect of antiepileptic drugs. Acta Neurologica Scand 1979; 60: 329–43

    Article  CAS  Google Scholar 

  70. Lefkowitz MM. Effects of diphenylhydantoin on disruptive behaviour. Arch Gen Psychiatry 1969; 20: 643–51

    Article  PubMed  CAS  Google Scholar 

  71. Malitz S, Kanzler M. Are antidepressants better than placebo? Am J Psychiatry 1971 Jun; 127(12): 1605–11

    PubMed  CAS  Google Scholar 

  72. Aldenkampf AP. Antiepileptic drug treatment and epileptic seizure effect on cognitive function. In: Trimble M, Schmitz B, editors. The Neuropsychiatry of Epilepsy. Cambridge: Cambridge University Press, 2002: 256–267

    Chapter  Google Scholar 

  73. Aldenkampf AP, De Krom M, Reijs R. Newer antiepileptic drugs and cognitive issues. Epilepsia 2003; 44Suppl. 4: 21–9

    Article  Google Scholar 

  74. Ortinski P, Meador KJ. Cognitive side effects of antiepileptic drugs. Epilepsy Behav 2004; 5Suppl. 1: 60–5

    Article  Google Scholar 

  75. Reijs R, Aldenkampf AP, De Krom M. Mood effects of antiepileptic drugs. Epilepsy Behav 2004; 5Suppl. 1: 66–76

    Article  Google Scholar 

  76. Yan QS, Mishra PK, Burger RL, et al. Evidence that carbamazepine and antiepilepsirine may produce a component of their anticonvulsant effects by activating serotonergic neurons in genetically epilepsy-prone rats. J Pharmacol Exp Ther 1992; 261: 652–9

    PubMed  CAS  Google Scholar 

  77. Dailey JW, Reith ME, Yan QS, et al. Carbamazepine increases extracellular serotonin concentration: lack of antagonism by tetrodoxin or zero Ca2+. Eur J Pharmacology 1997; 328: 153–62

    Article  CAS  Google Scholar 

  78. Grunze H, Amann B, Walden J. How might anticonvulsant drugs work in bipolar affective disorders. In: Trimble M, Schmitz B, editors. Seizures, affective disorders and anticonvulsant drugs. Guildford: Clarius Press Ltd, 2002: 117–30

    Google Scholar 

  79. Mclean MJ. Oxcarbazepine. Mechanisms of action. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 452–8

    Google Scholar 

  80. Kanner A. Is major depression a neurologic disorder with psychiatric symptoms? Epilepsy Behav 2004; 5: 636–44

    Article  PubMed  Google Scholar 

  81. Jobe P, Browning R. The serotonergic and noradrenergic effects of antidepressant drugs are anticonvulsant, not proconvulsant. Epilepsy Behav 2005; 7: 602–19

    Article  PubMed  Google Scholar 

  82. Stein G. Drug treatment of the personality disorders. British J Psychiatry 1992; 161: 167–84

    Article  CAS  Google Scholar 

  83. Dalby MA. Antiepileptic and psychotropic effect of carbamazepine (Tegretol) in the treatment of psychomotor epilepsy. Epilepsia 1971; 12: 325–34

    Article  PubMed  CAS  Google Scholar 

  84. Dodrill CB, Troupin AS. Psychotropic effects of carbamazepine in epilepsy: a double-blind comparison with phenytoin. Neurology 1977; 27: 1023–8

    Article  PubMed  CAS  Google Scholar 

  85. Dodrill CB, Troupin AS. Psychotropic effects of carbamazepine and phenytoin: a reanalysis. Neurology 1991; 41: 141–3

    Article  PubMed  CAS  Google Scholar 

  86. Bialer M. Oxcarbazepine. Chemistry, biotransformation, and pharmacokinetics. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 459–65

    Google Scholar 

  87. Clinckers R, Smolders I, Meurs A, et al. Quantitative in vivo microdialysis study on the influence of multidrug transporters on the blood-brain barrier passage of oxcarbazepin: concomitant use of hippocampal monoamines as pharmacodynamic markers for the anticonvulsant activity. J Pharm Exp Ther 2005; 314: 725–31

    Article  CAS  Google Scholar 

  88. Besag FM. Behavioral effect of the new anticonvulsants. Drug Saf 2000; 24: 513–36

    Article  Google Scholar 

  89. Aikia M, Kalviainen R, Sivenius J, et al. Cognitive effects of oxcarbazepine and phenytoin monotherapy in newly diagnosed epilepsy: one year follow-up. Epilepsy Research 1992; 11: 199–203

    Article  PubMed  CAS  Google Scholar 

  90. Laaksonen R, Kaimola K, Grahn-Teräväionen E, et al. A controlled clinical trial of the effects of carbamazepine and oxcarbazepine on memory and attention [abstract]. 16th International Epilepsy Congress; 1985 Sep 6-9; Hamberg

  91. Sabers A, Moller A, Dam M, et al. Cognitive function and anticonvulsant therapy: effect of monotherapy in epilepsy. Acta Neurol Scand 1995; 92: 19–27

    Article  PubMed  CAS  Google Scholar 

  92. Curran HV, Java R. Memory and psychomotor effects of oxcarbazepine in healthy human volunteers. Eur J Clin Pharmacology 1993; 44: 529–33

    Article  CAS  Google Scholar 

  93. Gillham RA, McKee PJW, Brodie MJ. Oxcarbazepine and cognitive function after a single dose and during double-blind placebo-controlled cross-over study [abstract]. Epilepsia 1993; 34Suppl. 2: 122

    Google Scholar 

  94. Krämer G. Oxcarbazepine. Adverse effects. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 479–86

    Google Scholar 

  95. Lösher W. Valproic acid. Mechanisms of action. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 767–79

    Google Scholar 

  96. Whitton PS, Oreskovic D, Jernej B, et al. Effect of valproic acid on 5-hydroxytryptamine turnover in mouse brain. J Pharm Pharmacology 1985; 37: 199–200

    Article  CAS  Google Scholar 

  97. Maes M, Calabrese J, Jayathilake K, et al. Effects of subchronic treatment with valproate on L-5-HTP-induced cortisol responses in mania: evidence for increased central serotonergic neurotransmission. Psychiatry Res 1997; 71: 67–76

    Article  PubMed  CAS  Google Scholar 

  98. Swann AC. Valproic acid: clinical efficacy and use in psychiatric disorders. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic Drugs. 5th edition. Philadelphia (PA): LWW, 2002: 828–36

    Google Scholar 

  99. Pies R, Adler DA, Ehrenberg BL. Sleep disorders and depression with atypical features: response to valproate. J Clin Psychopharmacology 1989; 9: 352–7

    Article  CAS  Google Scholar 

  100. Kemp LI. Sodium valproate as an antidepressant. Br J Psychiatry 1992; 160: 121–3

    Article  PubMed  CAS  Google Scholar 

  101. Davis LL, Kabel D, Patel D, et al. Valproate as an antidepressant in major depressive disorder. Psychopharmacol Bulletin 1996; 32: 647–52

    CAS  Google Scholar 

  102. Hollander E, Allen A, Lopez RP, et al. A preliminary double-blind, placebo-controlled trial of divalproex sodium in borderline personality disorder. J. Clin Psychiatry 2001; 62: 199–203

    Article  PubMed  CAS  Google Scholar 

  103. Lindenmayer JP, Kotsaftis A. Use of sodium valproate in violent and aggressive behaviors: a critical review. J Clin Psychiatry 2000; 61: 123–8

    Article  PubMed  CAS  Google Scholar 

  104. Kavoussi RJ, Coccaro EF. Divalproex sodium for impulsive aggressive behavior in patients with personality disorder. J Clin Psychiatry 1998; 59: 676–80

    Article  PubMed  CAS  Google Scholar 

  105. Trimble MR, Tompson PJ. Sodium valproate and cognitive function. Epilepsia 1984; 25Suppl. 1: S60–4

    Article  PubMed  Google Scholar 

  106. Genton P, Gelisse P. Valproic acid: adverse effects. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 837–51

    Google Scholar 

  107. Prevey ML, Delaney RC, Cramer JA, et al. Effect of valproate on cognitive functioning: comparison with carbamazepine. Arch Neurology 1996; 53: 1008–16

    Article  CAS  Google Scholar 

  108. Privitera MD, Twyman RE. Topiramate: clinical efficacy and use in epilepsy. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 740–52

    Google Scholar 

  109. Privitera M, Fincham R, Penry J, et al. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 600-, 800-, and 1000-mg daily dosages. Neurology 1996; 46: 1678–83

    Article  PubMed  CAS  Google Scholar 

  110. Faught E, Wilder BJ, Ramsay RE. Topiramate placebo-controlled dose ranging trial in refractory partial epilepsy using 200-, 400-, and 600-mg daily dosages. Neurology 1996; 46: 1684–90

    Article  PubMed  CAS  Google Scholar 

  111. White HS. Topiramate: mechanisms of action. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 719–26

    Google Scholar 

  112. Thompson PJ, Baxendale SA, Duncan JS, et al. Effects of topiramate on cognitive function. J Neurol Neurosurg Psychiatr 2000; 69: 636–41

    Article  PubMed  CAS  Google Scholar 

  113. Burton LA, Harden C. Effect of topiramate on attention. Epilepsy Research 1997; 27: 29–32

    Article  PubMed  CAS  Google Scholar 

  114. Aldencamp AP, Baker G, Mulder OG, et al. A multicentre randomized clinical study to evaluate the effect on cognitive function of topiramate compared with valproate as add-on therapy to carbamazepine in patients with partial-onset seizures. Epilepsia 2000; 41: 1167–78

    Article  Google Scholar 

  115. Mula M, Trimble MR, Sander JW. The role of hippocampal sclerosis in topiramate-related depression and cognitive deficits in people with epilepsy. Epilepsia 2003; 44(12): 1573–7

    Article  PubMed  Google Scholar 

  116. Mula M, Trimble MR, Lhatoo SD, et al. Topiramate and psychiatric adverse events in patients with epilepsy. Epilepsia 2003; 44: 659–63

    Article  PubMed  Google Scholar 

  117. Gould E. Serotonin and hippocampal neurogenesis. Neuropsychopharmacology 1999; 21Suppl.: S46–51

    Google Scholar 

  118. Toczek MT, Carson RE, Lang L, et al. PET imaging of 5-HT1A receptor binding in patients with temporal lobe epilepsy. Neurology 2003; 60: 749–56

    Article  PubMed  CAS  Google Scholar 

  119. Andermann F. Temporal pole and mesiotemporal epilepsy: introductory remarks. Epileptic disorders 2002; 4Suppl. 1: S7–8

    PubMed  Google Scholar 

  120. Kahane P, Chabardes S, Minotti L, et al. The role of temporal pole in the genesis of temporal lobe seizures. Epileptic disorders 2002; 4Suppl. 1: S51–8

    PubMed  Google Scholar 

  121. Abraham G. Topiramate-induced suicidality. Can J Psychiatry 2003; 48(2): 127–8

    PubMed  CAS  Google Scholar 

  122. Shorvon SD. Safety of topiramate: adverse events and relationship to dosing. Epilepsia 1996; 37(S2): 18–22

    Article  Google Scholar 

  123. Taylor CP. Gabapentin: mechanisms of action. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 321–34

    Google Scholar 

  124. Dimond KR, Pande AC, Lamoreus L, et al. Effect of gabapentin (Neurotin) on mood and well-being in patients with epilepsy. Prog Neuropsychopharmacol Biol Psychiatry 1996; 20: 407–17

    Article  PubMed  CAS  Google Scholar 

  125. Harden CL, Pick LH. Alterations in mood and anxiety in epilepsy patients treated with gabapentin [abstract]. Epilepsia 1996; 37(5): 137

    Google Scholar 

  126. Harden CL, Lazar LM, Pick LH, et al. A beneficial effect on mood in partial epilepsy patients treated with gabapentin. Epilepsia 1999; 40: 1129–34

    Article  PubMed  CAS  Google Scholar 

  127. Dodrill CB, Arnett JL, Hayes AG, et al. Cognitive abilities and adjustment with gabapentin: results of multisite study. Epilepsy Res 1999; 35: 109–21

    Article  PubMed  CAS  Google Scholar 

  128. Greist JH. Gabapentin: clinical efficacy and use in psychiatric disorders. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 349–59

    Google Scholar 

  129. Meador KJ, Loring DW, Ray PG, et al. Differential cognitive effects of carbamazepine and gabapentin. Epilepsia 1999; 40: 1279–85

    Article  PubMed  CAS  Google Scholar 

  130. Martin R, Meador K, Turrentine L, et al. Comparative cognitive effects of carbamazepine and gabapentin in healthy senior adults. Epilepsia 2001; 42: 764–71

    Article  PubMed  CAS  Google Scholar 

  131. Hudson JI, Pope HG. Affective spectrum disorder: does antidepressant response identify a family of disorders with a common pathophysiology? Am J Psychiatry 1990; 147(5): 552–64

    PubMed  CAS  Google Scholar 

  132. Frye MA, Ketter TA, Kimbrell TA, et al. A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. J Clin Psychopharmacol 2000; 20: 607–14

    Article  PubMed  CAS  Google Scholar 

  133. Giardina WJ. Tiagabine: mechanisms of action. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 675–80

    Google Scholar 

  134. Kälviäinen R. Tiagabine: clinical efficacy and use in epilepsy. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 698–704

    Google Scholar 

  135. Sveinbjornsdottir S, Sander J, Patsalos P, et al. Neuropsychological effects of tiagabine, a potential new antiepileptic drug. Seizure 1994; 3: 29–35

    Article  PubMed  CAS  Google Scholar 

  136. Dodrill CB, Arnett JL, Sommerville K, et al. Cognitive and quality of life effects of differing dosages of tiagabine in epilepsy. Neurology 1997; 48: 1025–31

    Article  PubMed  CAS  Google Scholar 

  137. Fritz N, Glogau S, Hoffmann J, et al. Efficacy and cognitive side effects of tiagabine and topiramate in patients with epilepsy. Epilepsy Behav 2005, 381

    Google Scholar 

  138. Pereira J, Marson AG, Hutton JL. Tiagabine add-on for drug resistant partial epilepsy. Cochrane Database Syst Rev 2002; 3: CD001908

    PubMed  Google Scholar 

  139. Grabowska-Grzyb A, Jedrzejczak J, Naganska E, et al. Risk factors for depression in patients with epilepsy. Epilepsy Behav 2006, 417

  140. Ben-Menachem E. Vigabatrin. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 855–63

    Google Scholar 

  141. Ferrie CD, Robinson RO, Panayitopoulos CP. Psychotic and severe behavioral reactions with vigabatrin: a review. Acta Neurol Scand 1996; 93: 1–8

    Article  PubMed  CAS  Google Scholar 

  142. Leach MJ, Randall AD, Stefani A, et al. Lamotrigine: mechanisms of action. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 363–9

    Google Scholar 

  143. Southam E, Kirkby D, Higgins GA, et al. Lamotrigine inhibits monoamine uptake in vitro and modulates 5-hydroxytryptamine uptake in rats. Eur J Pharmacolology 1998; 358: 19–24

    Article  CAS  Google Scholar 

  144. Smith D, Baker G, Davies G, et al. Outcomes of add-on treatment with lamotrigine in partial epilepsy. Epilepsia 1993; 34: 312–22

    Article  PubMed  CAS  Google Scholar 

  145. Brodie MJ, Richens A, Yuen AW, for the UK Lamotrigine/Carbamazepine Monotherapy Trial Group. Double blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. Lancet 1995; 345: 476–9

    Article  PubMed  CAS  Google Scholar 

  146. Edwards KR, Sackellares JC, Vuong A, et al. Lamotrigine monotherapy improves depressive symptoms in epilepsy: a double-blind comparison with valproate. Epilepsy Behav 2001; 2: 28–36

    Article  PubMed  Google Scholar 

  147. Cramer JA, Hammer AE, Kustra RP. Improved mood states with lamotrigine in patients with epilepsy. Epilepsy Behav 2004; 5: 702–7

    Article  PubMed  Google Scholar 

  148. Cramer JA, Hammer AE, Kustra RP. Quality of life improvement with conversion to lamotrigine monotherapy. Epilepsy Behav 2004; 5: 224–30

    Article  PubMed  Google Scholar 

  149. Kockelmann E, Elger CE, Helmstaedter C. Cognitive profile of topiramate as compared with lamotrigine in epilepsy patients on antiepileptic drug polytherapy: relationships to blood serum levels and comedication. Epilepsy Behav 2004; 5: 716–21

    Article  PubMed  Google Scholar 

  150. Cramer JA, Van Hammee G, N132 Study Group. Maintenance of improvement in health-related quality of life during long-term treatment with levetiracetam. Epilepsy Behav 2003; 4: 118–23

    Article  PubMed  Google Scholar 

  151. French J, Edrich P, Cramer J. A systematic review of the safety profile of levetiracetam: a new antiepileptic drug. Epilepsy Res 2001; 47: 77–90

    Article  PubMed  CAS  Google Scholar 

  152. Mula M, Trimble MR, Yuen A, et al. Psychiatric adverse events during levetiracetam therapy. Neurology 2003; 61(5): 704–6

    Article  PubMed  CAS  Google Scholar 

  153. Macdonald RL. Zonisamide: mechanisms of action. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 867–72

    Google Scholar 

  154. Frampton JE, Scott LJ. Zonisamide: a review of its use in the management of partial seizures in epilepsy. CNS Drugs 2005; 19(4): 347–67

    Article  PubMed  CAS  Google Scholar 

  155. Lee BI. Zonisamide: adverse effects. In: Levy RH, Mattson RH, Meldrun B, et al., editors. Antiepileptic drugs. 5th ed. Philadelphia (PA): LWW, 2002: 892–8

    Google Scholar 

  156. Miyamoto T, Kohsaka M, Koyama T. Psychotic episodes during zonisamide treatment. Seizure 2000; 9(1): 65–70

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

No sources of funding were used to assist in the preparation of this review. The author has no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Department of Brain Organic Disorders and Epilepsy, Moscow Research Institute of Psychiatry, Ministry of Health and Social Development, 107076 Poteshnaya Str. 3, Moscow, Russia

    Vladimir V. Kalinin

Authors
  1. Vladimir V. Kalinin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vladimir V. Kalinin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kalinin, V.V. Suicidality and Antiepileptic Drugs. Drug-Safety 30, 123–142 (2007). https://doi.org/10.2165/00002018-200730020-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-200730020-00003

Keywords

Search

Navigation