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Thirty Years of Clinical Experience with Carbamazepine in the Treatment of Bipolar Illness

Principles and Practice

Abstract

Carbamazepine began to be studied in a systematic fashion in the 1970s and became more widely used in the treatment of bipolar disorder in the 1980s. Interest in carbamazepine has been renewed by (i) the recent US FDA approval of a long-acting preparation for the treatment of acute mania; (ii) studies suggesting some efficacy in bipolar depression; and (iii) evidence of prophylactic efficacy in some difficult-to-treat subtypes of bipolar illness. A series of double-blind controlled studies of the drug were conducted at the US National Institute of Mental Health from the mid-1970s to the mid-1990s. This review summarises our experience in the context of the current literature on the clinical efficacy, adverse effects and pharmacokinetic interactions of carbamazepine.

Carbamazepine has an important and still evolving place in the treatment of acute mania and long-term prophylaxis. It may be useful in individuals with symptoms that are not responsive to other treatments and in some subtypes of bipolar disorder that are not typically responsive to a more traditional agent such as lithium. These subtypes might include those patients with bipolar II disorder, dysphoric mania, substance abuse co-morbidity, mood incongruent delusions, and a negative family history of bipolar illness in first-degree relatives. In addition, carbamazepine may be useful in patients who do not adequately tolerate other interventions as a result of adverse effects, such as weight gain, tremor, diabetes insipidus or polycystic ovarian syndrome.

We review our clinical and research experience with carbamazepine alone and in combination with lithium, valproic acid and other agents in complex combination treatment of bipolar illness. More precise clinical and biological predictors and correlates of individual clinical responsiveness to carbamazepine and other mood stabilisers are eagerly awaited.

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Notes

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    The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. 1.

    Ballenger JC, Post RM. Kindling as a model for alcohol withdrawal syndromes. Br J Psychiatry 1978; 133: 1–14

  2. 2.

    Post RM, Rubinow DR, Ballenger JC. Conditioning, sensitization, and kindling: implications for the course of affective illness. In: Post RM, Ballenger JC, editors. Neurobiology of mood disorders. Baltimore (MD): Williams and Wilkins, 1984: 432–66

  3. 3.

    Post RM, Uhde TW, Ballenger JC, et al. Carbamazepine, temporal lobe epilepsy, and manic-depressive illness. In: Mendlewicz J, Van Praag HM, editors. Advances in biological psychiatry. Vol. 8: temporal lobe epilepsy, mania, schizophrenia, and the limbic system. Basel: S. Karger AG, 1982: 117–56

  4. 4.

    Post RM, Uhde TW, Putnam FW, et al. Kindling and carbamazepine in affective illness. J Nerv Ment Dis 1982; 170: 717–31

  5. 5.

    Albright PS, Burnham WM. Development of a new pharmacological seizure model: effects of anticonvulsants on cortical-and amygdala-kindled seizures in the rat. Epilepsia 1980; 21: 681–9

  6. 6.

    Babington RG. The pharmacology of kindling. In: Hanin I, Usdin E, editors. Animal models of psychiatry and neurology. Oxford: Pergamon Press, 1977: 141–9

  7. 7.

    Papez JW. A proposed mechanism of emotion. Arch Neurol Psychiatry 1937; 38: 725–43

  8. 8.

    MacLean PD. The triune brain in conflict. Psychother Psychosom 1977; 28: 207–20

  9. 9.

    Marjerrison G, Jedlicki SM, Keogh RP, et al. Carbamazepine: behavioral, anticonvulsant and EEG effects in chronically-hospitalized epileptics. Dis Nerv Syst 1968; 29: 133–6

  10. 10.

    Penry JK, Daly DD. Complex partial seizures and their treatment: advances in neurology. Vol. 11. New York: Raven Press, 1975

  11. 11.

    Post RM, Uhde TW. Are the psychotropic effects of carbamazepine in manic-depressive illness mediated through the limbic system? Psychiatr J Univ Ottawa 1985; 10: 205–19

  12. 12.

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

  13. 13.

    Dalby MA. Behavioral effects of carbamazepine. In: Penry JK, Daly DD, editors. Complex partial seizures and their treatment: advances in neurology. Vol. 11. New York: Raven Press, 1975: 331–43

  14. 14.

    Okuma T, Kishimoto A, Inoue K, et al. Anti-manic and prophylactic effects of carbamazepine (Tegretol) on manic depressive psychosis: a preliminary report. Folia Psychiatr Neurol Jpn 1973; 27: 283–97

  15. 15.

    Okuma T, Kishimoto A. A history of investigation on the mood stabilizing effect of carbamazepine in Japan. Psychiatry Clin Neurosci 1998; 52: 3–12

  16. 16.

    Takezaki H, Hanaoka M. The use of carbamazepine (Tegretol) in the control of manic-depressive psychosis and other manic, depressive states. Clin Psychiatry 1971; 13: 173–82

  17. 17.

    Ballenger JC, Post RM. Therapeutic effects of carbamazepine in affective illness: preliminary report. Commun Psychopharmacol 1978; 2: 159–75

  18. 18.

    Ballenger JC, Post RM. Carbamazepine in manic-depressive illness: a new treatment. Am J Psychiatry 1980; 137: 782–90

  19. 19.

    Post RM, Uhde TW, Ballenger JC, et al. Prophylactic efficacy of carbamazepine in manic-depressive illness. Am J Psychiatry 1983; 140: 1602–4

  20. 20.

    Post RM, Uhde TW, Roy-Byrne PP, et al. Antidepressant effects of carbamazepine. Am J Psychiatry 1986; 143: 29–34

  21. 21.

    Post RM, Uhde TW, Roy-Byrne PP, et al. Correlates of anti-manic response to carbamazepine. Psychiatry Res 1987; 21: 71–83

  22. 22.

    Post RM, Luckenbaugh DA. Unique design issues in clinical trials of patients with bipolar affective disorder. J Psychiatr Res 2003; 37: 61–73

  23. 23.

    Okuma T, Inanaga K, Otsuki S, et al. Comparison of the antimanic efficacy of carbamazepine and chlorpromazine: a double-blind controlled study. Psychopharm 1979; 66: 211–7

  24. 24.

    Grossi E, Sacchetti E, Vita A, et al. Carbamazepine vs chlorpromazine in mania: a double-blind trial. In: Emrich HM, Okuma T, Muller AA, editors. Anticonvulsants in affective disorders. Amsterdam: Excerpta Medica, 1984: 177–87

  25. 25.

    Klein E, Bental E, Lerer B, et al. Carbamazepine and haloperidol vs placebo and haloperidol in excited psychoses. Arch Gen Psychiatry 1984; 41: 165–70

  26. 26.

    Goncalves N, Stoll KD. Carbamazepine in manic syndromes: a controlled double-blind study. Nervenarzt 1985; 56: 43–7

  27. 27.

    Lenzi A, Lazzerini F, Grossi E, et al. Use of carbamazepine in acute psychosis: a controlled study. J Int Med Res 1986; 14: 78–84

  28. 28.

    Stoll KD, Bisson HE, Fischer E, et al. Carbamazepine versus haloperidol in manic syndromes: first report of a multicentric study in Germany. In: Shagass C, Josiassen RC, Bridger WH, et al., editors. Biological Psychiatry 1985. Amsterdam: Elsevier Science Publishing Co. Inc., 1986: 332–4

  29. 29.

    Desai NG, Gangadhar BN, Channabasavanna SM, et al. Carbamazepine hastens therapeutic action of lithium in mania. Proceedings of the International Conference on New Directions in Affective Disorders. 1987 Apr 5–9; Jerusalem. New York: Springer Verlag, 1987: 97

  30. 30.

    Lerer B, Moore N, Meyendorff E, et al. Carbamazepine versus lithium in mania: a double-blind study. J Clin Psychiatry 1987; 48: 89–93

  31. 31.

    Lusznat RM, Murphy DP, Nunn CM. Carbamazepine vs lithium in the treatment and prophylaxis of mania. Br J Psychiatry 1988; 153:198–204

  32. 32.

    Okuma T, Yamashita I, Takahashi R, et al. A double-blind study of adjunctive carbamazepine versus placebo on excited states of schizophrenic and schizoaffective disorders. Acta Psychiatr Scand 1989; 80: 250–9

  33. 33.

    Brown D, Silverstone T, Cookson J. Carbamazepine compared to haloperidol in acute mania. Int Clin Psychopharmacol 1989; 4: 229–38

  34. 34.

    Moller HJ, Kissling W, Riehl T, et al. Double-blind evaluation of the antimanic properties of carbamazepine as a comedication to haloperidol. Prog Neuropsychopharmacol Biol Psych 1989; 13: 127–36

  35. 35.

    Okuma T, Yamashita I, Takahashi R, et al. Comparison of the antimanic efficacy of carbamazepine and lithium carbonate by double-blind controlled study. Pharmacopsychiatry 1990; 23: 143–50

  36. 36.

    Small JG, Klapper MH, Milstein V, et al. Carbamazepine compared with lithium in the treatment of mania. Arch Gen Psychiatry 1991; 48: 915–21

  37. 37.

    Weisler RH, Kalali AH, Ketter TA. A multicenter, randomized, double-blind, placebo-controlled trial of extended-release carbamazepine capsules as monotherapy for bipolar disorder patients with manic or mixed episodes. J Clin Psychiatry 2004; 65: 478–84

  38. 38.

    Weisler RH, Keck Jr PE, Swann AC, et al. Extended-release carbamazepine capsules as monotherapy for acute mania in bipolar disorder: a multicenter, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2005; 66: 323–30

  39. 39.

    Zhang ZJ, Kang WH, Tan QR, et al. Adjunctive herbal medicine with carbamazepine for bipolar disorders: a double-blind, randomized, placebo-controlled study. J Psychiatr Res 2007; 41: 360–9

  40. 40.

    Post RM, Speer AM. A brief history of anticonvulsant use in affective disorders. In: Trimble MR, Schmitz B, editors. Scizures, affective disorders and anticonvulsant drugs. Surrey: Clarius Press, 2002: 53–81

  41. 41.

    Licht RW. Drug treatment of mania: a critical review. Acta Psychiatr Scand 1998; 97: 387–97

  42. 42.

    Greil W, Kleindienst N, Erazo N, et al. Differential response to lithium and carbamazepine in the prophylaxis of bipolar disorder. J Clin Psychopharmacol 1998; 18: 455–60

  43. 43.

    Calabrese JR, Shelton MD, Rapport DJ, et al. A 20-month, double-blind, maintenance study of lithium vs divalproex in rapid cycling bipolar disorder. Am J Psychiatry 2005; 162: 2152–61

  44. 44.

    Post RM, Berrettini WH, Uhde TW, et al. Selective response to the anticonvulsant carbamazepine in manic-depressive illness: a case study. J Clin Psychopharmacol 1984; 4: 178–85

  45. 45.

    Frye MA, Ketter TA, Leverich GS, et al. The increasing use of polypharmacotherapy for refractory mood disorders: 22 years of study. J Clin Psychiatry 2000; 61: 9–15

  46. 46.

    Frangou S, Raymont V, Bettany D. The Maudsley bipolar disorder project: a survey of psychotropic prescribing patterns in bipolar I disorder. Bipolar Disord 2002; 4: 378–85

  47. 47.

    Post RM, Speer AM, Leverich GS. Complex combination therapy: the evolution toward rational polypharmacy in lithium-resistant bipolar illness. In: Akiskal HS, Tohen M, editors. Bipolar psychopharmacotherapy: caring for the patient. London: John Wiley & Sons Ltd, 2006: 135–67

  48. 48.

    Kowatch RA, Sethuraman G, Hume JH, et al. Combination pharmacotherapy in children and adolescents with bipolar disorder. Biol Psychiatry 2003; 53: 978–84

  49. 49.

    Levine J, Chengappa KN, Brar JS, et al. Psychotropic drug prescription patterns among patients with bipolar I disorder. Bipolar Disord 2000; 2: 120–30

  50. 50.

    Kowatch RA, Fristad M, Birmaher B, et al. Treatment guidelines for children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2005; 44: 213–35

  51. 51.

    Keck Jr PE, Perlis RH, Otto MW, et al. The expert consensus guideline series: treatment of bipolar disorder 2004. Postgrad Med Special Rep 2004 Dec: 1–120

  52. 52.

    Post RM, Speer AM, Obrocea GV, et al. Acute and prophylactic effects of anticonvulsants in bipolar depression. Clin Neurosci Res 2002; 2: 228–51

  53. 53.

    Hartong EG, Moleman P, Hoogduin CA, et al. Prophylactic efficacy of lithium versus carbamazepine in treatment-naive bipolar patients. J Clin Psychiatry 2003; 64: 144–51

  54. 54.

    Denicoff KD, Smith-Jackson EE, Disney ER, et al. Comparative prophylactic efficacy of lithium, carbamazepine, and the combination in bipolar disorder. J Clin Psychiatry 1997; 58: 470–8

  55. 55.

    Bowden CL, Calabrese JR, Sachs G, et al. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Arch Gen Psychiatry 2003; 60: 392–400

  56. 56.

    Calabrese JR, Bowden CL, Sachs G, et al. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. J Clin Psychiatry 2003; 64: 1013–24

  57. 57.

    Ketter TA, Calabrese JR. Stabilization of mood from below versus above baseline in bipolar disorder: a new nomenclature. J Clin Psychiatry 2002; 63: 146–51

  58. 58.

    Post RM, Altshuler LL. Mood disorders: treatment of bipolar disorders. In: Sadock BJ, Sadock VA, editors. Kaplan & Sadock’s comprehensive textbook of psychiatry. Philadelphia (PA): Lippincott Williams & Wilkins, 2005: 1661–707

  59. 59.

    Hogan RE, Garnett WR, Thadani VM. Tolerability and effects on quality of life of twice-daily extended-release carbamazepine in adults with seizure disorders: an open-label, 12- to 36-month continuation study. Clin Ther 2003; 25: 2586–96

  60. 60.

    Post RM. Extended-release carbamazepine: targeting acute bipolar mania. Curr Psychiatry 2005; 4: 72–80

  61. 61.

    Post RM, Weiss SR, Chuang DM. Mechanisms of action of anticonvulsants in affective disorders: comparisons with lithium. J Clin Psychopharmacol 1992; 12: 23–35S

  62. 62.

    Post RM, Chalecka-Franaszek E, Hough C. Mechanisms of action of anticonvulsants and new mood stabilizers. In: Soares JC, Gershon S, editors. Handbook of medical psychiatry. New York: Marcel Dekker, 2003: 767–91

  63. 63.

    Post RM, Chuang D-M. Mechanism of action of lithium: comparison and contrast with carbamazepine. In: Birch NJ, editor. Lithium and the cell: pharmacology and biochemistry. London: Academic Press, 1991: 199–241

  64. 64.

    Post RM, Weiss SRB, Chuang D-M, et al. Mechanisms of action of carbamazepine in seizure and affective disorders. In: Joffe RT, Calabrese JR, editors. Anticonvulsants in mood disorders. New York: Marcel Dekker, Inc., 1994: 43–92

  65. 65.

    Post RM, Weiss SRB, Clark M, et al. Lithium, carbamazepine, and valproate in affective illness: biochemical and neurobiological mechanisms. In: Manji H, Bowden CL, Belmaker RH, editors. Bipolar medications: mechanisms of action. Washington,DC: American Psychiatric Press, 2000: 219–48

  66. 66.

    Post RM, Leverich GS, Rosoff AS, et al. Carbamazepine prophylaxis in refractory affective disorders: a focus on long-term follow-up. J Clin Psychopharmacol 1990; 10: 318–27

  67. 67.

    Weiss SR, Clark M, Rosen JB, et al. Contingent tolerance to the anticonvulsant effects of carbamazepine: relationship to loss of endogenous adaptive mechanisms. Brain Res Brain Res Rev 1995; 20: 305–25

  68. 68.

    Post RM. Prophylaxis of bipolar affective disorders. Intl Rev Psych 1990; 2: 277–320

  69. 69.

    Post RM, Frye MA, Denicoff KD, et al. Anticonvulsants in the long-term prophylaxis of depression. In: Honig A, Van Praag HM, editors. Depression: neurobiological, psychopathological and therapeutic advances. Sussex: John Wiley & Sons, 1997: 483–98

  70. 70.

    Pazzaglia PJ, Post RM. Contingent tolerance and reresponse to carbamazepine: a case study in a patient with trigeminal neuralgia and bipolar disorder. J Neuropsychiatry Clin Neurosci 1992; 4: 76–81

  71. 71.

    Post RM, Weiss SRB. Convergences in course of illness and treatments of the epilepsies and recurrent affective disorders. Clin Electroencephalogr 2004; 35: 14–24

  72. 72.

    Post RM, Uhde TW, Ballenger JC, et al. Carbamazepine and its -10,11-epoxide metabolite in plasma and CSF: relationship to antidepressant response. Arch Gen Psychiatry 1983; 40: 673–6

  73. 73.

    Post RM, Uhde TW, Wolff EA. Profile of clinical efficacy and side effects of carbamazepine in psychiatric illness: relationship to blood and CSF levels of carbamazepine and its 10,11-epoxide metabolite. Acta Psychiatr Scand 1984; 69: 104–20

  74. 74.

    Ketter TA, Pazzaglia PJ, Post RM. Synergy of carbamazepine and valproic acid in affective illness: case report and review of the literature. J Clin Psychopharmacol 1992; 12: 276–81

  75. 75.

    Ketter TA, Wang PW, Post RM. Carbamazepine and oxcar-bazepine. In: Schatzberg AF, Nemeroff CB, editors. Textbook of psychopharmacology. Washington, DC: American Psychiatric Press, 2004: 581–606

  76. 76.

    Ketter TA, Flockhart DA, Post RM, et al. The emerging role of cytochrome P450 3A in psychopharmacology. J Clin Psychopharmacol 1995; 15: 387–98

  77. 77.

    Lammers MW, Hekster YA, Keyser A, et al. Neither dosage nor serum levels of antiepileptic drugs are predictive for efficacy and adverse effects. Pharm World Sci 1995; 17: 201–6

  78. 78.

    Bertilsson L, Tomson T. Clinical pharmacokinetics and pharmacological effects of carbamazepine and carbamazepine-10,11-epoxide: an update. Clin Pharmacokinet 1986; 11: 177–98

  79. 79.

    Ketter TA, Post RM, Worthington K. Principles of clinically important drug interactions with carbamazepine: part I. J Clin Psychopharmacol 1991; 11: 198–203

  80. 80.

    Ketter TA, Post RM, Worthington K. Principles of clinically important drug interactions with carbamazepine: part II. J Clin Psychopharmacol 1991; 11: 306–13

  81. 81.

    Ketter TA, Frye MA, Cora-Locatelli G, et al. Metabolism and excretion of mood stabilizers and new anticonvulsants. Cell Mol Neurobiol 1999; 19: 511–32

  82. 82.

    Hesslinger B, Normann C, Langosch JM, et al. Effects of carbamazepine and valproate on haloperidol plasma levels and on psychopathologic outcome in schizophrenic patients. J Clin Psychopharmacol 1999; 19: 310–5

  83. 83.

    Yatham LN, Grossman F, Augustyns I, et al. Mood stabilisers plus risperidone or placebo in the treatment of acute mania: international, double-blind, randomised controlled trial. Br J Psychiatry 2003; 182: 141–7

  84. 84.

    Crawford P. Interactions between antiepileptic drugs and hormonal contraception. CNS Drugs 2002; 16: 263–72

  85. 85.

    Kramlinger KG, Phillips KA, Post RM. Rash complicating carbamazepine treatment. J Clin Psychopharmacol 1994; 14: 408–13

  86. 86.

    Ketter TA, Kalali AH, Weisler RH. A 6-month, multicenter, open-label evaluation of beaded, extended-release carbamazepine capsule monotherapy in bipolar disorder patients with manic or mixed episodes. J Clin Psychiatry 2004; 65: 668–73

  87. 87.

    Vick NA. Suppression of carbamazepine-induced skin rash with prednisone [letter]. N Engl J Med 1983; 309: 1193–4

  88. 88.

    Murphy JM, Mashman J, Miller JD, et al. Suppression of carbamazepine-induced rash with prednisone. Neurology 1991; 41: 144–5

  89. 89.

    Coombes BW. Stevens-Johnson syndrome associated with carbamazepine (Tegretol). Med J Aust 1965; 1: 895–6

  90. 90.

    Rose SJ. Severe hypersensitivity secondary to extended carbamazepine administration [letter]. Clin Pharm 1985; 4: 19, 23

  91. 91.

    Sobotka JL, Alexander B, Cook BL. A review of carbamazepine’ s hematologic reactions and monitoring recommendations. DICP 1990; 24: 1214–9

  92. 92.

    Joffe RT, Post RM, Roy-Byrne PP, et al. Hematological effects of carbamazepine in patients with affective illness. Am J Psychiatry 1985; 142: 1196–9

  93. 93.

    Kramlinger KG, Post RM. Addition of lithium carbonate to carbamazepine: hematological and thyroid effects. Am J Psychiatry 1990; 147: 615–20

  94. 94.

    Boggs DR, Joyce RA. The hematopoietic effects of lithium. Semin Hematol 1983; 20: 129–38

  95. 95.

    Gram L, Bentsen KD. Hepatic toxicity of antiepileptic drugs: a review. Acta Neurol Scand Suppl 1983; 97: 81–90

  96. 96.

    Van Amelsvoort T, Bakshi R, Devaux CB, et al. Hyponatremia associated with carbamazepine and oxcarbazepine therapy: a review. Epilepsia 1994; 35: 181–8

  97. 97.

    Uhde TW, Post RM. Effects of carbamazepine on serum electrolytes: clinical and theoretical implications. J Clin Psychopharmacol 1983; 3: 103–6

  98. 98.

    Joffe RT, Post RM, Uhde TW. Effects of carbamazepine on serum electrolytes in affectively ill patients. Psychol Med 1986; 16: 331–5

  99. 99.

    Brewerton TD, Jackson CW. Prophylaxis of carbamazepine-induced hyponatremia by demeclocycline in six patients. J Clin Psychiatry 1994; 55: 249–51

  100. 100.

    Vieweg V, Glick JL, Herring S, et al. Absence of carbamazepine-induced hyponatremia among patients also given lithium. Am J Psychiatry 1987; 144: 943–7

  101. 101.

    Gold PW, Robertson GL, Ballenger JC, et al. Carbamazepine diminishes the sensitivity of the plasma arginine vasopressin response to osmotic stimulation. J Clin Endocrinol Metab 1983; 57: 952–7

  102. 102.

    Forrest Jr JN, Cohen AD, Torretti J, et al. On the mechanism of lithium-induced diabetes insipidus in man and the rat. J Clin Invest 1974; 53: 1115–23

  103. 103.

    Brown DW, Ketter TA, Crumlish J, et al. Carbamazepine-induced increases in total serum cholesterol: clinical and theoretical implications. J Clin Psychopharmacol 1992; 12: 431–7

  104. 104.

    O’Neill B, Callaghan N, Stapleton M, et al. Serum elevation of high density lipoprotein (HDL) cholesterol in epileptic patients taking carbamazepine or phenytoin. Acta Neurol Scand 1982; 65: 104–9

  105. 105.

    Bramswig S, Sudhop T, Luers C, et al. Lipoprotein(a) concentration increases during treatment with carbamazepine. Epilepsia 2003; 44: 457–60

  106. 106.

    Jones KL, Lacro RV, Johnson KA, et al. Pattern of malformations in the children of women treated with carbamazepine during pregnancy. N Engl J Med 1989; 320: 1661–6

  107. 107.

    Rosa FW. Spina bifida in infants of women treated with carbamazepine during pregnancy. N Engl J Med 1991; 324: 674–7

  108. 108.

    Sitland-Marken PA, Rickman LA, Wells BG, et al. Pharmacologic management of acute mania in pregnancy. J Clin Psychopharmacol 1989; 9: 78–87

  109. 109.

    Froescher W, Eichelbaum M, Niesen M, et al. Carbamazepine levels in breast milk. Ther Drag Monit 1984; 6: 266–71

  110. 110.

    Kuhnz W, Jager-Roman E, Rating D, et al. Carbamazepine and carbamazepine-10,11-epoxide during pregnancy and postnatal period in epileptic mothers and their nursed infants: pharma-cokinetics and clinical effects. Pediatric Pharmacol 1983; 3: 199–208

  111. 111.

    Pynnonen S, Kanto J, Sillanpaa M, et al. Carbamazepine: placental transport, tissue concentrations in foetus and newborn, and level in milk. Acta Pharmacol Toxicol (Copenh) 1977; 41: 244–53

  112. 112.

    Shimoyama R, Ohkubo T, Sugawara K. Monitoring of carbamazepine and carbamazepine 10,11-epoxide in breast milk and plasma by high-performance liquid chromatography. Ann Clin Biochem 2000; 37: 210–5

  113. 113.

    Frey B, Braegger CP, Ghelfi D. Neonatal cholestatic hepatitis from carbamazepine exposure during pregnancy and breast feeding. Ann Pharmacother 2002; 36: 644–7

  114. 114.

    Post RM. Valproate use in psychiatry: a focus on bipolar illness. In: Loscher W, editor. Valproate. Basel: Birkhauser Verlag, 1999: 167–201

  115. 115.

    Post RM, Frye MA. Carbamazepine. In: Sadock BJ, Sadock VA, editors. Kaplan & Sadock’s comprehensive textbook of psychiatry. Philadelphia (PA): Lippincott Williams & Wilkins, 2005: 2732–46

  116. 116.

    Calabrese JR, Vieta E, Shelton MD. Latest maintenance data on lamotrigine in bipolar disorder. Eur Neuropsychopharmacol 2003; 13 Suppl. 2: 57–66

  117. 117.

    Mattson RH, Cramer JA, Collins JF. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group. N Engl J Med 1992; 327: 765–71

  118. 118.

    Joffe RT, Post RM, Uhde TW. Effect of carbamazepine on body weight in affectively ill patients. J Clin Psychiatry 1986; 47: 313–4

  119. 119.

    Denicoff KD, Smith-Jackson EE, Bryan AL, et al. Valproate prophylaxis in a prospective clinical trial of refractory bipolar disorder. Am J Psychiatry 1997; 154: 1456–8

  120. 120.

    Rasgon N. The relationship between polycystic ovary syndrome and antiepileptic drags: a review of the evidence. J Clin Psychopharmacol 2004; 24: 322–34

  121. 121.

    Isojarvi JI, Tauboll E, Tapanainen JS, et al. On the association between valproate and polycystic ovary syndrome: a response and an alternative view. Epilepsia 2001; 42: 305–10

  122. 122.

    O’Donovan C, Kusumakar V, Graves GR, et al. Menstrual abnormalities and polycystic ovary syndrome in women taking valproate for bipolar mood disorder. J Clin Psychiatry 2002; 63: 322–30

  123. 123.

    Rasgon NL, Altshuler LL, Fairbanks L, et al. Reproductive function and risk for PCOS in women treated for bipolar disorder. Bipolar Disord 2005; 7: 246–59

  124. 124.

    MacPhee GJ, Larkin JG, Butler E. Circulating hormones and pituitary responsiveness in young epileptic men receiving long-term antiepileptic medication. Epilepsia 1988; 29: 468–75

  125. 125.

    Morrell MJ. Reproductive and metabolic disorders in women with epilepsy. Epilepsia 2003; 44 Suppl. 4: 11–20

  126. 126.

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

  127. 127.

    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

  128. 128.

    Yang JD, Elphick M, Sharpley AL, et al. Effects of carbamazepine on sleep in healthy volunteers. Biol Psychiatry 1989; 26: 324–8

  129. 129.

    Drake ME, Pakalnis A, Bogner JE, et al. Effects of antiepileptic drug monotherapy on nocturnal sleep. Epilepsia 1988; 29: 687

  130. 130.

    Lipper S, Davidson JRT, Grady TA, et al. Preliminary study of carbamazepine in post-traumatic stress disorder. Psychosomatics 1986; 27: 849–54

  131. 131.

    Marangell LB, George MS, Bissette G, et al. Carbamazepine increases cerebrospinal fluid thyrotropin-releasing hormone levels in affectively ill patients. Arch Gen Psychiatry 1994; 51: 625–8

  132. 132.

    Strandjord RE, Aanderad S, Myking OL, et al. Influence of carbamazepine on serum thyroxine and triiodothyronine in patients with epilepsy. Acta Neurol Scand 1981; 63: 111–21

  133. 133.

    Joffe RT, Gold PW, Uhde TW, et al. The effects of carbamazepine on the thyrotropin response to thyrotropin-releasing hormone. Psychiatry Res 1984; 12: 161–6

  134. 134.

    Roy-Byrne PP, Joffe RT, Uhde TW, et al. Carbamazepine and thyroid function in affectively ill patients. Clinical and theoretical implications. Arch Gen Psychiatry 1984; 41: 1150–3

  135. 135.

    Post RM, Rubinow DR, Uhde TW, et al. Dopaminergic effects of carbamazepine. Relationship to clinical response in affective illness. Arch Gen Psychiatry 1986; 43: 392–6

  136. 136.

    Silberman EK, Post RM, Nurnberger J, et al. Transient sensory, cognitive and affective phenomena in affective illness: a comparison with complex partial epilepsy. Br J Psychiatry 1985; 146: 81–9

  137. 137.

    Ali SO, Denicoff KD, Ketter TA, et al. Psychosensory symptoms in bipolar disorder. Neuropsychiatry Neuropsychol Behav Neurol 1997; 10: 223–31

  138. 138.

    Hayes SG, Goldsmith BK. Psychosensory symptomatology in anticonvulsant-responsive psychiatric illness. Ann Clin Psychiatry 1991; 3: 27–35

  139. 139.

    Hough C, Chuang DM. Carbamazepine acts through the peripheral benzodiazepine receptor to up-regulate β-adrenergic receptor mRNA. Soc Neurosci Abstracts 1995; 21: 1145

  140. 140.

    Montezinho LP, Castro MM, Duarte CB, et al. The interaction between dopamine D2-like and beta-adrenergic receptors in the prefrontal cortex is altered by mood-stabilizing agents. J Neurochem 2006; 96: 1336–48

  141. 141.

    Rubinow DR, Post RM, Gold PW, et al. Effect of carbamazepine on mean urinary free cortisol excretion in patients with major affective illness. Psychopharmacology (Berl) 1986; 88: 115–8

  142. 142.

    Osuch EA, Cora-Locatelli G, Frye MA, et al. Post-dexamethasone cortisol correlates with severity of depression before and during carbamazepine treatment in women but not men. Acta Psychiatr Scand 2001; 104: 397–401

  143. 143.

    Ketter TA, Kimbrell TA, George MS, et al. Baseline cerebral hypermetabolism associated with carbamazepine response, and hyponietabolism with nimodipine response in mood disorders. Biol Psychiatry 1999; 46: 1364–74

  144. 144.

    Grof P, Duffy A, Cavazzoni P, et al. Is response to prophylactic lithium a familial trait? J Clin Psychiatry 2002; 63: 942–7

  145. 145.

    Frye MA, Altshuler LL, McElroy SL, et al. Gender differences in prevalence, risk, and clinical correlates of alcoholism comorbidity in bipolar disorder. Am J Psychiatry 2003; 160: 883–9

  146. 146.

    Malcolm R, Myrick H, Roberts J, et al. The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial. J Gen Intern Med 2002; 17: 349–55

  147. 147.

    Ballenger JC, Post RM. Carbamazepine in alcohol withdrawal syndromes and schizophrenic psychoses. Psychopharmacol Bull 1984; 20: 572–84

  148. 148.

    Stuppaeck CH, Pycha R, Miller C, et al. Carbamazepine versus oxazepam in the treatment of alcohol withdrawal: a double-blind study. Alcohol Alcohol 1992; 27: 153–8

  149. 149.

    Chu NS. Carbamazepine: prevention of alcohol withdrawal seizures. Neurol 1979; 29: 1397–401

  150. 150.

    Malcolm R, Myrick H, Roberts J, et al. The differential effects of medication on mood, sleep disturbance, and work ability in outpatient alcohol detoxification. Am J Addict 2002; 11: 141–50

  151. 151.

    Kleindienst N, Greil W. Differential efficacy of lithium and carbamazepine in the prophylaxis of bipolar disorder: results of the MAP study. Neuropsychobiology 2000; 42 Suppl. 1: 2–10

  152. 152.

    Okuma T, Yamashita I, Takahashi R, et al. Clinical efficacy of carbamazepine in affective, schizoaffective, and schizophrenic disorders. Pharmacopsychiatry 1989; 22: 47–53

  153. 153.

    Post RM, Uhde TW. Anticonvulsants in non-epileptic psychosis. In: Trimble MR, Bolwig TG, editors. Aspects of epilepsy and psychiatry. Chichester: John Wiley and Sons, 1986: 177–212

  154. 154.

    Carpenter Jr WT, Kurz R, Kirkpatrick B, et al. Carbamazepine maintenance treatment in outpatient schizophrenics. Arch Gen Psychiatry 1991; 48: 69–72

  155. 155.

    Nachshoni T, Levin Y, Levy A, et al. A double-blind trial of carbamazepine in negative symptom schizophrenia. Biol Psychiatry 1994; 35: 22–6

  156. 156.

    Yassa R, Dupont D. Carbamazepine in the treatment of aggressive behavior in schizophrenic patients: a case report. Can J Psychiatry 1983; 28: 566–8

  157. 157.

    Patterson JF. Carbamazepine for assaultive patients with organic brain disease. Psychosomatics 1987; 28: 579–81

  158. 158.

    Patterson JF. A preliminary study of carbamazepine in the treatment of assaultive patients with dementia. J Geriatr Psychiatry Neurol 1988; 1: 21–3

  159. 159.

    Fichtner CG, Kuhlman DT, Gruenfeld MJ, et al. Decreased episodic violence and increased control of dissociation in a carbamazepine-treated case of multiple personality. Biol Psychiatry 1990; 27: 1045–52

  160. 160.

    Coons PM. The use of carbamazepine for episodic violence in multiple personality disorder and dissociative disorder not otherwise specified: two additional cases. Biol Psychiatry 1992; 32: 717–20

  161. 161.

    Keck PEJ, McElroy SL, Friedman LM. Valproate and carbamazepine in the treatment of panic and posttraumatic stress disorders, withdrawal states, and behavioral dyscontrol syndromes. J Clin Psychopharmacol 1992; 12: 36–41S

  162. 162.

    Brady KT, Sonne SC, Malcolm RJ, et al. Carbamazepine in the treatment of cocaine dependence: subtyping by affective disorder. Exp Clin Psychopharmacol 2002; 10: 276–85

  163. 163.

    Tohen M, Vieta E, Calabrese J, et al. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry 2003; 60: 1079–88

  164. 164.

    Calabrese JR, Keck Jr PE, Macfadden W, et al. A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry 2005; 162: 1351–60

  165. 165.

    March JS, Silva SG, Compton S, et al. The case for practical clinical trials in psychiatry. Am J Psychiatry 2005; 162: 836–46

  166. 166.

    Brodie MJ, Kwan P. The star systems: overview and use in determining antiepileptic drug choice. CNS Drugs 2001; 15: 1–12

  167. 167.

    Post RM, Ketter TA, Denicoff K, et al. Assessment of anticonvulsant drugs in patients with bipolar affective illness. In: Hindmarch I, Stonier PD, editors. Human psychopharmacology: methods and measures. Chichester: John Wiley & Sons, 1993: 211–45

  168. 168.

    Obrocea GV, Dunn RM, Frye MA, et al. Clinical predictors of response to lamotrigine and gabapentin monotherapy in refractory affective disorders. Biol Psychiatry 2002; 51: 253–60

  169. 169.

    Post RM, Kowatch RA. The heath care crisis of childhood onset bipolar illness: some recommendations for its amelioration. J Clin Psychiatry 2006; 67: 115–25

  170. 170.

    Kowatch RA, Suppes T, Carmody TJ, et al. Effect size of lithium, divalproex sodium, and carbamazepine in children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2000; 39: 713–20

  171. 171.

    Wagner KD, Kowatch RA, Emslie GJ, et al. A double-blind, randomised, placebo-controlled trial of oxcarbazepine in the treatment of bipolar disorder in children and adolescents. Am J Psychiatry 2006; 163(7): 1179–86

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Acknowledgements

This research was supported (in part) by the Intramural Research Program of the NIH, National Institutes of Mental Health.

Thomas Uhde has no conflicts of interest that are directly relevant to the content of this review. Robert Post and James Ballenger have received honoraria and consultancies from several pharmaceutical companies including Shire, GlaxoSmithKline, Bristol Myers Squibb, AstraZeneca and Abbott. Terence Ketter has received honoraria, consultancies and grants from a number of pharmaceutical companies including Shire.

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Correspondence to Prof. Terence A. Ketter.

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Post, R.M., Ketter, T.A., Uhde, T. et al. Thirty Years of Clinical Experience with Carbamazepine in the Treatment of Bipolar Illness. CNS Drugs 21, 47–71 (2007). https://doi.org/10.2165/00023210-200721010-00005

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Keywords

  • Bipolar Disorder
  • Carbamazepine
  • Valproic Acid
  • Lamotrigine
  • Oxcarbazepine