Summary
Psychotic patients not adequately relielved by neuroleptic drugs often improve when anticon-vulsants are added. In bipolar disorders and organic psychoses, anticonvulsants can sometimes be used to replace neuroleptics. No individual anticonvulsant is clearly, consistently superior. Patients who fail on one agent may improve on the next.
Clonazepam is an excellent adjunct to neuroleptic therapy, but there is little evidence that it is effective as monotherapy. However, it is safe, sedates rapidly, and has an excellent patient tolerability profile. Carbamazepine is the best established drug for patients with bipolar disorders, particularly for rapid cyclers, and is often effective monotherapy. The therapeutic profile of valproic acid (sodium valproate) is similar to that of carbamazepine, but its side effects are quite different and are often preferred. Other anticonvulsants are little studied, but might be chosen to avoid certain side effects, or after better-studied drugs have failed.
The pharmacological basis behind using anticonvulsants in psychoses is primarily empirical. In almost every case it has been clinicians who have first noted the beneficial effects of these drugs. Theories such as that of Post have followed.
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Altamura AC, Basile R, Mauri M, Cazzullo CL. Le valpromide (Depamide) dans le traitement d’etats psychotiques aigus. Une etude clinique ouverte. [Valpromide (Depamide) in the treatment of acute psychotic states. Open clinical study.] Acta Psychiatrica Belgica 86: 297–304, 1986
Altamura AC, Mauri MC, Mantero M, Brunetti M. Clonazepam/ haloperidol combination therapy in schizophrenia: a double blind study. Acta Psychiatrica Scandinavica 76: 702–706, 1987
Aronson TA, Shukla S, Hirschowitz J. Clonazepam treatment of five lithium-refractory patients with bipolar disorder. American Journal of Psychiatry 146: 77–80, 1989
Ballard CG. Successful therapeutic intervention in a schizophrenic patient with blepharospasm. Correspondence; comment. Journal of Neurology, Neurosurgery and Psychiatry 52: 1312, 1989
Ballenger JC. The use of anticonvulsants in manic-depressive illness. Journal of Clinical Psychiatry 49 (Suppl.): 21–25, 1988
Bhatia MS, Balkrishna, Singhai PK, Kaur N. Psychosis associated with anticonvulsant toxicity. Indian Pediatrics 24: 516–518, 1987
Brandwejn J, Shriqui C, Koszycki D, Meterissian G. Double-blind comparison of the effects of clonazepam and lorazepam in acute mania. Journal of Clinical Psychopharmacology 10: 403–408, 1990
Brodsky L, Shah A, Casenas E. Two distinct ‘paradoxical’ reactions to neuroleptics. Psychiatric Journal of the University of Ottawa 9: 61–64, 1984
Brown R. U.S. experience with valproate in manic depressive illness: a multicenter trial. Journal of Clinical Psychiatry 50 (Suppl.): 13–16, 1989
Budman CL, Vandersall TA. Clonazepam treatment of acute mania in an AIDS patient. Correspondence. Journal of Clinical Psychiatry 51: 212, 1990
Calabrese JR, Delucchi GA. Spectrum of efficacy of valproate in 55 patients with rapid-cycling bipolar disorder. American Journal of Psychiatry 147: 431–434, 1990
Calabrese JR, Markovitz PJ, Kimmel SE, Wagner SC. Spectrum of efficacy of valproate in 78 rapid cycling bipolar patients. Journal of Clinical Psychopharmacology 12 (Suppl. 1): 53S–56S, 1992
Carpenter WT Jr, Kurz R, Kirkpatrick B, Hanlon TE. Summerfelt AT, et al. Carbamazepine maintenance treatment in outpatient schizophrenics. Archives of General Psychiatry 48: 69–72, 1991
Chen PJ. Chung-Hua Shen Ching Ching Shen Ko Tsa Chih. [The efficacy and blood concentration monitoring of carbamazepine on mania.] Chinese Journal of Neurology and Psychiatry 23: 261–265, 318, 1990
Chouinard G. Clonazepam in acute and maintenance treatment of bipolar affective disorder. Journal of Clinical Psychiatry 48: 29–37, 1987
Chouinard G. The use of benzodiazepines in the treatment of manic-depressive illness. Journal of Clinical Psychiatry 49 (Suppl.): 15–20, 1988
Clothier J, Swann AC, Freeman T. Dysphoric mania. Journal of Clinical Psychopharmacology 12 (Suppl. 1): 13S–16S, 1992
Cohen S, Khan A, Johnson S. Pharmacological management of manic psychosis in an unlocked setting. Journal of Clinical Psychopharmacology 7: 261–264, 1987
Cohen LS, Rosenbaum JF. Clonazepam: new uses and potential problems. Journal of Clinical Psychiatry 48 (Suppl.): 50–56, 1987
Cold JA, Wells BG, Froemming JH. Seizure activity associated with antipsychotic therapy. DICP 24: 601–606, 1990
Coxhead N, Silverstone T, Cookson J. Carbamazepine versus lithium in the prophylmaxis of bipolar affective disorder. Acta Psychiatrica Scandinavica 85: 114–118, 1992
de Bard ML. Diazepam withdrawal syndrome: a case with psychosis, seizure, and coma. American Journal of Psychiatry 136: 104–105, 1979
de la Gandara Martin JJ, de Dios Francos A, Lopez Gomez I, Hernandez-Herrero H, Redondo-Martinez AL. Tratamiento de trastornos afectivos con clonazepan. [Treatment of affective disorders with clonazepam]. Actas Luso Espanolas de Neurologia, Psiquiatria y Ciencias Afines 19: 88–96, 1991
di Costanzo E, Schifano F. Lithium alone or in combination with carbamazepine for the treatment of rapid cycline bipolar affective disorder. Acta Psychiatrica Scandinavica 83: 456–459, 1991
Diehl LW. Psychosen bei Epilepsien. (Psychoses in epilepsy.) Psychiatrie, Neurologie und Medizinische Psychologie (Leipzig) 42: 513–537, 1990
Dose M, Apelt S, Emrieh HM. Carbamazepine as an adjunct of antipsychotic therapy. Psychiatry Research 22: 303–310, 1987
Dommisse J. Organic mania induced by phenytoin. Correspondence. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie 35: 457, 1990
Edwards R, Stephenson U, Flewett T. Clonazepam in acute mania: a double blind trial. Australian and New Zealand Journal of Psychiatry 25: 238–242, 1991
Engel J Jr. A practical guide for routine EEG studies in epilepsy. Journal of Clinical Neurophysiology 1: 109–142, 1984
Fawcett J. Valproate use in acute mania and bipolar disorder: an international perspective. Journal of Clinical Psychiatry 50 (Suppl.): 10–12, 1989
Franks RD, Richter AJ. Schizophrenia-like psychosis associated with anticonvulsant toxicity. American Journal of Psychiatry 136: 973–974, 1979
Freeman TW, Clothier JL, Pazzaglia P, Lesem MD, Swann AC. A double blind comparison of valproate and lithium in the treatment of acute mania. American Journal of Psychiatry 149: 108–111, 1992
Freyhan FA. Effectiveness of diphenylhydantoin in management of non-epileptic psychomotor excitement states. Archives of Neurology and Psychiatry 53: 370–374, 1945
Frykholm B. Clonazepam-antipsychotic effect in a case of schizophrenia-like psychosis with epilepsy and in three cases of atypical psychosis. Acta Psychiatrica Scandinavica 71: 539–542, 1985
Fukuzako H, Tominaga H, Izumi K, Koja T, Nomoto M, et al. Postural myoclonus associated with long-term administration of neuroleptics in schizophrenic patients. Biological Psychiatry 27: 1116–1126, 1990
Gerson SL, Lieberman JA, Friedenberg WR, Lee D, Marx JJ Jr, Meltzer H. Polypharmacy in fatal clozapine-associated agranulocytosis. Correspondence. Lancet 338: 262–3, 1991
Gross M. Pseudoepilepsy: a study in adolescent hysteria. American Journal of Psychiatry 136: 210–213, 1979
Gross RA, Herridge P. A maniclike illness associated with right frontal arteriovenous malformation. Journal of Clinical Psychiatry 49: 119–120, 1988
Hauser P, Devinsky O, De Bellis M, Theodore WH, Post RM. Benzodiazepine withdrawal delirium with catatonic features. Occurrence in patients with partial seizure disorders. Archives of Neurology 46: 696–699, 1989
Heh CW, Sramek J, Herrera J, Costa J. Exacerbation of psychosis after discontinuation of carbamazepine treatment. American Journal of Psychiatry 145: 878–879, 1988
Herrera JM, Sramek JJ, Costa JF. Efficacy of adjunctive carbamazepine in the treatment of chronic schizophrenia. Drug Intelligence and Clinical Pharmacy 21: 355–358, 1987
Horiguchi J, Inami Y, Effect of clonazepam on neuroleptic-in-duced oculogyric crisis. Acta Psychiatrica Scandinavica 80: 521–523, 1989
Iivanainen M, Bergstrom L, Nuutila A, Viukari-M. Psychosis-like absence status of elderly patients: successful treatment with sodium valproate. Journal of Neurology, Neurosurgery and Psychiatry 47: 965–969, 1984
Jarecke CR, De Moya VF, Ware MR. A case of mania secondary to hemodialysis: successful treatment with clonazepam. Correspondence. Journal of Clinical Psychopharmacology 10: 298–299,1990
Kallinowsky LB, Putnam TJ. Attempts at treatment of schizophrenia and other non-epileptic psychomotor psychoses with Dilantin. Archives of Neurology and Psychiatry 49: 414–420, 1943
Karson CN, Weinberger DR, Bigelow L, Wyatt RJ. Clonazepam treatment of chronic schizophrenia: negative results in a double-blind, placebo-controlled trial. American Journal of Psychiatry 139: 1627–1628, 1982
Kato H. Antiepileptic drugs and psychiatric disorders: mechanism involved in manifestation of psychic symptoms of high blood level of antiepileptics. Folia Psychiatrica et Neurologica Japonica 37: 283–289, 1983
Keats MM, Mukherjee S. Antiaggressive effect of adjunctive clonazepam in schizophrenia associated with seizure disorder. Journal of Clinical Psychiatry 49: 117–118, 1988
Klosterkotter J, Penin H. Epilepsiepsychosen und ihre medikamentose Behandlung. [Epileptic psychoses and their drug treatment.] Fortschritte der Neurologie-Psychiatrie 57: 61–69, 1989
Kluznik, JK: Diminution of polydypsia in schizophrenia following treatment with clozapine. American Psychiatric Association, Annual Meeting, May 15, 1991
Kostiukova EG. Sravnitel’nye osobennosti profilakticheskogo de-istviia karbamazepina i uglekislogo litiia pri affektivnykh i shi-zoaffektivnykh psikhozakh. [Comparative features of the preventive action of carbamazepine and lithium carbonate in affective and schizoaffective psychoses.] Zhurnal Nevropatologii i Psikhiatrii imeni S.S. Korsakova 89: 64–71, 1989.
Kramer MS. Menstrual epileptoid psychosis in an adolescent girl. American Journal of Diseases of Children 131: 316–317, 1977
Kramlinger KG, Post RM. Adding lithium carbonate to carbamazepine: antimanic efficacy in treatment-resistant mania. Acta Psychiatrica Scandinavica 79: 378–385, 1989
Kubanek JL, Rowell RC. The use of Dilantin in the treatment of psychotic patients unresponsive to other treatments. Diseases of the Nervous System 7: 47–50, 1946
Kutcher S, Williamson P, MacKenzie S, Marton P, Ehrlich M. Successful clonazepam treatment of neuroleptic-induced ak-athisia in older adolescents and young adults: a double-blind, placebo-controlled study. Journal of Clinical Psychopharmacology 9: 403–406, 1989
Leibovici A, Tariot PN. Carbamazepine treatment of agitation associated with dementia. Journal of Geriatric Psychiatry and Neurology 1: 110–112, 1988
Leinonen E, Lillsunde P, Laukkanen V, Ylitalo P. Effects of carbamazepine on serum antidepressant concentrations in psychiatric patients. Journal of Clinical Psychopharmacology 11: 313–318, 1991
Liu ZZ, Mei QY, Wan Y. Hua-Hsi I Ko Ta Hsueh Hsueh Pao. [A follow-up study on rapid cycling affective disorders.] Journal of West China University of Medical Sciences 20: 335–337, 1989
Marchevsky S, Isaacs G, Nitzan I. Behavioral disinhibition with clonazepam. Correspondence. General Hospital Psychiatry 10: 447, 1988
Martin-Munoz JC, Morinigo-Dominguez AV, Mateo-Martin I, Guajardo-Fajardo-Ibarra I, Noval-Lamos D. La carbamacepina: un tratamiento adjunto eficaz en las esquizofrenias. [Carbamazepine: an effective adjuvant treatment in the schizophrenias.] Actas Luso-Espanolas de Neurologia, Psiquiatria y Ciencias Afines 17: 245–250, 1989
Mauri M-C. Percudani M. Regazzetti M-G. Altamura A-C. Alternative prophylactic treatments to lithium in bipolar disorders. Clinical Neuropharmacology 13 (Suppl. 1): S90–96, 1990
McDanal Jr CE, Bolman WM. Delayed idiosyncratic psychosis with diphenylhydantoin. Journal of the American Medical Association 231: 1063, 1975
McElroy SL, Keck Jr PE, Pope Jr HG, Hudson JI, Morris D. Correlates of antimanic response to valproate. Psychopharmacology Bulletin 27: 127–133, 1991
McElroy SL, Keck PE Jr, Pope HG Jr, Hudson JI. Valproate in the treatment of bipolar disorder: literature review and clinical guidelines. Journal of Clinical Psychopharmacology 12 (Suppl. 1): 42S–52S, 1992
McFarland BH, Miller MR, Straumfjord AA. Valproate use in the older manic patient. Journal of Clinical Psychiatry 51: 479–481, 1990
McKee RJ, Larkin JG, Brodie MJ. Acute psychosis with carbamazepine and sodium valproate. Correspondence. Lancet 1(8630): 167, 1989
McKenna PJ, Kane JM, Parrish K. Psychotic syndromes in epilepsy. American Journal of Psychiatry 142: 895–904, 1985
Moller HJ, Kissling W, Riehl T, Bauml J, Binz U, Wendt G. Doubleblind evaluation of the antimanic properties of carbamazepine as a comedication to haloperidol. Progress in Neuro-Psychopharmacology and Biological Psychiatry 13: 127–136, 1989
Monroe RR. Limbic ictus and atypical psychoses. Journal of Nervous and Mental Diseases 170: 711–715, 1982
Morinigo A, Martin J, Gonzalez S, Mateo I. Treatment of resistant schizophrenia with valproate and neuroleptic drugs. Hillside Journal of Clinical Psychiatry 11: 199–207, 1989
Mosolov SN. [Comparative effectiveness of preventive use of lithium carbonate, carbamazepine and sodium valproate in affective and schizoaffective psychoses.] Zhurnal Nevropatologii i Psikhiatrii imeni S. S. Korsakova 91: 78–83, 1991
Okuma T, Yamashita I, Takahashi R, Itoh H, Kurihara M, et al. Clinical efficacy of carbamazepine in affective, schizoaffective, and schizophrenic disorders. Pharmacopsychiatry 22: 47–53, 1989a
Okuma T, Yamashita I, Takahashi R, Itoh H, Otsuki S, et al. A double-blind study of adjunctive carbamazepine versus placebo on excited states of schizophrenic and schizoaffective disorders. Acta Psychiatrica Scandinavica 80: 250–259, 1989b
Okuma T, Yamashita I, Takahashi R, Itoh H, Otsuki S, et al. Comparison of the antimanic efficacy of carbamazepine and lithium carbonate by double-blind controlled study. Pharmacopsychiatry 23: 143–150, 1990
Pakalnis A, Drake ME Jr, John K, Kellum JB. Forced normalization. Acute psychosis after seizure control in seven patients. Archives of Neurology 44: 289–292, 1987
Patten SB, Klein GM, Lussier C, Sawa R. Organic mania induced by phenytoin: a case report. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie 34: 827–828, 1989
Patterson JF. A preliminary study of carbamazepine in the treatment of assaultive patients with dementia. Journal of Geriatric Psychiatry and Neurology 1: 21–23, 1988
Peet M, Collier J. Use of carbamazepine in psychosis after neuroleptic malignant syndrome. British Journal of Psychiatry 156: 579–581, 1990
Pleak RR, Birmaher B, Gavrilescu A, Abichandani C, Williams DT. Mania and neuropsychiatric excitation following carbamazepine. Journal of the American Academy of Child and Adolescent Psychiatry 27: 500–503, 1988
Pope HG Jr, McElroy SL, Keck PE Jr, Hudson JI. Valproate in the treatment of acute mania. A placebo-controlled study. Archives of General Psychiatry 48: 62–68, 1991
Post RM. Time course of clinical effects of carbamazepine: implications for mechanisms of action. Journal of Clinical Psychiatry 49 (Suppl.): 35–48, 1988
Post RM, Weiss SR, Chuang DM. Mechanisms of action of anticon vulsants in affective disorders: comparisons with lithium. Journal of Clinical Psychopharmacology 12 (Suppl. 1): 23S–35S, 1992
Post RM. Sensitization and kindling perspectives for the course of affective illness: toward a new treatment with the anticon-vulsant carbamazepine. Pharmacopsychiatry 23: 3–17, 1990
Post RM, Leverich GS, Rosoff AS, Altshuler LL. Carbamazepine prophylaxis in refractory affective disorders: a focus on long-term follow-up. Journal of Clinical Psychopharmacology 10: 318–327, 1990
Post RM, Uhde TW, Roy-Byrne PP, Joffe RT. Correlates of antimanic response to carbamazepine. Psychiatry Research 21: 71–83, 1987
Richard P, Brenner RP. Absence status. Case reports and a review of the literature. Encephale 6: 385–392, 1980
Sandy R. Neuroleptic-induced, painful legs and moving toes, syndrome: successful treatment with clonazepam and baclofen. Italian Journal of Neurological Sciences 11: 573–576, 1990
Savard G, Andermann F, Olivier A, Remillard GM. Postictal psychosis after partial complex seizures: a multiple case study. Epilepsia 32: 225–231, 1991
Scher M, Neppe V. Carbamazepine adjunct for nonresponsive psychosis with prior hallucinogenic abuse. Journal of Nervous and Mental Disease 177: 755–757, 1989
Schnetzler JP, Preaubert G, Schnetzler F. L’association acide valproique-Diazepam (1) comme alternative au traitement neuroleptique. [A valproic acid-diazepam combination as an alternative to neuroleptic treatment.] Annales Medico-Psycho-logiques 146: 325–339, 1988
Small JG, Klapper MH, Milstein V. Kellams JJ, Miller MJ, et al. Carbamazepine compared with lithium in the treatment of mania. Archives of General Psychiatry 48: 915–921, 1991
Simopoulos AM, Pinto A, Ulenhuth EH, et al. Diphenylhydantoin: Effectiveness in the treatment of chronic schizophrenics. Archives of General Psychiatry 30: 106–111, 1974
Sitland-Marken PA, Rickman LA, Wells BG, Mabie WC. Pharmacologic management of acute mania in pregnancy. Journal of Clinical Psychopharmacology 9: 78–87, 1989
Smeraski PJ. Clonazepam treatment of multi-infarct dementia. Journal of Geriatric Psychiatry and Neurology 1: 47–48, 1989
Sovner R. The use of valproate in the treatment of mentally retarded persons with typical and atypical bipolar disorders. Journal of Clinical Psychiatry 50 (Suppl.): 40–43, 1989
Stevens JR. Psychiatric aspects of epilepsy. Journal of Clinical Psychiatry 49 (Suppl.): 49–57, 1988
Stone MH. The role of pharmacotherapy in the treatment of patients with borderline personality disorder. Psychopharmacology Bulletin 25: 564–571, 1989
Stuppaeck C, Barnas C, Miller C, Schwitzer J, Fleischhacker WW. Carbamazepine in the prophylaxis of mood disorders. Journal of Clinical Psychopharmacology 10: 39–42, 1990
Sultan S, Chouinard G, Beaudry P. Antiepileptic drugs in the treatment of neuroleptic-induced supersensitivity psychosis. Progress in Neuro-Psychopharmacology and Biological Psychiatry 14: 431–438, 1990
Tran-Johnson T, Herrera J, Sramek JJ, Costa JF, Heh C, Pi E. Time-dependent autoinduction of carbamazepine in schizophrenia. Correspondence. Drug Intelligence and Clinical Pharmacy 21: 835, 1987
Trimble MR. Psychiatric aspects of epilepsy. Psychiatric Developments 5: 285–300, 1987
Trimble MR. Cognitive hazards of seizure disorders. Epilepsia 29 (Suppl.): S19–24, 1988
Tyrer P, Seivewright N. Pharmacological treatment of personality disorders. Clinical Neuropharmacology 11: 493–499, 1988
Van Putten T, Marder SR, Wirshing WC, Aravagiri M, Chabert N. Neuroleptic plasma levels. Schizophrenia Bulletin 17: 197–216, 1991
Van Valkenburg C., Kluznik J, Merrill R, Erickson W. Therapeutic levels of valproate for psychosis. Psychopharmacology Bulletin 26: 254–255, 1990
Vencovsky E, Peterova E, Kabes J. [Preventive effect of dipro-pylacetamide in bipolar manic-depressive psychoses]. Die prophylaktische Wirkung von Dipropylazetamid bei bipolaren manisch-depressiven Psychosen. Psychiatrie, Neurologie und Medizinische Psychologie 39: 362–364, 1987
Vieweg WV, Weiss NM, David JJ, Rowe WT, Godleski LS, Spradlin WW. Treatment of psychosis, intermittent hypona-tremia, and polydipsia (PIP syndrome) using lithium and phenytoin. Biological Psychiatry 23: 25–30, 1988
Viswanathan R, Glickman L. Clonazepam in the treatment of steroid-induced mania in a patient after renal transplantation [letter]. New England Journal of Medicine 320: 319–320, 1989
Vovin R Ya, Skorik AI, Aksenova IO, Digilov AG, Firulev AA. Effektivnost’ finlepsina pri profilakticheskoi terapii fazno pro-tekaiushchikh affektivnykh psikhozov. [Effectiveness of finlepsin in the prophylactic therapy of phasic affective psychoses.] Zhurnal Nevropatologii i Psikhiatrii imeni S. S. Korsakova 87: 1396–1400, 1987
Wada Y, Kim Y, Yamaguchi N. Monosymptomatic hypochon-driacal psychosis: paroxysmal discharge in sleep and successful treatment with carbamazepine. Clinical Neuropharmacology 10: 568–572, 1987
Wells CE. Transient ictal psychosis. Archives of General Psychiatry 32: 1201–1203, 1975
Wessely P, Mayr N, Binder H, Klingler D. Neurologische Ausfallserscheinungen bei Diphenylhydantoin-Intoxikation. [Neurological signs in diphenylhydantoin intoxication (case reports and review) (author’s transl).] Wiener Klinische Wochenschrift 93: 315–321, 1981
Wetterling T. Open clinical trial of carbamazepine in chronic schizophrenic inpatients. Pharmacopsychiatry 20: 127–130, 1987
Wolf P. Acute behavioral symptomatology at disappearance of epileptiform EEG abnormality. Paradoxical or forced, normalization. Advances in Neurology 55: 127–142, 1991
Wolf P, Trimble MR. Biological antagonism and epileptic psychosis. British Journal of Psychiatry 146: 272–276, 1985
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Van Valkenburg, C., Kluznik, J. & Merrill, R. New Uses of Anticonvulsant Drugs in Psychosis. Drugs 44, 326–335 (1992). https://doi.org/10.2165/00003495-199244030-00003
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DOI: https://doi.org/10.2165/00003495-199244030-00003