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Psychiatric Symptoms of Epileptic Nature: An Old Hypothesis in Light of Current Psychopharmacologic Advances

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DOI: 10.4236/ojpsych.2015.51012    4,337 Downloads   4,781 Views  


This paper analyses a hypothesis according to which many positive psychiatric symptoms should be interpreted as symptoms of epileptic nature. When we first raised this proposition, almost fifteen years ago, it was inconsistent with the widespread conviction among psychiatrists that psychopharmacological drugs used to suppress psychiatric symptoms were proconvulsant. But lately, there have appeared numerous neuroscientific investigations that defend the anticonvulsant effect of most psychopharmacological drugs, hence supporting our hypothesis. We have carried out bibliographical reviews in search of the pro- or anticonvulsant role of these substances, particularly lithium, selective serotonin reuptake inhibitors, dual antidepressants, and antipsychotic drugs.These researches show abundant evidence regarding the anticonvulsant action of these substances, a fact that contributes to a better comprehension of paradoxical relationship between epilepsy and psychoses.

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Alvarez-Rodriguez, J. (2015) Psychiatric Symptoms of Epileptic Nature: An Old Hypothesis in Light of Current Psychopharmacologic Advances. Open Journal of Psychiatry, 5, 113-120. doi: 10.4236/ojpsych.2015.51012.


[1] Wilson, S.A. (1928) Modern Problems in Neurology. Edward Arnold, London.
[2] Ey, H. (1954) études Psychiatriques. Desclée de Brower, Paris.
[3] álvarez, J. (2001) Neuronal Hypersyncronization, Creativity and Endogenous Psychoses. Medical Hypotheses, 56, 672-685.
[4] Alvarez-Rodriguez, J., Alvarez-Silva, S. and Alvarez-Silva, I. (2005) Epilepsy and Psychiatry: Automatic Psychic Paroxysms. Medical Hypotheses, 65, 671-675.
[5] Alvarez-Rodriguez, J. (2014) Psychic Neuronal Hypersynchronies: A New Psychiatric Paradigm? Health (Irvine, California), 6, 2089-2099.
[6] Devinsky, O. and Luciano, D. (1991) Psychic Phenomena in Partial Seizures. Seminars in Neurology, 11, 100-109.
[7] Jaspers, K. (1997) General Psychopathology. The Johns Hopkins University Press, Baltimore.
[8] Mendez, M. (2000) Comprehensive Textbook of Psychiatry. In: Sadock, B. and Sadock, V., Eds., Neuropsychiatric Aspects of Epilepsy, Lippincott Williams & Wilkins, Philadelphia, 261-273.
[9] Clifford, D.B., Olney, J.W., Maniotis, A., Collins, R.C. and Zozumski, C.F. (1987) The Functional Anatomy and Pathology of Lithium-Pilocarpine and High-Dose Pilocarpine Seizures. Neuroscience, 23, 953-968.
[10] Pisani, F., Oteri, G., Costa, C., Di Raimondo, G. and Di Perri, R. (2002) Effects of Psychotropic Drugs on Seizure Threshold. Drug Safety, 25, 91-110.
[11] Rosenstein, D.L., Nelson, J.C. and Jacobs, S.C. (1993) Seizures Associated with Antidepressants: A Review. Journal of Clinical Psychiatry, 54, 289-299.
[12] Krishnamoorthy, E.S. (2003) Treatment of Depression in Patients with Epilepsy: Problems, Pitfalls, and Some Solutions. Epilepsy & Behavior, 4, S46-S54.
[13] Dailey, J.W. and Naritoku, D.K. (1996) Antidepressants and Seizures: Clinical Anecdotes Overshadow Neuroscience. Biochemical Pharmacology, 52, 1323-1329.
[14] Barry, J.J. (2003) The Recognition and Management of Mood Disorders as a Comorbidity of Epilepsy. Epilepsia, 44, 30-40.
[15] Cole, N. and Parker, G. (2012) Cade’s Identification of Lithium for Manic-Depressive Illness—The Prospector Who Found a Gold Nugget. Journal of Nervous & Mental Disease, 200, 1101-1104.
[16] Ghasemi, M. and Dehpour, A.R. (2011) The NMDA Receptor/Nitric Oxide Pathway: A Target for the Therapeutic and Toxic Effects of Lithium. Trends in Pharmacological Sciences, 32, 420-434.
[17] Li, B., Zhang, S., Li, M., Zhang, H., Hertz, L. and Peng, L. (2009) Down-Regulation of GluK2 Kainate Receptor Expression by Chronic Treatment with Mood-Stabilizing Anti-Convulsants or Lithium in Cultured Astrocytes and Brain, but Not in Neurons. Neuropharmacology, 57, 375-385.
[18] Young, W. (2009) Review of Lithium Effects on Brain and Blood. Cell Transplantation, 18, 951-975.
[19] Pérez-Siles, G., Morreale, A., Leo-Macías, A., Pita, G., Ortíz, AR. and Aragon, C. (2011) Molecular Basis of the Differential Interaction with Lithium of Glycine Transpoerters GLYT1 and GLTY2. Journal of Neurochemistry, 118, 195-204.
[20] Valdes, J.J. (2009) Estrogen and Lithium: Facilitating Factors Involved in Brain Cell Signaling Pathways. FIU Electronic Theses and Dissertations, Paper 105.
[21] Phiel, C.J., Zhang, F., Huang, E.Y., Guenther, M.G., Lazar, M.A. and Kein, P.S. (2001) Histone Deacetylase Is a Direct Target of Valproic acid, a Potent Anticonvulsant, Mood Stabilizer, and Teratogen. The Journal of Biological Chemistry, 276, 36734-36741.
[22] Andrini, O., Meinild, A.K., Ghezzi, C., Murer, H. and Forster, I.C. (2011) Lithium Interactions with Na+-Coupled Inorganic Phosphate Cotransporters: Insights into the Mechanism of Sequential Cation Binding. American Journal of Physiology-Cell Physiology, 302, C539-C554.
[23] Zhou, Y., Zomot, E. and Kanner, B.I. (2006) Identification of a Lithium Interaction Site in the Gamma-Aminobutyric Acid (GABA) Transporter GAT-1. The Journal of Biological Chemistry, 281, 22092-22099.
[24] Hong, L. and Bainbridge, J.L. (2014) Anticonvulsant Effects of SSRIs. Mental Health Clinician, 2, 19.
[25] Buchanan, G.F., Murray, N.M., Hajek, M.A. and Richerson, G.B. (2014) Serotonin Neurones Have Anti-Convulsant Effects and Reduce Seizure-Induced Mortality. The Journal of Physiology, 592, 4395-4410.
[26] Faingold, C.L. and Randall, M. (2013) Effects of Age, Sex, and Sertraline Administration on Seizure-Induced Respiratory Arrest in the DBA/1 Mouse Model of Sudden Unexpected Death in Epilepsy (SUDEP). Epilepsy & Behavior, 28, 78-82.
[27] Vermoesen, K., Massie, A., Smolders, I. and Clinckers, R. (2012) The Antidepressants Citalopram and Reboxetine Reduce Seizure Frequency in Rats with Chronic Epilepsy. Epilepsia, 53, 870-878.
[28] Mostert, J.P., Koch, M.W., Heerings, M., Heersman, D.J. and De Heyser, J. (2008) Therapeutic Potential of Fluoxetine in Neurological Disorders. CNS Neuroscience & Therapeutics, 14, 152-164.
[29] Magyar, J., Rusnák, Z., Harasztosi, C., K?rtvélv, A., Pacher, P. and Bánvász, T. (2003) Differential Effects of Fluoxetine Enantiomers in Mammalian Neural and Cardiac Tissues. International Journal of Molecular Medicine, 11, 535-542.
[30] Favale, E., Audenino, D., Cocito, L. and Albano, C. (2003) The Anticonvulsant Effect of Citalopram as an Indirect Evidence of Serotonergic Impairment in Human Epileptogenesis. Seizure, 12, 316-318.
[31] Jabourian, A.P., Erlich, M., Desvignes, C., el Hadjam, M. and Bitton, R. (1992) Panic Attacks and 24-Hour Ambulatory EEG Monitoring. Annales Médico-Psychologiques, 150, 240-244.
[32] Sakakihara, Y., Oka, A., Kubota, M. and Ohash, Y. (1995) Reduction of Seizure Frequency with Clomipramine in Patients with Complex Partial Seizures. Brain & Development, 17, 291-293.
[33] Yang, Y.-C. and Kuo, C.-C. (2002) Inhibition of Na+ Current by Imipramine and Related Compounds: Different Binding Kinetics as an Inactivation Stabilizer and as an Open Channel Blocker. Molecular Pharmacology, 62, 1228-1237.
[34] Jobe, P.C. and Browing, R.A. (2005) The Serotonergic and Noradrenergic Effects of Antidepressant Drugs Are Anticonvulsant, Not Proconvulsant. Epilepsy & Behavior, 7, 602-619.
[35] Alper, K., Schwaetz, K.A., Kilts, R.L. and Khan. A. (2007) Seizure Incidence in Psychopharmacological Clinical Trials: An Analysis of Food and Drug Administration (FDA) Summary Basis of Approval Reports. Biological Psychiatry, 62, 345-354.
[36] Borowicz, K.K., Golyaska, D., Luszczki, J.J. and Czuczwar, S.J. (2011) Effect of Acutely and Cronichally Administered Venlafaxine on the Anticonvulsant Action of Classical Antiepileptic Drugs in the Mouse Maximal Electroshock Model. European Journal of Pharmacology, 670, 114-120.
[37] Hedges, D., Jeppson, K. and Whitehead, P. (2003) Antipsychotic Medication and Seizures: A Review. Drugs of Today, 39, 551-557.
[38] de Leon, J. (2014) False-Negative Studies May Systematically Contaminate the Literature on the Effects of Inducers in Neuropsychopharmacology. Part I: Focus on Epilepsy. Journal of Clinical Psychopharmacology, 34, 177-183.
[39] Marx, C.E., VanDroren, M.J., Duncan, G.E., Lieberman, J.A. and Morrow, A.L. (2003) Olanzapine and Clozapine Increase the GABAergic Neuroactive Steroid Allopregnanolone in Rodents. Neuropsychopharmacology, 28, 1-13.
[40] Mead, A., Li, M. and Kapur, S. (2008) Clozapine and Olanzapine Exhibit an Intrinsic Anxiolytic Property in Two Conditioned Fear Paradigms: Contrast with Haloperidol and Chlordiazepoxide. Pharmacology Biochemistry and Behavior, 90, 551-562.
[41] Sun, T., He, W., Hu, G. and Li, M. (2010) Anxiolitic-Like Property of Risperidone and Olanzapine as Examined in Multiple Measures of Fear Rats. Pharmacology Biochemistry and Behavior, 95, 298-307.
[42] Rogóz, Z. and Skuza, G. (2011) Anxiolitic-Effects of Olanzapine, Risperidone and Fluoxetine in Elevated Plus-Maze Test in Rats. Pharmacological Reports, 63, 547-552.
[43] Kantrowitz, J. and Javvit, DC. (2012) Glutamatergic Transmission in Schizophrenia: From Basic Research to Clinical Practice. Current Opinion in Psychiatry, 52, 96-102.
[44] Moghaddam, B. and Javvit, D. (2012) From Revolution to Evolution: The Glutamatergic Hypothesis of Schizophrenia and Its Implication for Treatment. Neuropsychopharmacology, 37, 4-15.
[45] Sendt, K.V., Giarolly, G. and Tracy, D.K. (2012) Beyond Dopamine: Glutamate as a Target for Future Antipsychotics. ISRN Pharmacology, 2012, Article ID: 427267.
[46] Paz, R.D., Tardito, S., Atzori, M. and Tseng, K.Y. (2008) Glutamatergic Dysfunction in Schizophrenia: From Basic Neuroscience to Clinical Psychopharcology. European Neuropsychopharmacology, 18, 773-786.
[47] Diaz, F., Eap, C.B., Ansermot, N., Cretoll, S., Spina, E. and de Leon, J. (2014) Can Valproic Acid Be an Inducer of Clozapine Metabolism? Pharmacopsychiatry, 47, 89-96.
[48] Italiano, D., Spina, E. and de Leon, J. (2014) Pharmacokinetic and Pharmacodinamic Interactions between Antiepileptic and Antidepressant. Expert Opinion on Drug Metabolism & Toxicology, 10, 1457-1489.
[49] Cepeda, C., André, V.M., Jocoy, E.L. and Levine, M.S. (2009) NMDA and Dopamine: Diverse Mechanisms Applied to Interacting Receptors Systems. In: Van Dongen, A.M., Ed., Biology of the NMDA Receptor, Taylor and Francis Group, Boca Raton, 41-57.
[50] Uva, L., Librizzi, L., Wendling, F. and Curtis, M. (2005) Propagation Dynamics of Epileptiform Activity Acutely Induced by Bicuculline in the Hippocampal-Parahippocampal Region of the Isolated Guinea Pig Brain. Epilepsia, 46, 1914-1925.
[51] Gale, K. (1993) Focal Trigger and Pathways of Propagation in Seizure Generation. In: Schwartzkroin, P.A., Ed., Epilepsy: Models, Mechanisms and Concepts, Cambridge University Press, Cambridge, 48-93.
[52] Wilson, W.A. and Bragdon, A. (1993) Brain Slice Models for The Study of Seizures and Interictal Spikes. In: Schwartzkroin, P.A., Ed., Epilepsy: Models, Mechanisms and Concepts, Cambridge University Press, Cambridge, 371-387.
[53] Traynelis, S.F., Wollmuth, L.P., McBrain, C.J., Meniti, F.S., Vance, K.M. and Ogden, K.K. (2010) Glutamate Receptor Ions Channels: Structure, Regulation, and Function. Pharmacological Reviews, 62, 405-496.
[54] Starr, M.S. (1996) The Role of Dopamine in Epilepsy. Synapse, 22, 159-194.<159::AID-SYN8>3.0.CO;2-C
[55] Wolf, P. (1991) Acute Behavioral Symptomatology at Disappearance of Epileptiform EEG Abnormality. Paradoxical or “Forced” Normalization. Advances in Neurology, 55, 127-142.
[56] Pollock, D.C. (1987) Models for Understanding the Antagonism between Seizures and Psychosis. Progress in Neuro-Psychopharmacology Biological Psychiatry, 11, 483-504.
[57] Finn, M. (1986) Convulsive Therapy and Epilepsy Research. In: Trimble, M.R. and Reynolds, E.H., Eds., What Is Epilepsy? Churchill Livingstone, Edinburgh, 217-228.
[58] Van Ameringen, M., Manzini, C., Pipe, B. and Benett. M. (2004) Antiepileptic Drugs in Treatment of Anxiety Disorders: Role in Therapy. Drugs, 64, 2199-2220.
[59] Landmark, C.J. and Johannessen, S.I. (2010) New Antiepileptic Drugs in Neuropsychiatric Disorders. In: Ritchner, M.S., Ed., Brain Protection in Schizophrenia, Mood and Cognitive Disorders, Springer, New York, 485-504.
[60] Cookson, J. and Elliot, B. (2006) The Use of Anticonvulsants in the Aftermath of Mania. Journal of Psychopharmacology, 20, 23-30.
[61] Mazza, M., Di Nicola, M., Della Marca, G., Janiri, L., Bria, P. and Mazza. S. (2007) Bipolar Disorder and Epilepsy: A Biridectional Relation? Neurobiological Underpinings, Current Hypotheses, and Future Research Directions. Neurocientist, 13, 392-404.

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