Psychotropic effects of antiepileptic drugs

Background: Mood disorder symptoms are common in patients with epilepsy. Since antiepileptic drugs (AEDs) can affect these symptoms, knowledge of the psychotropic properties of AEDs is crucial. We review most studies of the psychotropic effects of AEDs that have involved potential psychiatric applications and have been reported in the psychiatric literature. Methods: We conducted a comprehensive literature search to identify relevant clinical trial reports on the efficacy of AEDs for mood disorders. Results: There have been few randomized controlled trials studying AED psychotropic properties in patients with epilepsy, but some randomized controlled trials of potential psychiatric indications for AEDs have been published. Data from these studies suggest that specific AEDs have mood stabilizing, anxiolytic, and antidepressant properties, while others may elicit depression, agitation, or psychosis. Conclusion: Antiepileptic drug selection should consider potential effects on mood and behavior.

[1]  P. Keck,et al.  Extended-release carbamazepine capsules as monotherapy for acute mania in bipolar disorder: a multicenter, randomized, double-blind, placebo-controlled trial. , 2005, The Journal of clinical psychiatry.

[2]  F. Besag.  Behavioural effects of the newer antiepileptic drugs: an update , 2004, Expert opinion on drug safety.

[3]  L. Lamoreaux,et al.  Effect of gabapentin (neurotonin®) on mood and well-being in patients with epilepsy , 1996, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[4]  T. Ketter,et al.  A multicenter, randomized, double-blind, placebo-controlled trial of extended-release carbamazepine capsules as monotherapy for bipolar disorder patients with manic or mixed episodes. , 2004, The Journal of clinical psychiatry.

[5]  C. Normann,et al.  Lamotrigine as adjunct to paroxetine in acute depression: a placebo-controlled, double-blind study. , 2002, The Journal of clinical psychiatry.

[6]  F. Cendes,et al.  Acute psychotic disorders induced by topiramate: report of two cases. , 2002, Arquivos de neuro-psiquiatria.

[7]  Joyce Cramer,et al.  Depression and comorbidity in community-based patients with epilepsy or asthma , 2004, Neurology.

[8]  E. Kossoff,et al.  Levetiracetam Psychosis in Children with Epilepsy , 2001, Epilepsia.

[9]  J. Calabrese,et al.  A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. Lamictal 614 Study Group. , 2000, The Journal of clinical psychiatry.

[10]  O. Devinsky,et al.  Two Cases of Nonconvulsive Status Epilepticus in Association with Tiagabine Therapy , 1999, Epilepsia.

[11]  J. Calabrese,et al.  A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. , 2003, Archives of general psychiatry.

[12]  Jullie W Pan,et al.  Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults , 1999, Neurology.

[13]  T. Ketter,et al.  Gabapentin augmentation therapy in bipolar depression. , 2002, Bipolar disorders.

[14]  H. Duggal,et al.  Worsening of psychosis or topiramate-induced adverse event? , 2004, General hospital psychiatry.

[15]  D. Labar,et al.  A Pilot Study of Mood in Epilepsy Patients Treated with Vagus Nerve Stimulation , 2000, Epilepsy & Behavior.

[16]  M. Trimble,et al.  Depression but not seizure frequency predicts quality of life in treatment-resistant epilepsy , 2004, Neurology.

[17]  G. Stores.  Behavioural Effects of Anti‐epileptic Drugs , 1975, Developmental medicine and child neurology.

[18]  Dean K. Naritoku,et al.  Enhanced recognition memory following vagus nerve stimulation in human subjects , 1999, Nature Neuroscience.

[19]  Josemir W Sander,et al.  Topiramate and Psychiatric Adverse Events in Patients with Epilepsy , 2003, Epilepsia.

[20]  A. Sólyom,et al.  Dose‐dependent Safety and Efficacy of Zonisamide: A Randomized, Double‐blind, Placebo‐controlled Study in Patients with Refractory Partial Seizures , 2005, Epilepsia.

[21]  J. Calabrese,et al.  Double-blind 18-month trial of lithium versus divalproex maintenance treatment in pediatric bipolar disorder. , 2005, Journal of the American Academy of Child and Adolescent Psychiatry.

[22]  Y. Bersudsky,et al.  Controlled double-blind trial of phenytoin vs. fluoxetine in major depressive disorder. , 2005, The Journal of clinical psychiatry.

[23]  W. Nolen,et al.  Prophylactic efficacy of lithium versus carbamazepine in treatment-naive bipolar patients. , 2003, The Journal of clinical psychiatry.

[24]  L. H. van den Berg,et al.  Increase of sural nerve T cells in progressive axonal polyneuropathy and monoclonal gammopathy , 2003, Neurology.

[25]  S. McElroy,et al.  A 52-week, open-label continuation study of lamotrigine in the treatment of bipolar depression. , 2004, The Journal of clinical psychiatry.

[26]  T. Suppes,et al.  Open-label adjunctive zonisamide in the treatment of bipolar disorders: a prospective trial. , 2005, The Journal of clinical psychiatry.

[27]  F. Goodwin,et al.  Effect of lamotrigine on cognitive complaints in patients with bipolar I disorder. , 2004, The Journal of clinical psychiatry.

[28]  G. Bersani.  Levetiracetam in bipolar spectrum disorders: first evidence of efficacy in an open, add‐ on study , 2004, Human psychopharmacology.

[29]  Peter K. Leiberich,et al.  Lamotrigine treatment of aggression in female borderline-patients: a randomized, double-blind, placebo-controlled study , 2005, Journal of psychopharmacology.

[30]  P. Crumrine,et al.  Phenobarbital treatment and major depressive disorder in children with epilepsy. , 1987, Pediatrics.

[31]  J. Walden,et al.  Levetiracetam in the treatment of acute mania: an open add-on study with an on-off-on design. , 2003, The Journal of clinical psychiatry.

[32]  M. Frye,et al.  Acute antimanic efficacy and safety of oxcarbazepine in an open trial with an on-off-on design. , 2002, Bipolar disorders.

[33]  P. Jansen,et al.  Sodium valproate in the treatment of aggressive behavior in patients with dementia—a randomized placebo controlled clinical trial , 2002, International journal of geriatric psychiatry.

[34]  R. Hirschfeld,et al.  Prevalence of bipolar symptoms in epilepsy vs other chronic health disorders , 2005, Neurology.

[35]  R. Ostroff,et al.  Reversal of symptomatic hyperprolactinemia by aripiprazole. , 2005, American Journal of Psychiatry.

[36]  D. Reith,et al.  Tolerability of topiramate in children and adolescents , 2003, Journal of paediatrics and child health.

[37]  J. Nurnberger,et al.  A preliminary open-label study of zonisamide treatment for bipolar depression in 10 patients. , 2005, Journal of Clinical Psychiatry.

[38]  Peter K. Leiberich,et al.  Treatment of aggression with topiramate in male borderline patients: A double-blind, placebo-controlled study , 2005, Biological Psychiatry.

[39]  A. Mishory,et al.  Prophylactic effect of phenytoin in bipolar disorder: a controlled study. , 2003, Bipolar disorders.

[40]  C. Dodrill,et al.  Effects of Tiagabine Monotherapy on Abilities, Adjustment, and Mood , 1998, Epilepsia.

[41]  M. Stanford,et al.  A comparison of anticonvulsants in the treatment of impulsive aggression. , 2005, Experimental and clinical psychopharmacology.

[42]  M. Frye,et al.  Tiagabine in treatment refractory bipolar disorder: a clinical case series. , 2002, Bipolar disorders.

[43]  J. Calabrese,et al.  A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. , 1999, The Journal of clinical psychiatry.

[44]  J. Calabrese,et al.  A Randomized, Placebo-Controlled 12-Month Trial of Divalproex and Lithium in Treatment of Outpatients With Bipolar I Disorder , 2000 .

[45]  D. Benson,et al.  Depression in epilepsy. Significance and phenomenology. , 1986, Archives of neurology.

[46]  Christian E Elger,et al.  Vagus nerve stimulation is associated with mood improvements in epilepsy patients , 2000, Epilepsy Research.

[47]  T. Ketter,et al.  Divalproex therapy in medication-naive and mood-stabilizer-naive bipolar II depression. , 2001, Journal of affective disorders.

[48]  N. Simon,et al.  An open-label study of levetiracetam for the treatment of social anxiety disorder. , 2004, The Journal of clinical psychiatry.

[49]  M. Nahata,et al.  Gabapentin Associated with Aggressive Behavior in Pediatric Patients with Seizures , 1996, Epilepsia.

[50]  G. Cassano,et al.  Oxcarbazepine as add-on treatment in patients with bipolar manic, mixed or depressive episode. , 2004, Journal of affective disorders.

[51]  M. Berk,et al.  Lamotrigine Compared with Lithium in Mania: A Double-Blind Randomized Controlled Trial , 2000, Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists.

[52]  T. Miyamoto,et al.  Psychotic episodes during Zonisamide treatment , 2000, Seizure.

[53]  J. Csernansky,et al.  Hippocampal atrophy in recurrent major depression. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[54]  C. Dodrill,et al.  Neuropsychological effects of carbamazepine and phenytoin , 1991, Neurology.

[55]  M. Rosenthal.  Tiagabine for the treatment of generalized anxiety disorder: a randomized, open-label, clinical trial with paroxetine as a positive control. , 2003, The Journal of clinical psychiatry.

[56]  Sidney H Kennedy,et al.  Topiramate versus bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: a preliminary single-blind study. , 2002, Bipolar disorders.

[57]  J. Wuu,et al.  A past psychiatric history may be a risk factor for topiramate-related psychiatric and cognitive adverse events , 2003, Epilepsy & Behavior.

[58]  G. Morris,et al.  Postmarketing Experience with Topiramate and Cognition , 2001, Epilepsia.

[59]  J. Cramer,et al.  A systematic review of the behavioral effects of levetiracetam in adults with epilepsy, cognitive disorders, or an anxiety disorder during clinical trials , 2003, Epilepsy & Behavior.

[60]  S. Moshé,et al.  Gabapentin Toxicity in Children Manifesting as Behavioral Changes , 1995, Epilepsia.

[61]  W. Fleischhacker,et al.  Worsening of psychosis after replacement of adjunctive valproate with topiramate in a schizophrenia patient. , 2003, The Journal of clinical psychiatry.

[62]  C. Normann,et al.  Tiagabine appears not to be efficacious in the treatment of acute mania. , 1999, The Journal of clinical psychiatry.

[63]  A. Rush,et al.  Effect size of lithium, divalproex sodium, and carbamazepine in children and adolescents with bipolar disorder. , 2000, Journal of the American Academy of Child and Adolescent Psychiatry.

[64]  K. Meador,et al.  Clinical assessment of Axis I psychiatric morbidity in chronic epilepsy: a multicenter investigation. , 2005, The Journal of neuropsychiatry and clinical neurosciences.

[65]  R. Belmaker,et al.  Phenytoin as an antimanic anticonvulsant: a controlled study. , 2000, The American journal of psychiatry.

[66]  G. Huster,et al.  Symptoms of depression in adolescents with epilepsy. , 1999, Journal of the American Academy of Child and Adolescent Psychiatry.

[67]  J. Lieberman,et al.  Olanzapine and Clozapine Increase the GABAergic Neuroactive Steroid Allopregnanolone in Rodents , 2003, Neuropsychopharmacology.

[68]  D. Janowsky,et al.  Effects of Topiramate on Aggressive, Self-Injurious, and Disruptive/Destructive Behaviors in the Intellectually Disabled: An Open-Label Retrospective Study , 2003, Journal of clinical psychopharmacology.

[69]  Barry R. Rittberg,et al.  A One-Year Comparison of Vagus Nerve Stimulation with Treatment as Usual for Treatment-Resistant Depression , 2005, Biological Psychiatry.

[70]  S. Helmers,et al.  Behavioral Side Effects of Gabapentin in Children , 1996, Epilepsia.

[71]  T. Suppes,et al.  Open-label adjunctive topiramate in the treatment of bipolar disorders , 2000, Biological Psychiatry.

[72]  Mustafa M. Husain,et al.  Vagus Nerve Stimulation for Treatment-Resistant Depression: A Randomized, Controlled Acute Phase Trial , 2005, Biological Psychiatry.

[73]  N. Kleindienst,et al.  Differential response to lithium and carbamazepine in the prophylaxis of bipolar disorder. , 1998, Journal of clinical psychopharmacology.

[74]  J. Davidson,et al.  Efficacy of the Novel Anxiolytic Pregabalin in Social Anxiety Disorder: A Placebo-Controlled, Multicenter Study , 2004, Journal of clinical psychopharmacology.

[75]  J. Calabrese,et al.  A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. , 2003, The Journal of clinical psychiatry.

[76]  J. Herranz,et al.  Clinical Side Effects of Phenobarbital, Primidone, Phenytoin, Carbamazepine, and Valproate During Monotherapy in Children , 1988, Epilepsia.

[77]  Peter K. Leiberich,et al.  Topiramate treatment of aggression in female borderline personality disorder patients: a double-blind, placebo-controlled study. , 2004, The Journal of clinical psychiatry.

[78]  J. Sackellares,et al.  Improvement in depression associated with partial epilepsy in patients treated with lamotrigine , 2002, Epilepsy & Behavior.

[79]  J. Cramer,et al.  Improved mood states with lamotrigine in patients with epilepsy , 2004, Epilepsy & Behavior.

[80]  T. Ketter,et al.  A 6-month, multicenter, open-label evaluation of beaded, extended-release carbamazepine capsule monotherapy in bipolar disorder patients with manic or mixed episodes. , 2004, The Journal of clinical psychiatry.

[81]  M. Berk,et al.  A double-blind, randomized, placebo-controlled trial of augmentation with lamotrigine or placebo in patients concomitantly treated with fluoxetine for resistant major depressive episodes. , 2003, The Journal of clinical psychiatry.

[82]  R. Post,et al.  Benzodiazepine withdrawal delirium with catatonic features. Occurrence in patients with partial seizure disorders. , 1989, Archives of neurology.

[83]  Shlomo Shinnar,et al.  Seizure Clustering: Risks and Outcomes , 2005, Epilepsia.

[84]  R. Fieve,et al.  Efficacy of Pregabalin in the Treatment of Generalized Anxiety Disorder: Double-blind, Placebo-Controlled Comparison of BID versus TID Dosing , 2005, Journal of clinical psychopharmacology.

[85]  R. Shrivastava,et al.  A Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose, Multicenter Study of Pregabalin in Patients With Generalized Anxiety Disorder , 2003, Journal of clinical psychopharmacology.

[86]  D. Labar,et al.  A Beneficial Effect on Mood in Partial Epilepsy Patients Treated with Gabapentin , 1999, Epilepsia.

[87]  E. Demet,et al.  Gabapentin as an Adjunct to Standard Mood Stabilizers in Outpatients with Mixed Bipolar Symptomatology , 1999, Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists.