The emerging differential roles of GABAergic and antiglutamatergic agents in bipolar disorders.

Treatment options to relieve the diverse symptoms encountered in patients with bipolar disorders include not only mood stabilizers, but also anxiolytics, new anticonvulsants, antidepressants, and antipsychotics. These agents have widely varying mechanisms of action, which could contribute to the heterogeneity of clinical effects seen in practice. Several of these medications, especially those with anticonvulsant effects, enhance gamma-aminobutyric acid (GABA) inhibitory neurotransmission and/or attenuate glutamate excitatory neurotransmission. We review the efficacy and tolerability of these diverse treatment options in bipolar disorders and explore possible relationships between clinical effects and GABAergic and antiglutamatergic mechanisms of action.

[1]  J. Krystal,et al.  Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. , 2002, The American journal of psychiatry.

[2]  A. Harris,et al.  Critical review of GABA-ergic drugs in the treatment of schizophrenia. , 1999, Journal of clinical psychopharmacology.

[3]  P. Skolnick,et al.  Adaptation of cortical NMDA receptors by chronic treatment with specific serotonin reuptake inhibitors. , 1998, European journal of pharmacology.

[4]  R. Post,et al.  Lack of beneficial effects of l-baclofen in affective disorder. , 1991, International clinical psychopharmacology.

[5]  K. Ice,et al.  A 3-week, double-blind, randomized trial of ziprasidone in the acute treatment of mania , 2000, European Neuropsychopharmacology.

[6]  D. Jody,et al.  Aripiprazole versus placebo in acute mania , 2002, European Neuropsychopharmacology.

[7]  M. Tohen,et al.  Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group. , 2000, Archives of general psychiatry.

[8]  M. Backonja Gabapentin Monotherapy for the Symptomatic Treatment of Painful Neuropathy: A Multicenter, Double‐blind, Placebo‐controlled Trial in Patients With Diabetes Mellitus 1 , 1999, Epilepsia.

[9]  G. Sachs,et al.  Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety. , 2002, The American journal of psychiatry.

[10]  K. Kaufman Adjunctive Tiagabine Treatment of Psychiatric Disorders: Three Cases , 1998, Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists.

[11]  J. Lieberman,et al.  Olanzapine increases allopregnanolone in the rat cerebral cortex , 2000, Biological Psychiatry.

[12]  M. Pollack,et al.  Placebo-controlled study of gabapentin treatment of panic disorder. , 2000, Journal of clinical psychopharmacology.

[13]  T. Ketter,et al.  Olanzapine in diverse syndromal and subsyndromal exacerbations of bipolar disorders. , 2002, Bipolar disorders.

[14]  J. Calabrese,et al.  Efficacy of Divalproex vs Lithium and Placebo in the Treatment of Mania , 1994 .

[15]  J. Calabrese,et al.  Third generation anticonvulsants in bipolar disorder: a review of efficacy and summary of clinical recommendations. , 2002, The Journal of clinical psychiatry.

[16]  M. Tohen,et al.  Olanzapine Versus Placebo in the Treatment of Acute Mania , 1999, American Journal of Psychiatry.

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

[18]  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.

[19]  J. Davidson,et al.  Treatment of social phobia with gabapentin: a placebo-controlled study. , 1999, Journal of clinical psychopharmacology.

[20]  A. Hufnagel,et al.  Different Effects of Gabaergic Anticonvulsants on 4-Aminopyridine-Induced Spontaneous Gabaergic Hyperpolarizations of Hippocampal Pyramidal Cells—Implication for their Potency in Migraine Therapy , 2000, Cephalalgia : an international journal of headache.

[21]  B. Birmaher,et al.  Is bipolar disorder specifically associated with panic disorder in youths? , 2002, The Journal of clinical psychiatry.

[22]  H. Kraemer,et al.  Clinical outcome in a randomized 1-year trial of clozapine versus treatment as usual for patients with treatment-resistant illness and a history of mania. , 1999, The American journal of psychiatry.

[23]  C. Schaffer,et al.  Tiagabine and the treatment of refractory bipolar disorder. , 1999, The American journal of psychiatry.

[24]  B. Dean,et al.  Clozapine and olanzapine treatment decreases rat cortical and limbic GABA(A) receptors. , 1998, European journal of pharmacology.

[25]  T. Iwamoto,et al.  Aripiprazole versus placebo in acute mania , 2003, Schizophrenia Research.

[26]  T. Ketter,et al.  Felbamate monotherapy has stimulant-like effects in patients with epilepsy , 1996, Epilepsy Research.

[27]  Daniel T. Crane Tiagabine for the Treatment of Anxiety , 2003, Depression and anxiety.

[28]  R. Hafner,et al.  The Prevalence of Comorbid Anxiety in Schizophrenia, Schizoaffective Disorder and Bipolar Disorder , 1998, The Australian and New Zealand journal of psychiatry.

[29]  P. Suppes,et al.  Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy. Gabapentin Bipolar Disorder Study Group. , 2000, Bipolar disorders.

[30]  J. Potash,et al.  Comorbid bipolar disorder and panic disorder in families with a high prevalence of bipolar disorder. , 2002, The American journal of psychiatry.

[31]  A. Guidotti,et al.  Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[32]  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.

[33]  Ellen Frank,et al.  Demographic and clinical characteristics of individuals in a bipolar disorder case registry. , 2002, The Journal of clinical psychiatry.

[34]  G. Chouinard The use of benzodiazepines in the treatment of manic-depressive illness. , 1988, The Journal of clinical psychiatry.

[35]  J. Bradwejn,et al.  Double-blind comparison of the effects of clonazepam and lorazepam in acute mania. , 1990, Journal of clinical psychopharmacology.

[36]  J. Coyle,et al.  The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. , 2001, The American journal of psychiatry.

[37]  C. Schaffer,et al.  An open case series on the utility of tiagabine as an augmentation in refractory bipolar outpatients. , 2002, Journal of affective disorders.

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

[39]  M. Frye,et al.  A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. , 2000, Journal of clinical psychopharmacology.

[40]  P. Skolnick,et al.  Adaptation of the N-methyl-D-aspartate receptor complex following chronic antidepressant treatments. , 1994, The Journal of pharmacology and experimental therapeutics.