Effect of sodium valproate on mania

Abstract

A possible antimanic property of the GABA-ergic anticonvulsant valproate was examined by use of a double-blind placebo-controlled ABA design in 5 acutely ill manic patients. In 4 cases a marked improvement was observed after valproate medication whereas one patient showed no response. Seven further patients with frequently recurrent episodes of a manic or maniform schizoaffective psychosis, irresponsive to lithium prophylaxis, were chronically treated with valproate in combination with low doses of lithium (one case only with valproate). Over an observation period of 1 1/2-3 years none of the patients exhibited a relapse. It is proposed that, in general, GABA-ergic anticonvulsants possess antimanic properties and that the specific antimanic effect of lithium is due to a GABA-ergic mode of action. The possible role of GABA-systems in affective disorders and in organic types of psychoses (e.g.,porphyria-psychosis, delirium tremens) is discussed on the basis of pharmacopsychiatric considerations.

Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways

“…The neurotransmitter GABA acts on ionotropic GABA A and GABA C receptors as well as metabotropic GABA B receptors [43]. Emrich et al [44] proposed the involvement of GABAergic dysfunction in mood disorders based on studies with the mood stabilizer, valproate, which effectively treats bipolar patients. Since valproate causes an enhancement in the concentration of GABA in the brain, the authors postulated that the pathophysiology of mood disorders involved GABAergic deficiency [44,45].…”

“…Emrich et al [44] proposed the involvement of GABAergic dysfunction in mood disorders based on studies with the mood stabilizer, valproate, which effectively treats bipolar patients. Since valproate causes an enhancement in the concentration of GABA in the brain, the authors postulated that the pathophysiology of mood disorders involved GABAergic deficiency [44,45]. Data obtained on the levels of GABA in plasma and cerebrospinal fluid are conflicting, with some studies reporting decreases and others no change [44].…”

“…Since valproate causes an enhancement in the concentration of GABA in the brain, the authors postulated that the pathophysiology of mood disorders involved GABAergic deficiency [44,45]. Data obtained on the levels of GABA in plasma and cerebrospinal fluid are conflicting, with some studies reporting decreases and others no change [44]. However, neuroimaging studies suggest the involvement of reduced GABAergic neurotransmission in major depressive disorder [46].…”

“…However, neuroimaging studies suggest the involvement of reduced GABAergic neurotransmission in major depressive disorder [46]. In addition, benzodiazepenes, anxiolytics used in the treatment of depression, directly enhance GABA function by interacting allosterically with the α 2 and α 5 subunits of the GABA A receptor [44]. Furthermore, the selective GABA reuptake inhibitor, tiagabine, which targets the GABA transporter GAT-1, has been effectively used in the treatment of anxiety-related behaviors in mouse and human studies [47].…”

“…GABA can induce the activity of norepinephrine in the rat brain [44]. Activation of GABA A receptors increases the release of norepinephrine in the rat hippocampus and cortex [55].…”