Mood Stabilizers and Ion Regulation

Abstract

Understanding the pathogenesis and pathophysiology of bipolar disorder is a prerequisite for accelerating the development of effective therapeutic agents and interventions. One of the best clues to these processes lies in shared mechanisms of action of mood-stabilizing agents. All effective mood stabilizers share the ability to attenuate the influx and intracellular accumulation of sodium in an activity-dependent manner. When coupled with independent observations of aberrant ion regulation in mania and bipolar depression, this shared characteristic is potentially significant. A unified hypothesis is presented in which lithium, valproic acid, and carbamazepine are suggested to produce antimanic effects by modifying ion flux and intracellular ion concentrations.

The ketogenic diet for type II bipolar disorder

“…This is in line with the presumed mechanism of action. Intracellular sodium elevations are an established abnormality in ill bipolar patients (El-Mallakh & Huff, 2001). Furthermore, bipolar patients may be less able to maintain normal intraneuronal pH (Gao et al, 2010).…”

“…Many anticonvulsant treatments have shown efficacy in bipolar disorder. This commonality appears to be related to the ability of these mood stabilizing anticonvulsants to reduce intracellular accumulation of sodium ions in an activity dependent manner (El-Mallakh & Huff, 2001).…”

Long-Term Use of Pramipexole in Bipolar Depression: A Naturalistic Retrospective Chart Review

“…Quetiapine may work through the active metabolite, N-desalkylquetiapine, which is a potent norepinephrine reuptake inhibitor (therefore, sometimes called norequetiapine) [15]. Lamotrigine's antidepressant mechanism is not known, but its action on the sodium channel and glutamate activity are purported to be important in its mood stabilizing properties [6]. These diverse mechanisms suggest that these may be many neuropsychopharmacologic targets in the treatment of bipolar depression.…”

“…Though the use of mood stabilizers in treating mania is effective, their use in the treatment of episodes with depression has been sub optimal [7]; El-Mallakh et al [6]). Antidepressants have been used in adjunct with mood stabilizers to treat depression, but this strategy may not be effective [21,22,25].…”

“…Antidepressants have been used in adjunct with mood stabilizers to treat depression, but this strategy may not be effective [21,22,25]. Specifically, antidepressants do not appear to provide any additional efficacy in the treatment of depression when added to mood stabilizers [25]; El-Malllakh et al [6]; [21]. Additionally, antidepressants have been associated with elevated risk of manic induction, mood destabilization, and irritable dysphoria [7].…”