It. is noteworthy, however, that Hough and colleagues49 have demonstrated that the mood stabilizers lithium, valproate, carbamazepine, and lamotrigine are all weak inhibitors of calcium influx through the glutamate N-methyl-D-aspartic acid (NMDA) receptor,
further suggesting that, modulation of this major excitatory neurotransmitter system in brain through other approaches could prove clinically useful for patients with bipolar disorder. To the extent that the ostensibly opposing behaviors and symptomatology exhibited in depression versus mania are attributable to excess Inhibitors,research,lifescience,medical activity in either inhibitory or excitatory neural substrates, one could envision how dampening neural excitability could be of potential use in both phases of the illness. Among the anticonvulsants, the sodium-channel
blockers, which inhibit, glutamate release, appear to be among those best, demonstrating antimanic efficacy compared with agents which enhance GABAergic mechanisms (gabapentin, Inhibitors,research,lifescience,medical tiagabine, topiramate) which, with the exception Inhibitors,research,lifescience,medical of valproate, do not, appear to exhibit, acute antimanic efficacy. Thus, modulation of glutamate mechanisms both to dampen overexcitability in both depression and mania, and potentially enhance glutamatergic tone for new learning and deconditioning, would appear to be valuable new potential approaches to the therapeutics of bipolar disorder. Considerable Inhibitors,research,lifescience,medical evidence implicates alteration in cytokine levels and functioning in the affective disorders.50,51 Preliminary attempts at using anti-inflammatory approaches, such as with antagonists of tumor necrosis factor, have been successful, and suggest a whole new approach to therapeutics in the future. Decreases in BDNF and increases in oxidative stress have also been seen during episodes of both mania and depression.52 As noted above, N-acctyl cysteine (NAC) is an antioxidant and a glutathione Inhibitors,research,lifescience,medical precursor. Recently, Harvey et al53 have shown significant effects of NAC over placebo in preventing bipolar episodes, particularly depressive recurrences in a selleck screening library 1-year
double-blind study. As an agent with few side effects and having the major asset, of preventing depressive episodes, this compound holds click here considerable therapeutic promise, both in its own right, and as a stalking horse for a new class of therapies. Also intriguing are the effects of NAC in decreasing cocaine intake noted above,15,54 and in reducing pathological gambling,55 problems not. uncommon in patients with bipolar illness. Vitamins, fatty acids, and other augmenting agents Megavitamin therapy has not. been proven to be effective in controlled clinical trials, but specific substances remain promising. For example, augmentation with folic acid (1 mg/day) is now widely recommended in refractory depression, based on a.