both have been shown to exacerbate depression, such that these agents which are effective in

the primary comorbid condition would not. appear to have utility in patients with bipolar disorder. Animal models of biphasic mood alterations While there are a number of useful models for acute antidepressant and antimanic efficacy, the field suffers from a lack of models representing biphasic alterations in mood and behavior, and the inherent cyclicity or mood phase reversal and recurrence of the disorder. One of the few exceptions to this is Antelman’s model of intermittent stressors or cocaine Inhibitors,research,lifescience,medical administration, which appears to be associated with inductions of alterations in hyperactive and inhibited behavior.62 Interestingly, in this model, inositol appears to improve and stabilize both the behavioral and Inhibitors,research,lifescience,medical neurochemical alterations evident, in this model. Examination of the efficacy of inositol in acute depression has led to equivocal results and perhaps deserves further exploration as a potential longterm therapeutic tool.63,64 Inhibitors,research,lifescience,medical One of the more intriguing features of bipolar illness is its potential for recurrence and behavioral oscillation to opposite poles at almost any frequency from intermittent and infrequent, episodic recurrences to more rapid, ultrarapid, and even ultradian cycling,

wherein mood can fluctuate numerous times within a single 24-hour period. Thus, examination of mechanisms

involved in this extraordinarily wide range Inhibitors,research,lifescience,medical of temporal manifestations of opposing mood and behavior in bipolar disorders would be a. fruitful avenue of investigation beyond the phenomena that show regular and invariant cyclicity in a given time Inhibitors,research,lifescience,medical domain. Thus, studies of diurnal alterations in circadian rhythms have been a primary focus of theoretical and empirical inquiry directed at. therapeutics of bipolar disorder, but may not, be adequate to deal with the extraordinary variability and aperiodicity that can be manifest in the illness. The Sitaxentan dihydropyridine L-type calcium channel blocker nimodipine has shown preliminary success in some patients with ultrafast (ultradian) mood switches,65 and this class of INCB28060 compounds deserves further exploration, even though a new dihydropyridine did not differ from placebo. Overview There are obviously a. multiplicity of novel potential approaches to the therapeutics of bipolar illness, as briefly outlined here. While each requires much further exploration in order to validate its potential utility, such exploration is also likely to yield many surprises, and some approaches will be developed much more rapidly than we can currently anticipate and envision. We have only preliminarily dealt with the issue of psychotherapy in conjunction with other approaches, but emphasize that there is a.