Calcium bipolar disorder

INTRACELLULAR CALCIUM SIGNALING STUDIES IN BIPOLAR DISORDER 899... 

Calcium ions play a critical role in regulating the synthesis and release of neurotransmitters, in neuronal excitability, and in long-term neuroplastic events, and it is thus not surprising that a number of studies have investigated intracellular Ca2+ in peripheral cells, particularly in bipolar disorder. 

Ziprasidone Geodon Capsule 20, 40,60, 80 mg Calcium channel blockers Not FDA approved for bipolar disorder 40-160 mg/day in divided doses ... 

Carbamazepine produces complex effects in a variety of neurotransmitters, receptors, and second messenger and neuropeptide systems (Post et al. 1992, 1994a). Determining which of these effects is most closely associated with its psychotropic properties in bipolar disorder and which of these or other effects may be responsible for the augmentation response in combination therapy with dihydropyridine L-type CCBs remains to be further evaluated. However, discussion of two possibilities might be beneficial. One possibility, of course, is that actions of carbamazepine unrelated to calcium dynamics account for its augmenting effects with nimodipine. The plethora of these other... 

Dubovsky SL, Murphy J, Christiano J, et al The calcium second messenger system in bipolar disorders data supporting new research directions. J Neuropsychiatry Chn Neurosci 4 3-14, 1992b... 

Kusumi 1, Koyama T, Yamashita 1 Thrombin-induced platelet calcium mobilization is enhanced in bipolar disorders. Biol Psychiatry 32 731-734, 1992... 

Levy NA, Janicak PG. Calcium channel antagonists for the treatment of bipolar disorder. Bipolar Disora 2000 2 108-119. 

Calcium channel blockers Not FDA-approved for bipolar disorder ... 

There is some evidence that lithium may be effective in its treatment of bipolar disorder because it regulates the magnesium—calcium balance in the body. Would this appear to make sense from an inorganic chemist s point of view Why or why not ... 

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

Oarbamazepine is increasingly recognized as an effective treatment for bipolar affective illness, whereas the data on nimodipine and related calcium channel blockers [CCBs] are much more preliminary. In this chapter, we review data on the efficacy and putative mechanisms of action of carbamazepine and nimodipine in the recurrent affective disorders. 

FKiURE 6 5C. Efficacy of dihydropyridine L-type calcium channel blockers. Mean deviation from euthymia ratings (number of days in parentheses) in a patient with bipolar 11 disorder with ultra-ultrarapid cycling showing the following efficacy of nimodipine monotherapy efficacy of nimodipine-carbamazepine combination therapy unsuccessful transition from nimodipine to verapamil successful reinstitution of nimodipine-carbamazepine combination therapy and, finally, successful transition to isradipine-carbamazepine combination therapy. P <. 05 "nimodipine slowly tapered to zero. 

Berk M, Bodemer W, Van Oudenhove T, et al Dopamine increases platelet intracellular calcium in bipolar affective disorder and controls. Int Clin Psychopharmacol 9 291-293, 1994... 

Dubovsky SL, Thomas M, Hijazi A, et al Intracellular calcium signalhng in peripheral cells of patients with bipolar affective disorder. Eur Arch Psychiatry Clin Neurosci 243 229-234, 1994... 

Emamghoreishi M, Schhchter L, li PP, et al High intracellular calcium concentrations in transformed lymphoblasts from subjects with bipolar I disorder. Am J Psychiatry 154 976-982, 1997... 

Manna V [Bipolar affective disorders and role of intraneuronal calcium. Therapeutic effects of the treatment with lithium salts and/or calcium antagonist in patients with rapid polar inversion]. Minerva Med 82 757-763, 1991... 

In a series of studies, Dubovsky et al. ( 34) measured intracellular calcium ion concentrations in bipolar manic and depressed patients. They found decreases in mean concentrations in four bipolar, manic, and five bipolar, depressed, patients, in comparison with seven normothymic subjects without personal or first-degree relative histories of psychiatric disorders. Their findings were consistent with a diffuse abnormality in the mechanisms modulating intracellular calcium homeostasis. Further, this phenomenon s presence in both platelets and lymphocytes lends credence to a disruption in the cell membrane, the G-protein, or other mechanisms involved in the homeostasis of intracellular calcium ion concentrations. This may also support an extension of their findings from peripheral to neuronal tissue. 

These and other nonreceptor elements of the calcium-phosphoinositide signaling pathway are of considerable importance in pharmacotherapy. For example, lithium ion, used in treatment of bipolar (manic-depressive) disorder, affects the cellular metabolism of phosphoinositides (see Chapter 29). 

El Khoury A, Petterson U, Kallner G, Aberg-Wistedt A, Stain-Malmgren R. Calcium homeostasis in long-term lithium-treated women with bipolar affective disorder. Prog Neuropsychopharmacol Biol Psychiatry 2002 26(6) 1063-9. 

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