Bipolar disorder INDEX

To date, there have only been a limited number of studies directly examining PKC in bipolar disorders [77], Although undoubtedly an oversimplification, particulate (membrane) PKC is sometimes viewed as the more active form of PKC, and thus an examination of the subcellular partitioning of this enzyme can be used as an index of the degree of activation. Friedman etal. [78] investigated PKC activity and PKC translocation in response to serotonin in platelets obtained from bipolar-disorder patients before and during lithium treatment. They reported that the ratios of platelet-membrane-bound to cytosolic PKC activities were elevated in the manic patients. In addition, serotonin-elicited platelet PKC translocation was found to be enhanced in those patients. With respect to brain tissue, Wang and Friedman [74] measured PKC isozyme levels, activity and translocation in postmortem brain tissue from patients with bipolar disorder, and reported increased PKC activity and translocation in the brains of bipolar patients compared with controls, effects which were accompanied by elevated levels of selected PKC isozymes in cortices of bipolar disorder patients. 

Lithium is used in the prophylaxis and treatment of mania and in the prophylaxis of bipolar disorders and recurrent depression. Lithium should be stopped 24 hours before major surgery but the normal dose can be continued for minor surgery, with careful monitoring of fluids and electrolytes. After major surgery, renal function is reduced and this may compromise clearance of lithium. Lithium is a drug with a narrow therapeutic index and it should be avoided if possible in patients with renal impairment. Renal function should be tested before initiating treatment. If lithium is given to patients with renal impairment, a reduced dose should be used and serum lithium concentrations should be monitored closely. 

In contrast with lithium, valproate has been associated with a good antimanic response in patients with concurrent depressive symptoms or syndromes. Calabrese and colleagues [Calabrese and Delucchi 1990 Calabrese et al. 1992, 1993a, 1993b] have reported favorable responses in patients with rapid-cycling bipolar disorder with index episodes of either mixed or pure mania who received open-label valproate alone or in combination with other psychotropic medication. For those patients who received valproate alone, 18 [95%] of 19 patients with pure mania had a moderate or better response, and 8 [80%] of 10 with mixed mania did similarly. T. W. Freeman et al. [1992] reported on 14 patients treated with valproate in a double-blind trial with lithium carbonate and found that patients responding to valproate had signifi-... 

In summary, although lithium has revolutionized the treatment of bipolar disorder, its narrow therapeutic index, numerous adverse effects, and relative ineffectiveness in a large proportion of bipolar patients has led to an expanding number of alternative approaches, including the following ... 

Recent extensive reviews describe current indications for lithium therapy primarily in bipolar disorders and experimentally in unipolar depression as well as schizo-affective schizophrenia, alcoholism, premenstrual cramps and character disorders. These reports also call attention to the narrow therapeutic index associated with its use and the need for careful moniterlng of serum levels. Serum levels of 0.6 to 1.5 mEq per liter are usually sufficient for management of symptoms. A dose of 300mg of lithium carbonate t.i.d. or q.l.d. is recommended to maintain these... 

I Lamotrigine has shown efficacy in rapid cycling bipolar disorder and prevents relapse into bipolar depression after index episodes of both mania and bipolar depression where it may be more effective than hthium. 

Popovic D, ReinaresM, Gaikolea JM, BonninCM, Gonzalez-Pinto A, Vieta E. Polarity index of pharmacological agents used for maintenance treatment of bipolar disorder. Fur Neuropsychopharmacol 2012 22(5) 339 6. 

Lithium is commonly used for bipolar affective disorders. Lithium however has a narrow therapeutic index and high risk for toxicity (Groleau 1994). The use of loop diuretics or ACE-inhibitors significantly increases the risk of hospitalisation for lithium toxicity in the elderly (Juurlink et al. 2004). Treatment of elderly patients with lithium should be thoroughly monitored. 

I Advantages. Valproic acid is available in multiple dosage formulations. It has a wide therapeutic index and can be considered a broad-spectrum AED. It also may be useful in other neurologic or psychiatric disorders, including migraine headache and bipolar-affective disorder. 

Biotechnology Industry Organization British Institute of Regulatory Affairs Biologic License Application Bioresearch Monitoring Branch Body Mass Index Bipolar Affective Disorder... 

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