title: Lithium therapy in the treatment of manic-depressive illness. Present status and future perspectives. A critical review.
abstract: This article reviews critically the present status of lithium in the treatment and prophylaxis of manic-depressive illness compared to the two anticonvulsant drugs, carbamazepine and valproic acid. Lithium is used successfully in the prophylaxis and treatment of manic-depression. The mechanism by which it exerts its effects is still not very clear. There is much evidence to indicate that lithium may exert its therapeutic action by interfering with the metabolism of phosphoinositides which play an important role in synaptic transmission. Because of lithium's narrow therapeutic/toxic ratio, blood concentration monitoring is crucial. Published data suggest that, compared to lithium, carbamazepine is similar in its relative specificity in treating mania. It is often faster in achieving its antimanic effects and best established as an alternative for patients not responding or intolerant to lithium. Carbamazepine is a good substitute for lithium when severe renal problems exclude the use of lithium. The therapeutic profile of valproic acid in manic-depression, although less extensively studied, appears to be similar to that of carbamazepine. As carbamazepine, it seems to be best indicated in patients with rapid cycles. Whereas lithium inhibits myo-inositol monophosphatase, carbamazepine shows a stimulating effect and valproic acid has no effect on this biochemical target. The implication of the inositol pathway in the pathogenesis of adverse effects, such as neurotoxicity and dermatological irritation, is discussed. A further understanding of this pathway is important for the future development of new lithium-like compounds in order to maximize the therapeutic benefits without the adverse effects.
authors.affiliation: Bristol Myers Squibb, Pharmaceutical Research Institute, Waterloo, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Emilien
authors.forename: J M
authors.initials: JM
authors.lastname: Maloteaux
authors.forename: A
authors.initials: A
authors.lastname: Seghers
authors.forename: G
authors.initials: G
authors.lastname: Charles
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001667:Binding, Competitive; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002220:Carbamazepine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007295:Inositol Phosphates / Q000037:antagonists & inhibitors; D008094:Lithium / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014635:Valproic Acid / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D002121:Calcium Channel Blockers; D007295:Inositol Phosphates; D002220:Carbamazepine; D014635:Valproic Acid; C047872:inositol 2-monophosphate; D008094:Lithium; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase